Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Eye movements during visual search in patients with glaucoma

Background: Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search. Methods: Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: –5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity. Results: The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman’s rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman’s rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman’s rho = −0.65; P < 0.001) but this was not apparent in the controls. Conclusions: The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease

Usefulness and acceptability of a standardised orientation and mobility training for partially-sighted older adults using an identification cane

<p>Abstract</p> <p>Background</p> <p>Orientation and mobility (O&M) training in using an identification (ID) cane is provided to partially-sighted older adults to facilitate independent functioning and participation in the community. Recently, a protocolised standardised O&M-training in the use of the ID cane was developed in The Netherlands. The purpose of this study is to assess the usefulness and acceptability of both the standardised training and the regular training for participants and O&M-trainers in a randomised controlled trial (NCT00946062).</p> <p>Methods</p> <p>The standardised O&M-training consists of two structured face-to-face sessions and one telephone follow-up, in which, in addition to the regular training, self-management and behavioural change techniques are applied. Questionnaires and interviews were used to collect data on the training’s usefulness, e.g. the population reached, self-reported benefits or achievements, and acceptability, e.g. the performance of the intervention according to protocol and participants’ exposure to and engagement in the training.</p> <p>Results</p> <p>Data was collected from 29 O&M-trainers and 68 participants. Regarding the self-reported benefits, outcomes were comparable for the standardised training and the regular training according the trainers and participants e.g., about 85% of the participants in both groups experienced benefits of the cane and about 70% gained confidence in their capabilities. Participants were actively involved in the standardised training. Nearly 40% of the participants in the standardised training group was not exposed to the training according to protocol regarding the number of sessions scheduled and several intervention elements, such as action planning and contracting.</p> <p>Conclusions</p> <p>The standardised and regular O&M-training showed to be useful and mostly acceptable for the partially-sighted older adults and trainers. Yet, a concern is the deviation from the protocol of the standardised O&M-training by the O&M-trainers regarding distinguishing elements such as action planning. Overall, participants appreciated both trainings and reported benefit.</p

Beta catenin and cytokine pathway dysregulation in patients with manifestations of the "PTEN hamartoma tumor syndrome"

Background. The "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues. The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration. Methods. We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques. Results. Our data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed. Conclusion. In light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers

Assessment of Night Vision Problems in Patients with Congenital Stationary Night Blindness

Congenital Stationary Night Blindness (CSNB) is a retinal disorder caused by a signal transmission defect between photoreceptors and bipolar cells. CSNB can be subdivided in CSNB2 (rod signal transmission reduced) and CSNB1 (rod signal transmission absent). The present study is the first in which night vision problems are assessed in CSNB patients in a systematic way, with the purpose of improving rehabilitation for these patients. We assessed the night vision problems of 13 CSNB2 patients and 9 CSNB1 patients by means of a questionnaire on low luminance situations. We furthermore investigated their dark adapted visual functions by the Goldmann Weekers dark adaptation curve, a dark adapted static visual field, and a two-dimensional version of the ‘‘Light Lab’’. In the latter test, a digital image of a living room with objects was projected on a screen. While increasing the luminance of the image, we asked the patients to report on detection and recognition of objects. The questionnaire showed that the CSNB2 patients hardly experienced any night vision problems, while all CSNB1 patients experienced some problems although they generally did not describe them as severe. The three scotopic tests showed minimally to moderately decreased dark adapted visual functions in the CSNB2 patients, with differences between patients. In contrast, the dark adapted visual functions of the CSNB1 patients were more severely affected, but showed almost no differences between patients. The results from the ‘‘2D Light Lab’’ showed that all CSNB1 patients were blind at low intensities (equal to starlight), but quickly regained vision at higher intensities (full moonlight). Just above their dark adapted thresholds both CSNB1 and CSNB2 patients had normal visual fields. From the results we conclude that night vision problems in CSNB, in contrast to what the name suggests, are not conspicuous and generally not disabling

Looking to Score: The Dissociation of Goal Influence on Eye Movement and Meta-Attentional Allocation in a Complex Dynamic Natural Scene

