Altered white matter structure in auditory tracts following early monocular enucleation

Purpose: Similar to early blindness, monocular enucleation (the removal of one eye) early in life results in crossmodal behavioral and morphological adaptations. Previously it has been shown that partial visual deprivation from early monocular enucleation results in structural white matter changes throughout the visual system (Wong et al., 2018). The current study investigated structural white matter of the auditory system in adults who have undergone early monocular enucleation compared to binocular control participants. Methods: We reconstructed four auditory and audiovisual tracts of interest using probabilistic tractography and compared microstructural properties of these tracts to binocularly intact controls using standard diffusion indices. Results: Although both groups demonstrated asymmetries in indices in intrahemispheric tracts, monocular enucleation participants showed asymmetries opposite to control participants in the auditory and A1-V1 tracts. Monocularenucleation participants also demonstrated significantly lower fractional anisotropy in the audiovisual projections contralateral to the enucleated eye relative to control participants. Conclusions: Partial vision loss from early monocular enucleation results in altered structuralYork University Librarie

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Enhanced Audiovisual Processing in People with one Eye: Unaltered by Increased Temporal Load

We investigate whether the loss of one eye leads to enhanced multisensory processing. Previously, we measured speed detection and discrimination of auditory, visual, and audiovisual targets presented as a stream of paired objects and familiar sounds in people with one eye compared to controls viewing binocularly or with one eye patched. All participants were equally able to detect the presence of auditory, visual, or bimodal targets; however, when discriminating between the unimodal and bimodal targets, both control groups demonstrated the Colavita visual dominance effect, preferential processing of visual over auditory information for the bimodal stimuli. People with one eye, however, showed no Colavita effect but rather equal preference for processing visual and auditory stimuli. In the current experiment we increased the temporal processing load in an attempt to favour auditory processing and thereby reverse Colavita visual dominance with a one-back stimulus repetition detection and discrimination paradigm. The Colavita effect was reduced in both control groups, but people with one eye continued to show no Colavita effect. People with one eye display equal auditory and visual processing, suggesting better multisensory processing, likely as a form of cross-modal adaptation and compensation for their loss of binocularity

Optimal Audiovisual Integration in People with One Eye

Abstract People with one eye show altered sensory processing. Such changes might reflect a central reweighting of sensory information that might impact on how multisensory cues are integrated. We assessed whether people who lost an eye early in life differ from controls with respect to audiovisual integration. In order to quantify the relative weightings assigned to each sensory system, participants were asked to spatially localize audiovisual events that have been previously shown to be optimally combined and perceptually fused from the point of view of location in a normal population, where the auditory and visual components were spatially disparate. There was no difference in the variability of localizing unimodal visual and auditory targets by people with one eye compared to controls. People with one eye did however, demonstrate slower reaction times to localize visual stimuli compared to auditory stimuli and were slower than binocular and eye-patched control groups. When localizing bimodal targets, the weightings assigned to each sensory modality in both people with one eye and controls were predictable from their unimodal performance, in accordance with Maximum Likelihood Estimation and the time it took all three groups to localize the bimodal targets was faster than for vision alone. Regardless of demonstrating a longer response time to visual stimuli, people with one eye appear to integrate the auditory and visual components of multisensory events optimally when determining spatial location

Presentation_1_Perception of the McGurk effect in people with one eye depends on whether the eye is removed during infancy or adulthood.pdf

BackgroundThe visual system is not fully mature at birth and continues to develop throughout infancy until it reaches adult levels through late childhood and adolescence. Disruption of vision during this postnatal period and prior to visual maturation results in deficits of visual processing and in turn may affect the development of complementary senses. Studying people who have had one eye surgically removed during early postnatal development is a useful model for understanding timelines of sensory development and the role of binocularity in visual system maturation. Adaptive auditory and audiovisual plasticity following the loss of one eye early in life has been observed for both low-and high-level visual stimuli. Notably, people who have had one eye removed early in life perceive the McGurk effect much less than binocular controls.MethodsThe current study investigates whether multisensory compensatory mechanisms are also present in people who had one eye removed late in life, after postnatal visual system maturation, by measuring whether they perceive the McGurk effect compared to binocular controls and people who have had one eye removed early in life.ResultsPeople who had one eye removed late in life perceived the McGurk effect similar to binocular viewing controls, unlike those who had one eye removed early in life.ConclusionThis suggests differences in multisensory compensatory mechanisms based on age at surgical eye removal. These results indicate that cross-modal adaptations for the loss of binocularity may be dependent on plasticity levels during cortical development.</p

