Notes

[Use of the non-invasive respiratory system assistance in the geriatric advanced beginner attention unit : Your Geneva experience].
The present findings provide an insight at the protein level, into the mechanisms leading to an efficient bone reconstruction by blood/BCP composites. STATEMENT OF SIGNIFICANCE Upon implantation, scaffolds for bone repair are exposed to the patient's blood. Blood proteins adhere to bone substitute surface and this protein layer affects both biomaterial bioactivity and bone healing. Therefore, for the best outcome for patients, it is crucial to understand the molecular interactions between blood and bone scaffolds. ARV825 Biphasic calcium phosphate (BCP) ceramics are considered as the gold standard in bone reconstruction surgery. Here, using proteomic analyses we showed that the osteogenic properties of 80-200 µm BCP particles embedded in a blood clot is associated with a higher expression of fibrinogen. Fibrinogen upregulates the Myd88- and NF-κB-dependent TLR4 pathway in blood cells and, BCP-induced TLR4 activation is mediated by the LBP and CD14 proteins.Symptoms of COVID-19 range from asymptomatic/mild symptoms to severe illness and death, consequence of an excessive inflammatory process triggered by SARS-CoV-2 infection. The diffuse inflammation leads to endothelium dysfunction in pulmonary blood vessels, uncoupling eNOS activity, lowering NO production, causing pulmonary physiological alterations and coagulopathy. On the other hand, iNOS activity is increased, which may be advantageous for host defense, once NO plays antiviral effects. However, overproduction of NO may be deleterious, generating a pro-inflammatory effect. In this review, we discussed the role of endogenous NO as a protective or deleterious agent of the respiratory and vascular systems, the most affected in COVID-19 patients, focusing on eNOS and iNOS roles. link2 We also reviewed the currently available NO therapies and pointed out possible alternative treatments targeting NO metabolism, which could help mitigate health crises in the present and future CoV's spillovers.Dietary nitrate (NO3-) supplementation via beetroot juice (BR) has been reported to lower oxygen cost (i.e., increased exercise efficiency) and speed up oxygen uptake (VO2) kinetics in untrained and moderately trained individuals, particularly during conditions of low oxygen availability (i.e., hypoxia). However, the effects of multiple-day, high dose (12.4 mmol NO3- per day) BR supplementation on exercise efficiency and VO2 kinetics during normoxia and hypoxia in well-trained individuals are not resolved. In a double-blinded, randomized crossover study, 12 well-trained cyclists (66.4 ± 5.3 ml min-1∙kg-1) completed three transitions from rest to moderate-intensity (~70% of gas exchange threshold) cycling in hypoxia and normoxia with supplementation of BR or nitrate-depleted BR as placebo. Continuous measures of VO2 and muscle (vastus lateralis) deoxygenation (ΔHHb, using near-infrared spectroscopy) were acquired during all transitions. Kinetics of VO2 and deoxygenation (ΔHHb) were modeled using mono-exponential functions. Our results showed that BR supplementation did not alter the primary time constant for VO2 or ΔHHb during the transition from rest to moderate-intensity cycling. While BR supplementation lowered the amplitude of the VO2 response (2.1%, p = 0.038), BR did not alter steady state VO2 derived from the fit (p = 0.258), raw VO2 data (p = 0.231), moderate intensity exercise efficiency (p = 0.333) nor steady state ΔHHb (p = 0.224). Altogether, these results demonstrate that multiple-day, high-dose BR supplementation does not alter exercise efficiency or oxygen uptake kinetics during normoxia and hypoxia in well-trained athletes.Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. link3 Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research.Venous thromboembolism (VTE) prophylaxis in the setting of blunt traumatic visceral injury remains controversial. A total of 181 patients underwent splenic artery embolization (SAE) and began pharmacologic VTE prophylaxis at a median time of 59.5 hours (interquartile range, 46 hours). Six patients required splenectomy for rebleed. Fifty-one patients underwent SAE but did not receive anticoagulation therapy since they were considered low risk for VTE, and no splenectomies were performed (P = 1). Multivariate analysis showed no increased risk of need for splenectomy after beginning anticoagulation within 24 hours after SAE (P =.441). This study suggests that patients found to be at a high VTE risk should be considered for thromboprophylaxis within 24 hours after SAE.
To investigate and compare venous sac and feeding artery embolization (VFE) with feeding artery embolization (FAE) alone for treatment of pulmonary arteriovenous malformations (PAVMs), based on difference in outcomes in decrease of the size of the draining vein.

