Pharmacological modulation of cardiac function and blood vessel calibre

Sympathomimetics such as noradrenaline, adrenaline and dopamine all have a positive inotropic effect and may be useful in treating different aspects of cardiovascular collapse. Digoxin, which inhibits the cardiac Na⁺/K⁺ adenosine triphosphatase pump and the phosphodiesterase III inhibitors milrinone and amironone, which both increase in cyclic adenosine monophosphate may also be useful for treatment of angina and heart failure respectively. The cardiac effects of β-blockers, L-type Ca²⁺ channel antagonists, K⁺ channel openers, I(f) inhibitors and nitrovasodilators and their role in angina are described in this article. The list of pharmacological control mechanisms that regulate the calibre of blood vessels is ever expanding and, for ease of understanding, they have been divided into neural, humoral and local mechanisms capable of inducing either vasodilation or vasoconstriction. Moment-to-moment sympathetic nerves and α₁ adrenoceptors maintain vascular tone but, locally, L-type Ca²⁺ channels (LTCC) also have an important function. LTCC antagonists inhibit influx at three sites on the α-subunit of the channel (dihydropyridine, phenylalkylamines and benzothiazepines) to alleviate hypertension. Inhibiting circulating hormones or the receptor targets for hormones, such as angiotensin-II or vasopressin may also be useful for the treatment of hypertension or shock. Nitric oxide (NO) is also one of the most important vasodilator local-control mechanisms, via stimulation of guanylyl cyclase and increased cyclic guanosine monophosphate, and this is counteracted by endothelin-1, one of the most potent vasoconstrictors, which, like NO, also has an important role in diseases such as sepsis.     

Functional neuroimaging of the interference between working memory and the control of periodic ankle movement timing

Background

Limited information processing capacity in the brain necessitates task prioritisation and subsequent adaptive behavioural strategies for the dual-task coordination of locomotion with severe concurrent cognitive loading. Commonly observed strategies include prioritisation of gait at the cost of reduced performance in the cognitive task. Alternatively alterations of gait parameters such as gait velocity have been reported presumably to free processing capacity for the benefit of performance in the cognitive task. The aim of this study was to describe the neuroanatomical correlates of adaptive behavioural strategies in cognitive-motor dual-tasking when the competition for information processing capacity is severe and may exceed individuals’ capacity limitations.

Methods

During an fMRI experiment, 12 young adults performed slow continuous, auditorily paced bilateral anti-phase ankle dorsi-plantarflexion movements as an element of normal gait at .5 Hz in single and dual task modes. The secondary task involved a visual, alphabetic N-back task with presentation rate jittered around .7 Hz. The N-back task, which randomly occurred in 0-back or 2-back form, was modified into a silent counting task to avoid confounding motor responses at the cost of slightly increasing the task′s general coordinative complexity. Participants’ ankle movements were recorded using an optoelectronic motion capture system to derive kinematic parameters representing the stability of the movement timing and synchronization. Participants were instructed to perform both tasks as accurately as possible.

Results

Increased processing complexity in the dual-task 2-back condition led to significant changes in movement parameters such as the average inter-response interval, the coefficient of variation of absolute asynchrony and the standard deviation of peak angular velocity. A regions-of-interest analysis indicated correlations between these parameters and local activations within the left inferior frontal gyrus (IFG) such that lower IFG activations coincided with performance decrements.

Conclusions

Dual-task interference effects show that the production of periodically timed ankle movements, taken as modelling elements of the normal gait cycle, draws on higher-level cognitive resources involved in working memory. The interference effect predominantly concerns the timing accuracy of the ankle movements. Reduced activations within regions of the left IFG, and in some respect also within the superior parietal lobule, were identified as one factor affecting the timing of periodic ankle movements resulting in involuntary ‘hastening’ during severe dual-task working memory load. This ‘hastening’ phenomenon may be an expression of re-automated locomotor control when higher-order cognitive processing capacity can no longer be allocated to the movements due to the demands of the cognitive task. The results of our study also propose the left IFG as a target region to improve performance during dual-task walking by techniques for non-invasive brain stimulation.     

Illness representations and psychological adjustment of Greek couples dealing with a recently-diagnosed cancer: dyadic,interaction and perception-dissimilarity effects

The aim was to examine the impact of the dyadic, interaction and dissimilarity effects of the illness representations on the psychological health of recently diagnosed cancer patients and spouses in Greece. The sample consisted of 298 individuals nested in 149 couples. Effects were examined with the Actor–Partner Interdependence Model. Both actor (i.e., within person) and partner (i.e., between partners) effects were detected for both patients’ and spouses’ psychological symptoms. The negative association of patients’ psychological symptoms with their representations of illness coherence was weak at the higher and medium levels, and stronger at the lower levels of spouse corresponding representations. Patient–partner discrepancy in perceived illness consequences was associated with more psychological symptoms in patients. Adaptation to cancer is a dyadic process within the context of which patient and partner psychological well-being is affected by each other’s understanding of illness. Thus, the parallel examination of the illness representations of both partners is needed from the early phases of the illness trajectory.     

