Distinguishing intentional from nonintentional actions through eeg and kinematic markers.

How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also be done intentionally. Furthermore, blinking is often spared in patients with severe brain injuries, and for some, it is the only way to report complex meanings. Using kinematic and EEG-based measures, we found that intentional and spontaneous blinking are preceded by different brain activities, even when they are indistinguishable. Unlike spontaneous ones, intentional blinks are characterized by a slow negative EEG drift, resembling the classic readiness potential. We investigated the theoretical implication of this finding in stochastic decision models as well as the practical significance of using brain-based signals to improve the discrimination between intentional and nonintentional actions. As proof of principle, we considered three brain-injured patients with rare neurological syndromes characterized by motor and communicative impairments. Although further research is needed, our results indicate that brain-based signals can offer a feasible way to infer intentionality even in absence of overt communication.

Exercise training and atrial fibrillation: a systematic review and literature analysis.

OBJECTIVE: There are concerns in maintaining adequate levels of physical activity in patients with atrial fibrillation (AF). This could be related to the type of exercise delivered, different among studies, as the words used to describe it as treatment. We have analysed the state-of-art of the role of the exercise in AF by a mathematical analysis. This analysis documented the connections between topics and updated the available evidence through a systematic review of the current literature. MATERIALS AND METHODS: A literature search was conducted using specific terms for studies published between 2000 and 2019. For the descriptive analysis of the current literature, we used the LExical Network analysed by the Graph THeory (LENGTH) method, while to perform our review we followed the PRISMA statement. Downs and Black Quality Index was also used to assess the quality of studies. The LENGTH approach indicated nonspecific terms as "exercise", "physical" and "activity" as more representative than "rehabilitation" to describe the intervention. RESULTS: The systematic review identified nine studies on 882 patients of moderate (n=4) to good (n=5) quality. Training consisted of a combination of supervised ambulatory and home-based outpatient programs, focused on aerobic elements (endurance and resistance training, walking, treadmill and bicycle ergometer). Significant improvements in 6-minute walking test distance and peak oxygen uptake and in quality of life were obtained, with high adherence to training and no serious/significant adverse events. Only one trial was based on cardiac rehabilitation principles. CONCLUSIONS: Adequate exercise training can get a favourable cardiovascular outcome in patients with AF.

Use of Levosimendan as bridge therapy to surgical correction of post-infarction ventricular septal defect: a case report.

OBJECTIVE: Ventricular septal defect (VSD) is an uncommon but frequently fatal complication following acute myocardial infarction. In medically treated patients, mortality rates exceed 90%, while the surgical repair is associated with better outcomes, even though optimal surgical timing is still under debate. CASE REPORT: We present the case of a 78-years-old man with no previous remarkable cardiological history admitted to our Emergency Department with the diagnosis of anterior ST-elevation myocardial infarction and significant reduction of left ventricular ejection fraction. The emergency coronary angiography showed sub-occlusion of the left anterior descending coronary artery, treated with stent implantation. The post-procedural echocardiography unveiled the presence of an apical VSD with a large left-to-right shunt, significant right ventricular overload and dysfunction. An intra-aortic balloon pump (IABP) was positioned and, after Heart Team evaluation, a delayed surgical approach was planned. As a bridge to the intervention Levosimendan infusion was administered, on top of IABP support, and a significant improvement in bi-ventricular function and pressure profiles was obtained. Cardiac surgery was successfully performed 9 days after the admission without periprocedural complications. CONCLUSIONS: This unique case supports the use of Levosimendan as a valid pharmacological strategy for perioperative management of VSD.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Revealing interfacial disorder at the growth-front of thick many-layer epitaxial graphene on SiC: a complementary neutron and X-ray scattering investigation.

Epitaxial graphene on SiC provides both an excellent source of high-quality graphene as well as an architecture to support its application. Although single-layer graphene on Si-face SiC has garnered extensive interest, many-layer graphene produced on C-face SiC could be significantly more robust for enabling applications. Little is known, however, about the structural properties related to the growth evolution at the buried interface for thick many-layer graphene. Using complementary X-ray scattering and neutron reflectivity as well as electron microscopy, we demonstrate that thick many-layer epitaxial graphene exhibits two vastly different length-scales of the buried interface roughness as a consequence of the Si sublimation that produces the graphene. Over long lateral length-scales the roughness is extremely large (hundreds of Å) and it varies proportionally to the number of graphene layers. In contrast, over much shorter lateral length-scales we observe an atomically abrupt interface with SiC terraces. Graphene near the buried interface exhibits a slightly expanded interlayer spacing (∼1%) and fluctuations of this spacing, indicating a tendency for disorder near the growth front. Nevertheless, Dirac cones are observed from the graphene while its domain size routinely reaches micron length-scales, indicating the persistence of high-quality graphene beginning just a short distance away from the buried interface. Discovering and reconciling the different length-scales of roughness by reflectivity was complicated by strong diffuse scattering and we provide a detailed discussion of how these difficulties were resolved. The insight from this analysis will be useful for other highly rough interfaces among broad classes of thin-film materials.

