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The ubiquitin-proteasome system (UPS) degrades intracellular proteins through the 26S proteasome. We analysed how cold stress affects the UPS in glial cells. Together with a reduction in the 20S proteolytic activity and increased levels of polyubiquitinated proteins, exposure of glial cell cultures to cold induces a partial disassembly of the 26S proteasome. In particular, we found that Rpt5, a subunit of the 19S proteasome, relocates to cold-stable microtubules, although no apparent cytoskeletal redistribution was detected for other analysed subunits of the 19S or 20S complexes. Furthermore, we demonstrate that both the expression of the microtubule-associated protein MAP6 and the post-translational acetylation of α-tubulin modulate the association of Rpt5 with microtubules. This reversible association could be related to functional preservation of the proteolytic complex during cold stress.
Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF.
Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC.
The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/μL (0.31-2.15) and 3.41/μL (1.78-4.54), respectively, P< .0001. The total EPCs collected per patient were 3.3×10
(0.8×10
-6.8×10
).
We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.
We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.
The data concerning the use of bioresorbable vascular scaffolds (BVS) in coronary bifurcation lesions are limited.
The objective of the study was to evaluate the early and very long-term clinical outcomes of bifurcation stenting with ABSORB BVS.
One hundred consecutive patients with coronary bifurcation lesions treated with BVS were included. A total of 124 BVS were implanted. Provisional side branch stenting was performed in 66 patients, distal main stenting in 14 patients, systematic T stenting in 2, and T with minimal protrusion (TAP) in 5 patients. Side branch ostial stenting was performed in additional 12 patients.
The procedural success was achieved in 98% of patients. In long-term follow-up, the rate of cardiac death was 4.0%, target vessel myocardial infarction was 5.0%, and target vessel revascularization (TVR) was 11%. The cumulative incidence of definite/probable scaffold thrombosis (ST) was 2% at long-term follow-up. Comparison with the historical drug-eluting stents (DES) group revealed higher mortality and major adverse cardiac events rate in the ABSORB group.
Stenting of coronary bifurcation lesions of low-to-moderate complexity with BVS was feasible with good acute performance and acceptable results. However, the risk of death and major adverse cardiovascular events was higher as compared with DES.
Stenting of coronary bifurcation lesions of low-to-moderate complexity with BVS was feasible with good acute performance and acceptable results. However, the risk of death and major adverse cardiovascular events was higher as compared with DES.
Despite improvement in acute myocardial infarction (AMI) treatment, post-discharge mortality remains high. The outcomes are supposed to be even worse in patients with post-MI heart failure (HF), as only a half of patients with newly diagnosed HF survive four years.
The study aimed to analyze whether managed care after acute myocardial infarction (MC-AMI) is associated with better survival in AMI survivors with a pre-existing diagnosis of HF.
The study included 7228 patients with a pre-existing diagnosis of HF who survived the hospitalization for AMI in Poland between November 2017 and December 2020, of whom 2268 (31.4%) were referred for the MC-AMI program. The median follow-up was 1.5 (0.7-2.3) years. In the unmatched analysis, patients without MC-AMI had more than twice higher 12-month mortality (21.8% vs. 9.9%; P <0.01) than MC-AMI participants. The difference remained significant after propensity score matching (16,8% vs. 10.0%; P <0.01). In multivariable analysis, participation in MC-AMI was an independent factor of 12-month survival. MC-AMI participants had a lower stroke rate (1.5% vs. 3.0%; P <0.01) and fewer hospital admissions due to HF (22.9% vs. 27.6%; P <0.01).
After propensity score matching, participation in MC-AMI was associated with lower rates of stroke, HF hospitalizations, and all-cause mortality in the 12-month follow-up and was an independent factor of 12-month survival in AMI survivors with pre-existing HF.
After propensity score matching, participation in MC-AMI was associated with lower rates of stroke, HF hospitalizations, and all-cause mortality in the 12-month follow-up and was an independent factor of 12-month survival in AMI survivors with pre-existing HF.
Probiotics in fermented foods or commercially available supplements benefit the host by providing metabolites and peptides. The production of these metabolites varies with the available substrates or prebiotics present in the system and their concentration. In this study, 0.5% peanut flour (PF) was used to stimulate the growth and production of metabolites of wild-type Lactobacillus casei (LCwt) and compare with an engineered L. casei (LCCLA) capable of converting a higher amount of conjugated linoleic acid (CLA). The total extracellular metabolites present in the cell-free cultural supernatant (CFCS) of LCwt (without peanut), LCwt+PF (with peanut), and LCCLA were collected after 24 and 48 h of incubation, and their antagonistic activities against enterohemorrhagic Escherichia coli (EHEC EDL933) growth and pathogenesis were evaluated. All collected metabolites exhibited varying efficiency in restraining EHEC EDL933 growth, whereas supplementing a low concentration of CLA to the 48-h CFCS from LCwt showed augmented antagonism toward EHEC EDL933. S63845 molecular weight A downregulation of key virulence genes was observed from metabolites collected at the 48-h time point. These observations indicate that the presence of metabolites in CFCSs-including CLA, which is produced by Lactobacillus and was identified by gas chromatography-mass spectrometry-plays a critical role. This study demonstrates the potential applicability of Lactobacillus-originated CLA in the prevention of EHEC EDL933-mediated illnesses.
