Effects of transcranial alternating current stimulation on repetitive finger movements in healthy humans

Transcranial alternating current stimulation (tACS) is a noninvasive neurophysiological technique that can entrain brain oscillations. Only few studies have investigated the effects of tACS on voluntary movements. We aimed to verify whether tACS, delivered over M1 at beta and gamma frequencies, has any effect on repetitive finger tapping as assessed by means of kinematic analysis. Eighteen healthy subjects were enrolled. Objective measurements of repetitive finger tapping were obtained by using a motion analysis system. M1 excitability was assessed by using single-pulse TMS and measuring the amplitude of motor-evoked potentials (MEPs). Movement kinematic measures and MEPs were collected during beta, gamma, and sham tACS and when the stimulation was off. Beta tACS led to an amplitude decrement (i.e., progressive reduction in amplitude) across the first ten movements of the motor sequence while gamma tACS had the opposite effect. The results did not reveal any significant effect of tACS on other movement parameters, nor any changes in MEPs. These findings demonstrate that tACS modulates finger tapping in a frequency-dependent manner with no concurrent changes in corticospinal excitability. The results suggest that cortical beta and gamma oscillations are involved in the motor control of repetitive finger movements

Efficacy and toxicity of bevacizumab in recurrent ovarian disease: an update meta-analysis on phase III trials

Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Materials and Methods: Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4

Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy

Background: Cardiovascular Magnetic resonance (CMR) with the late gadolinium enhancement (LGE) technique allows the detection of myocardial fibrosis in Hypertrophic cardiomyopathy (HCM). The aim of this study was to compare different methods of automatic quantification of LGE in HCM patients. Methods: Forty HCM patients (mean age 48 y, 30 males) and 20 normal subjects (mean age 38 y, 16 males) underwent CMR, and we compared 3 methods of quantification of LGE: 1) in the SD2 method a region of interest (ROI) was placed within the normal myocardium and enhanced myocardium was considered as having signal intensity>2 SD above the mean of ROI; 2) in the SD6 method enhanced myocardium was defined with a cut-off of 6 SD above mean of ROI; 3) in the RC method a ROI was placed in the background of image, a Rayleigh curve was created using the SD of that ROI and used as ideal curve of distribution of signal intensity of a perfectly nulled myocardium. The maximal signal intensity found in the Rayleigh curve was used as cut-off for enhanced myocardium. Parametric images depicting non enhanced and enhanced myocardium was created using each method. Three investigators assigned a score to each method by the comparison of the original LGE image to the respective parametric map generated. Results: Patients with HCM had lower concordance between the measured curve of distribution of signal intensity and the Rayleigh curve than controls (63.7 ± 12.3 % vs 92.2 ± 2.3%, p < 0.0001)

Congenital supravalvar mitral ring: An underestimated anomaly

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Field clinical study evaluating the efficacy and safety of an oral formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of the zoonotic canine infection by Dirofilaria repens

Dirofilaria repens is the causative agent of subcutaneous dirofilariosis of dogs, other animals and humans. This nematode is transmitted by mosquitoes of Aedes, Anopheles and Culex genera. In dogs, the parasite may cause subclinical infection or cutaneous signs. Recently, D. repens has emerged and spread in different geographical areas, with an increase of cases in dogs and humans. Chemoprevention in dogs in endemic areas is the most reliable approach for controlling this infection. This paper describes a randomized, blocked and multicentric clinical field study investigating the efficacy of an oral, chewable formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of subcutaneous dirofilariosis in dogs. METHODS: This study was conducted in endemic areas of Italy. A total of 249 dogs, at two sites, negative for D. repens, were allocated into two groups (i.e. Treated -T1 vs Untreated-T2) with a ratio of 1:1, and subjected to clinical visits and blood sampling once monthly until the end of the study. All blood samples were microscopically and genetically examined. Animals belonging to T1 group received a minimum target dose of 0.5 mg/kg bodyweight of milbemycin oxime and 5 mg/kg of praziquantel in commercial tablets (Milbemax®) according body weight once every 4 weeks. Animals of group T2 were not treated with Milbemax® but received, when necessary, specific parasiticide treatments. The study duration was 336 ± 2 days for each dog. RESULTS: A total of 219 dogs completed the study (i.e. 111 in T1 and 108 in T2), while 30 dogs (i.e. 13 in T1, 17 in T2) were withdrawn for a variety of reasons unrelated to administration of Milbemax®. The percentages of animals not showing microfilariae of D. repens were 100% (111 animals) in T1 and 94.7% (108 animals out of 114) in group T2. Milbemax® was shown to be safe in treated dogs. CONCLUSIONS: The results of this study confirm that the monthly use of Milbemax® in dogs is effective and safe for the prevention of subcutaneous dirofilariosis in endemic areas

Chronic cerebrospinal venous insufficiency in multiple sclerosis: a highly prevalent age-dependent phenomenon

