ADC mapping of the aging frontal lobes in mild cognitive impairment

Normal aging, leukoaraiosis (LA) and vascular disease particularly involve the human frontal lobes. We decided to investigate a population of elderly patients referred for neuroimaging because of progressive minor cognitive deficits but no dementia. They underwent conventional Magnetic resonance imaging (MRI) using axial T1 and T2-weighted imaging as well as coronal FLAIR sequences in addition to the axial diffusion-weighted MRI. MRI allowed us to differentiate patients with leukoaraïosis (LA+) from those without it (LA-) and mapping of the apparent diffusion coefficient (ADC) to investigate local tissular water motion.We observed an increase in the ADC in all investigated patients with increasing age (r=0.326, p=0.002). This increase was observed in both patients groups (LA+ and LA-) . In addition, the LA+ group had significant higher ADC values than the LA- group after controlling for age (p<0.0001

Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.

In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors

Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

74sireservedObjective: Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. Design: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). Setting: Tertiary and University hospitals. Interventions: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). Measurements: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. Conclusions: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.mixedMonti G.; Galbiati C.; Toffoletto F.; Calabro M.G.; Colombo S.; Ferrara B.; Giardina G.; Lembo R.; Marzaroli M.; Moizo E.; Mucci M.; Pasculli N.; Plumari V.P.; Scandroglio A.M.; Tozzi M.; Momesso E.; Boffa N.; Lobreglio R.; Montrucchio G.; Guarracino F.; Benedetto U.; Biondi-Zoccai G.; D'Ascenzo F.; D'Andrea N.; Paternoster G.; Ananiadou S.; Ballestra M.; De Sio A.; Pota V.; Cotoia A.; Della Selva A.; Bruni A.; Iapichino G.; Bradic N.; Corradi F.; Gemma M.; Nogtev P.; Petrova M.; Agro F.E.; Cabrini L.; Forfori F.; Likhvantsev V.; Bove T.; Finco G.; Landoni G.; Zangrillo A.; Ajello S.; Cappelletti A.M.; Fominskiy E.; Nisi F.G.; Pazzanese V.; Pieri M.; Canavosio F.; Palmesino F.; Bernasconi M.; Gallioli G.; Marino G.; Vetrugno L.; Millin C.; Missio D.; Gallicchio F.; Azzali B.; Bozzetti M.; Cristadoro D.; Perone R.; Cantatore L.P.; Curci G.; Pabon I.M.; Garofalo E.; Mainetti M.; Calamai I.; Maraggia D.; Mattei A.; Yavorovskiy A.Monti, G.; Galbiati, C.; Toffoletto, F.; Calabro, M. G.; Colombo, S.; Ferrara, B.; Giardina, G.; Lembo, R.; Marzaroli, M.; Moizo, E.; Mucci, M.; Pasculli, N.; Plumari, V. P.; Scandroglio, A. M.; Tozzi, M.; Momesso, E.; Boffa, N.; Lobreglio, R.; Montrucchio, G.; Guarracino, F.; Benedetto, U.; Biondi-Zoccai, G.; D'Ascenzo, F.; D'Andrea, N.; Paternoster, G.; Ananiadou, S.; Ballestra, M.; De Sio, A.; Pota, V.; Cotoia, A.; Della Selva, A.; Bruni, A.; Iapichino, G.; Bradic, N.; Corradi, F.; Gemma, M.; Nogtev, P.; Petrova, M.; Agro, F. E.; Cabrini, L.; Forfori, F.; Likhvantsev, V.; Bove, T.; Finco, G.; Landoni, G.; Zangrillo, A.; Ajello, S.; Cappelletti, A. M.; Fominskiy, E.; Nisi, F. G.; Pazzanese, V.; Pieri, M.; Canavosio, F.; Palmesino, F.; Bernasconi, M.; Gallioli, G.; Marino, G.; Vetrugno, L.; Millin, C.; Missio, D.; Gallicchio, F.; Azzali, B.; Bozzetti, M.; Cristadoro, D.; Perone, R.; Cantatore, L. P.; Curci, G.; Pabon, I. M.; Garofalo, E.; Mainetti, M.; Calamai, I.; Maraggia, D.; Mattei, A.; Yavorovskiy, A

Foxp1 and Lhx1 Coordinate Motor Neuron Migration with Axon Trajectory Choice by Gating Reelin Signalling

Topographic neuronal maps arise as a consequence of axon trajectory choice correlated with the localisation of neuronal soma, but the identity of the pathways coordinating these processes is unknown. We addressed this question in the context of the myotopic map formed by limb muscles innervated by spinal lateral motor column (LMC) motor axons where the Eph receptor signals specifying growth cone trajectory are restricted by Foxp1 and Lhx1 transcription factors. We show that the localisation of LMC neuron cell bodies can be dissociated from axon trajectory choice by either the loss or gain of function of the Reelin signalling pathway. The response of LMC motor neurons to Reelin is gated by Foxp1- and Lhx1-mediated regulation of expression of the critical Reelin signalling intermediate Dab1. Together, these observations point to identical transcription factors that control motor axon guidance and soma migration and reveal the molecular hierarchy of myotopic organisation

Genetic pathways implicated in speech and language

Item does not contain fulltex