Effect of valsartan and ramipril on atrial fibrillation recurrence and P-wave dispersion in hypertensive patients with recurrent symptomatic lone atrial fibrillation

This study compared the effect of antihypertensive treatment with valsartan or ramipril on atrial fibrillation (AF) recurrence, on P-wave dispersion, (PWD) and on serum procollagen type I carboxy terminal peptide (PIP).A total of 369 mild hypertensive (systolic blood pressure (SBP) >140 and/or 90 < diastolic blood pressure (DBP) < 110 mm Hg) outpatients in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to valsartan (n = 122), ramipril (n = 124), or amlodipine (n = 123) for 1 year. Clinic blood pressure (BP) and a 24-h electrocardiogram (ECG) were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. PWD and serum PIP levels were evaluated before and after each treatment period.SBP and DBP were significantly reduced by the three treatments (P < 0.001). A total of 46 (47.4\%) patients treated with amlodipine had a recurrence of AF as did 26 (27.9\%) patients treated with ramipril (P < 0.01 vs. amlodipine) and 16 (16.1\%) patients treated with valsartan (P < 0.01 vs. amlodipine and P < 0.05 vs. ramipril). The Kaplan-Meyer analysis showed a significant reduction of AF episodes in the valsartan group (P = 0.005 log-rank test) as well as in the ramipril group (P = 0.021), even if at a lesser degree. PWD values were significantly reduced by ramipril (-4.2 ms, P < 0.05) and even more by valsartan (-11.2 ms, P < 0.01), the difference being significant (P < 0.01). Serum PIP levels were reduced by ramipril (-49.7 microg, P < 0.001) and valsartan (-49.3 microg, P < 0.001).Despite similar BP lowering, valsartan and ramipril were more effective than amlodipine in preventing new episodes of AF, but the effect of valsartan was greater than that of ramipril. This could be related to the greater PWD reduction observed with valsartan

Non-alcoholic fatty liver disease is associated with early left ventricular dysfunction in childhood acute lymphoblastic leukaemia survivors.

Background: Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction. Methods: In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study. Results: NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P &lt; 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P &lt; 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction. Conclusions: Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients

Population protocols with faulty interactions: The impact of a leader

We consider the problem of simulating traditional popula-tion protocols under weaker models of communication, which include one-way interactions (as opposed to two-way interactions) and omission faults (i.e., failure by an agent to read its partner’s state during an inter-action), which in turn may be detectable or undetectable. We focus on the impact of a leader, and we give a complete characterization of the models in which the presence of a unique leader in the system allows the construction of simulators: when simulations are possible, we give explicit protocols; when they are not, we give proofs of impossibility. Specifically, if each agent has only a finite amount of memory, the simulation is pos-sible only if there are no omission faults. If agents have an unbounded amount of memory, the simulation is possible as long as omissions are detectable. If an upper bound on the number of omissions involving the leader is known, the simulation is always possible, except in the one-way model in which one side is unable to detect the interaction

Oblivious permutations on the plane

We consider a distributed system of n identical mobile robots operating in the two dimensional Euclidian plane. As in the previous studies, we consider the robots to be anonymous, oblivious, dis-oriented, and without any communication capabilities, operating based on the Look-Compute-Move model where the next location of a robot depends only on its view of the current configuration. Even in this seemingly weak model, most formation problems which require constructing specific configurations, can be solved quite easily when the robots are fully synchronized with each other. In this paper we introduce and study a new class of problems which, unlike the studied formation problems, cannot always be solved even in the fully synchronous model with atomic and rigid moves. This class of problems requires the robots to permute their locations in the plane. In particular, we are interested in implementing two special types of permutations - permutations without any fixed points and permutations of order n. The former (called Move-All) requires each robot to visit at least two of the initial locations, while the latter (called Visit-All) requires every robot to visit each of the initial locations in a periodic manner. We provide a characterization of the solvability of these problems, showing the main challenges in solving this class of problems for mobile robots. We also provide algorithms for the feasible cases, in particular distinguishing between one-step algorithms (where each configuration must be a permutation of the original configuration) an

Excellent Response to OnabotulinumtoxinA : Different Definitions, Different Predictors

The identification of patients who can benefit the most from the available preventive treatments is important in chronic migraine. We explored the rate of excellent responders to onabotulinumtoxinA in a multicenter European study and explored the predictors of such response, according to different definitions. A pooled analysis on chronic migraineurs treated with onabotulinumtoxinA and followed-up for, at least, 9 months was performed. Excellent responders were defined either as patients with a ≥75% decrease in monthly headache days (percent-based excellent responders) or as patients with <4 monthly headache days (frequency-based excellent responders). The characteristics of excellent responders at the baseline were compared with the ones of patients with a <30% decrease in monthly headache days. Percent-based excellent responders represented about 10% of the sample, whilst frequency-based excellent responders were about 5% of the sample. Compared with non-responders, percent-based excellent responders had a higher prevalence of medication overuse and a higher excellent response rate even after the 1st and the 2nd injection. Females were less like to be frequency-based excellent responders. Chronic migraine sufferers without medication overuse and of female sex may find fewer benefits with onabotulinumtoxinA. Additionally, the excellent response status is identifiable after the first cycle

RFC1 expansions are a common cause of idiopathic sensory neuropathy

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sj\uf6gren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome

RET PLCγ Phosphotyrosine Binding Domain Regulates Ca2+ Signaling and Neocortical Neuronal Migration

The receptor tyrosine kinase RET plays an essential role during embryogenesis in regulating cell proliferation, differentiation, and migration. Upon glial cell line-derived neurotrophic factor (GDNF) stimulation, RET can trigger multiple intracellular signaling pathways that in concert activate various downstream effectors. Here we report that the RET receptor induces calcium (Ca2+) signaling and regulates neocortical neuronal progenitor migration through the Phospholipase-C gamma (PLCγ) binding domain Tyr1015. This signaling cascade releases Ca2+ from the endoplasmic reticulum through the inositol 1,4,5-trisphosphate receptor and stimulates phosphorylation of ERK1/2 and CaMKII. A point mutation at Tyr1015 on RET or small interfering RNA gene silencing of PLCγ block the GDNF-induced signaling cascade. Delivery of the RET mutation to neuronal progenitors in the embryonic ventricular zone using in utero electroporation reveal that Tyr1015 is necessary for GDNF-stimulated migration of neurons to the cortical plate. These findings demonstrate a novel RET mediated signaling pathway that elevates cytosolic Ca2+ and modulates neuronal migration in the developing neocortex through the PLCγ binding domain Tyr1015