Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

Background: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P,0.05). Conclusion: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity

Drought-related root morphological traits and non-structural carbohydrates in the seedlings of the alien Quercus rubra and the native Quercus robur: possible implication for invasiveness

Quercus rubra L. is a moderately shade-tolerant tree species native to eastern North America, readily regenerating since its introduction in the Central and Southern European forests to displace the native pedunculate oak (Quercus robur). Under a scenario of increasing drought, understanding the seedling responses of these two species to water limitation is critical for forest conservation and management. To this aim, morphological, physiological and non-structural carbohydrates analyzes were performed on very-fine and fine roots of Q. robur and Q. rubra seedlings grown under controlled conditions and exposed to two levels of drought before allowing them to recover. Results show significant differences between species for all the investigated traits. The alien Q. rubra showed lower shoot and root biomasses than the native Q. robur, particularly for the thicker fine root 1–2 mm diameter class. However, both species equally invested more biomass in the shoot than the root system (R:S ratio <1). A significant response to drought was observed for the 0.5–1 mm fine root class, with moderate and severe droughted seedlings showing slightly higher biomass than control, particularly in Q. rubra. The overall growth reduction of Q. rubra suggests that the costs associated with the construction and maintenance outweigh the inputs from aboveground, as supported by the lower values of photochemical efficiency (Fv/Fm), quantum yield (ΦPSII) of PSII and stomatal conductance. In particular, the reduced stomatal conductance assured high midday leaf water potential (i.e., tissue hydration levels) at the expense of growth. The low starch concentration in Q. rubra’s very-fine roots correlated positively with the low photochemical efficiency under drought conditions, probably due to the reduction of photosynthate inputs from aboveground. In contrast to the anisohydric behavior reported, these outcomes highlight a rather isohydric behavior for Q. rubra, at least at the seedling stage and in the adopted experimental conditions, making this species highly competitive under the drier condition in the canopy openings during the summer period

Possible predicative role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients. preliminary data

Background:Transcatheter aortic valve replacement (TAVR) is an effective procedure capable to change the natural history of the degenerative aortic valve stenosis. Despite the TAVR, the patients with advanced valve disease and severe myocardial damage (low flow, gradient and ejection fraction)show high mortality level. Aim of this study was toevaluate the predicative power of a noninvasive and inexpensive test obtained by means of a simple standard 12-leads electrocardiogram,known as the Electrical Risk Score (ERS). Methods: ERS was composed by seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms), left ventricular hypertrophy (Sokolow-Lyon criteria), delayed QRS transition zone (≥ V4), frontal QRS-T angle (>90°), long QTBazett (>450 ms for men and >460 in women) or JTBazett(330 ms for men and > 340 ms for women);long T peak to T end interval (Tp-e)( >89 ms). An ERS ≥ 4was considered high risk for all-cause or cardiovascular mortality.We calculated retrospectively the pre-procedure ERS in 40 TAVR patients after one year of follow-up. Results: In the follow up the all-cause and cardiovascular mortality were respectively 25% and 15%.None of survivors reported ERS ≥ 4,moreover, the ERS was the strongest predictor of all-cause (odd ratio 3.73, 95% CI: 1.44-9.66, p<0.05) or cardiovascular (odd ratio 3.95, 95% CI: 1.09-14.27, p<0.05) mortality.ROC curves showed that ERS had the widest significant sensitivity-specificity area under the curve (auc) predicting all-cause (auc: 0.855, p<0.05) or cardiovascular mortality (auc: 0.908, p<0.05). Conclusions:In this pivotal study, ERS resulted an useful tool to stratify the risk of mortality in one-year follow-up TAVR patients. Obviously, it is necessary to confirm these data in large prospective studies

Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p &lt; 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p &lt; 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p &lt; 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p &lt; 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p &lt; 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated

time and frequency domain analysis of beat to beat p wave duration pr interval and rr interval can predict asystole as form of syncope during head up tilt

