The use of opioid medications for pain management after surgery is a leading antecedent to persistent opioid use.
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The negative effects of these agents underscore the need for more nonopioid ...alternatives to treat postoperative pain; however, years of research and attempts to bring alternative agents to market have failed. Sodium channels, which are essential to depolarization and propagation of sensory information in neurons and axons, are a logical target for pain reduction. Attempts to use systemic nonselective sodium channel blockers have not succeeded because of dose-limiting side effects. Now, years of research on sodium channel blockers that are specific to . . .
Behavior, perception and cognition are strongly shaped by the synthesis of information across the different sensory modalities. Such multisensory integration often results in performance and ...perceptual benefits that reflect the additional information conferred by having cues from multiple senses providing redundant or complementary information. The spatial and temporal relationships of these cues provide powerful statistical information about how these cues should be integrated or “bound” in order to create a unified perceptual representation. Much recent work has examined the temporal factors that are integral in multisensory processing, with many focused on the construct of the multisensory temporal binding window – the epoch of time within which stimuli from different modalities is likely to be integrated and perceptually bound. Emerging evidence suggests that this temporal window is altered in a series of neurodevelopmental disorders, including autism, dyslexia and schizophrenia. In addition to their role in sensory processing, these deficits in multisensory temporal function may play an important role in the perceptual and cognitive weaknesses that characterize these clinical disorders. Within this context, focus on improving the acuity of multisensory temporal function may have important implications for the amelioration of the “higher-order” deficits that serve as the defining features of these disorders.
•The review focuses on altered multisensory function in developmental disabilities.•Multisensory temporal acuity is altered in autism, dyslexia and schizophrenia.•The construct of the multisensory temporal binding window is critical in perception.•Perceptual training may have utility in improving multisensory function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Using a health impact assessment framework, we estimated the population health effects arising from alternative land-use and transport policy initiatives in six cities. Land-use changes were ...modelled to reflect a compact city in which land-use density and diversity were increased and distances to public transport were reduced to produce low motorised mobility, namely a modal shift from private motor vehicles to walking, cycling, and public transport. The modelled compact city scenario resulted in health gains for all cities (for diabetes, cardiovascular disease, and respiratory disease) with overall health gains of 420–826 disability-adjusted life-years (DALYs) per 100 000 population. However, for moderate to highly motorised cities, such as Melbourne, London, and Boston, the compact city scenario predicted a small increase in road trauma for cyclists and pedestrians (health loss of between 34 and 41 DALYs per 100 000 population). The findings suggest that government policies need to actively pursue land-use elements—particularly a focus towards compact cities—that support a modal shift away from private motor vehicles towards walking, cycling, and low-emission public transport. At the same time, these policies need to ensure the provision of safe walking and cycling infrastructure. The findings highlight the opportunities for policy makers to positively influence the overall health of city populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Altered sensory and perceptual function is recognized as an important characteristic of Autism Spectrum Disorder (ASD).•Disrupted oscillatory synchronization in ASD is observable in numerous sensory ...and perceptual tasks and in multiple frequency bands of the oscillatory hierarchy.•Oscillatory changes in ASD are consistent with a disturbance in the balance of excitation and inhibition, as well as disruption of thalamic function.•Altered network synchronization makes contributions to both perceptual enhancement and impairment in ASD.
Autism Spectrum Disorder (ASD) is a highly prevalent developmental disability characterized by deficits in social communication and interaction, restricted interests, and repetitive behaviors. Recently, anomalous sensory and perceptual function has gained an increased level of recognition as an important feature of ASD. A specific impairment in the ability to integrate information across brain networks has been proposed to contribute to these disruptions. A crucial mechanism for these integrative processes is the rhythmic synchronization of neuronal excitability across neural populations; collectively known as oscillations. In ASD there is believed to be a deficit in the ability to efficiently couple functional neural networks using these oscillations. This review discusses evidence for disruptions in oscillatory synchronization in ASD, and how disturbance of this neural mechanism contributes to alterations in sensory and perceptual function. The review also frames oscillatory data from the perspective of prevailing neurobiologically-inspired theories of ASD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Multisensory processes are fundamental in scaffolding perception, cognition, learning, and behavior. How and when stimuli from different sensory modalities are integrated rather than treated as ...separate entities is poorly understood. We review how the relative reliance on stimulus characteristics versus learned associations dynamically shapes multisensory processes. We illustrate the dynamism in multisensory function across two timescales: one long term that operates across the lifespan and one short term that operates during the learning of new multisensory relations. In addition, we highlight the importance of task contingencies. We conclude that these highly dynamic multisensory processes, based on the relative weighting of stimulus characteristics and learned associations, provide both stability and flexibility to brain functions over a wide range of temporal scales.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
During our everyday lives, we are confronted with a vast amount of information from several sensory modalities. This multisensory information needs to be appropriately integrated for us to ...effectively engage with and learn from our world. Research carried out over the last half century has provided new insights into the way such multisensory processing improves human performance and perception; the neurophysiological foundations of multisensory function; the time course for its development; how multisensory abilities differ in clinical populations; and, most recently, the links between multisensory processing and cognitive abilities. This review summarizes the extant literature on multisensory function in typical and atypical circumstances, discusses the implications of the work carried out to date for theory and research, and points toward next steps for advancing the field.
