Contact-force monitoring increases accuracy of right ventricular voltage mapping avoiding “false scar” detection in patients with no evidence of structural heart disease

Purpose: Electroanatomical mapping (EAM) could increase cardiac magnetic resonance imaging (CMR) sensitivity in detecting ventricular scar. Possible bias may be scar over-estimation due to inadequate tissue contact. Aim of the study is to evaluate contact-force monitoring influence during EAM, in patients with idiopathic right ventricular arrhythmias. Methods: 20 pts (13 M; 43 ± 12 y) with idiopathic right ventricular outflow tract (RVOT) arrhythmias and no structural abnormalities were submitted to Smarttouch catheter Carto3 EAM. Native maps included points collected without considering contact-force. EAM scar was defined as area ≥1 cm2 including at least 3 adjacent points with signal amplitude (bipolar <0.5 mV, unipolar 3,5 mV), surrounded by low-voltage border zone. EAM were re-evaluated offline, removing points collected with contact force <5 g. Finally, contact force-corrected maps were compared to the native ones. Results: An EAM was created for each patient (345 ± 85 points). After removing poor contact points, a mean of 149 ± 60 points was collected. The percentage of false scar, collected during contact force blinded mapping compared to total volume, was 6.0 ± 5.2% for bipolar scar and 7.1 ± 5.9% for unipolar scar, respectively. No EAM scar was present after poor contact points removal. Right ventricular areas analysis revealed a greater number of points with contact force < 5 g acquired in free wall, where reduced mean bipolar and unipolar voltage were recorded. Conclusions: To date this is the first work conducted on structurally normal hearts in which contact-force significantly increases EAM accuracy, avoiding “false scar” related to non-adequate contact between catheter and tissue

Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a 5-year survival rate less than 8%, which has remained unchanged over the last 50 years. Early detection is particularly difficult due to the lack of disease-specific symptoms and a reliable biomarker. Multimodality treatment including chemotherapy, radiotherapy (used sparingly) and surgery has become the standard of care for patients with PDAC. Carbohydrate antigen 19–9 (CA 19–9) is the most common diagnostic biomarker; however, it is not specific enough especially for asymptomatic patients. Non-coding RNAs are often deregulated in human malignancies and shown to be involved in cancer-related mechanisms such as cell growth, differentiation, and cell death. Several micro, long non-coding and circular RNAs have been reported to date which are involved in PDAC. Aim of this review is to discuss the roles and functions of non-coding RNAs in diagnosis and treatments of PDAC

Detailed Analysis of a Contiguous 22-Mb Region of the Maize Genome

Most of our understanding of plant genome structure and evolution has come from the careful annotation of small (e.g., 100 kb) sequenced genomic regions or from automated annotation of complete genome sequences. Here, we sequenced and carefully annotated a contiguous 22 Mb region of maize chromosome 4 using an improved pseudomolecule for annotation. The sequence segment was comprehensively ordered, oriented, and confirmed using the maize optical map. Nearly 84% of the sequence is composed of transposable elements (TEs) that are mostly nested within each other, of which most families are low-copy. We identified 544 gene models using multiple levels of evidence, as well as five miRNA genes. Gene fragments, many captured by TEs, are prevalent within this region. Elimination of gene redundancy from a tetraploid maize ancestor that originated a few million years ago is responsible in this region for most disruptions of synteny with sorghum and rice. Consistent with other sub-genomic analyses in maize, small RNA mapping showed that many small RNAs match TEs and that most TEs match small RNAs. These results, performed on ∼1% of the maize genome, demonstrate the feasibility of refining the B73 RefGen_v1 genome assembly by incorporating optical map, high-resolution genetic map, and comparative genomic data sets. Such improvements, along with those of gene and repeat annotation, will serve to promote future functional genomic and phylogenomic research in maize and other grasses

CA 19-9: Biochemical and Clinical Aspects

CA19-9 (carbohydrate antigen 19-9, also called cancer antigen 19-9 or sialylated Lewis a antigen) is the most commonly used and best validated serum tumor marker for pancreatic cancer diagnosis in symptomatic patients and for monitoring therapy in patients with pancreatic adenocarcinoma. Normally synthesized by normal human pancreatic and biliary ductal cells and by gastric, colon, endometrial and salivary epithelia, CA 19-9 is present in small amounts in serum, and can be over expressed in several benign gastrointestinal disorders. Importantly, it exhibits a dramatic increase in its plasmatic levels during neoplastic disease. However, several critical aspects for its clinical use, such as false negative results in subjects with Lewis (a-b-) genotype and false positive elevation, occasional and transient, in patients with benign diseases, together with its poor positive predictive value (72.3 %), do not make it a good cancer-specific marker and renders it impotent as a screening tool. In the last years a large number of putative biomarkers for pancreatic cancer have been proposed, most of which is lacking of large scale validation. In addition, none of these has showed to possess the requisite sensitivity/specificity to be introduced in clinical use. Therefore, although with important limitations we well-know, CA 19-9 continues being the only pancreatic cancer marker actually in clinical use

