Search

Permanent magnet synchronous machines (PMSMs) drives are attractive and have been used in several applications, because of their noteworthy advantages. In some applications, the continuous operation is necessary, and then the PMSM drive outage is unacceptable or may cause great losses. Thus, several studies have been accomplished in order to detect incipient faults in PMSMs. In this context, the electrical signature analysis (ESA) technique is highlighted, because of the feasibility and non-invasive features. ESA allows the fault detection by only analyzing the electrical machine quantities. This paper proposes a study of ESA for PMSM condition monitoring. The review of some fault patterns is presented as well as the development of a scale model laboratory to simulate faults in a real PMSM in operation. The PMSM is used to drive a fluid pumping system, and different types of fluids are tested, being different load conditions from the PMSM point of view. The presented results are promising, encouraging ESA based methodologies for PMSM fault detection.

Purpose: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg -1 ., Methods: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg -1 of crystalloids in 10 (FC 10 ) or 20 (FC 20 ) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (d max ), time when the d max was observed (t max ), change from baseline at 1-min (d 1 ) and 5-min (d 5 ) after FC end., Results: After FC 10 and FC 20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The d max and the t max were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end., Conclusions: The infusion time of FC administration affects fluid responsiveness, being higher for FC 10 as compared to FC 20 . The effect on flow variables of either FCs fades 5 min after the end of infusion., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

BRAF V600E is the most frequent oncogenic mutation identified in papillary thyroid cancer (PTC). In PTC patients who do not respond to standard treatment, BRAF inhibitors are currently tested as alternative strategies. However, as observed for other targeted therapies, patients eventually develop drug resistance. The mechanisms of BRAF inhibitors response are still poorly understood in a thyroid cancer (TC) context. In this study, we investigated in BRAF V600E mutated TC cell lines the effects of Vemurafenib and Dabrafenib, two BRAF inhibitors currently used in a clinical setting. We assessed cell proliferation, and the expression and activity of the thyroid function related transporter NIS following the treatment with BRAF inhibitors. In addition, we investigated the global gene expression by microarray, the relevant modulated biological processes by gene set enrichment analysis (GSEA), and TC specific gene signatures related to MAPK pathway activation, thyroid differentiation, and transcriptional profile associated with BRAF V600E or RAS mutation. We found that both inhibitors induce antiproliferative and redifferentiative effects on TC cells, as well as a rewiring of the MAPK pathway related to RAS signaling. Our results suggest a possible mechanism of drug response to the BRAF inhibitors Vemurafenib or Dabrafenib, supporting very recent findings in TC patients treated with targeted therapies.

Introduction: Serine/threonine kinase 11 (LKB1/STK11) is one of the most mutated genes in NSCLC accounting for approximately one-third of cases and its activity is impaired in approximately half of KRAS-mutated NSCLC. At present, these patients cannot benefit from any specific therapy., Methods: Through CRISPR/Cas9 technology, we systematically deleted LKB1 in both wild-type (WT) and KRAS-mutated human NSCLC cells. By using these isogenic systems together with genetically engineered mouse models we investigated the cell response to ERK inhibitors both in vitro and in vivo., Results: In all the systems used here, the loss of LKB1 creates vulnerability and renders these cells particularly sensitive to ERK inhibitors both in vitro and in vivo. The same cells expressing a WT LKB1 poorly respond to these drugs. At the molecular level, in the absence of LKB1, ERK inhibitors induced a marked inhibition of p90 ribosomal S6 kinase activation, which in turn abolished S6 protein activation, promoting the cytotoxic effect., Conclusions: This work shows that ERK inhibitors are effective in LKB1 and LKB1/KRAS-mutated tumors, thus offering a therapeutic strategy for this prognostically unfavorable subgroup of patients. Because ERK inhibitors are already in clinical development, our findings could be easily translatable to the clinic. Importantly, the lack of effect in cells expressing WT LKB1, predicts that treatment of LKB1-mutated tumors with ERK inhibitors should have a favorable toxicity profile., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front., Competing Interests: The authors declare no conflict of interest.

Background: The Spritztube is a new supraglottic airway device combining the ability to allow extraglottic ventilation of the lungs with the opportunity to perform fibreoptic-assisted intubation., Objectives: To compare the Spritztube tracheal cannula with the Laryngeal Mask Airway Supreme (LMA-S) in anaesthetised adult patients., Design: A single-centre, randomised controlled study., Setting: Tertiary hospital., Patients: Mechanically ventilated patients undergoing elective surgery in the supine position under general anaesthesia were included. Main exclusion criteria were a history of, or predicted, difficult airway management according to SIAARTI guidelines and absence of written informed consent., Interventions: Patients received the LMA-S or Spritztube tracheal cannula to facilitate ventilation of the lungs., Main Outcome Measures: Successful placement (primary outcome), time required for insertion, number of attempts, subjective assessment of ease of insertion, safety and incidence of complications were recorded., Results: One hundred and sixty seven patients were allocated to the LMA-S or Spritztube group, respectively, a total of 334 patients. In the LMA-S group, the device insertion failed in nine patients, compared with none in the Spritztube group (P = 0.002). Spritztube insertion was easy in 100% of cases compared with 94.6% of the cases in the LMA-S group (P = 0.03). The number of attempts was significantly higher with the LMA-S compared with the Spritztube (P = 0.0007), whereas the insertion times were comparable (P = 0.06). Except for the incidence of blood-staining, which was higher in the LMA-S group (P = 0.01), the number of complications was comparable in the two groups., Conclusion: The Spritztube was as effective as the LMA-S in maintaining the airway with all patients being successfully ventilated without difficulty. The success rate of achieving a patent airway was comparable between the groups, with a similar occurrence of complications., Trial Registration: NCT03443219.

Copper, the highly toxic micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1 (high-affinity copper transporter 1), a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes. DMT1 cannot be a donor of catalytic copper because it does not have a cytosol domain which is required for copper transfer to the Cu-chaperons that assist the formation of cuproenzymes. Here, we assume that DMT1 can mediate copper way required for a regulatory copper pool. To verify this hypothesis, we used CRISPR/Cas9 to generate H1299 cell line with CTR1 or DMT1 single knockout (KO) and CTR1 / DMT1 double knockout (DKO). To confirm KOs of the genes qRT-PCR were used. Two independent clones for each gene were selected for further studies. In CTR1 KO cells, expression of the DMT1 gene was significantly increased and vice versa. In subcellular compartments of the derived cells, copper concentration dropped, however, in nuclei basal level of copper did not change dramatically. CTR1 KO cells, but not DMT1 KO, demonstrated reduced sensitivity to cisplatin and silver ions, the agents that enter the cell through CTR1. Using single CTR1 and DMT1 KO, we were able to show that both, CTR1 and DMT1, provided the formation of vital intracellular cuproenzymes (SOD1, COX), but not secretory ceruloplasmin. The loss of CTR1 resulted in a decrease in the level of COMMD1, XIAP, and NF-κB. Differently, the DMT1 deficiency induced increase of the COMMD1, HIF1α, and XIAP levels. The possibility of using CTR1 KO and DMT1 KO cells to study homeodynamics of catalytic and signaling copper selectively is discussed.

The purpose of our study was to evaluate, during the early phase, the coronary anatomy of the patients who suffered from an acute non-Q myocardial infarction (non-Q MI) and to correlate it with the ECG findings and with clinical evolution. We studied 76 patients (pts.), mean age 56 +/- 9 years, who had their a first non-Q MI (reinfarctions non included). They all underwent angiographic examination within an average period of 18 days (range 5-30 days). In the whole group of patients it is worthwhile noting: A) the elevated occurrence of left main lesions (11% of pts.) and multivessel disease (60%); B) the great percentage (41%) of patients with open infarct-related vessel but with very critical residual stenosis (above 90% of total lumen); C) the presence of collateral vessels in almost all the pts. (91%) with totally occluded infarct-related artery. During the 12 month follow-up, in all groups was a high occurrence (above 70%) of coronary events (postinfarction angina, reinfarction, aortocoronary by pass or PTCA). Furthermore, it is possible to identify a subgroup of patients presenting ST-segment depression with very unfavourable coronary anatomy (80% had multivessel disease, 30% of which had a left main critical stenosis) and high prognostic risk (90% occurrence of coronary events). In the subgroup with ST-segment elevation there was an elevated percentage (65%) of open infarct-related vessel, but with an important residual stenosis. Considering the advantages of revascularization interventions in these high risk patients with extensive residual jeopardized myocardium, we conclude that it is important that all patients with non-Q MI undergo early coronary angiography.

Unlabelled: The purpose of our study was to evaluate, with noninvasive procedures, the incidence and the clinical picture of right ventricular involvement in patients with acute transmural inferior myocardial infarction. Our study group was constituted of 107 consecutive patients admitted to our Coronary Care Unit within 10 hours from the onset of symptoms; in every patient a standard 12-leads ECG and the precordial leads V3R and V4R were obtained at admission in CCU and then every 12 hours. 80 patients underwent B-mode echocardiographic evaluation within 36 hours and in 93 patients a myocardial scintigraphy was performed, between the 48th and 72nd hour from the onset of chest pain, 1-2 hours after injection of Tc-99m-pyrophosphate., Results: 45 patients (42.1%) had ECG positive for right ventricular infarction, 49 patients (51.6%) had positive Tc-99m-pyrophosphate scintigraphy and 24 patients (30%) positive echocardiography. By using the positivity of ECG and another method at least, patients were separated into 2 groups: group A (associated inferior and right infarction) was constituted of 45 patients, and group B (isolated inferior infarction) was constituted of 62 patients. In group A we noted a higher incidence of hypotension (systolic blood pressure less than 100 mmHg) and oliguria (less than 30 ml/h)- p less than 0.01-, of 2nd and 3rd A-V blocks-p less than 0.001- and primary ventricular fibrillation -p less than 0.01. The incidence of parossistic atrial fibrillation, severe bradycardia or SA blocks and of mortality was not statistically different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)