Investigating Intra-Individual Networks of Response Inhibition and Interference Resolution using 7T MRI.

Response inhibition and interference resolution are often considered subcomponents of an overarching inhibition system that utilizes the so-called cortico-basal-ganglia loop. Up until now, most previous functional magnetic resonance imaging (fMRI) literature has compared the two using between-subject designs, pooling data in the form of a meta-analysis or comparing different groups. Here, we investigate the overlap of activation patterns underlying response inhibition and interference resolution on a within-subject level, using ultra-high field MRI. In this model-based study, we furthered the functional analysis with cognitive modelling techniques to provide a more in-depth understanding of behaviour. We applied the stop-signal task and multi-source interference task to measure response inhibition and interference resolution, respectively. Our results lead us to conclude that these constructs are rooted in anatomically distinct brain areas and provide little evidence for spatial overlap. Across the two tasks, common BOLD responses were observed in the inferior frontal gyrus and anterior insula. Interference resolution relied more heavily on subcortical components, specifically nodes of the commonly referred to indirect and hyperdirect pathways, as well as the anterior cingulate cortex, and pre-supplementary motor area. Our data indicated that orbitofrontal cortex activation is specific to response inhibition. Our model-based approach provided evidence for the dissimilarity in behavioural dynamics between the two tasks. The current work exemplifies the importance of reducing inter-individual variance when comparing network patterns and the value of UHF-MRI for high resolution functional mapping.

Reconsidering electrophysiological markers of response inhibition in light of trigger failures in the stop-signal task.

This study investigates the neural correlates underpinning response inhibition using a parametric ex-Gaussian model of stop-signal task performance, fit with hierarchical Bayesian methods, in a large healthy sample (N = 156). The parametric model accounted for both stop-signal reaction time (SSRT) and trigger failure (i.e., failures to initiate the inhibition process). The returned SSRT estimate (SSRTEXG3 ) was attenuated by ≈65 ms compared to traditional nonparametric SSRT estimates (SSRTint ). The amplitude and latency of the N1 and P3 event-related potential components were derived for both stop-success and stop-failure trials and compared to behavioral estimates derived from traditional (SSRTint ) and parametric (SSRTEXG3 , trigger failure) models. Both the fronto-central N1 and P3 peaked earlier and were larger for stop-success than stop-failure trials. For stop-failure trials only, N1 peak latency correlated with both SSRT estimates as well as trigger failure and temporally coincided with SSRTEXG3 , but not SSRTint . In contrast, P3 peak and onset latency were not associated with any behavioral estimates of inhibition for either trial type. While the N1 peaked earlier for stop-success than stop-failure trials, this effect was not found in poor task performers (i.e., high trigger failure/slow SSRT). These findings are consistent with attentional modulation of both the speed and reliability of the inhibition process, but not for poor performers. Together with the absence of any P3 onset latency effect, our findings suggest that attentional mechanisms are important in supporting speeded and reliable inhibition processes required in the stop-signal task.

Clinical Results and Serum Metal Ion Concentrations following Ceramic-on-Metal Total Hip Arthroplasty at a Mean Follow-Up of 60 Months.

Background. Increased metal ion levels following total hip arthroplasty (THA) with metal-on-metal bearings are a highly debated topic. Local soft tissue reactions with chronic pain and systemic side effects such as neuropathy are described. The aim of the current study was to determine the serum metal ion concentrations of Cobalt (Co) and Chrome (Cr) after THA with a ceramic-on-metal (CoM) bearing. Patients and Methods. Between 2008 and 2010, 20 patients underwent THA using a CoM bearing. Clinical function was evaluated by standardized scores systems (Harris Hip Score and WOMAC Score) and radiological examination included X-rays. Patient's blood samples were obtained for metal ion analysis and correlation analysis was done between these results and implant position. Results. Overall, 13 patients with 14 CoM devices were available for the current series. The mean age at time of surgery was 61 years (range, 41 to 85). The postoperative follow-up ranged from 49 to 68 months (mean, 58). Metal ion determination showed mean concentrations of 3,1 µg/L (range, 0,3-15,2 µg/L) for Co and 1,6 µg/L (range, 0,1-5,5 µg/L) for Cr, respectively. A correlation between cup anteversion and Co and Cr concentrations was shown. Conclusion. The current series showed increments for Co and Cr following CoM THA. However, these levels are lower compared to metal ion concentrations in patients with metal-on-metal bearings and the international accepted threshold for revision of MoM devices. We recommend routine follow-up including at least one obligatory evaluation of serum metal ion concentrations and an MRI once to exclude local soft tissue reactions.