Image_1_Perception of the McGurk effect in people with one eye depends on whether the eye is removed during infancy or adulthood.tif

BackgroundThe visual system is not fully mature at birth and continues to develop throughout infancy until it reaches adult levels through late childhood and adolescence. Disruption of vision during this postnatal period and prior to visual maturation results in deficits of visual processing and in turn may affect the development of complementary senses. Studying people who have had one eye surgically removed during early postnatal development is a useful model for understanding timelines of sensory development and the role of binocularity in visual system maturation. Adaptive auditory and audiovisual plasticity following the loss of one eye early in life has been observed for both low-and high-level visual stimuli. Notably, people who have had one eye removed early in life perceive the McGurk effect much less than binocular controls.MethodsThe current study investigates whether multisensory compensatory mechanisms are also present in people who had one eye removed late in life, after postnatal visual system maturation, by measuring whether they perceive the McGurk effect compared to binocular controls and people who have had one eye removed early in life.ResultsPeople who had one eye removed late in life perceived the McGurk effect similar to binocular viewing controls, unlike those who had one eye removed early in life.ConclusionThis suggests differences in multisensory compensatory mechanisms based on age at surgical eye removal. These results indicate that cross-modal adaptations for the loss of binocularity may be dependent on plasticity levels during cortical development.</p

Evidence of multisensory plasticity: Asymmetrical medial geniculate body in people with one eye

The medial geniculate body (MGB) plays a central role in auditory processing with both efferent and afferent tracts to primary auditory cortex. People who have lost one eye early in life have enhanced sound localization, lack visual over auditory dominance and integrate auditory and visual information optimally, similar to controls, despite taking longer to localize unimodal visual stimuli. Compared to controls, people with one eye have decreased lateral geniculate nuclei (LGN) volume as expected given the 50% deafferentation of the visual system. However, LGN volume is larger than predicted contralateral to the remaining eye, indicating altered structural development likely through recruitment of deafferented LGN cells. Purpose: the current study investigated whether structural MGB changes are also present in this group given the changes they exhibit in auditory processing. Methods: MGB volumes were measured in adults who had undergone early unilateral eye enucleation and were compared to binocularly intact controls. Results: unlike controls, people with one eye had a significant asymmetry with a larger left compared to right MGB, independent of eye of enucleation. MGB volume correlated positively with LGN volume in people with one eye. Conclusions: volume asymmetry in the MGB in people with one eye may represent increased interactions between the left MGB and primary auditory cortex. This interaction could contribute to increased auditory and other left hemisphere-dominant processing, including language, as compensation for the loss of one half of visual inputs early in life. The positive correlation between MGB and LGN volume is not due to space constraints but rather indicates increased plasticity in both auditory and visual sensory systems following early eye enucleation

Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine derivatives as highly potent and selective human A3 adenosine receptor antagonists: Influence of the chain at the N8 pyrazole nitrogen

An enlarged series of pyrazolotriazolopyrimidines previously reported, in preliminary form (Baraldi et al. J. Med. Chem. 1999, 42, 4473-4478), as highly potent and selective human A3 adenosine receptor antagonists is described. The synthesized compounds showed A3 adenosine receptor affinity in the sub-nanomolar range and high levels of selectivity evaluated in radioligand binding assays at human A1, A(2A), A(2B), and A3 adenosine receptors. In particular, the effect of the chain at the N8 pyrazole nitrogen was analyzed. This study allowed us to identify the derivative with the methyl group at the N8 pyrazole combined with the 4-methoxyphenylcarbamoyl moiety at the N5 position as the compound with the best binding profile in terms of both affinity and selectivity (hA3 = 0.2 nM, hA1/hA3 = 5485, hA2A/hA3 = 6950, hA(2B)/hA3 = 1305). All the compounds proved to be full antagonists in a specific functional model where the inhibition of cAMP generation by IB-MECA was measured in membranes of CHO cells stably transfected with the human A3 receptor. The new compounds are among the most potent and selective A3 antagonists so far described. The derivatives with higher affinity at human A3 adenosine receptors proved to be antagonists, in the cAMP assay, capable of inhibiting the effect of IB-MECA with IC50 values in the nanomolar range, with a trend strictly similar to that observed in the binding assay. Also a molecular modeling study was carried out, with the aim to identify possible pharmacophore maps. In fact, a sterically controlled structure-activity relationship was found for the N8 pyrazole substituted derivatives, showing a correlation between the calculated molecular volume of pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine derivatives and their experimental K(i) values