The role of somatosensation in automatic visuo-motor control: a comparison of congenital and acquired sensory loss.

Studies of chronically deafferented participants have illuminated how regaining some motor control after adult-onset loss of proprioceptive and touch input depends heavily on cognitive control. In this study we contrasted the performance of one such man, IW, with KS, a woman born without any somatosensory fibres. We postulated that her life-long absence of proprioception and touch might have allowed her to automate some simple visually-guided actions, something IW appears unable to achieve. We tested these two, and two age-matched control groups, on writing and drawing tasks performed with and without an audio-verbal echoing task that added a cognitive demand. In common with other studies of skilled action, the dual task was shown to affect visuo-motor performance in controls, with less well-controlled drawing and writing, evident as increases in path speed and reduction in curvature and trial duration. We found little evidence that IW was able to automate even the simplest drawing tasks and no evidence for automaticity in his writing. In contrast, KS showed a selective increase in speed of signature writing under the dual-task conditions, suggesting some ability to automate her most familiar writing. We also tested tracing of templates under mirror-reversed conditions, a task that imposes a powerful cognitive planning challenge. Both IW and KS showed evidence of a visuo-motor planning conflict, as did the controls, for shapes with sharp corners. Overall, IW was much faster than his controls to complete tracing shapes, consistent with an absence of visuo-proprioceptive conflict, whereas KS was slower than her controls, especially as the corners became sharper. She dramatically improved after a short period of practice while IW did not. We conclude that KS, who developed from birth without proprioception, may have some visually derived control of movement not under cognitive control, something not seen in IW. This allowed her to automate some writing and drawing actions, but impaired her initial attempts at mirror-tracing. In contrast, IW, who lost somatosensation as an adult, cannot automate these visually guided actions.

Perception of body shape and size without touch or proprioception: evidence from individuals with congenital and acquired neuropathy.

The degree to which mental representations of the body can be established and maintained without somatosensory input remains unclear. We contrast two "deafferented" adults, one who acquired large fibre sensory loss as an adult (IW) and another who was born without somatosensation (KS). We compared their responses to those of matched controls in three perceptual tasks: first accuracy of their mental image of their hands (assessed by testing recognition of correct hand length/width ratio in distorted photographs and by locating landmarks on the unseen hand); then accuracy of arm length judgements (assessed by judgement of reaching distance), and finally, we tested for an attentional bias towards peri-personal space (assessed by reaction times to visual target presentation). We hypothesised that IW would demonstrate responses consistent with him accessing conscious knowledge, whereas KS might show evidence of responses dependent on non-conscious mechanisms. In the first two experiments, both participants were able to give consistent responses about hand shape and arm length, but IW displayed a better awareness of hand shape than KS (and controls). KS demonstrated poorer spatial accuracy in reporting hand landmarks than both IW and controls, and appears to have less awareness of her hands. Reach distance was overestimated by both IW and KS, as it was for controls; the precision of their judgements was slightly lower than that of the controls. In the attentional task, IW showed no reaction time differences across conditions in the visual detection task, unlike controls, suggesting that he has no peri-personal bias of attention. In contrast, KS did show target location-dependent modulation of reaction times, when her hands were visible. We suggest that both IW and KS can access a conscious body image, although its accuracy may reflect their different experience of hand action. Acquired sensory loss has deprived IW of any subconscious body awareness, but the congenital absence of somatosensation may have led to its partial replacement by a form of visual proprioception in KS.

Issues of rehabilitation of the patients with symblepharon using oral mucosal autografts.