Low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes: Benefit or risk?

Primary prevention aims to avert the onset of cardiovascular disease (CVD) by targeting its natural causes and risk factors; secondary prevention includes strategies and therapies that address preclinical or clinical evidence of CVD progression. The value of aspirin for primary CVD prevention is controversial because of increased bleeding, which may offset the overall modest benefits in patients with no overt CVD. In contrast, the benefits of aspirin for secondary prevention have been repeatedly and convincingly demonstrated to outweigh the risk of bleeding. Diabetes mellitus is a strong risk factor for cardiovascular events, and has been associated with an increased risk of both first and recurrent atherothrombotic events. Therefore, prevention of CVD, the major cause of mortality in patients with diabetes, is one of the most important therapeutic goals. Although the benefit of low-dose aspirin for secondary prevention of CVD is well established, its role for primary prevention remains inconclusive and controversial in diabetes patients. The benefit of aspirin for patients with CVD clearly exceeds the risk of bleeding, and even though a modest benefit has also been demonstrated in primary prevention, the trade-off for aspirin initiation against the increased risk of intracranial and gastrointestinal bleeding is more uncertain. Thus, aspirin for primary CVD prevention should be highly individualized, based on a benefit-risk ratio assessment for the given patient. In conclusion, the mere presence of diabetes is apparently not enough for aspirin to confer a benefit that clearly outweighs the risk of bleeding, and further evidence to the contrary is now needed.

Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial.

Although the role of homocysteine (HCys) in secondary cardiovascular prevention has been scaled down, hyper-homocysteinemia remains a risk factor for cerebrovascular events. The aim of this study was to investigate the efficacy of nutraceuticals in lowering HCys serum levels versus a conventional vitamin supplementation in hypertensive subjects at low cardiovascular risk. One-hundred and four patients (mean age 62.8±14.5 years, 63.5% males), 52 for each treatment group, were enrolled. The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys ≥15 µmol/L), without a history of cardiovascular and cerebrovascular disease. They were sequentially randomized to receive a combined nutraceutical containing 400 µg folate-6-5-methyltetrahydrofolate, 3 mg vitamin B6, 5 µg vitamin B12, 2.4 mg vitamin B2, 12.5 mg zinc and 250 mg betaine (Normocis400®) once daily for two months, or supplementation with highly dosed folic acid (5 mg/day) (control group). Differences in serum HCys values were compared by ANOVA for repeated measures. A significant HCys reduction in comparison to baseline was found in both groups at the end of the study treatment, from 21.5±8.7 to 10.0±1.7 µmol/L for Normocis400® subjects (p less than 0.0001), and from 22.6±6.2 to 14.3±2.8 µmol/L for controls (p less than 0.0001). HCys reduction was significantly higher among patients treated with Normocis400® (p less than 0.035). The ideal HCys level (i.e. less than 10 µmol/L) was reached in 55.8% of cases in theNormocis400® group, and it was significantly higher than in controls. No side effects were observed in either treatment group. Randomized clinical trials are ongoing to test the effect of folate, B6, and B12 supplementation in primary prevention of cardiovascular and cerebrovascular events. In the meantime, especially when the ideal HCys level is far from being reached, Normocis400® appears to be safe, well tolerated and effective in reducing HCys levels.

Effects of the Antihypertensive Fixed-Dose Combinations on an Early Marker of Hypertensive Cardiac Damage in Subjects at Low Cardiovascular Risk.

