Granule cell ascending axon excitatory synapses onto Golgi cells implement a potent feedback circuit in the cerebellar granular layer.

The function of inhibitory interneurons within brain microcircuits depends critically on the nature and properties of their excitatory synaptic drive. Golgi cells (GoCs) of the cerebellum inhibit cerebellar granule cells (GrCs) and are driven both by feedforward mossy fiber (mf) and feedback GrC excitation. Here, we have characterized GrC inputs to GoCs in rats and mice. We show that, during sustained mf discharge, synapses from local GrCs contribute equivalent charge to GoCs as mf synapses, arguing for the importance of the feedback inhibition. Previous studies predicted that GrC-GoC synapses occur predominantly between parallel fibers (pfs) and apical GoC dendrites in the molecular layer (ML). By combining EM and Ca(2+) imaging, we now demonstrate the presence of functional synaptic contacts between ascending axons (aa) of GrCs and basolateral dendrites of GoCs in the granular layer (GL). Immunohistochemical quantification estimates these contacts to be ∼400 per GoC. Using Ca(2+) imaging to identify synaptic inputs, we show that EPSCs from aa and mf contacts in basolateral dendrites display similarly fast kinetics, whereas pf inputs in the ML exhibit markedly slower kinetics as they undergo strong filtering by apical dendrites. We estimate that approximately half of the local GrC contacts generate fast EPSCs, indicating their basolateral location in the GL. We conclude that GrCs, through their aa contacts onto proximal GoC dendrites, define a powerful feedback inhibitory circuit in the GL.journal articleresearch support, non-u.s. gov't2013 Jul 24importe

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector

A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fb−1 − 1 of √ s = 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, ̃ t ~ , which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV<̃<410 100 GeV < m t ~ < 410 GeV GeV are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV<̃<470 100 GeV < m t ~ < 470 GeV GeV and 480 GeV<̃<610 480 GeV < m t ~ < 610 GeV GeV . Additional limits are set on the pair-production of massive colour-octet resonances

Measurements of electroweak Wjj production and constraints on anomalous gauge couplings with the ATLAS detector

Measurements of the electroweak production of a W boson in association with two jets at high dijet invariant mass are performed using root s = 7 and 8 TeV proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb(-1) of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a W boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process

Classical Electrodynamics as a nonlinear dynamical system

We report on preliminary investigations, of numerical and analytical character, on the dynamical properties of the classical Hamiltonian model for the interaction of electromagnetic radiation with a nonrelativistic charged point particle. We investigate the distribution of energy among the field normal modes when the energy is initially given to the particle, and we find that the high frequency modes have a tendency to be frozen, a fact that is in agreement with the qualitative trend expected from Nekhoroshev's theorem for systems of weakly coupled harmonic oscillators. Moreover we point out that, as a consequence of the dynamical interaction with the radiation field, the charged particle appears to have a highly fluctuating motion

Action potential-evoked Ca2+ signals and calcium channels in axons of developing rat cerebellar interneurones

Axonal [Ca2+] transients evoked by action potential (AP) propagation were studied by monitoring the fluorescence of the high-affinity calcium-sensitive dye Oregon Green 488 BAPTA-1, introduced through whole-cell recording pipettes in the molecular layer of interneurones from cerebellar slices of young rats.The spatiotemporal profile of Ca2+-dependent fluorescence changes was analysed in well-focused axonal stretches a few tens of micrometres long. AP-evoked Ca2+ signals were heterogeneously distributed along axons, with the largest and fastest responses appearing in hot spots on average ∼5 μm apart.The spatial distribution of fluorescence responses was independent of the position of the focal plane, uncorrelated to basal dye fluorescence, and independent of dye concentration. Recordings using the low-affinity dye mag-fura-2 and a Cs+-based intracellular solution revealed a similar pattern of hot spots in response to depolarisation, ruling out measurement artefacts or possible effects of inhomogeneous dye distribution in the generation of hot spots.Fluorescence responses to a short train of APs in hot spots decreased by 41–76 % after bath perfusion of ω-conotoxin MVIIC (5–6 μM), and by 17–65 % after application of ω-agatoxin IVA (500 nM). ω-Conotoxin GVIA (1 μM) had a variable, small effect (0–31 % inhibition), and nimodipine (5 μM) had none. Somatically recorded voltage-gated currents during depolarising pulses were unaffected in all cases. These data indicate that P/Q-type Ca2+ channels, and to a lesser extent N-type channels, are responsible for a large fraction of the [Ca2+] rise in axonalhot spots.[Ca2+] responses never failed during low-frequency (≤ 0.5 Hz) stimulation, indicating reliable AP propagation to the imaged sites. Axonal branching points coincided with a hot spot in ∼50 % of the cases.The spacing of presynaptic varicosities, as determined by a morphological analysis of Neurobiotin-filled axons, was ∼10 times larger than the one measured for hot spots. The latter is comparable to the spacing reported for varicosities in mature animals.We discuss the nature of hot spots, considering as the most parsimonious explanation that they represent functional clusters of voltage-dependent Ca2+ channels, and possibly other [Ca2+] sources, marking the position of developing presynaptic terminals before the formation of en passant varicosities

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"

BackroundUse of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium.AimThis analysis, from the Delirium Day 2015, a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients.MethodsPatients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age>65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score4: possible delirium; scores 1-3: possible cognitive impairment).ResultsAmong 1867 hospitalized patients (mean age 82.07.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.47.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia.DiscussionWe confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents.ConclusionEnvironmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence