The self in conflict: the role of executive processes during truthful and deceptive responses about attitudes

This study sought to extend previous results regarding deceptions about specific memories by investigating the role of executive processes in deceptions about evaluative judgments. In addition, given that previous studies of deception have not included valence manipulations, we also wanted to determine whether the goodness/badness aspect of the items would affect the processes used during deception. Thus, we compared behavioral and event-related potential (ERP) activity while participants made truthful and directed lie (i.e., press opposite of the truth) responses about attitude items with which they either strongly agreed or disagreed. Consistent with previous results, deceptive responses required greater cognitive control as indicated by slower RTs, larger medial frontal negativities (MFN) and smaller late positive components than truthful responses. Furthermore, the magnitude of these deception-related effects was dependent on the valence that participants assigned to the items (i.e., agree/disagree). Directed lie responses about attitudes also resulted in greatly reduced pre-response positivities, an indication that participants strategically monitored their responses even in the absence of explicit task demands. Item valence also differentially affected the amplitude of three ERP components in a 650 ms pre-response interval, independently of whether truthful or deceptive responses were made. Analyses using dipole locations based on results from fMRI studies of evaluative judgments and deception indicated a high degree of overlap between the ERP and fMRI results and revealed the possible temporal characteristics of the hemodynamic activations.     

Complete correction of hemophilia A with adeno-associated viral vectors containing a full-size expression cassette

Hemophilia A is caused by a deficiency in the factor VIII (FVIII) gene. Constrained by limited packaging capacity, even the 4.3-kb B domain-deleted FVIII remained a challenge for delivery by a single adeno-associated viral (AAV) vector. Studies have shown that up to a 6.6-kb vector sequence may be packaged into AAV virions, which suggested an alternative strategy for hemophilia A gene therapy. To explore the usefulness of AAV vectors carrying an oversized FVIII gene, we constructed the AAV-FVIII vector under the control of a beta-actin promoter with a cytomegalovirus enhancer (CB) and a bovine growth hormone (bGH) poly(A) sequence. The CB promoter plus bGH signal was shown to be 3- to 5-fold more potent than the mini-transthyretin (TTR) promoter with a synthetic poly(A) sequence for directing FVIII expression in the liver. Despite the 5.75-kb genome size of pAAV-CB-FVIII, sufficient AAV vectors were produced for in vivo testing. Approximately 3- to 5-fold more FVIII secretion was observed in animals receiving AAV-CB-FVIII vectors than in those receiving standard-sized AAV-TTR-FVIII vectors. Both the activated partial thromboplastin time assay and the whole blood thromboelastographic analysis confirmed that AAV-FVIII vectors fully corrected the bleeding phenotype of hemophilia mice. These results suggest that AAV vectors with an oversized genome should be useful for not only hemophilia A gene therapy but also other diseases with large cDNA such as muscular dystrophy and cystic fibrosis.     

Human health exposure factor estimates based upon a creel/angler survey of the lower Passaic River (part 3)

The results of an analysis of site-specific creel and angler information collected for the lower 6 miles of the Passaic River in Newark, NJ (Study Area), demonstrate that performing a site-specific creel/angler survey was essential to capture the unique characteristics of the anglers using the Study Area. The results presented were developed using a unique methodology for calculating site-specific, human exposure estimates from data collected in this unique urban/industrial setting. The site-specific human exposure factors calculated and presented include (1) size of angler population and fish-consuming population, (2) annual fish consumption rate, (3) duration of anglers' fishing careers, (4) cooking methods for the fish consumed, and (5) demographic information. Sensitivity and validation analyses were performed, and results were found to be useful for performing a site-specific, human health risk assessment. It was also concluded that site-specific exposure factor values are preferable to less representative "default values." The results of the analysis showed that the size of the angling population at the Study Area is estimated to range from 154 to 385 anglers, based on different methods of matching intercepts with anglers. Thirty-four anglers were estimated to have consumed fish; 37 people consumed fish from the river. The fish consumption rate for anglers using this area was best represented as 0.42 g/day for the central tendency and 1.8 g/day for the 95th percentile estimates. Anglers fishing at the river have relatively short fishing careers with a median of 0.9 yr, an average of 1.5 yr, and a 95th percentile of 4.8 yr. Consuming anglers tend to fry the fish they caught. The demographics of anglers who consume fish do not appear to differ substantially from those who do not, with no indication of a subsistence angling population.     

From “Spongy” and “Cold” Hearts to Cellular Cardiomyoplasty: Tales of Canadian Contribution to Global Cardiac Surgery

Despite the small size of its population and the number of its cardiac surgeons, Canadians have participated actively in the birth and development of cardiac surgery during the past half century, with pioneers such as Arthur Vineberg and Wilfred Bigelow leading the way. New and innovative cardiac surgical techniques and their scientific bases were developed and shared globally over the years. Canadian surgeons continue to be productive and are contributing to advances in this field at the dawn of the twenty-first century. Some of these efforts and achievements are illustrated in this review.     