BACKGROUND: In hypertensive subjects (HTs), isolated left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac damage and is associated with poor prognosis. However, few intervention trials investigated the effects of antihypertensive therapy on isolated LVDD regression. This study investigates the blood pressure (BP)-lowering efficacy and the effect on LVDD of antihypertensive drugs administered as fixed-dose combinations in untreated HTs with isolated LVDD. METHODS: A total of 168 HTs (23% of them having impaired fasting glucose (IFG)) aged 48±4.2 years were randomized to receive open-label once-daily oral treatment of beta-blocker + diuretic, angiotensin-converting enzyme inhibitor (ACEI) + diuretic, angiotensin II receptor blocker (ARB) + diuretic, ARB + calcium channel blocker (CCB), or ACEI + CCB. Clinic and 24-hour ambulatory BP values were measured before randomization and at the follow-up. Regression of LVDD was defined as normalization of both the E/A (ratio of early-to-late ventricular filling wave velocity) and E/E' (mitral velocity to early diastolic velocity of the mitral annulus) ratios. Comparisons were made between categorical variables using the χ(2) test and between continuous variables by gender using analysis of variance for repeated measures. RESULTS: BP reduction did not differ between groups. LVDD regression was significantly more prevalent in the ARB + CCB or ACEI + CCB groups than with other combinations; in HTs with IFG, it was most prevalent (46%) with ACEI + CCB. CONCLUSIONS: Independently of BP reduction, the fixed-dose combinations ARB + CCB and ACEI + CCB led to regression of isolated LVDD. In those with an IFG, ACEI + CCB was most effective.

(99m)Tc-DTPA scintigraphy assesses the absence of glomerular filtration rate impairment of Aliskiren in high-risk hypertensive subjects. A 12-month follow-up study.

AIM: Glomerular filtration rate (GFR) is commonly calculated using the modification of diet in renal disease (MDRD) and Cockroft-Gault (CG) formulas and recently by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm and not directly measured, so that the real impact of antihypertensive therapy on GFR could not be well defined. In this study, the effect of Aliskiren on the GFR measured by radionuclide clearance of 99mTc-diethylene triamine penta-acetic acid (DTPA) was investigated. METHODS: In 106 hypertensive subjects (53% men) aged 61.9±12.7 years with uncontrolled blood pressure (BP) receiving at least 2 antihypertensive medications, Aliskiren was added once-daily at a dose of 150-300 mg for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while 24-hours ambulatory BP and GFR (in mL/min/1.73 m2) were evaluated at baseline and at the end of the follow-up. Analysis of variance for repeated measures of BP, GFR and microalbuminuria was provided. RESULTS: With the use of Aliskiren a significant reduction of BP and microalbuminuria was found (P<0.0001). Only in male population, a significant reduction in GFR calculated with CKD-EPI (82.4±15 vs. 78.6±18.2, P<0.01) and CG (81.6±29.5 vs. 74.2±28.4, P<0.0001) formulas was observed. This impairment of GFR was not found either with MDRD formula (70.5±19.6 vs. 68.3±23.4) or by radionuclide clearance (62.4±18.6 vs. 61.4±20.5). CONCLUSION: This study seems to demonstrate that the efficacy on BP control of Aliskiren is not accompanied by an impairment of GFR. In order to evaluate the effect of Aliskiren on GFR scintigraphy technique or MDRD formula resulted to be the most accurate methods.

Factors Determining Survival and Retention among HIV-Infected Children and Adolescents in a Community Home-Based Care and a Facility-Based Family-Centred Approach in Kampala, Uganda: A Cohort Study.

We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11-109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, P < 0.001). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, P = 0.308, adjusted, P = 0.489), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, P < 0.001, adjusted P = 0.006). Irrespective of model of care, children receiving ART had better retention in care and survival.

In PCOS patients the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone.

BACKGROUND & AIMS: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism and by insulin resistance and related metabolic alterations. Both metformin and anti-androgens, such as spironolactone, are used to ameliorate the different aspects of this disorder. We investigated whether therapy with metformin plus low-dose spironolactone is more effective than metformin alone in PCOS patients. METHODS AND RESULTS: Fifty-six PCOS patients were randomized in two groups: group A (28 patients) was treated with metformin (1700 mg/die) and group B (28 patients) was treated with metformin (1700 mg/die) plus low-dose spironolactone (25 mg/die). Anthropometric, hormonal and metabolic parameters were evaluated at baseline and after six months of treatment. After therapy regular menses were restored in approximately 82% of group A patients (P < 0.001) and in 68% of group B patients (P < 0.001). Circulating testosterone, Δ-4-androstenedione and Hirsutism Score (HS) significantly decreased in both groups. However, dehydro-epiandrosterone sulphate significantly decreased only in group B, and HS underwent a stronger reduction in group B (P < 0.001). At baseline, 39/56 (69.6%) patients met the diagnostic criteria for metabolic syndrome, but only one patient met these criteria after treatment. CONCLUSIONS: This study confirms the beneficial effects of metformin in PCOS patients. It also indicates that the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism as compared to metformin alone.

