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

Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model.

Altered neuronal excitability is emerging as an important feature in Alzheimer's disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca(2+)]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain

Sequence analysis of a microsatellite and its flanking regions in intraspecific hybrids of grapevine (Vitis vinifera L.)

Microsatellite (MS) VVMD21 (BOWERS et al. 1999) was taken as a model to explore the molecular basis of polymorphism in a panel of 6 grapevine accessions (Vitis vinifera L.), consisting of Sangiovese and Cabernet Sauvignon and 4 F1 plants derived from crossing both varieties. The 12 alleles of both parents and the progeny were cloned and sequenced. The microsatellite repeat (AG)n>6 was found in each sequence, together with a poly-T rich region that showed irregularity. Furthermore, single nucleotide deletion or exchange (point mutations) were found in the microsatellite flanking regions

Resistance to apramycin of Salmonella and E.coli isolated from swine

The aim of this study was to determine the prevalence of aminoglycosides antibiotic resistance in Salmonella spp. and E. coli strains. 32 E. coli, and 47 Salmonella spp., isolated from cases of enteritis in growers and fatteners from 1998 to 2002 in Umbria and Marche regions, were tested. Susceptibility to gentamicin, tobramycin and streptomycin was determined by Kirby-Bauer method, apramycin by microdilution method. 92,4 % of the strains tested were susceptible to apramycin, 77,2 % to gentamicin, 67,1 % to tobramycin and 35,4 % to streptomycin. A positive statistical association between gentamicin and apramycin (RR = 7,63; p = 0,014), tobramycin and apramycin (RR = 9,22; p = 0,027) was demonstrated. There is no difference between the association apramycin-streptomycin, suggesting a mechanism of resistance related to the presence of the aminoglycoside acetyltranspherase IV enzyme. The trend based on estimated OR from the resistance of the strains for every year considered was significant (p = 0,00049), showing a progressive decrease from 1998 (OR = 1) to 2002 (OR = 0,3)

The role of cooperation amongst cities, universities, research bodies and civil society organizations on urban food policies in Africa as innovative actions in the cadre of the Milan urban food policy pact

Within the framework of the international debate focusing on experiences emerging from cities in the global North, this paper aims to explore urban food policies under the lens of a global South perspective, paying particular attention to African cities and taking into account the common elements they present -compared with other urban contexts and territories- but also the specificities and uniqueness of them with respect to the process of urbanization and the linkages existing amongst cities and food. Urban food policies are powerful institutional actions, able to build more sustainable food systems of contemporary cities. These innovative policies are designed with a systemic and cross-sectoral approach, capable of acting at the intersection of different issues and fields such as water, waste, planning, health, transport, education, environment, trade, but also food and nutrition security, self-sufficiency and food sovereignty. We will describe an overview of initiatives developed in African cities, in view of the values stemming from the New Urban Agenda and the recommended actions by the recent Milan Urban Food Policy Pact, as an inspiring and propelling opportunity for new forms of territorial partnerships which could promote new types of cooperation amongst cities, universities, research bodies and civil society organizations from global North and South. Our research follows also the broader Italian development agenda. Under this light we will describe the mobilization of a number of institutional actors towards enhancing collaboration with the African context, drawing a geography of priorities, places and initiatives that are being activated in this field. The paper will identify a series of cross-cutting issues (such as land tenure, climate change, urban agriculture, rural-urban migration, waste management) to create a set of interpretative geographies, comparing cases across different African perspectives (for instance, environmental and socio-cultural) to identify common grounds and regional features

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