Could specific EKG markers identify a pharmacologically induced type 1 Brugada pattern? Insights from a large, single-centre cohort

Abstract Funding Acknowledgements Type of funding sources: None. Background. Pharmacological (Ajmaline) induction of a type 1 Brugada pattern is currently considered mandatory for the diagnosis of Brugada syndrome. However, performing the test requires time and healthcare resources. Some EKG markers have been proposed as predictors of positive result at Ajmaline test. Aim. To evaluate in a large population the predictive value of multiple EKG markers for Ajmaline test results. Methods. We retrospectively analysed consecutive patients (pts) referred to our Centre to perform Ajmaline test. All pts had type 2 Brugada pattern detected at a conventional EKG or were relatives of pts with positive Ajmaline test, with or without type 2 Brugada pattern at EKG. All pts performed the Ajmaline pharmacological test (1 mg/Kg iv) with EKG "superior" right precordial unipolar derivations monitoring. To determine whether clinical parameters (age, gender, cardiomyopathy, history of arrhythmias, symptoms, familiarity) and EKG markers (heart rate (HR), PR duration, R1V1 and SV6 duration and amplitude, QRSV1/QRSV6 duration, V1 and V2 ST amplitude (coved or saddle back pattern) were independently associated to positivity at Ajmaline test, a logistic regression model was applied. Results. From January 2010 to December 2019 we evaluated 442 consecutive pts: mean age 40.1 ± 14.5 years; 273 (65%) male; 352 (80%) pts were included because of type 2 Brugada pattern at EKG and 90 (20%) for familial screening. The Ajmaline test was positive in 150 (34%) pts. At multivariate logistic regression analysis adjusted for baseline confounders, age > 45 years (OR= 1.64, 95%CI: 1.03 to 2.54; p = 0.0385), female gender (OR = 1.79, 95%CI: 1.12 to 2.85; p = 0.0141), HR > 60 bpm (OR = 2.44, 95%CI: 1.48 to 4.03; p = 0.0005), QRSV1/QRSV6 duration (msec) >1 (OR = 5.34, 95%CI: 3.28 to 8.69; p < 0.0001) and non isoelectric pattern (coved/saddle back) in V2 (OR = 1.93, 95%CI: 1.03 to 3.63, p = 0.0416) remained associated with a positive Ajmaline test. The percentage of pts with positive Ajmaline test increased according to the presence of significant EKG markers in their risk profile: 11.3% (8 out 71, absence of both QRSV1/QRSV6 duration (msec) >1 and V2 non isoelectric pattern), 24.3% (50 out 206, presence of only V2 non isoelectric pattern), 48.5% (16 out 33, presence of only QRSV1/QRSV6 duration (msec) >1), 57.6% (76 out 132, presence of both factors). Conclusions. In our large population: 1) we confirmed the positive predictive power of QRSV1/QRSV6 duration (msec) >1 and of a non isoelectric pattern (coved/saddle back) in V2 for a pharmacologically induced type 1 Brugada pattern; 2) we observed a non-negligible percentage of pts who would not be correctly diagnosed for type 1 Brugada pattern, if selected according to an EKG parameters-based prescreening

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al

Notulae to the Italian alien vascular flora: 3

In this contribution, new data concerning the Italian distribution of alien vascular flora are presented. It includes new records, exclusions, confirmations, and status changes for Italy or for Italian administrative regions for taxa in the genera Acer, Amaranthus, Araujia, Aubrieta, Avena, Bidens, Calycanthus, Celtis, Elaeagnus, Eragrostis, Euonymus, Fallopia, Ficus, Hedera, Lantana, Ligustrum, Ludwigia, Morus, Oenothera, Opuntia, Oxalis, Parkinsonia, Paspalum, Paulownia, Platycladus, Pleuropterus, Rumex, Salvia, Senecio, Setaria, Syagrus, Tradescantia, Trifolium and Yucca. Furthermore, a new combination in the genus Vicia is proposed

Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer

<p>Abstract</p> <p>Background</p> <p>Activating mutations of the epidermal growth factor receptor (<it>EGFR</it>) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.</p> <p>Methods</p> <p>Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.</p> <p>Results</p> <p>EGFR protein overexpression (EGFR_high) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFR_hightumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFR_low). Microarray analysis did not reveal any differences in gene expression between EGFR_highand EGFR_lowtumours. Conversely, in EGFR_hightumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFR_high(n=3) and mutated/EGFR_lowtumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.</p> <p>Conclusions</p> <p>Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.</p

Effect of thermal processing on the tribology of nanocrystalline Ni/TiO2 coatings

yesThe tribological performance of a nanocrystalline coating is heavily influenced by its composition, morphology, and microstructural characteristics. This research work describes the effect of heat treatment temperature on the microstructural, morphological, and mechanical behavior of nanocrystalline Ni/TiO2 coatings produced by electrophoresis. The surface morphology and coating cross section were characterized by scanning electron microscopy (SEM). The composition of coatings and the percentage of TiO2 nanoparticles incorporated in the Ni matrix were studied and estimated by using an energy-dispersive spectroscopic (EDS) analysis, while x-ray diffractometry (XRD) was used to investigate the effect of heat treatment temperature on phase structure. The results showed agglomeration of TiO2 nanoparticles on the surface of the coating. The high hardness and wear resistance recorded for the as-deposited coating was attributed to the uniform distribution of TiO2 nanoparticle clusters throughout the cross section of the coating. Heat treatment of the Ni/TiO2 coatings to temperatures above 200 °C led to significant grain growth that changed the surface morphology of the coating and reduced the strengthening effects of the nanoparticles, thus causing a reduction in the hardness and wear resistance of the coatings

Pathobiological Implications of the Expression of EGFR, pAkt, NF-κB and MIC-1 in Prostate Cancer Stem Cells and Their Progenies

The progression of prostate cancers (PCs) to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-κB) and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser473-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of 76 cases of prostatic adenocarcinoma specimens during the disease progression and these biomarkers were expressed in a small subpopulation of CD133+ PC cells and the bulk tumor mass of CD133− PC cells. Importantly, all of these biomarkers were also overexpressed in 80–100% of 30 PC metastasis bone tissue specimens. Moreover, the results have indicated that the EGF-EGFR signaling pathway can provide critical functions for the self-renewal of side population (SP) cells endowed with stem cell-like features from highly invasive WPE1-NB26 cells. Of therapeutic interest, the targeting of EGFR, pAkt, NF-κB or MIC-1 was also effective at suppressing the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells, inducing disintegration of SP cell-derived prostaspheres and decreasing the viability of SP and non-SP WPE1-NB26 cell fractions. Also, the targeting of these oncogenic products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26 cells and enhanced their sensibility to the cytotoxic effects induced by docetaxel. These findings suggest that the combined use of EGFR, pAkt, NF-κB and/or MIC-1 may represent promising strategies for improving the accuracy of current diagnostic and prognostic methods and efficacy of treatments of PC patients in considering the disease heterogeneity, thereby preventing PC progression to metastatic and lethal disease states

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

Slice-level rate-distortion optimized multiple description coding for H.264/AVC

We propose a novel standard-compliant multiple description coding (MDC) method that exploits the H.264/AVC redundant slice tool, performing rate-distortion optimization at the slice level. The strategy to allocate redundancy to each slice jointly takes into account its contribution to distortion, its position in the GOP, the effect of decoder error concealment, and the transmission conditions. This makes the algorithm more accurate with respect to previous frame-based solutions, and experimental results show that it compares favorably with other state-of-the-art standard-compliant MDC techniques