Deficits in Reach Planning and On-Line Grasp Control in Adults With Amblyopia.

Purpose: Adults with amblyopia exhibit impairments when reaching to grasp three-dimensional objects. We examined whether their deficits derive from problems with feedforward planning of these prehension movements or in using visual feedback to control them on-line. Methods: Twenty-one adults with mild to severe anisometropic and/or strabismic amblyopia and reduced binocularity participated, along with 21 normally sighted age- and gender-matched controls. Subjects used their preferred hand to reach for, precision grasp, and then lift cylindrical table-top objects (two sizes, two distances) using binocular, dominant eye, or amblyopic/non-sighting eye vision just to plan their movements during a 1-second task preview with vision then occluded so feedback was absent or to plan and execute them (i.e., with visual feedback fully available). Kinematic and error measures of the timing and accuracy of the reach and grasp were quantified by view and feedback and compared by ANOVA. Results: The amblyopic adults performed generally worse than controls across all three views in both feedback conditions. With vision for planning only, their movement initiation and duration times were significantly increased, as were their initial reach times and error rates, especially when using the amblyopic eye alone, whatever its visual acuity loss. These relative planning deficits were only partially rectified with visual feedback available on-line. Relative grasp planning deficits were less evident in the amblyopia group, who instead produced significantly increased grip times and errors under binocular and amblyopic eye visual feedback conditions, although the subgroup with unmeasurable stereovision also formed wider (inaccurate) grasps across all conditions. Conclusions: Adults with amblyopia seem to have problems constructing reliable internal spatial representations for the feedforward planning of prehension, particularly with their affected eye and mainly affecting their reach, with additional deficits in on-line grasp control related to poor binocularity.

Practical limitations of emergency donor panels as a risk mitigation in small-scale short-term training team operations.

Haemostatic resuscitation with blood products has become the expected standard of care for trauma casualties. As UK Defence increases its deployment of small-scale, short-term training teams (STTTs) in Defence Engagement and influence operations, ever greater reliance is being placed on emergency donor panels (EDP) as a source of whole blood. This paper outlines the practical limitations of using EDPs as a risk mitigation in conventional STTTs which must be considered prior to every deployment.

Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis.

BACKGROUND: Allergic disorders such as atopic dermatitis (AD) are strongly associated with an impairment of the epithelial barrier, in which tight junctions and/or filaggrin expression can be defective. Skin barrier assessment shows potential to be clinically useful for prediction of disease development, improved and earlier diagnosis, lesion follow-up, and therapy evaluation. This study aimed to establish a method to directly assess the in vivo status of epithelial barrier using electrical impedance spectroscopy (EIS). METHODS: Thirty-six patients with AD were followed during their 3-week hospitalization and compared with 28 controls. EIS and transepidermal water loss (TEWL) were measured in lesional and non-lesional skin. Targeted proteomics by proximity extension assay in serum and whole-genome sequence were performed. RESULTS: Electrical impedance spectroscopy was able to assess epithelial barrier integrity, differentiate between patients and controls without AD, and characterize lesional and non-lesional skin of patients. It showed a significant negative correlation with TEWL, but a higher sensitivity to discriminate non-lesional atopic skin from controls. During hospitalization, lesions reported a significant increase in EIS that correlated with healing, decreased SCORAD and itch scores. Additionally, EIS showed a significant inverse correlation with serum biomarkers associated with inflammatory pathways that may affect the epithelial barrier, particularly chemokines such as CCL13, CCL3, CCL7, and CXCL8 and other cytokines, such as IRAK1, IRAK4, and FG2, which were significantly high at admission. Furthermore, filaggrin copy numbers significantly correlated with EIS on non-lesional skin of patients. CONCLUSIONS: Electrical impedance spectroscopy can be a useful tool to detect skin barrier dysfunction in vivo, valuable for the assessment of AD severity, progression, and therapy efficacy.

pQCT- and Ultrasound-based Muscle and Fat Estimate Errors after Resistance Exercise.