To seek possible differences in short-period temporal RR interval, P-wave and PR interval dispersion and spectral coherence in patients with a head-up tilt test positive for vasovagal syncope with or without prolonged asystole, severe symptoms and at high risk of trauma. We retrospectively reviewed 5 min ECG and blood pressure recordings obtained at baseline, at rest and during head-up tilt in 40 patients diagnosed as having recurrent vasovagal syncope confirmed at a head-up tilt test. We analysed autoregressive spectral power for all the ECG-derived variables, focusing on temporal P-wave and PR interval dispersion indexes as well as their spectral coherence calculated on the same 5 min recordings at rest and during tilt. ECG recordings obtained during tilt before syncope showed significantly lower P → PR spectral coherence and higher RR standard deviations in patients with tilt-induced asystole than in those without (0.567 ± 0.097 versus 0.670 ± 0.127, p: 0.010 and 84 ± 36 versus 46 ± 22 ms2, p < 0.0001). Differences in the RR standard deviations persisted also on the last hundred beats (−100) (113 ± 54 versus 34 ± 17 ms2, p < 0.0001). Multiple regression analysis identified a significantly negative association between the maximum RR intervals and P → PR coherence at rest (β: −0.3, p < 0.05) and positive association with RR−100 standard deviation during tilt-induced syncope (β: 0.621, p < 0.001). P → PR spectral coherence could be used to assess the risk of prolonged asystole in patients with tilt-induced vasovagal syncope as well as as a possible surrogate for tilt-testing during these patients' follow-up

Oscillatory behavior of P wave duration and PR interval in experimental congestive heart failure: a preliminary study

Objective: The relationship between the autonomic nervous system (ANS) modulation of the sinus node and heart rate variability has been extensively investigated. The current study sought to evaluate, in an animal experimental model of pacing-induced tachycardia congestive heart failure (CHF), a possible ANS influence on the P wave duration and PR interval oscillations. Approach: Short-term (5 min) time and frequency domain analysis has been obtained in six dogs for the following electrocardiographic intervals: P wave duration (P), from the onset to peak of P wave (P p), from the onset of P wave to the q onset (PR) and from the end of P wave to the onset of q wave (P e R). Direct vagal nerve activity (VNA), stellate ganglion nerve activity (SGNA) and electrocardiogram (ECG) intervals have been evaluated contextually by implantation of three bipolar recording leads. Main results: At the baseline, multiple regression analysis pointed out that VNA was strongly positively associated with the standard deviation of PP and P e R intervals (r 2:0.997, p < 0.05). The same variable was also positively associated with high-frequency (HF) of P expressed in normalized units, of P p, and of P e R (b: 0.001) (r 2: 0.993; p < 0.05). During CHF, most of the time and frequency domain variability significantly decreased from 20% to 50% in comparison to the baseline values (p < 0.05) and SGNA correlated inversely with the low frequency (LF) obtained from P e R (p < 0.05) and PR (p < 0.05) (r 2:0.899, p < 0.05). LF components, expressed in absolute and normalized power, obtained from all studied intervals, were reduced significantly during CHF. Any difference between the RR and PP spectral components was observed. Significance: The data showed a significant relationship between ANS and atrial ECG variables, independent of the cycle duration. In particular, the oscillations were vagal mediated at the baseline, while sympathetic mediated during CHF. Whereas P wave variability might have a clinical utility in CHF management, it needs to be addressed in specific studies

SP420LOW PROTEIN DIETS IN CKD: MULTIPLE AND FEASIBLE. A MULTICENTER STUDY (THE TOPI STUDY)

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Correction of Mutant p63 in EEC Syndrome Using siRNA Mediated Allele-Specific Silencing Restores Defective Stem Cell Function

Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is a rare autosomal dominant disease caused by heterozygous mutations in the p63 gene and characterized by limb defects, orofacial clefting, ectodermal dysplasia, and ocular defects. Patients develop progressive total bilateral limbal stem cell deficiency, which eventually results in corneal blindness. Medical and surgical treatments are ineffective and of limited benefit. Oral mucosa epithelial stem cells (OMESCs) represent an alternative source of stem cells capable of regenerating the corneal epithelium and, combined with gene therapy, could provide an attractive therapeutic avenue. OMESCs from EEC patients carrying the most severe p63 mutations (p.R279H and p.R304Q) were characterized and the genetic defect of p.R279H silenced using allele-specific (AS) small interfering RNAs (siRNAs). Systematic screening of locked nucleic acid (LNA)-siRNAs against R279H-p63 allele in (i) stable WT-\u394Np63\u3b1-RFP and R279H-\u394Np63\u3b1-EGFP cell lines, (ii) transient doubly transfected cell lines, and (iii) p.R279H OMESCs, identified a number of potent siRNA inhibitors for the mutant allele, which had no effect on wild-type p63. In addition, siRNA treatment led to longer acquired life span of mutated stem cells compared to controls, less accelerated stem cell differentiation in vitro, reduced proliferation properties, and effective ability in correcting the epithelial hypoplasia, thus giving rise to full thickness stratified and differentiated epithelia. This study demonstrates the phenotypic correction of mutant stem cells (OMESCs) in EEC syndrome by means of siRNA mediated AS silencing with restoration of function. The application of siRNA, alone or in combination with cell-based therapies, offers a therapeutic strategy for corneal blindness in EEC syndrome

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis &lt; 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11&nbsp;years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982