Involvement of a Salmonella genomic island 1 gene in the rumen protozoan-mediated enhancement of invasion for multiple-antibiotic-resistant Salmonella enterica serovar Typhimurium

Multiple-antibiotic-resistant Salmonella enterica serotype Typhimurium is a food-borne pathogen that may be more virulent than related strains lacking the multiresistance phenotype. Salmonella enterica serotype Typhimurium phage type DT104 is the most prevalent of these multiresistant/hypervirulent strains. Multiresistance in DT104 is conferred by an integron structure, designated Salmonella genomic island 1 (SGI1), while we recently demonstrated DT104 hyperinvasion mediated by rumen protozoa (RPz) that are normal flora of cattle. Hyperinvasion was also observed in other Salmonella strains, i.e., other S. enterica serovar Typhimurium phage types and other S. enterica serovars, like S. enterica serovar Infantis, possessing SGI1, while DT104 strains lacking SGI1 were not hyperinvasive. Herein we attempted to identify SGI1 genes involved in the RPz-mediated hyperinvasion of Salmonella strains bearing SGI1. Transposon mutagenesis, coupled with a novel reporter system, revealed the involvement of an SGI1 gene previously designated SO13. Disruption of SO13 expression led to an abrogation of hyperinvasion as assessed by tissue culture invasion assays and by bovine challenge experiments. However, hyperinvasion was not observed in non-SGI1-bearing strains of Salmonella engineered to express SO13. That is, SO13 and another SGI1 gene(s) may coordinately upregulate invasion in DT104 exposed to RPz.     

Matrix protein mediated shutdown of host cell metabolism limits vesicular stomatitis virus-induced interferon-alpha responses to plasmacytoid dendritic cells

Upon infection with many different viruses, plasmacytoid dendritic cells (pDC) produce large amounts of type I interferon (IFN-alpha/beta). To address why upon vesicular stomatitis virus (VSV) infection pDC, but not conventional myeloid DC (mDC), are induced to produce IFN-alpha, pDC and mDC were differentiated from bone marrow cells (BM-DC). Upon VSV infection BM-pDC produced IFN-alpha, whereas BM-mDC did not. Notably, upon infection with VSV-M2, a VSV variant expressing a M51R mutant matrix (M) protein that showed a reduced sequestration of host cell metabolism, BM-pDC and BM-mDC mounted massive IFN-alpha responses. Both DC subsets showed comparable RNA levels of retinoic acid inducible gene-I (RIG-I) and Toll-like receptor (TLR) 7 and were able to respond upon triggering with double-stranded RNA (dsRNA) or single-stranded RNA (ssRNA) analogs. Moreover, upon VSV-M2 infection IFN-alpha production by both DC subsets was largely dependent on viral replication. Interestingly, upon virus infection BM-pDC, but not BM-mDC, up-regulated mRNA levels of nuclear export factors Nup96/98, probably reflecting cellular mechanisms to circumvent viral escape strategies. Collectively, these results indicated that cell types induced to produce IFN-alpha upon viral infection are not primarily defined by cellular receptor configurations but rather by complex virus/host cell interactions.     

Neural correlates of disparity-defined shape discrimination in the human brain

Binocular disparity, the slight differences between the images registered by our two eyes, provides an important cue when estimating the three-dimensional (3D) structure of the complex environment we inhabit. Sensitivity to binocular disparity is evident at multiple levels of the visual hierarchy in the primate brain, from early visual cortex to parietal and temporal areas. However, the relationship between activity in these areas and key perceptual functions that exploit disparity information for 3D shape perception remains an important open question. Here we investigate the link between human cortical activity and the perception of disparity-defined shape, measuring fMRI responses concurrently with psychophysical shape judgments. We parametrically degraded the coherence of shapes by shuffling the spatial position of dots whose disparity defined the 3D structure and investigated the effect of this stimulus manipulation on both cortical activity and shape discrimination. We report significant relationships between shape coherence and fMRI response in both dorsal (V3, hMT+/V5) and ventral (LOC) visual areas that correspond to the observers' discrimination performance. In contrast to previous suggestions of a dichotomy of disparity-related processes in the ventral and dorsal streams, these findings are consistent with proposed interactions between these pathways that may mediate a continuum of processes important in perceiving 3D shape from coarse contour segmentation to fine curvature estimation.