PURPOSE: Resistance exercise increases blood flow, induces osmotic and hydrostatic fluid shifts during and immediately after exercise, and may trigger inflammatory responses for several days in the working muscle. The resultant muscle swelling can subsequently affect muscle size and quality assessments. However, the effects of muscle swelling on x-ray attenuation of adipose estimate errors are unknown. METHODS: Peripheral quantitative computed tomography (pQCT) and ultrasonography were used to assess muscle and adipose tissue properties of both upper arms before, 24, 48, and 72 h after unilateral resistance exercise. Recreationally active participants (n = 17) completed the exercise while their contralateral limb served as a control. RESULTS: Resistance exercise resulted in a significant increase in pQCT-derived muscle cross-sectional area (includes intermuscular adipose tissue [IMAT] area), muscle area (excludes IMAT area) and IMAT area, and ultrasound-derived muscle thickness at 24, 48, and 72 h. A significant decrease in pQCT-derived muscle density was also detected as well as an increase in ultrasound-derived echo intensity at 48 and 72 h. The changes in muscle area, IMAT area, and muscle density were significantly correlated with changes in echo intensity, whereas the changes in muscle cross-sectional area and IMAT area were significantly correlated with changes in muscle thickness. CONCLUSION: Unaccustomed resistance exercise can cause errors in pQCT- and ultrasound-based muscle and adipose estimates for at least 72 h. These errors are the result of muscle swelling likely caused by muscle blood flow and inflammation-dependent fluid shifts in muscle. These findings may have implications for measurements in other inflammatory conditions.

Direct assessment of skin epithelial barrier by electrical impedance spectroscopy.

BACKGROUND: Many skin and mucosal inflammatory disorders, such as atopic dermatitis, have been associated with an impaired epithelial barrier function, which allows allergens, pollutants, or microbes to enter the tissue and activate the immune response. The aim of this study was to establish a method to directly assess in vivo the epidermal barrier function by electrical impedance (EI) spectroscopy. METHODS: Mice epidermal barrier was damaged by epicutaneous application of proteases and cholera toxin and by tape stripping. EI and transepidermal water loss (TEWL) were measured before and after the application. Additionally, histological analysis, immunofluorescence staining, and RT-PCR were performed on skin biopsies to evaluate the epithelial barrier. RESULTS: A few hours after papain application, a dose-dependent reduction of EI was detected, reflecting the decreased barrier function. At the same time, an increase of TEWL was observed, with a significant negative correlation with EI, demonstrating that EI changes were directly linked to barrier defects. Twenty-four and 48 hours after the treatment, EI starts to increase to background levels, indicating tissue healing and restoration of skin barrier. Barrier disruption was confirmed by histological analysis showing an impaired stratum corneum and higher cellular infiltration after papain application. In addition, immunofluorescence staining and RT-PCR showed downregulation of molecules involved in the barrier function, such as filaggrin, occludin, and claudin-1, and mRNA levels of filaggrin, loricrin, and involucrin. Comparable results were observed after tape stripping and cholera toxin treatment. CONCLUSION: Electrical impedance spectroscopy is a rapid and reliable diagnostic tool to detect skin barrier defects.

Some binocular advantages for planning reach, but not grasp, components of prehension.

Proficient (fast, accurate, precise) hand actions for reaching-to-grasp 3D objects are known to benefit significantly from the use of binocular vision compared to one eye alone. We examined whether these binocular advantages derive from increased reliability in encoding the goal object's properties for feedforward planning of prehension movements or from enhanced feedback mediating their online control. Adult participants reached for, precision grasped and lifted cylindrical table-top objects (two sizes, 2 distances) using binocular vision or only their dominant/sighting eye or their non-dominant eye to program and fully execute their movements or using each of the three viewing conditions only to plan their reach-to-grasp during a 1 s preview, with vision occluded just before movement onset. Various kinematic measures of reaching and grasping proficiency, including corrective error rates, were quantified and compared by view, feedback and object type. Some significant benefits of binocular over monocular vision when they were just available for pre-movement planning were retained for the reach regardless of target distance, including higher peak velocities, straighter paths and shorter low velocity approach times, although these latter were contaminated by more velocity corrections and by poorer coordination with object contact. By contrast, virtually all binocular advantages for grasping, including improvements in peak grip aperture scaling, the accuracy and precision of digit placements at object contact and shorter grip application times preceding the lift, were eliminated with no feedback available, outcomes that were influenced by the object's size. We argue that vergence cues can improve the reliability of binocular internal representations of object distance for the feedforward programming of hand transport, whereas the major benefits of binocular vision for enhancing grasping performance derive exclusively from its continuous presence online.

