Classification of Epileptic Activity Through Temporal and Spatial Characterization of Intracranial Recordings

Focal epilepsy is a chronic condition characterized by hyper-activity and abnormal synchronization of a specific brain region. For pharmacoresistant patients, the surgical resection of the critical area is considered a valid clinical solution, therefore, an accurate localization is crucial to minimize neurological damage. In current clinical routine the characterization of the Epileptogenic Zone (EZ) is performed using invasive methods, such as Stereo-ElectroEncephaloGraphy (SEEG). Medical experts perform the tag of neural electrophysiological recordings by visually inspecting the acquired data, a highly time consuming and subjective procedure. Here we show the results of an automatic multi-modal classification method for the evaluation of critical areas in focal epileptic patients. The proposed method represents an attempt in the characterization of brain areas which integrates the anatomical information on neural tissue, inferred using Magnetic Resonance Imaging (MRI) in combination with spectral features extracted from SEEG recordings

Indication, from Pioneer 10/11, Galileo, and Ulysses Data, of an Apparent Anomalous, Weak, Long-Range Acceleration

Radio metric data from the Pioneer 10/11, Galileo, and Ulysses spacecraft indicate an apparent anomalous, constant, acceleration acting on the spacecraft with a magnitude $\sim 8.5\times 10^{-8}$ cm/s$^2$, directed towards the Sun. Two independent codes and physical strategies have been used to analyze the data. A number of potential causes have been ruled out. We discuss future kinematic tests and possible origins of the signal.Comment: Revtex, 4 pages and 1 figure. Minor changes for publicatio

an outbreak of severe invasive meningococcal disease due to a capsular switched neisseria meningitidis hypervirulent strain b cc11

Abstract Objectives The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia. Methods Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS). Results Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18–21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented. Conclusions We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action

An outbreak of severe invasive meningococcal disease due to a capsular switched Neisseria meningitidis hypervirulent strain B:cc11

Objectives: The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia. Methods: Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS). Results: Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18–21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented. Conclusions: We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action

The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling. A 10-Year Follow-Up of the RIGENERA Study

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 +/- 4 years vs. 12 +/- 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment

Interplay between myocardial bridging and coronary spasm in patients with myocardial ischemia and non-obstructive coronary arteries: Pathogenic and prognostic implications

BACKGROUND: Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evalu-ating their prognostic relevance in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) or stable NOCAD. METHODS AND RESULTS: We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non-fatal myocardial infarc-tion, and rehospitalization for unstable angina, was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow-up (median, 22 months; interquartile range, 13–32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P<0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. CONCLUSIONS: Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long-term follow-up with a low rate of hard events

Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial

Introduction: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to have beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) in primary prevention and in those with a high CV risk profile. However, the mechanism(s) responsible for these CV benefits remain elusive and unexplained. The aim of the DAPAHEART study will be to demonstrate that treatment with SGLT-2 inhibitors is associated with greater myocardial insulin sensitivity in patients with T2D, and to determine whether this improvement can be attributed to a decrease in whole-body (and tissue-specific) insulin resistance and to increased myocardial perfusion and/or glucose uptake. We will also determine whether there is an appreciable degree of improvement in myocardial-wall conditions subtended by affected and non-affected coronary vessels, and if this relates to changes in left ventricular function. Methods: The DAPAHEART trial will be a phase III, single-center, randomized, two-arm, parallel-group, double-blind, placebo-controlled study. A cohort of 52 T2D patients with stable coronary artery disease (without any previous history of myocardial infarction, with or without previous percutaneous coronary intervention), with suboptimal glycemic control (glycated hemoglobin [HbA1c] 7\u20138.5%) on their current standard of care anti-hyperglycemic regimen, will be randomized in a 1:1 ratio to dapagliflozin or placebo. The primary outcome is to detect changes in myocardial glucose uptake from baseline to 4 weeks after treatment initiation. The main secondary outcome will be changes in myocardial blood flow, as measured by 13N-ammonia positron emission tomography/computed tomography (PET/CT). Other outcomes include cardiac function, glucose uptake in skeletal muscle, adipose tissue, liver, brain and kidney, as assessed by fluorodeoxyglucose (FDG) PET-CT imaging during hyperinsulinemic-euglycemic clamp; pericardial, subcutaneous and visceral fat, and browning as observed on CT images during FDG PET-CT studies; systemic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp, glycemic control, urinary glucose output; and microbiota modification. Discussion: SGLT-2 inhibitors, in addition to their insulin-independent plasma glucose-lowering effect, are able to directly (substrate availability, fuel utilization, insulin sensitivity) as well as indirectly (cardiac after-load reduction, decreased risk factors for heart failure) affect myocardial functions. Our study will provide novel insights into how these drugs exert CV protection in a diabetic population. Trial registration: EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes

Objective: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. Methods: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. Results: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. Conclusions: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits

Aging Kit Mutant Mice Develop Cardiomyopathy

Both bone marrow (BM) and myocardium contain progenitor cells expressing the c-Kit tyrosine kinase. The aims of this study were to determine the effects of c-Kit mutations on: i. myocardial c-Kit+ cells counts and ii. the stability of left ventricular (LV) contractile function and structure during aging. LV structure and contractile function were evaluated (echocardiography) in two groups of Kit mutant (W/Wv and W41/W42) and in wild type (WT) mice at 4 and 12 months of age and the effects of the mutations on LV mass, vascular density and the numbers of proliferating cells were also determined. In 4 month old Kit mutant and WT mice, LV ejection fractions (EF) and LV fractional shortening rates (FS) were comparable. At 12 months of age EF and FS were significantly decreased and LV mass was significantly increased only in W41/W42 mice. Myocardial vascular densities and c-Kit+ cell numbers were significantly reduced in both mutant groups when compared to WT hearts. Replacement of mutant BM with WT BM at 4 months of age did not prevent these abnormalities in either mutant group although they were somewhat attenuated in the W/Wv group. Notably BM transplantation did not prevent the development of cardiomyopathy in 12 month W41/W42 mice. The data suggest that decreased numbers and functional capacities of c-Kit+ cardiac resident progenitor cells may be the basis of the cardiomyopathy in W41/W42 mice and although defects in mutant BM progenitor cells may prove to be contributory, they are not causal