Differential neuropsychological profiles in Parkinsonian patients with or without vascular lesions.

The purpose of this study is to compare the neuropsychological profile of patients affected by parkinsonism and vascular lesions to that in patients with PD alone (PD) and to evaluate whether the brain vascular lesion load is associated with neuropsychological variables. Thirty-six nondemented patients with parkinsonism were divided into 3 groups of 12 patients each, according to both clinical history and the presence of brain vascular lesions and/or dopaminergic denervation as revealed by magnetic resonance and dopamine transporter imaging, respectively. The first group had vascular lesions without dopaminergic denervation (VP group); the second group had vascular lesions and dopaminergic denervation (DD) (VP+DD group); and the third group consisted of patients with dopaminergic denervation (PD group) without vascular lesions. All patients underwent neurological and neuropsychological assessments. The groups differed in disease duration, age at onset, and cerebrovascular risk factors. The VP and VP+DD groups performed worse than the PD group on frontal/executive tasks. Regardless of the presence of dopaminergic denervation, cerebrovascular lesions in hemispheric white matter, basal ganglia, and cerebellum have an important effect in determining early onset and severity of cognitive impairment in patients with parkinsonism

Nonmotor symptoms in Parkinson's disease: classification and management

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Pathological gambling in Parkinson's disease. A comprehensive review

Pathological gambling (PG) and other Impulse Control Disorders (ICDs), such as hypersexuality, compulsive eating and buying, are often reported in Parkinson's disease (PD). The prevalence of PG is 2.2%-7% in treated PD patients, which is higher than the background population rate. As other non motor symptoms in PD, PG is frequently under-reported by patients and caregivers and may be under-recognized by the treating physicians. Factors associated with PG include male sex, younger age or younger age at PD onset, personal or family history of substance abuse or ICD, a personality profile characterized by impulsiveness, and treatment with dopamine agonists (DA) more than with levodopa (l-dopa). The DA effect seems to be a class effect and not specific for any DA. Neurofunctional studies suggest that medication-induced downregulation of frontostriatal connections and upregulation of striatum might combine to induce impulsive behavior. A dysfunction of fronto-subcortical circuits in PD patients with PG is also supported by neuropsychological findings of impaired executive control and monitoring abilities. Management of ICDs in PD is complex, and until now only discontinuation and/or tapering of DA treatment seem to be an effective management strategy for ICDs in PD. There is no empirical evidence supporting the use of psychiatric drugs for PG such as antipsychotics and antidepressants. Data regarding the effect of deep brain stimulation (DBS), particularly of subthalamic nucleus, on PG and ICDs in PD are still limited and sometimes conflicting since improvement of PG or new onset of PG after surgery have been reported

the use of smartphones to assess the feasibility of a cooperative intelligent transportation safety system based on surrogate measures of safety

Abstract The future of road transportation is going to be shaped by connectivity and autonomous driving. Connected and autonomous vehicles are expected to increase safety and reduce traffic congestion. Once all the vehicles are connected and geo-localized there might still be a need to integrate a different level of autonomous vehicles on the road: from the human driven vehicle to the fully autonomous vehicle. While surrogate safety measures have been extensively considered to estimate the risk of accidents due to improper driving, there has been no attempt to use them to help drivers achieve a better driving style. This paper presents an experimentation on the idea to warn drivers when they are driving in such a way (owing to their interactions with other vehicles) that could potentially lead to an accident. In the proposed system the driver is warned of the risk of collision by the combined use of localization (GPS) gathered information and the application of road safety indicators such as Deceleration Rate to Avoid a Crash, Time To Collision and others. The experimentation involving car-following vehicles showed the feasibility, with existing technologies, of using surrogate measures of safety to assist the driver in keeping a better driving trajectory. Once connected vehicles are introduced on the market, the presented results can be a base to develop commercial smartphone applications that will allow users of "not connected" old vehicles to also take advantage of real time driving assistance for a safer use of the road

Pretreatment with verapamil in patients with persistent or chronic atrial fibrillation who underwent electrical cardioversion

AbstractOBJECTIVESTo evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion (C).BACKGROUNDThe increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload.METHODSOne hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C.RESULTSDuring the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04).CONCLUSIONSSix days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone

Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1

Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 μg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines

The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures

: Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC

Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice

Dopamine (DA) controls a wide variety of physiological functions in the central nervous system as well as in the neuroendocrine and gastrointestinal systems. DA signaling is mediated by five cloned receptors named D1-D5. Knockout mouse models for the five receptors have been generated, and, albeit impaired for some important DA-mediated functions, they are viable and can reproduce. D1 and D2 receptors are the most abundant and widely expressed DA receptors. Cooperative/synergistic effects mediated by these receptors have been suggested, in particular, in the control of motor behaviors. To analyze the extent of such interrelationship, we have generated double D1/D2 receptor mutants. Interestingly, in contrast to single knockouts, we found that concurrent ablation of the D1 and D2 receptors is lethal during the second or third week after birth. This dramatic phenotype is likely to be related to altered feeding behavior and dysfunction of the gastrointestinal system, especially because major anatomical changes were not identified in the brain. Similarly, in the absence of functional D1, heterozygous D2 mutants (D1r -/-;D2r +/-) showed severe growth retardation and did not survive their postweaning period. The analysis of motor behavior in D1r/D2r compound mutants showed that loss of D2-mediated functions reduces motor abilities, whereas the effect of D1r ablation on locomotion strongly depends on the experimental paradigms used. These studies highlight the interrelationship between D1 and D2 receptor-mediated control of motor activity, food intake, and gastrointestinal functions, which has been elusive in the single-gene ablation studies