BACKGROUND: This study aimed to investigate the prevalence and clinical relevance of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients and healthy controls using extra- and intracranial colour Doppler sonography. METHODS: We examined 146 MS patients, presenting with a clinically isolated syndrome, relapsing-remitting, secondary progressive, or primary progressive MS, and 38 healthy controls. Sonographic examination was performed according to Zamboni’s protocol and was performed by three independent sonographers. The results of sonographic examination were compared with clinical and demographic characteristics of the patients. RESULTS: CCSVI, defined as the presence of at least two positive Zamboni’s criteria, was found in 76% of MS patients and 16% of control subjects. B-mode anomalies of internal jugular veins, such as stenosis, malformed valves, annuli, and septa were the most common lesions detected in MS patients (80.8%) and controls (47.4%). We observed a positive correlation between sonographic diagnosis of CCSVI and the patients’ age (p = 0.003). However, such a correlation was not found in controls (p = 0.635). Notably, no significant correlations were found between sonographic signs of CCSVI and clinical characteristics of MS, except for absent flow in the jugular veins, which was found more often in primary (p<0.005) and secondary (p<0.05) progressive patients compared with non-progressive patients. Absent flow in jugular veins was significantly correlated with patients’ age (p < 0.0001). CONCLUSIONS: Sonographically defined CCSVI is common in MS patients. However, CCSVI appears to be primarily associated with the patient’s age, and poorly correlated with the clinical course of the disease

A model for predicting the phenology of Philaenus spumarius

The design and implementation of Philaenus spumarius control strategies can take advantage of properly calibrated models describing and predicting the phenology of vector populations in agroecosystems. We developed a temperature-driven physiological-based model based on the system of Kolmogorov partial differential equations to predict the phenological dynamics of P. spumarius. The model considers the initial physiological age distribution of eggs, the diapause termination process, and the development rate functions of post-diapausing eggs and nymphal stages, estimated from data collected in laboratory experiments and field surveys in Italy. The temperature threshold and cumulative degree days for egg diapause termination were estimated as 6.5 °C and 120 DD, respectively. Preimaginal development rate functions exhibited lower thresholds ranging between 2.1 and 5.0 °C, optimal temperatures between 26.6 and 28.3 °C, and upper threshold between 33.0 and 35 °C. The model correctly simulates the emergence of the 3rd, 4th, and 5th nymphal instars, key stages to target monitoring actions and control measures against P. spumarius. Precision in simulating the phenology of the 1st and 2nd nymphal stages was less satisfactory. The model is a useful rational decision tool to support scheduling monitoring and control actions against the late and most important nymphal stages of P. spumarius

2C-Cas9: a versatile tool for clonal analysis of gene function

CRISPR/Cas9-mediated targeted mutagenesis allows efficient generation of loss-of-function alleles in zebrafish. To date this technology has been primarily used to generate genetic knockout animals. Nevertheless, the study of the function of certain loci might require tight spatiotemporal control of gene inactivation. Here, we show that tissue-specific gene disruption can be achieved by driving Cas9 expression with the Gal4/UAS system. Furthermore, by combining the Gal4/UAS and Cre/loxP systems, we establish a versatile tool to genetically label mutant cell clones, enabling their phenotypic analysis. Our technique has the potential to be applied to diverse model organisms, enabling tissue-specific loss-of-function and phenotypic characterization of live and fixed tissues

Measurement of {\eta} meson production in {\gamma}{\gamma} interactions and {\Gamma}({\eta}-->{\gamma}{\gamma}) with the KLOE detector

We present a measurement of {\eta} meson production in photon-photon interactions produced by electron-positron beams colliding with \sqrt{s}=1 GeV. The measurement is done with the KLOE detector at the \phi-factory DA{\Phi}NE with an integrated luminosity of 0.24 fb^{-1}. The e^+e^- --> e^+e^-{\eta} cross section is measured without detecting the outgoing electron and positron, selecting the decays {\eta}-->{\pi}^+{\pi}^-{\pi}^0 and {\eta}-->{\pi}^0{\pi}^0{\pi}^0. The most relevant background is due to e^+e^- --> {\eta}{\gamma} when the monochromatic photon escapes detection. The cross section for this process is measured as {\sigma}(e^+e^- -->{\eta}{\gamma}) = (856 \pm 8_{stat} \pm 16_{syst}) pb. The combined result for the e^+e^- -->e^+e^-{\eta} cross section is {\sigma}(e^+e^- -->e^+e^-{\eta}) = (32.72 \pm 1.27_{stat} \pm 0.70_{syst}) pb. From this we derive the partial width {\Gamma}({\eta}-->{\gamma}{\gamma}) = (520 \pm 20_{stat} \pm 13_{syst}) eV. This is in agreement with the world average and is the most precise measurement to date.Comment: Version accepted by JHE

Cardiac Magnetic Resonance as Risk Stratification Tool in Non-Ischemic Dilated Cardiomyopathy Referred for Implantable Cardioverter Defibrillator Therapy—State of Art and Perspectives

Non-ischemic dilated cardiomyopathy (DCM) is a disease characterized by left ventricular dilation and systolic dysfunction. Patients with DCM are at higher risk for ventricular arrhythmias and sudden cardiac death (SCD). According to current international guidelines, left ventricular ejection fraction (LVEF) <= 35% represents the main indication for prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with DCM. However, LVEF lacks sensitivity and specificity as a risk marker for SCD. It has been seen that the majority of patients with DCM do not actually benefit from the ICD implantation and, on the contrary, that many patients at risk of SCD are not identified as they have preserved or mildly depressed LVEF. Therefore, the use of LVEF as unique decision parameter does not maximize the benefit of ICD therapy. Multiple risk factors used in combination could likely predict SCD risk better than any single risk parameter. Several predictors have been proposed including genetic variants, electric indexes, and volumetric parameters of LV. Cardiac magnetic resonance (CMR) can improve risk stratification thanks to tissue characterization sequences such as LGE sequence, parametric mapping, and feature tracking. This review evaluates the role of CMR as a risk stratification tool in DCM patients referred for ICD