In vitro placenta barrier model using primary human trophoblasts, underlying connective tissue and vascular endothelium.

Fetal development may be compromised by adverse events at the placental interface between mother and fetus. However, it is still unclear how the communication between mother and fetus occurs through the placenta. In vitro - models of the human placental barrier, which could help our understanding and which recreate three-dimensional (3D) structures with biological functionalities and vasculatures, have not been reported yet. Here we present a 3D-vascularized human primary placental barrier model which can be constructed in 1 day. We illustrate the similarity of our model to first trimester human placenta, both in its structure and in its ability to respond to altered oxygen and to secrete factors that cause damage cells across the barrier including embryonic cortical neurons. We use this model to highlight the possibility that both the trophoblast and the endothelium within the placenta might play a role in the fetomaternal dialogue.

Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease.

Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. To investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as on levels of glutamate and γ-aminobutyric acid receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta-conditioned medium showed that the secretion profile of extracellular microRNAs, small post-transcriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The present study provides further evidence that the diseased placenta may release factors that damage cortical cells and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders.

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.

Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing.

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered.

Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.

Tilted frames of reference have similar effects on the perception of gravitational vertical and the planning of vertical saccadic eye movements.

We investigated the effects of a tilted reference frame (i.e., allocentric visual context) on the perception of the gravitational vertical and saccadic eye movements along a planned egocentric vertical path. Participants (n = 5) in a darkened room fixated a point in the center of a circle on an LCD display and decided which of two sequentially presented dots was closer to the unmarked '6 o'clock' position on that circle (i.e., straight down toward their feet). The slope of their perceptual psychometric functions showed that participants were able to locate which dot was nearer the vertical with a precision of 1°-2°. For three of the participants, a square frame centered at fixation and tilted (in the roll direction) 5.6° from the vertical caused a strong perceptual bias, manifest as a shift in the psychometric function, in the direction of the traditional 'rod-and-frame' effect, without affecting precision. The other two participants showed negligible or no equivalent biases. The same subjects participated in the saccade version of the task, in which they were instructed to shift their gaze to the 6 o'clock position as soon as the central fixation point disappeared. The participants who showed perceptual biases showed biases of similar magnitude in their saccadic endpoints, with a strong correlation between perceptual and saccadic biases across all subjects. Tilting of the head 5.6° reduced both perceptual and saccadic biases in all but one observer, who developed a strong saccadic bias. Otherwise, the overall pattern and significant correlations between results remained the same. We conclude that our observers' saccades-to-vertical were dominated by perceptual input, which outweighed any gravitational or head-centered input.

A predictive model of the cat cortical connectome based on cytoarchitecture and distance.

Information processing in the brain is strongly constrained by anatomical connectivity. However, the principles governing the organization of corticocortical connections remain elusive. Here, we tested three models of relationships between the organization of cortical structure and features of connections linking 49 areas of the cat cerebral cortex. Factors taken into account were relative cytoarchitectonic differentiation ('structural model'), relative spatial position ('distance model'), or relative hierarchical position ('hierarchical model') of the areas. Cytoarchitectonic differentiation and spatial distance (themselves uncorrelated) correlated strongly with the existence of inter-areal connections, whereas no correlation was found with relative hierarchical position. Moreover, a strong correlation was observed between patterns of laminar projection origin or termination and cytoarchitectonic differentiation. Additionally, cytoarchitectonic differentiation correlated with the absolute number of corticocortical connections formed by areas, and varied characteristically between different cortical subnetworks, including a 'rich-club' module of hub areas. Thus, connections between areas of the cat cerebral cortex can, to a large part, be explained by the two independent factors of relative cytoarchitectonic differentiation and spatial distance of brain regions. As both the structural and distance model were originally formulated in the macaque monkey, their applicability in another mammalian species suggests a general principle of global cortical organization.

Reach-to-precision grasp deficits in amblyopia: Effects of object contrast and low visibility.