Aliskiren improves blood pressure control and prevents cardiac damage in high-risk hypertensive subjects.

AIM: Longitudinal study aimed to evaluate the antihypertensive efficacy, safety and the effect on cardiac damage of Aliskiren, administered to a group of high-risk hypertensive patients with mild impairment of renal function and uncontrolled blood pressure (BP) despite a two-drug antihypertensive treatment. METHODS: One hundred and six patients (56 men and 50 females) aged 61.9±12.7 years, were assigned to receive Aliskiren 150-300 mg once-daily for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while biochemical tests, estimated glomerular filtration rate (eGFR), 24-hours ambulatory BP measurements (ABMP) and echocardiography were evaluated at baseline and at the end of follow-up. Analysis of variance for repeated measures compared BP, left ventricular mass index (LVMI) and eGFR values changes. RESULTS: A significant reduction (all P<0.0001) of clinic systolic (-28.6 mmHg) and diastolic (-12.8 mmHg) BP values, mean 24h-systolic (-12.3 mmHg) and 24h-diastolic (-6.5 mmHg), day-time systolic (-11.5 mmHg) and diastolic (-6.4 mmHg), night-time systolic (-11.9 mmHg) and diastolic (-7 mmHg) ABPM values and in the use of antihypertensive drugs was observed (3.0±0.9 vs. 2.0±0.7, p=0.01). LVMI was significantly reduced (130.2±36.1 vs. 115.9±33.4 g/m2, P<0.0001); eGFR was steady (75.3±17.3 vs. 73.1±21.5 ml/min/1.73m2, P>0.05). Putative adverse events caused withdrawal of 7 subjects (6 for gastrointestinal disturbances, 1 for alopecia). CONCLUSION: Aliskiren was effective in decreasing both clinical and ABPM values and in reducing LVMI in both genders without any influence on eGFR. The treatment resulted safe, even in combination with ACE-inhibitors and angiotensin II receptor blockers. A significant reduction in the use of concomitant antihypertensive drugs was observed.

Gestational diastolic hypertension with gene mutation-related pheochromocytoma positive at 18F-DOPA PET/CT: Diagnostic and therapeutic implications / Hipertensión diastólica gestacional con feocromocitoma relacionado a mutación genética y PET/TC con 18F-DOPA positiva: implicaciones diagnósticas y terapéuticas

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Aliskiren improves blood pressure control and prevents cardiac damage in high-risk hypertensive subjects.

Aim: Longitudinal study aimed to evaluate the antihypertensive efficacy, safety and the effect on cardiac damage of Aliskiren, administered to a group of high-risk hypertensive patients with mild impairment of renal function and uncontrolled blood pressure (BP) despite a two-drug antihypertensive treatment. Methods: One hundred and six patients (56 men and 50 females) aged 61.9±12.7 years, were assigned to receive Aliskiren 150-300 mg once-daily for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while biochemical tests, estimated glomerular filtration rate (eGFR), 24-hours ambulatory BP measurements (ABMP) and echocardiography were evaluated at baseline and at the end of follow-up. Analysis of variance for repeated measures compared BP, left ventricular mass index (LVMI) and eGFR values changes. Results: A significant reduction (all P<0.0001) of clinic systolic (-28.6 mmHg) and diastolic (-12.8 mmHg) BP values, mean 24h-systolic (-12.3 mmHg) and 24h-diastolic (-6.5 mmHg), day-time systolic (-11.5 mmHg) and diastolic (-6.4 mmHg), night-time systolic (-11.9 mmHg) and diastolic (-7 mmHg) ABPM values and in the use of antihypertensive drugs was observed (3.0±0.9 vs. 2.0±0.7, p=0.01). LVMI was significantly reduced (130.2±36.1 vs. 115.9±33.4 g/m2, P<0.0001); eGFR was steady (75.3±17.3 vs. 73.1±21.5 ml/min/1.73m2, P>0.05). Putative adverse events caused withdrawal of 7 subjects (6 for gastrointestinal disturbances, 1 for alopecia). Conclusion: Aliskiren was effective in decreasing both clinical and ABPM values and in reducing LVMI in both genders without any influence on eGFR. The treatment resulted safe, even in combination with ACE-inhibitors and angiotensin II receptor blockers. A significant reduction in the use of concomitant antihypertensive drugs was observed.