How I do it: endovascular stent deployment using a novel technique that obviates the need for introducer-sheath upsizing

A case is presented and a novel technique is described by which an endovascular stent is deployed in the venous outflow system of an arteriovenous fistula without the traditional exchange to a larger diameter introducer sheath.     

Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats

Previous clinical and animal studies suggest that selective activators of M(1) and/or M(4) muscarinic acetylcholine receptors (mAChRs) have potential as novel therapeutic agents for treatment of schizophrenia and Alzheimer's disease. However, highly selective centrally penetrant activators of either M(1) or M(4) have not been available, making it impossible to determine the in vivo effects of selective activation of these receptors. We previously identified VU10010 [3-amino-N-(4-chlorobenzyl)-4, 6-dimethylthieno[2,3-b]pyridine-2-carboxamide] as a potent and selective allosteric potentiator of M(4) mAChRs. However, unfavorable physiochemical properties prevented use of this compound for in vivo studies. We now report that chemical optimization of VU10010 has afforded two centrally penetrant analogs, VU0152099 [3-amino-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4,6-dimethylthieno[2,3-b]pyridine carboxamide] and VU0152100 [3-amino-N-(4-methoxybenzyl)-4,6-dimethylthieno[2,3-b]pyridine carboxamide], that are potent and selective positive allosteric modulators of M(4). VU0152099 and VU0152100 had no agonist activity but potentiated responses of M(4) to acetylcholine. Both compounds were devoid of activity at other mAChR subtypes or at a panel of other GPCRs. The improved physiochemical properties of VU0152099 and VU0152100 allowed in vivo dosing and evaluation of behavioral effects in rats. Interestingly, these selective allosteric potentiators of M(4) reverse amphetamine-induced hyperlocomotion in rats, a model that is sensitive to known antipsychotic agents and to nonselective mAChR agonists. This is consistent with the hypothesis that M(4) plays an important role in regulating midbrain dopaminergic activity and raises the possibility that positive allosteric modulation of M(4) may mimic some of the antipsychotic-like effects of less selective mAChR agonists.     

Auditory-somatosensory multisensory interactions in front and rear space

The information conveyed by our senses can be combined to facilitate perception and behaviour. One focus of recent research has been on the factors governing such facilitatory multisensory interactions. The spatial register of neuronal receptive fields (RFs) appears to be a prerequisite for multisensory enhancement. In terms of auditory-somatosensory (AS) interactions, facilitatory effects on simple reaction times and on brain responses have been demonstrated in caudo-medial auditory cortices, both when auditory and somatosensory stimuli are presented to the same spatial location and also when they are separated by 100 degrees in frontal space. One implication is that these brain regions contain large spatial RFs. The present study further investigated this possibility and, in particular, the question of whether AS interactions are restricted to frontal space, since recent research has revealed some fundamental differences between the sensory processing of stimuli in front and rear space. Twelve participants performed a simple reaction time task to auditory, somatosensory, or simultaneous auditory-somatosensory stimuli. The participants placed one of their arms in front of them and the other behind their backs. Loudspeakers were placed close to each hand. Thus, there were a total of eight stimulus conditions - four unisensory and four multisensory - including all possible combinations of posture and loudspeaker location. A significant facilitation of reaction times (RTs), exceeding that predicted by probability summation, was obtained following multisensory stimulation, irrespective of whether the stimuli were in spatial register or not. These results are interpreted in terms of the likely RF organization of previously identified auditory-somatosensory brain regions.     

Discharges in ventromedial frontal cortex during absence spells

Neural mechanisms of conscious attention require thalamic control of widespread cortical networks. Absence spells involve a momentary loss of voluntary control of attention, during which the person is inactive and unresponsive. The spike-wave seizure discharges of these spells rapidly engage both cerebral hemispheres in the classic sign of a "generalized" seizure. Animal evidence suggests that spike-wave seizures are caused by a disruption of thalamic circuitry, with extensive spread to cortex through thalamocortical propagation. We applied advanced methods of electrical source analysis to dense array (256-channel) electroencephalographic recordings of spike-wave discharges of absence spells. Neither the onset nor the spread of these seizures is generalized. Rather, the slow waves of the discharges are restricted to frontotemporal networks, and the spikes represent a highly localized and stereotyped progression of electrophysiological activity in ventromedial frontal networks. Given the current knowledge of the neurophysiology of absence seizures, this specificity of the frontal cortical discharges suggests the hypothesis that absence spells are associated with pathology in a circuit comprising ventromedial frontal cortex, rostral thalamic reticular nucleus, and limbic nuclei of the thalamus. Disrupted in absence, this circuit appears to regulate important aspects of the voluntary control of conscious attention.     

Anger Expression Moderates the Effects of Psychological Reactance to Sexual Health Messages

This study examined how anger expression tendencies moderate the negative consequences of state reactance. An experiment was conducted whereby participants (N = 226) read a health public service announcement (PSA) that encouraged conversations about sexual health history prior to sexual encounters with new partners and that varied in freedom-threatening language. As hypothesized, the freedom-threatening appeal increased perceived threat to freedom and subsequent reactance. However, the negative relationship between reactance and attitude was mitigated for people who were lower in dispositional anger expression. The results showed that the extent to which state reactance resulted in unhealthy outcomes depended on the degree to which people tend to communicate anger. These findings are discussed in terms of theoretical implications for reactance scholars and practical utility for health message designers.