The nuclear pore protein Nup153 associates with chromatin and regulates cardiac gene expression in dystrophic mdx hearts.

Aims Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmdmdx/J). Methods and results Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls. Accordingly, lysine acetyl transferase (KAT) activity associated with Nup153 was higher in mdx hearts paralleling increased binding with the lysine acetylases P300/CBP-associated factor (PCAF) and p300. Interestingly, Nup153 silencing in mdx organotypic heart tissue slices caused a reduction in PCAF- and p300-specific activities. Remarkably, the level of nitric oxide (NO), which is reduced in mdx mice, was important for KAT-dependent regulation of Nup153. In fact, treatment of mdx heart tissue with an NO donor or the KAT inhibitor anacardic acid normalized Nup153 protein expression. Nup153 was recruited to chromatin and regulated the transcription of genes involved in cardiac remodelling, including the actin-binding protein nexilin. Accordingly, nexilin protein expression was abrogated by Nup153 silencing in mdx organotypic cultures. Electrophysiological and molecular experiments revealed that Nup153 overexpression in normal cardiomyocytes increases Cav1.2 calcium channel expression and function. Alterations in Nup153 protein expression and intracellular localization were also found in dystrophic cardiomyocytes derived from patient-specific induced pluripotent stem cells. Importantly, Nup153 up-regulation and increased acetylation were also found in the heart of Duchenne muscular dystrophy patients. Conclusions Our data indicate that Nup153 is an epigenetic regulator which, upon altered NO signalling, mediates the activation of genes potentially associated with early dystrophic cardiac remodelling

Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors

Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study

<p>Abstract</p> <p>Background</p> <p>Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.</p> <p>Methods</p> <p>Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.</p> <p>Results</p> <p>One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.</p> <p>Conclusions</p> <p>This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10001146.</p

The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: Study protocol for a randomized controlled trial

Background: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G-CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. Methods/Design: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) ≤45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1year. Discussion: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. Trial registration: ClinicalTrials.gov: NCT02502747(29 June 2015); EudraCT: 2015-002189-21 (10 July 2015)

Uneven Accuracy of Home Blood Pressure Measurement: A Multicentric Survey

Home blood pressure monitoring (HBPM) is increasingly commonly performed, but the concordance between patient HBPM measurement technique and prevailing recommendations has not been well-assessed according to the literature. The authors performed a multicentric survey to evaluate the degree of patients' adherence to current recommendations on HBPM, and investigate potential predictors of a higher-quality self-measurement. A structured questionnaire was administered to 725 Italian outpatient hypertensive patients (mean age, 52.2±14.4 years). Overall, ≥10 recommended procedures were followed by 52.8% of the participants; only 1.0% followed all recommendations. A total of 49.7% of participants rested for ≥5 minutes before the measurement, 36.8% recorded BP more than once in each measurement session, and 34.3% used a chair or bed saddle to support their back. Less than 40% of the patients received some form of training by health professionals. After multivariate analysis, patients receiving/reading instructions showed higher-quality HBPM (P<.01). The accuracy of HBPM needs to be improved, and more efforts should be devoted to provide patient training on HBPM, especially on the less-frequently followed recommendations

Hard Events AfteR Orsiro Sirolimus-Eluting Stent (HEROES) in STEMI: A Multicenter Registry

To evaluate the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Specific drug-eluting stent (DES) platforms might influence pPCI success rate in the mid-to-long term. Orsiro, a hybrid sirolimus DES with thin struts and a biodegradable polymer, may potentially cause less stent malapposition, stent-induced inflammation, and mechanical damage, improving clinical outcomes

Smoking abstinence and cessation, difference in the number of daily cigarette smoked and self-reported health: results of the multivariate analyses.

<p>OR = Odds Ratio. CI = Confidence Interval.</p><p>^A Random-effect logistic regression with region as the cluster level, adjusting for the following baseline characteristics: age, gender, BMI, marital status, educational level, occupation, alcohol use, hypertension, hypercholesterolemia, diabetes, self-reported health, years of tobacco smoking (former smoking for e-cigarette users), n. of tobacco cigarettes smoked per day (or puffs per day for e-cigarette only smokers). 903 subjects were included in the final model due to 56 missing items in the self-reported health item at baseline.</p><p>^B E-cigarette only smokers were not included. Random-effect linear regression with region as the cluster level, adjusting for the following baseline characteristics: age, gender, BMI, marital status, educational level, occupation, alcohol use, hypertension, hypercholesterolemia, diabetes, self-reported health, years of tobacco smoking, n. of tobacco cigarettes smoked per day. 685 subjects were included in the final model due to 38 missing items in the self-reported health item at baseline.</p><p>^C Random-effect linear regression with region as the cluster level, adjusting for the following baseline characteristics: age, gender, BMI, marital status, educational level, occupation, alcohol use, hypertension, hypercholesterolemia, diabetes, self-reported health, years of tobacco smoking (former smoking for e-cigarette users), n. of tobacco cigarettes smoked per day (or puffs per day for e-cigarette only smokers). 874 subjects were included in the final model due to 56 missing items in the self-reported health item at baseline and 29 missing items in the self-reported health at twelve months.</p><p>Smoking abstinence and cessation, difference in the number of daily cigarette smoked and self-reported health: results of the multivariate analyses.</p

Main outcomes at twelve months.

<p>SD = Standard deviation.</p><p>P<0.01 for the comparison</p><p>* Tobacco only vs electronic cigarettes only</p><p>** Tobacco only vs both tobacco and electronic cigarettes (dual smoking)</p><p>*** E-cigarettes only vs both tobacco and electronic cigarettes (dual smoking).</p><p>^€ EuroQol final item, ranging from 1 (feel very bad) to 10 (perfectly healthy).</p><p>^ψ Chronic obstructive pulmonary diseases, stroke, heart failure, myocardial infarction, angina, pneumonia, cancer of: larynx or oral cavity, lung, stomach, pancreas, cervix, kidney, bladder, myeloid leukaemia.</p><p>Main outcomes at twelve months.</p

Smoking status after twelve months of follow-up, by smoking status at baseline.

<p>Smoking status after twelve months of follow-up, by smoking status at baseline.</p

Baseline characteristics of the subjects completing the 12-month follow-up.

<p>^€ EuroQol final question, ranging from 1 (feel very bad) to 10 (perfectly healthy). This item had 56 missing values.</p><p>^Ψ Cigars or tobacco chewing.</p><p>^Ω Nicotine patch or gums.</p><p>^φ More than one answer allowed.</p><p>^¥ Years of former tobacco smoking for e-cigarette only smokers.</p><p>P<0.01 for the comparison</p><p>* Tobacco only vs electronic cigarettes only</p><p>** Tobacco only vs dual smoking</p><p>*** E-cigarettes only vs dual smoking.</p><p>Baseline characteristics of the subjects completing the 12-month follow-up.</p