Twenty-six patients (7 male and 19 female; median age [interquartile range], 58 years [46-65 years]) with 42 simple PAVMs treated with coil embolization between August 2005 and December 2018 were retrospectively evaluated. Twenty PAVMs were treated with FAE early in the study period and compared with 22 PAVMs treated with VFE later in the study period. Follow-up computed tomography images obtained 8-20 months after embolotherapy were used for outcome analysis. Data related to patient demographics; follow-up period; baseline diameters of the feeding artery, venous sac, and draining vein; draining vein diameter after treatment; and decrease in the size of the draining vein, including the number reaching a threshold of 70% decrease, were compared between the 2 groups.

The draining vein decreased in size by a median of 46.4% in the FAE group and 66.3% in the VFE group, and the difference between the 2 groups was statistically significant (P= .009). There were no significant differences in the other parameters.

VFE leads to a greater decrease in the size of the draining vein than FAE, suggesting that VFE results in more complete occlusion than FAE for treatment of PAVMs.
VFE leads to a greater decrease in the size of the draining vein than FAE, suggesting that VFE results in more complete occlusion than FAE for treatment of PAVMs.
To evaluate the utility of computed tomography (CT) angiography before transarterial embolization (TAE) in predicting TAE's technical success for type II endoleaks (T2ELs).

Fifty-eight patients (mean age, 74.4 years; range, 46-89 years) who underwent attempted TAE for T2EL from July 2014 to August 2019 and underwent CT angiography before the procedure were included. Each CT angiography result was assessed for a feeding artery that was traceable over its entire course from either the superior mesenteric artery or the internal iliac artery to the endoleak cavity. TAE was performed using coils and was considered technically successful if embolization of the endoleak cavity and feeding artery was performed. The technical success rates were compared between patients with and without traceable feeding arteries.

A fully traceable feeding artery supplying 75% (44/59) of endoleaks in the cohort was identified. TAE was technically successful in 95% (42/44) of these cases but only in 13% (2/15) of the cases withou high failure rate when the feeding artery was not fully traceable suggests that translumbar embolization can be considered as an initial approach for theses patients.Various 6-alkynyl analogues of a known 3-nitro-2-(trifluoromethyl)-2H-chromene antagonist 3 of the Gq-coupled P2Y6 receptor (P2Y6R) were synthesized using a Sonogashira reaction to replace a 6-iodo group. The analogues were tested in a functional assay consisting of inhibition of calcium mobilization in P2Y6R-expressing astrocytoma cells elicited by native P2Y6R agonist UDP. 6-Ethynyl and 6-cyano groups were installed, and the alkynes were extended through both alkyl and aryl spacers. The most potent antagonists, with IC50 of ~1 µM, were found to be trialkylsilyl-ethynyl 7 and 8 (3-5 fold greater affinity than reference 3), t-butyl prop-2-yn-1-ylcarbamate 14 and p-carboxyphenyl-ethynyl 16 derivatives, and 3 and 8 displayed surmountable antagonism of UDP-induced production of inositol phosphates. Other chain-extended terminal carboxylate derivatives were less potent than the corresponding methyl ester derivatives. Thus, the 6 position in this chromene series is suitable for derivatization with flexibility of substitution, even with sterically extended chains, without losing P2Y6R affinity. However, a 3-carboxylic acid or 3-ester substitution did not serve as a nitro bioisostere, as the affinity was eliminated. These compounds provide additional ligand tools for the underexplored P2Y6R, which is a target for inflammatory, neurodegenerative and metabolic diseases.Marine alkaloids were divided into five categories from the perspective of anti-tumor activity. The optimization process, chemical synthesis, anti-tumor activity evaluation and structure-activity relationship of various compounds were discussed.Cellular therapies based on induced pluripotent stem cells (iPSCs) come out of age and an increasing number of clinical trials applying iPSC-based transplants are ongoing or in preparation. Recent studies, however, demonstrated a high number of small-scale mutations in iPSCs. Although the mutational load in iPSCs seems to be largely derived from their parental cells, it is still unknown whether reprogramming may enrich for individual mutations that could lead to loss of functionality and tumor formation from iPSC derivatives. 30 hiPSC lines were analyzed by whole exome sequencing. High accuracy amplicon sequencing showed that all analyzed small-scale variants pre-existed in their parental cells and that individual mutations present in small subpopulations of parental cells become enriched among hiPSC clones during reprogramming. Among those, putatively actionable driver mutations affect genes related to cell-cycle control, cell death, and pluripotency and may confer a selective advantage during reprogramming. Finally, a short hairpin RNA (shRNA)-based experimental approach was applied to provide additional evidence for the individual impact of such genes on the reprogramming efficiency. In conclusion, we show that enriched mutations in curated onco- and tumor suppressor genes may account for an increased tumor risk and impact the clinical value of patient-derived hiPSCs.
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