Suppression of extinction with TMS in humans: From healthy controls to patients.

We review a series of studies exemplifying some applications of single-pulse and paired-transcranial magnetic stimulation (TMS) in the study of spatial attention and of its deficits. We will focus primarily on sensory extinction, the failure to consciously perceive a contralesional sensory stimulus only during bilateral stimulation of homologous surfaces. TMS studies in healthy controls show that it is possible either to interfere or modulate the excitability of the parietal cortex during sensory (i.e. tactile and visual) attentional tasks, thus reproducing a condition of virtual extinction. TMS studies in patients with unilateral (mainly right) brain damage show that the modulation of the unbalance in conical excitability between the two cerebral hemispheres transiently improves contralesional sensory extinction. These studies show the possible application of TMS not only as a research method in healthy subjects, but also as a tool for inducing brain excitability changes in patients with sensory extinction, which could be useful for supporting the rehabilitation of this deficit

Modafinil-Induced changes in functional connectivity in the cortex and cerebellum of healthy elderly subjects

In the past few years, cognitive enhancing drugs (CEDs) have gained growing interest and the focus of investigations aimed at exploring their use to potentiate the cognitive performances of healthy individuals. Most of this exploratory CED-related research has been performed on young adults. However, CEDs may also help to maintain optimal brain functioning or compensate for subtle and or subclinical deficits associated with brain aging or early-stage dementia. In this study, we assessed effects on resting state brain activity in a group of healthy elderly subjects undergoing acute administration of modafinil, a wakefulness-promoting agent. To that aim, participants (n = 24) were investigated with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and after the administration of a single dose (100 mg) of modafinil. Effects were compared to age and size-matched placebo group. Rs-fMRI effects were assessed, employing a graph-based approach and Eigenvector Centrality (EC) analysis, by taking in account topological changes occurring in functional brain networks. The main finding of the study is that modafinil promotes enhanced centrality, a measure of the importance of nodes within functional networks, of the bilateral primary visual (V1) cortex. EC analysis also revealed that modafinil-treated subjects show increased functional connectivity between the V1 and specific cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal sulcus and left middle frontal gyrus) regions. Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brai

Demographic structure suggests migration of the sea urchin Paracentrotus lividus in a coastal lagoon

The demographic structure of a population of Paracentrotus lividus living in a coastal Mediterranean lagoon was studied in 1990. Analysis of this structure revealed that the population examined was made up of four distinct cohorts which represented individuals 2, 3, 4 and over of age. The variability in demographic structure as a function of biotope revealed that sea urchin migration occurred from the pebble area (recruitment area. high sea urchin density and overgrazing facies) towards areas made up of Cymodocea nodosa sea grass beds (growth areas, low density and abundant prefered food). These migrations seem to have been caused by food limitation in the former biotope coupled with a shift in diet in young individuals

Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry

Ion channels and transporters typically consist of biomolecules that play key roles in a large variety of physiological and pathological processes. Traditional therapies include many ionchannel blockers, and some activators, although the exact biochemical pathways and mechanisms that regulate ion homeostasis are yet to be fully elucidated. An emerging area of research with great innovative potential in biomedicine pertains the design and development of synthetic ion channels and transporters, which may provide unexplored therapeutic opportunities. However, most studies in this challenging and multidisciplinary area are still at a fundamental level. In this review, we discuss the progress that has been made over the last five years on ion channels and transporters, touching upon biomolecules and synthetic supramolecules that are relevant to biological use. We conclude with the identification of therapeutic opportunities for future exploratio

Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson's disease patients

Background: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder. It is well established that different motor subtypes of PD evolve with different clinical courses and prognoses. The complete psychiatric profile underlying these different phenotypes since the very early stage of the disease is debated. Aims of the study: We aimed at investigating the psychiatric profile of the three motor subtypes of PD (akinetic-rigid, tremor-dominant, and mixed) in de novo drug-naïve patients with PD. Methods: Sixty-eight patients with PD, divided into 39 akinetic-rigid (AR), seven mixed (MIX), and 22 tremor-dominant (TD) patients underwent a complete assessment of psychiatric, cognitive, and motor symptoms. Results: No significant differences were found among groups. Conclusions: Our results suggest that a differentiation of the psychiatric symptoms associated with specific motor subtypes of PD is not detectable in de novo drug-naïve patients. Previous evidence that emerges later along the disease progression may be a consequence of the dopaminergic and nondopaminergic damage increase

Zinc(II)-methimazole complexes: synthesis and reactivity

The tetrahedral S-coordinated complex [Zn(MeImHS)(4)](ClO4)(2), synthesised from the reaction of [Zn(ClO4)(2)] with methimazole (1-methyl-3H-imidazole-2-thione, MeImHS), reacts with triethylamine to yield the homoleptic complex [Zn(MeImS)(2)] (MeImS = anion methimazole). ESI-MS and MAS C-13-NMR experiments supported MeImS acting as a (N, S)-chelating ligand. The DFT-optimised structure of [Zn(MeImS)(2)] is also reported and the main bond lengths compared to those of related Zn-methimazole complexes. The complex [Zn(MeImS)(2)] reacts under mild conditions with methyl iodide and separates the novel complex [Zn(MeImSMe)(2)I-2] (MeImSMe = S-methylmethimazole). X-ray diffraction analysis of the complex shows a ZnI2N2 core, with the methyl thioethers uncoordinated to zinc. Conversely, the reaction of [Zn( MeImS)(2)] with hydroiodic acid led to the formation of the complex [Zn(MeImHS)(2)I-2] having a ZnI2S2 core with the neutral methimazole units S-coordinating the metal centre. The Zn-coordinated methimazole can markedly modify the coordination environment when changing from its thione to thionate form and vice versa. The study of the interaction of the drug methimazole with the complex [Zn(MeIm)(4)](2+) (MeIm = 1-methylimidazole) - as a model for Zn-enzymes containing a N-4 donor set from histidine residues shows that methimazole displaces only one of the coordinated MeIm molecules; the formation constant of the mixed complex [Zn(MeIm)(3)(MeImHS)](2+) was determined

Disability through COVID-19 pandemic: neurorehabilitation cannot wait.

Coronavirus disease 2019 (CoViD-19) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time-dependent diseases, <sup>1</sup> including CoViD-19 complications. <sup>2,3</sup> Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection, <sup>4</sup> has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey, <sup>5</sup> possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger

The Ising M-p-spin mean-field model for the structural glass: continuous vs. discontinuous transition

The critical behavior of a family of fully connected mean-field models with quenched disorder, the $M-p$ Ising spin glass, is analyzed, displaying a crossover between a continuous and a random first order phase transition as a control parameter is tuned. Due to its microscopic properties the model is straightforwardly extendable to finite dimensions in any geometry.Comment: 10 pages, 1 figure, 1 tabl

Unlocking Plum Genetic Potential: Where Are We At?

Plums are a large group of closely related stone fruit species and hybrids of worldwide economic importance and diffusion. This review deals with the main aspects concerning plum agrobiodiversity and its relationship with current and potential contributions offered by breeding in enhancing plum varieties. The most recent breeding achievements are revised according to updated information proceeding from relevant scientific reports and official inventories of plum genetic resources. A special emphasis has been given to the potential sources of genetic traits of interest for breeding programs as well as to the need for efficient and coordinated efforts aimed at efficaciously preserving the rich and underexploited extant plum agrobiodiversity. The specific objective of this review was to: (i) analyze and possibly evaluate the degree of biodiversity existing in the cultivated plum germplasm, (ii) examine the set of traits of prominent agronomic and pomological interest currently targeted by the breeders, and (iii) determine how and to what extent this germplasm was appropriately exploited in breeding programs or could represent concrete prospects for the future