Patients with COVID-19 often present with life-threatening hypoxemia without dyspnea or signs of respiratory distress. Termed silent or happy hypoxia, it has puzzled clinicians and challenged and defied our understanding of normal respiratory physiology. A range of host- and pathogen-related factors appears to contribute to its development, including SARS-CoV-2's ability to produce different COVID-19 phenotypes; induce endothelial damage and elicit a vascular distress response; invade cells of the central nervous system and disrupt normal interoception and response; and modulate transcription factors involved in hypoxic responses. Because hypoxemia in COVID-19 is associated with increased mortality risk and poorer survival, early detection and prompt treatment is essential to prevent potential complications. Interventions to prevent hypoxemia and improve oxygen delivery to the blood and the tissues include home pulse-oximetry monitoring, optimization of patient positioning, judicious use of supplemental oxygen, breathing control exercises, and timely and appropriate use of ventilatory modalities and adjuncts.
Cereal grains are usually ensiled to improve their nutritional value and are one of the main sources of feed for dairy cattle. However, during storage, grains can be contaminated with toxicogenic fungi. Sorghum is one of the most economically important cereals in the world. Therefore, the aim of this work was to evaluate the influence of storage duration and tannin and moisture content (MC) on toxicogenic fungal populations in sorghum grain storage. Samples that were prepared with varieties high in tannins (genotypes Morgan 108 and ACA 558, >5 g/kg dry matter) and with varieties low in tannin content (genotypes Flash 10 and ACA 546, <1 g/kg dry matter) were collected and manually compacted in experimental laboratory silos where they received different MC treatments low (15 to 25%), medium (26 to 32%), and high (33 to 42%). Freshly harvested grains were analyzed at time 0, and stored grains were analyzed at 30, 90, and 180 days. Fungal isolation and identification were performed following conventional mycological methods. Penicillium citrinum (34%), Aspergillus flavus (60%), and Fusarium nygamai (68%) were the most abundant species. Rapid detection of aflatoxins and fumonisins in each sample was performed using enzyme-linked immunosorbent assay according to the AOAC method, and the quantification of aflatoxin B1 was performed using high-performance liquid chromatography. In four samples of pre- and poststorage grains, aflatoxins were detected with levels of 6.7 to 28.8 μg/kg and aflatoxin B1 with a level of 2 to 14 μg/kg. Fumonisins were only detected in two freshly harvested samples, with levels of 500 to 900 μg/kg. In general, storage time favored the increase of Penicillium populations and reduced Aspergillus and Fusarium. Conversely the abundance of the three populations was not affected by the MC. The results of this study show that fungal populations must be analyzed at different times.
The publication of ISO 4135, Anaesthetic and respiratory equipment-Vocabulary, fourth edition, highlights expansion of the scope of the International Organization for Standardization (ISO) Technical Committee (TC) 121 and its Subcommittees and Working Groups during two decades of work. This document stands alongside ISO 192232019, Lung ventilators and related equipment-Vocabulary and semantics, to promote consistency and specificity of terminology across ISO/TC 121 standards.Vaccine-induced thrombotic thrombocytopenia (VITT) is triggered by vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2-S). In this observational study, we followed VITT patients for changes in their reactivity of platelet-activating antiplatelet factor 4 (PF4) immunoglobulin G (IgG) antibodies by an anti-PF4/heparin IgG enzyme immunoassay (EIA) and a functional test for PF4-dependent, platelet-activating antibodies, and new thrombotic complications. Sixty-five VITT patients (41 females; median, 51 years; range, 18-80 years) were followed for a median of 25 weeks (range, 3-36 weeks). In 48/65 patients (73.8%; CI, 62.0% to 83.0%) the functional assay became negative. The median time to negative functional test result was 15.5 weeks (range, 5-28 weeks). In parallel, EIA optical density (OD) values decreased from median 3.12 to 1.52 (P 11 weeks. None of the 29 VITT patients who received a second vaccination dose with an mRNA COVID-19 vaccine developed new thromboses or relevant increase in anti-PF4/heparin IgG EIA OD, regardless of whether PF4-dependent platelet-activating antibodies were still present.