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CMK, FFLJ, NUK, UL, UM, UPUK
Summary
Eggplant (Solanum melongena L.) is an important horticultural crop and one of the most widely grown vegetables from the Solanaceae family. It was domesticated from a wild, prickly progenitor ...carrying small, round, non‐anthocyanic fruits. We obtained a novel, highly contiguous genome assembly of the eggplant ‘67/3’ reference line, by Hi‐C retrofitting of a previously released short read‐ and optical mapping‐based assembly. The sizes of the 12 chromosomes and the fraction of anchored genes in the improved assembly were comparable to those of a chromosome‐level assembly. We resequenced 23 accessions of S. melongena representative of the worldwide phenotypic, geographic, and genetic diversity of the species, and one each from the closely related species Solanum insanum and Solanum incanum. The eggplant pan‐genome contained approximately 51.5 additional megabases and 816 additional genes compared with the reference genome, while the pan‐plastome showed little genetic variation. We identified 53 selective sweeps related to fruit color, prickliness, and fruit shape in the nuclear genome, highlighting selection leading to the emergence of present‐day S. melongena cultivars from its wild ancestors. Candidate genes underlying the selective sweeps included a MYBL1 repressor and CHALCONE ISOMERASE (for fruit color), homologs of Arabidopsis GLABRA1 and GLABROUS INFLORESCENCE STEMS2 (for prickliness), and orthologs of tomato FW2.2, OVATE, LOCULE NUMBER/WUSCHEL, SUPPRESSOR OF OVATE, and CELL SIZE REGULATOR (for fruit size/shape), further suggesting that selection for the latter trait relied on a common set of orthologous genes in tomato and eggplant.
Significance Statement
Chromosome conformation capture (Hi‐C) was applied for improving a short read‐based genome assembly of eggplant (Solanum melongena). The enhanced assembly, combined with resequencing data of accessions representing the genetic and phenotypic diversity of the species and of its closest wild relatives, allowed the construction of the first eggplant pan‐genome and pan‐plastome and the identification of selective sweeps and candidate genes likely involved in eggplant domestication and breeding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Human multisensory systems are known to bind inputs from the different sensory modalities into a unified percept, a process that leads to measurable behavioral benefits. This integrative process can ...be observed through multisensory illusions, including the McGurk effect and the sound-induced flash illusion, both of which demonstrate the ability of one sensory modality to modulate perception in a second modality. Such multisensory integration is highly dependent upon the temporal relationship of the different sensory inputs, with perceptual binding occurring within a limited range of asynchronies known as the temporal binding window (TBW). Previous studies have shown that this window is highly variable across individuals, but it is unclear how these variations in the TBW relate to an individual's ability to integrate multisensory cues. Here we provide evidence linking individual differences in multisensory temporal processes to differences in the individual's audiovisual integration of illusory stimuli. Our data provide strong evidence that the temporal processing of multiple sensory signals and the merging of multiple signals into a single, unified perception, are highly related. Specifically, the width of right side of an individuals' TBW, where the auditory stimulus follows the visual, is significantly correlated with the strength of illusory percepts, as indexed via both an increase in the strength of binding synchronous sensory signals and in an improvement in correctly dissociating asynchronous signals. These findings are discussed in terms of their possible neurobiological basis, relevance to the development of sensory integration, and possible importance for clinical conditions in which there is growing evidence that multisensory integration is compromised.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Abstract
Objective
To apply the sequential up–down method to a human experimental pain model in order to examine the opioid-sparing effect of oral pregabalin on intravenous alfentanil.
Design
...Double-blind, randomized, crossover.
Setting
Academic university medical center.
Subjects
Thirty-one healthy males.
Methods
The median effective plasma concentration of intravenous alfentanil was determined under two conditions: alfentanil alone (phase I) and alfentanil+ pregabalin (300 mg orally) (phase II). The alfentanil plasma level (after a computer-controlled infusion) producing a success criterion (at least 30% intradermal capsaicin-induced pain reduction compared with placebo) was used to determine higher or lower doses for each sequential subject. The median dose producing a success criterion and its confidence interval were determined.
Results
On the basis of the t test for a difference across phase and regression coefficients across groups, there was no opioid-sparing effect of pregabalin on alfentanil. Four subjects in phase I and five subjects in phase II did not complete the study. Two in phase I were technical failures, with the rest in both phases stopped because of side effects. Of the subjects who completed the study, six of 19 subjects in phase I and 11 of 12 subjects in phase II reported side effects.
Conclusions
When the intradermal capsaicin-induced pain model was used in healthy volunteers, oral pregabalin had no opioid-sparing effects on intravenous alfentanil. This experimental model may be useful in studying analgesic interactions.
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