Cefepime as treatment for osteomyelitis and other severe bacterial infections.

Cefepime, a novel, injectable alpha-methoxyimino aminothiazolyl cephalosporin, is active in vitro against many of the Gram-positive and Gram-negative bacteria which cause severe infections, including Pseudomonas aeruginosa. It is more active than existing third-generation cephalosporins against multiply-resistant strains of Enterobacteriaceae because of its low affinity for beta-lactamases and its resistance to hydrolysis by these enzymes. Cefepime retains its high potency of activity against methicillin-susceptible Staphylococcus aureus, coagulase-negative staphylococci and streptococci other than enterococci. Seventy-four patients (46 male and 28 female) were treated with cefepime 2 g i.v. every 12 h; 61 patients were evaluable for efficacy (39 male and 22 female). The infections included pneumonia caused by Gram-negative bacilli (21 patients, six with bacteraemia), septicaemia (seven), pyelonephritis (two), osteomyelitis (23, mainly caused by S. aureus), septic arthritis (four) and soft tissue infections (four, one with bacteraemia). Responses were as follows: 52 (85.3%) patients cured; three (4.9%) improved and six (9.8%) failed. The failures included three patients with osteomyelitis, one with pyelonephritis and two with pneumonia. The pathogens and eradication rates were: S. aureus 23/24 (96%), Staphylococcus epidermidis 4/4, Streptococcus spp. 10/10 (100%), P. aeruginosa 11/14 (79%), Enterobacteriaceae 28/28 (100%), Haemophilus spp. 3/3 and others 7/7. Clinical adverse effects included diarrhoea in 11 patients (14.9%) nausea in five (6.8%) and pruritus in three (4.1%). Laboratory abnormalities included leucopenia in three patients (4.1%) and direct Coombs' conversion in 32 (43.2%). Patients were treated for an average of 31.8 days for osteomyelitis and 11.9 days for other infections.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo administration of tumor necrosis factor-alpha is associated with antiviral activity in human peripheral mononuclear cells.

Tumor necrosis factor-alpha (TNF-alpha) has a spectrum of biologic effects and has been shown to exert antiviral effects in fibroblasts in vitro. The in vivo administration of TNF-alpha (40-160 micrograms/m2 intravenously over 2 hr) and its effects on vesicular stomatitis virus (VSV) replication in peripheral blood mononuclear cells (PBMC) from patients with malignancy was investigated. Blood was obtained before, during, and after infusion. The PBMC were separated and infected with VSV at a multiplicity of infection of 0.005 plaque-forming units/cell and virus yields were determined 72 h later. The TNF-alpha inhibited VSV yields by as much as 99% in a dose-dependent manner with the inhibition initially observed during the first hour of infusion. Despite a rapid reduction in TNF-alpha serum levels, the higher doses still produced antiviral effects 4 hr after the infusion. Sera obtained at identical times had no interferon activity. Human gamma-interferon (25 micrograms/ml) added in vitro augmented the TNF-alpha-induced inhibitory activity in both magnitude and duration. Percentages of lymphocytes and monocytes in peripheral blood were reduced at 4 hr after TNF-alpha administration and the monocyte to lymphocyte ratio was diminished and temporally coincided with the loss of TNF-induced antiviral state. These data suggest that the in vivo administration of TNF has a direct inhibitory activity on VSV replication in human peripheral blood mononuclear cells that was enhanceable by gamma-interferon and possibly monocyte mediated.

Assessment of the presence of cytomegalovirus-neutralizing antibody by a plaque-reduction assay.

Evaluation of the in vitro neutralizing activity of 30 immunoglobulin G (IgG) preparations and seven batches of pooled plasma against human cytomegalovirus (CMV) was performed by plaque-reduction assays. There were definite differences detected by these methods that could permit the selection of preparations with highest titers for clinical trials. The addition of guinea pig complement to the plaque-reduction assay enhanced inhibition of CMV; thus, guinea pig complement should be used in assays of IgG preparations. There was no relationship between the ELISA-derived optical density values of the IgG samples and the titers determined by plaque neutralization. These data suggest that the results of plaque-reduction neutralization assays provide important information about preparations of antibody that may be selected for patient administration. The preparations selected for their high titers by neutralization assays differ significantly from those identified by another method.