Adults with a history of unilateral amblyopia and abnormal binocularity have a range of visual deficits, with some of the 'higher' levels ones generalizing to their dominant (non-amblyopic) eye and linked to widespread binocular cortical network dysfunctions. Our interests are in how these problems also impact on their hand action control in real-world situations. We investigated whether eye-hand coordination deficits, known to exist in amblyopia when goal objects are presented under full-lighting and at high contrast, are exacerbated under low object-background contrast or in dim lighting/low visibility conditions. Hand movement parameters were recorded and quantified in 13 amblyopia and 13 control subjects while they reached-to-precision grasp objects using both eyes together or just their dominant or amblyopic/non-dominant eye alone under these 3 task conditions. Compared to controls, the amblyopia subjects spent significantly longer in preparing their movements, in the initial (planned) periods of their reach and grasp and in applying their grip, while making more reach and grasp errors under all 3 views and tasks. Deficits in planning and controlling the grasp were also selectively accentuated in the low contrast condition, but with no evidence of relatively worse performance under low environmental illumination. We suggest that the dysfunctions in amblyopia are associated with generalized difficulties in obtaining reliable visual evidence about the target's 3D properties during movement planning and in selecting and guiding the proper course of action, especially when segregating the object from background is more challenging.

Age- and stereovision-dependent eye-hand coordination deficits in children with amblyopia and abnormal binocularity.

PURPOSE: To examine factors contributing to eye-hand coordination deficits in children with amblyopia and impaired stereovision. METHODS: Participants were 55 anisometropic or strabismic children aged 5.0 to 9.25 years with different degrees of amblyopia and abnormal binocularity, along with 28 age-matched visually-normal controls. Pilot data were obtained from four additional patients studied longitudinally at different treatment stages. Movements of the preferred hand were recorded using a 3D motion-capture system while subjects reached-to-precision grasp objects (two sizes, three locations) under binocular, dominant eye, and amblyopic/nonsighting eye conditions. Kinematic and "error" performance measures were quantified and compared by viewing condition and subject group using ANOVA, stepwise regression, and correlation analyses. RESULTS: Movements of the younger amblyopes (age 5-6 years; n = 30) were much slower, particularly in the final approach to the objects, and contained more spatial errors in reaching (∼×1.25-1.75) and grasping (∼×1.75-2.25) under all three views (P < 0.05) than their age-matched controls (n = 13). Amblyopia severity was the main contributor to their slower movements with absent stereovision a secondary factor and the unique determinant of their increased error-rates. Older amblyopes (age 7-9 years; n = 25) spent longer contacting the objects before lifting them (P = 0.015) compared with their matched controls (n = 15), with absence of stereovision still solely related to increases in reach and grasp errors, although these occurred less frequently than in younger patients. Pilot prospective data supported these findings by showing positive treatment-related associations between improved stereovision and reach-to-grasp performance. CONCLUSIONS: Strategies that children with amblyopia and abnormal binocularity use for reach-to-precision grasping change with age, from emphasis on visual feedback during the "in-flight" approach at ages 5 to 6 years to more reliance on tactile/kinesthetic feedback from object contact at ages 7 to 9 years. However, recovery of binocularity confers increasing benefits for eye-hand coordination speed and accuracy with age, and is a better predictor of these fundamental performance measures than the degree of visual acuity loss.

Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions.

Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during foetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and foetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytotrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca(2+)]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers invitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.

A system for the management, display and integration of pre-hospital healthcare activity in the deployed environment.

AIM: To create and implement a system through which pre-hospital healthcare activity across an entire operational theatre could be made available in real-time to support healthcare delivery, governance and assurance activity. METHODS: An IT-based system was created that could display, manage and integrate the pre-hospital healthcare activity on Op HERRICK 18. The system was based on the Defence Medical Services Common Assurance Framework and run through Microsoft Office SharePoint. RESULTS: Pre-hospital healthcare activity was made available and visible across an operational theatre. This supported delivery, assurance and governance at any time. Activity from each medical facility could be integrated and display automatically improving theatre wide situational awareness. The availability of information resulted in a shift towards a more continuous process of assurance and governance rather than reliance on inherently threatening and increasingly intermittent inspection regimes. DISCUSSION: The ability to review healthcare activity remotely at anytime significantly improves the validity of assurance possible for a deployed force. Governance activity can be more responsive and less reliant on the fixed timescale and datasets of reports from outlying medical facilities. However, assurance and governance authorities must not allow such a wealth of information to impact local leadership and innovation through a perception of, or actual, micro-management.