Mitochondrial proteomic approaches for new potential diagnostic and prognostic biomarkers in cancer

Mitochondrial dysfunction and mutations in mitochondrial DNA have been implicated in a wide variety of human diseases, including cancer. In recent years, considerable advances in genomic, proteomic and bioinformatic technologies have made it possible the analysis of mitochondrial proteome, leading to the identification of over 1,000 proteins which have been assigned unambiguously to mitochondria. Defining the mitochondrial proteome is a fundamental step for fully understanding the organelle functions as well as mechanisms underlying mitochondrial pathology. In fact, besides giving information on mitochondrial physiology, by characterizing all the components of this subcellular organelle, the application of proteomic technologies permitted now to study the proteins involved in many crucial properties in cell signaling, cell differentiation and cell death and, in particular, to identify mitochondrial proteins that are aberrantly expressed in cancer cells. An improved understanding of the mitochondrial proteome could be essential to shed light on the connection between mitochondrial dysfunction, deregulation of apoptosis and tumorigenesis and to discovery new therapeutic targets for mitochondria-related diseases

Tailoring the ablative strategy for atrial fibrillation. A state-of-the-art review

In spite of technological progress and the improving skills of operators, atrial fibrillation (AF) ablation results appear to date to be at a plateau. In any case, the superiority of ablation over pharmacological therapy in terms of effectiveness, reduction of hospitalizations, and improvement has been well demonstrated in recent randomized trials. Triggers, substrate, and modulating factors (elements of Coumel's triangle) play different roles in paroxysmal and persistent AF, so induction and perpetuation mechanisms of arrhythmia may be different in each patient. Although effective ablative strategies are available for the treatment of paroxysmal AF triggers and persistent AF substrates, an adequate clinical evaluation of the patient is crucial in order to increase the chances of success. Recognizing triggers allows not only performing an effective ablation but also to avoid unnecessary lesions and at the same time reducing the risk of complications. AF beginning and triggers could be recorded by 12-lead ECG, continuous Holter monitoring, or implantable devices. In case of an unsuccessful noninvasive evaluation, nonpulmonary vein triggers should be investigated with an electrophysiological study. Persistent AF needs more effort to perform an accurate substrate characterization. Among the many methods proposed, recently the use of high-density mapping and multipolar catheters seems of particular benefit in order to clarify the arrhythmia mechanisms. Surgical and hybrid techniques allow to treat regions such as the posterior wall or Bachmann's bundle, which is fundamental for an ablative strategy that goes beyond just pulmonary vein isolation. Too often, patients are referred to electrophysiology laboratories without adequate preprocedural screening and planning in order to submit them to a standard "ready-made"procedure. The accurate search for triggers in paroxysmal AF and the correct recognition of the link between a possible underlying heart disease and the substrate in persistent AF could allow us to tailor the interventional approach in order to overcome the current plateau, increasing ablative procedure success and minimizing complications

Managing athletes with palpitations of unknown origin with an external loop recorder. A cohort study

BACKGROUND: Palpitations in athletes are usually benign, but the presence of major cardiac arrhythmias should be ruled out despite the infrequent appraisal of symptoms. External loop recorders (ELR) are promising to identify arrhythmias in these circumstances, but experiences in athletes are lacking. We aimed to investigate the feasibility and diagnostic yield of an ELR in athletes with unexplained palpitations in a cohort study. METHODS: One hundred twenty-two consecutive subjects (61 athletes and 61 sedentary controls) with sporadic palpitations and inconclusive diagnosis were enrolled and equipped with an ELR. Findings were categorized as major and minor arrhythmic findings, non-arrhythmic findings or negative monitoring. RESULTS: Long-term ELR monitoring was feasible in all subjects, with median duration of 12 (11; 15) days. Major arrhythmic events during palpitations were found in 9 (14.8%) athletes: 7 experienced sustained paroxysmal supraventricular tachycardia, and 2 had non sustained ventricular tachycardia. Minor arrhythmic events (premature supraventricular or ventricular beats) were observed in 13 athletes (21.3%). Nonarrhythmic findings (i.e., sinus rhythm or sinus tachycardia) were recorded in 28 athletes (45.9%), whereas 11 (18%) had negative monitoring. In the sedentary group, arrhythmic events were similar for types and frequency to athletes. The diagnostic yield of loop monitoring was 82.8% in the overall population and 82.0% in the athlete's group. CONCLUSIONS: In the management of an athlete symptomatic with unexplained palpitations after 24-hour ECG monitoring and stress test, ELR is an efficient tool to identify major arrhythmic events, which can be present in up to 10% of symptomatic athletes during practice and competition