Effects of botulinum toxin A on functional outcome during distraction osteogenesis.

Distraction osteogenesis is useful for correcting limb length inequality, deformities, or short stature. Despite success with bone formation, soft tissue maladaptations including muscle and joint contracture may lead to undesirable results. Botulinum toxin A has been useful in treating spasticity in cerebral palsy, and has been used clinically in select cases to allay contracture in distraction osteogenesis. This study examines the toxin's efficacy in preventing distraction-induced loss of muscle strength and range of motion. The left tibias of 15 New Zealand White rabbits were distracted 1.5 mm/day until approximately a 20% gain was achieved. Each treatment group was divided into animals injected with saline or botulinum toxin in either the gastrocnemius or tibialis anterior muscles. A control group of two additional animals underwent no surgical procedure. Strength and range of motion were assessed prior to, and following, the experiment. At the study's end, animals were euthanized and muscles were harvested, when lengths and weights were recorded. All muscles injected with botulinum toxin showed decreased wet weight and persistent weakness upon completion of the study. Range of motion decreased in all distracted animals. When the gastrocnemius was injected, its strength was reduced but the tibialis anterior strength was preserved, and the limb achieved 22% greater dorsiflexion than saline controls (p = 0.016). When the tibialis anterior received the toxin, plantarflexion was increased by 23% (p = 0.049). Botulinum toxin injection prior to limb distraction increases the "post-lengthened" excursion of the injected muscle and this increased length may have a protective effect on its antagonist. In toxin-injected gastrocnemius muscles, the level of equinus contracture is reduced due to length gains in the Achilles tendon while the anterior tibialis maintains its ability to generate torque. Injection of botulinum toxin in the gastrocnemius may minimize equinus contracture and protect the anterior tibialis from damage during human tibial lengthening. Longer follow-up studies are needed to ensure that toxin-induced muscle weakness resolves with time.     

Comparative in vivo uroselectivity profiles of anticholinergics, tested in a novel anesthetized rabbit model

The aim of this study was to describe a new experimental animal model for simultaneous measurement of carbachol-induced increase in intravesical pressure and salivary secretion in rabbits. Further, we also compared the in vivo potency and urinary bladder versus salivary gland selectivity profiles of Oxybutynin, Tolterodine, Solifenacin and Darifenacin. The intravesical pressure and salivary secretion were evoked by intra-arterial injection of carbachol (1.5 microg/kg). The carbachol-induced increase in intravesical pressure and salivation was simultaneously recorded before and after increasing doses of test drugs administered intravenously. The basal mean changes in intravesical pressure and salivation subsequent to carbachol administration were in the range of 6.7-7.5 mm Hg and 0.5-0.7 g respectively. Repeated administration of vehicle did not elicit any appreciable changes in intravesical pressure and salivary secretion to carbachol administration from the basal values till 3 h. All the test drugs exhibited a dose-dependent inhibition of carbachol-induced increase in intravesical pressure and salivary secretion. Darifenacin demonstrated a greater potency compared to other muscarinic receptor antagonists for inhibiting carbachol-induced increase in intravesical pressure. It also exhibited functional selectivity for the urinary bladder versus salivary gland. In contrast, Oxybutynin was functionally more selective in inhibiting carbachol-induced increase in salivary secretion. The observed urinary bladder versus salivary selectivity values were 0.6+/-0.2, 1.1+/-0.2, 1.7+/-0.5, and 2.3+/-0.5 for Oxybutynin, Tolterodine, Solifenacin and Darifenacin respectively. These results suggest that the functional selectivity of muscarinic receptor antagonists between urinary bladder and salivary glands can be readily detected in this model. Thus rabbits may represent a useful animal model for evaluating putative bladder selective muscarinic receptor antagonists for the treatment of overactive bladder.     

Regional cerebral perfusion during the premonitory phase of triggered migraine: A double-blind randomized placebo-controlled functional imaging study using pseudo-continuous arterial spin labeling

Objective

To identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)-triggered migraine attacks.

Background

PS could provide insights into attack initiation and alterations in neuronal function prior to headache onset.

Methods

We undertook a functional imaging study using a double-blind placebo-controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine-like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty-three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo-continuous arterial spin labeling (3D pCASL).

Results

The primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p < 0.05 family-wise error-corrected) during NTG-induced PS. A separate region of interest analysis revealed significant CBF increases in the region of the hypothalamus (p = 0.006, effect size 0.77). Post hoc analyses revealed significant reductions in CBF over the occipital cortices in participants with a history of migraine with underlying aura (n = 14).

Conclusions

We identified significant regional CBF changes associated with NTG-induced PS, consistent with other investigations and with novel findings, withstanding statistical comparison against placebo. These findings were not present in patients who continually took preventive medication. Additional findings were identified only in participants who experience migraine with aura. Understanding this biological and treatment-related heterogeneity is vital to evaluating functional imaging outcomes in migraine research.