Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals.

Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia

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

The mitochondrial Na+/Ca2+ exchanger upregulates glucose dependent Ca2+ signalling linked to insulin secretion.

Mitochondria mediate dual metabolic and Ca(2+) shuttling activities. While the former is required for Ca(2+) signalling linked to insulin secretion, the role of the latter in β cell function has not been well understood, primarily because the molecular identity of the mitochondrial Ca(2+) transporters were elusive and the selectivity of their inhibitors was questionable. This study focuses on NCLX, the recently discovered mitochondrial Na(+)/Ca(2+) exchanger that is linked to Ca(2+) signalling in MIN6 and primary β cells. Suppression either of NCLX expression, using a siRNA construct (siNCLX) or of its activity, by a dominant negative construct (dnNCLX), enhanced mitochondrial Ca(2+) influx and blocked efflux induced by glucose or by cell depolarization. In addition, NCLX regulated basal, but not glucose-dependent changes, in metabolic rate, mitochondrial membrane potential and mitochondrial resting Ca(2+). Importantly, NCLX controlled the rate and amplitude of cytosolic Ca(2+) changes induced by depolarization or high glucose, indicating that NCLX is a critical and rate limiting component in the cross talk between mitochondrial and plasma membrane Ca(2+) signalling. Finally, knockdown of NCLX expression was followed by a delay in glucose-dependent insulin secretion. These findings suggest that the mitochondrial Na(+)/Ca(2+) exchanger, NCLX, shapes glucose-dependent mitochondrial and cytosolic Ca(2+) signals thereby regulating the temporal pattern of insulin secretion in β cells

Truly scalable K-Truss and max-truss algorithms for community detection in graphs

The notion of k-truss has been introduced a decade ago in social network analysis and security for community detection, as a form of cohesive subgraphs less stringent than a clique (set of pairwise linked nodes), and more selective than a k-core (induced subgraph with minimum degree k). A k-truss is an inclusion-maximal subgraph Hin which each edge belongs to at least k-2triangles inside H. The truss decomposition establishes, for each edge e, the maximum kfor which ebelongs to a k-truss. Analogously to the largest clique and to the maximum k-core, the strongest community for k-truss is the max-truss, which corresponds to the k-truss having the maximum k. Even though the computation of truss decomposition and of the max-truss takes polynomial time, on a large scale, it suffers from handling a potentially cubic number of wedges. In this paper, we provide a new algorithm FMT, which advances the state of the art on different sides: lower execution time, lower memory usage, and no need for expensive hardware. We compare FMT experimentally with the most recent state-of-the-art algorithms on a set of large real-world and synthetic networks with over a billion edges. The massive improvement allows FMT to compute the max-truss of networks of tens of billions of edges on a single standard server machine

Mesenteric closure with polymer-ligating clips after right colectomy with complete mesocolic excision for cancer and mesentery-based ileocolic resection for Crohn's disease

Mesenteric closure following right colectomy remains controversial and, following the advent of laparoscopic surgery, many surgeons do not routinely close the mesentery after colorectal resection. Nevertheless, especially after the introduction of operations such as right colectomy with complete mesocolic excision and ileocolic resections with extensive mesentery removal for Crohn's disease, the wide mesenteric defect resulting from the dissections can certainly expose the patients to complications such as internal hernias or volvuli. In general, mesenteric closure requires intracorporeal suturing. We describe a simple technique for the closure of the mesentery after surgical resection using polymer-ligating clips. This novel technique seems to minimize the time, effort and risk inherent to the procedure, even after large mesenteric excisions