PURPOSE: To systematize clinical variants of symblepharon and to analyze rehabilitation availability boundaries in patients with different forms of symblepharons. METHODS: Retrospective analysis of clinical cases included 26 patients with local, subtotal, and total symblepharon (ankyloblepharon) with a normal or anophthalmic orbit. In all patients, symblepharon was operated using split- or full-thickness oral mucosal autografts and their fixation with U-shaped stitches and compression plates. Preoperatively and postoperatively, best-corrected visual acuity, IOP, extraocular motility, results of Schirmer I test, and tear break-up time with slit-lamp biomicroscopy were analyzed, as well as additional ultrasound and electrophysiological studies were performed in some cases. Follow-up period lasted from 1.5 to 6 years. RESULTS: The proposed surgical technique using mucosal autografts in all patients allowed complete anatomical restoration of conjunctival fornices and cavity. It resulted in improvement of visual function in patients with local symblepharon, full restoration of ocular motility in patients with a presence of the eye and provided an opportunity to wear artificial eye in patients with anophthalmia. Nonetheless, loss of conjunctival Krause's and Wolfring lacrimal glands, goblet cells, meibomian glands, and limbal stem cells prevents from further optic keratoplasty in patients with total or subtotal symblepharon on potentially sighted eye. CONCLUSION: The most difficult patients for visual rehabilitation were the ones with subtotal or total symblepharon (ankyloblepharon) on potentially sighted eye due to the loss of conjunctival goblet cells, meibomian glands, and limbal stem cells.

A Novel Method for Complex Diagnostics of Globes' Position.

Spiral computed tomography is a gold standard in diagnostics of intraorbital pathological changes. Modern software provides great opportunities at viewing and analyzing DICOM files. Earlier, the authors introduced a method of computed exophthalmometry for precise measurement of globes' position even in the cases of lateral orbital rim fracture. However, eye proptosis is known to be depending on the eye length (ocular component), retrobulbar volume (orbital component), as well as anatomy of neurocranium and brain (cerebral component). Nevertheless, conventional Hertel exophthalmometry and other proposed methods do not specify the component, involved in the pathogenesis of enophthalmos or exophthalmos, that is why additional examinations are required. In this article, the authors propose a novel approach, which can complement and/or substitute instrumental methods used for differential diagnostics of enophthalmos or exophthalmos.

Computed exophthalmometry is an accurate and reproducible method for the measuring of eyeballs' protrusion.

PURPOSE: The aim of this study was to assess reproducibility of the repeated measurements from proposed computed exophthalmometry and to make a comparison with the Hertel exophthalmometer. METHODS: Computed tomography scans of patients with pathological (group 1) and intact orbits (group 2) were included in this retrospective study. In both groups, a single investigator measured a difference of eyeballs' protrusion using the proposed method of computed exophthalmometry. Briefly, the distances from the corneal apices of the left and right eyeballs to the line placed through the styloid processes of the temporal bones were measured and compared to each other three times independently. RESULTS: In some patients with intact lateral orbital rims the results of computed exophthalmometry correlated with the measurements from the Hetrel exophthalmometer. The analysis of the triple measurements with computed exophthalmometry revealed no significant difference in the value of standard deviation of the results in patients with intact and pathological orbits. In comparison with the Hertel-type exophthalmometry, the proposed method demonstrated very low variability and high repeatability of the measurements. The difference of 0.10-0.87 mm in the eyeballs protrusion should be considered as normal. Computed exophthalmometry is an accurate and reproducible method, which can be used for the measurements of eyeballs' protrusion.

Synthesis of New Congeners of 1-methyl-3-aminoisoquinolines, Evaluation of Their Cytotoxic Activity, In Silico and In Vitro Study of Their Molecular Targets as PDE4B.

To examine the cytotoxic activity of congeners of 3-amino-isoquinoline, we performed the phenotypic screening using panel of 60 cell lines and found that (N-(6,7-dimethoxy-1-methyl-isoquinolin-3-yl)-4-{[(1-ethyl-4-methyl-1H-pyrazol-3-yl)methyl]amino}benzamide (4d)) exhibited the significant effect against different tumor cell lines while showing the high activity toward human colorectal cancer HCT-116 cells (IC50 = 18 µm) and human breast cancer T-47D cells (GI50 = 1.9 µm). Virtual screening indicated that these compounds target protein kinases and phosphodiesterases (PDE). However, wet screening among panel of protein kinases did not show any significant activity. By contrast, 50 µm of 4c and 4d inhibited the growth of HKe3-mtKRAS spheroids in the 3D floating (3DF) culture suggesting that 4c and 4d target PDE4B which is selectively upregulated by mtKRAS in 3DF culture.