Several studies have reported that task instructions influence eye-movement behavior during static image observation. In contrast, during dynamic scene observation we show that while the specificity of the goal of a task influences observers’ beliefs about where they look, the goal does not in turn influence eye-movement patterns. In our study observers watched short video clips of a single tennis match and were asked to make subjective judgments about the allocation of visual attention to the items presented in the clip (e.g., ball, players, court lines, and umpire). However, before attending to the clips, observers were either told to simply watch clips (non-specific goal), or they were told to watch the clips with a view to judging which of the two tennis players was awarded the point (specific goal). The results of subjective reports suggest that observers believed that they allocated their attention more to goal-related items (e.g. court lines) if they performed the goal-specific task. However, we did not find the effect of goal specificity on major eye-movement parameters (i.e., saccadic amplitudes, inter-saccadic intervals, and gaze coherence). We conclude that the specificity of a task goal can alter observer’s beliefs about their attention allocation strategy, but such task-driven meta-attentional modulation does not necessarily correlate with eye-movement behavior

Influence of Low-Level Stimulus Features, Task Dependent Factors, and Spatial Biases on Overt Visual Attention

Visual attention is thought to be driven by the interplay between low-level visual features and task dependent information content of local image regions, as well as by spatial viewing biases. Though dependent on experimental paradigms and model assumptions, this idea has given rise to varying claims that either bottom-up or top-down mechanisms dominate visual attention. To contribute toward a resolution of this discussion, here we quantify the influence of these factors and their relative importance in a set of classification tasks. Our stimuli consist of individual image patches (bubbles). For each bubble we derive three measures: a measure of salience based on low-level stimulus features, a measure of salience based on the task dependent information content derived from our subjects' classification responses and a measure of salience based on spatial viewing biases. Furthermore, we measure the empirical salience of each bubble based on our subjects' measured eye gazes thus characterizing the overt visual attention each bubble receives. A multivariate linear model relates the three salience measures to overt visual attention. It reveals that all three salience measures contribute significantly. The effect of spatial viewing biases is highest and rather constant in different tasks. The contribution of task dependent information is a close runner-up. Specifically, in a standardized task of judging facial expressions it scores highly. The contribution of low-level features is, on average, somewhat lower. However, in a prototypical search task, without an available template, it makes a strong contribution on par with the two other measures. Finally, the contributions of the three factors are only slightly redundant, and the semi-partial correlation coefficients are only slightly lower than the coefficients for full correlations. These data provide evidence that all three measures make significant and independent contributions and that none can be neglected in a model of human overt visual attention

Auditory spatial representations of the world are compressed in blind humans

Compared to sighted listeners, blind listeners often display enhanced auditory spatial abilities such as localization in azimuth. However, less is known about whether blind humans can accurately judge distance in extrapersonal space using auditory cues alone. Using virtualization techniques, we show that auditory spatial representations of the world beyond the peripersonal space of blind listeners are compressed compared to those for normally sighted controls. Blind participants overestimated the distance to nearby sources, and underestimated the distance to remote sound sources, in both reverberant and anechoic environments, and for speech, music and noise signals. Functions relating judged and actual virtual distance were well fitted by compressive power functions, indicating that the absence of visual information regarding the distance of sound sources may prevent accurate calibration of the distance information provided by auditory signals

The reference frame for encoding and retention of motion depends on stimulus set size

YesThe goal of this study was to investigate the reference frames used in perceptual encoding and storage of visual motion information. In our experiments, observers viewed multiple moving objects and reported the direction of motion of a randomly selected item. Using a vector-decomposition technique, we computed performance during smooth pursuit with respect to a spatiotopic (nonretinotopic) and to a retinotopic component and compared them with performance during fixation, which served as the baseline. For the stimulus encoding stage, which precedes memory, we found that the reference frame depends on the stimulus set size. For a single moving target, the spatiotopic reference frame had the most significant contribution with some additional contribution from the retinotopic reference frame. When the number of items increased (Set Sizes 3 to 7), the spatiotopic reference frame was able to account for the performance. Finally, when the number of items became larger than 7, the distinction between reference frames vanished. We interpret this finding as a switch to a more abstract nonmetric encoding of motion direction. We found that the retinotopic reference frame was not used in memory. Taken together with other studies, our results suggest that, whereas a retinotopic reference frame may be employed for controlling eye movements, perception and memory use primarily nonretinotopic reference frames. Furthermore, the use of nonretinotopic reference frames appears to be capacity limited. In the case of complex stimuli, the visual system may use perceptual grouping in order to simplify the complexity of stimuli or resort to a nonmetric abstract coding of motion information