Enhanced human contrast sensitivity with increased stimulation of melanopsin in intrinsically photosensitive retinal ganglion cells.

The intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to serve non-image-forming functions, such as photoentrainment of the circadian rhythm and pupillary light reflex. However, how they affect human spatial vision is largely unknown. The spatial contrast sensitivity function (CSF), which measures contrast sensitivity as a function of spatial frequency, was used in the current study to investigate the function of ipRGCs in pattern vision. To compare the effects of different background lights on the CSF, we utilized the silent substitution technique. We manipulated the stimulation level of melanopsin (i.e., the visual pigment of ipRGCs) from the background light while keeping the cone stimulations constant, or vice versa. We conducted four experiments to measure the CSFs at various spatial frequencies, eccentricities, and levels of background luminance. Results showed that melanopsin stimulation from the background light enhances spatial contrast sensitivity across different eccentricities and luminance levels. Our finding that melanopsin contributes to CSF, combined with the receptive field analysis, suggests a role for the magnocellular pathway and challenges the conventional view that ipRGCs are primarily responsible for non-visual functions.

Theta activity in semantic priming under visual crowding as revealed by magnetoencephalography.

Crowding refers to impaired object recognition of peripheral visual targets caused by nearby flankers. It has been shown that the response to a word was faster when it was preceded by a semantically related than unrelated crowded prime, demonstrating that semantic priming survives crowding. This study examines neural correlates of semantic priming under visual crowding using magnetoencephalography with four conditions: prime (isolated, crowded) x prime-target relationship (related, unrelated). Participants judged whether the target was a word or a nonword. We found significant differences in θ activity at the left inferior frontal gyrus (IFG) for both isolated and crowded primes when comparing the unrelated and related conditions, although the activation was delayed with the crowded prime compared to the isolated prime. The locations within the IFG were also different: theta-band activation was at BA 45 in the isolated condition and at BA 47 in the crowded condition. Phase-locking-value analysis revealed that bilateral IFG was more synchronized with unrelated prime-target pairs than related pairs regardless of whether the primes were isolated or crowded, indicating the recruitment of the right hemisphere when the prime-target semantic relationship was remote. Finally, the distinct waveform patterns found in the isolated and crowded conditions from both the source localization and PLV analysis suggest different neural mechanisms for processing semantic information with isolated primes versus crowded primes.

Seeing food fast and slow: Arousing pictures and words have reverse priorities in accessing awareness.

Previous studies have shown that stimuli triggering higher arousal (e.g., attractiveness) can access awareness faster than those triggering lower arousal, yet no studies have examined the effect of food calories. Since food brings us energy, satiety, and positive emotions, food stimuli bringing higher arousal would likely have higher priority in accessing awareness over those with lower arousal. We used high-calorie and low-calorie food stimuli as representatives for high and low arousal stimuli, respectively, based on the tight relationship between calorie and arousal. By adopting the breaking continuous flash suppression (b-CFS) paradigm, we had high-calorie and low-calorie food pictures or words presented dichoptically with dynamic Mondrian masks and measured the time for food stimuli to be released from suppression. Our results showed that high-calorie food pictures could access visual awareness faster than low-calorie food pictures (Experiment 1), and the reverse pattern was observed for food words (Experiment 2). We ruled out the possibility of the difference in low-level features (Experiment 3) and post-perceptual response bias (Experiment 4) as the causes for the observed b-CFS time differences. This study revealed the dissociation of the unconscious processing of pictures and words, which may rely on mechanisms related to attentional capture. High-arousing stimuli do not always enjoy priority in accessing visual awareness.

A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.

Purpose: Drug delivery to posterior ocular tissues via topical eye drop administration is arduous due to the unique anatomy and physiology of the eye. Therefore, treatments for posterior eye disease have to be administered via intravitreal injection or systemic route, both of which have their drawbacks. Herein, the objective of this work was to demonstrate that a specially designed eye drop formulation could effectively deliver small-molecule vascular endothelial growth factor (VEGF) inhibitor to posterior ocular tissues for antiangiogenic therapy. Methods: The unique eye drop formulation, termed ITRI AXN eye drops, was obtained from self-assembly of (2-hydroxypropyl)-ß-cyclodextrin with a VEGF tyrosine kinase inhibitor, a hydrophilic polymer, hypromellose, and a complex stabilizer, caffeine. In vivo ocular pharmacokinetics studies were performed with New Zealand White (NZW) rabbits and Non Human Primates (NHP). The antiangiogenesis effect was evaluated on the Long-Evans rat with laser-induced choroidal neovascularization and pigmented Dutch-Belted rabbits with VEGF-induced retinal neovascularization. Results: The successful drug transport from ocular surface to posterior ocular cavity was indicated by a drug biodistribution pattern in pharmacokinetic studies. Excellent drug exposure in the choroid and retina with the concentrations of 900- and 750-fold greater than drug IC50 0.5 hours post the eye drop administration (drug level: 0.8%) was observed on the NHP study. The obtained formulation also demonstrated a comparable antiangiogenic outcome with the intravitreal injection of anti-VEGF antibody on rat and rabbit disease models. Conclusions: Our eye drop formulation has demonstrated great promise in antiangiogenic therapy against retinal and choroidal neovascularization in animal models. The results suggest that the aim of this work can be successfully achieved by the novel eye drop formulation. Translational Relevance: The preclinical results provide evidence that ITRI AXN eye drops could effectively deliver therapeutics to the choroid and retina for antiangiogenic therapy.

Age-Related Differences in the Uncanny Valley Effect.

BACKGROUND: Due to declining birthrates and an increasing aging population, shortage of the caregiving labor force has become a global issue. Among various efforts toward the solution, introducing robotic products for assistance could provide an effective way to help older adults in their daily lives. As previous studies have indicated that older adults' acceptance of robots is lower than that of younger adults, enhancing older adults' acceptance of robots is imperative. Because older adults' first impressions based on a robot's appearance might affect their acceptance of the robot, we investigated the uncanny valley effect (UVE) here. The UVE refers to the phenomenon that people rate robots more positively as robots become more humanlike, but only up to a certain point; as robots approach a near-perfect similarity to human appearance, likeability drops and forms the uncanny valley. Nevertheless, evidence for the UVE came mainly from younger adults. OBJECTIVE: The present study aimed to examine whether the UVE varies across different age groups and whether a robot's appearance would affect participants' acceptance of the robot's service or companionship. METHODS: An online questionnaire study was conducted with 255 participants, including younger (n = 77, age 18-39 years), middle-aged (n = 87, age 40-59 years), and older (n = 91, age 60-87 years) adults. Participants were asked to view each picture in a set selected from a total of 83 robot pictures and evaluate their impressions of each robot and the intention of use regarding robot function as a service provider or a companion. RESULTS: The UVE was found in younger and middle-aged adults; however, older adults did not show the UVE. Older adults preferred humanlike over non-humanlike robots, regardless of robot function. CONCLUSION: The design of assistive robots should take the UVE into consideration by customizing robot appearance based on the age group of the intended user.

The modulation of background color on perceiving audiovisual simultaneity.

Perceiving simultaneity is critical in integrating visual and auditory signals that give rise to a unified perception. We examined whether background color modulates people's perception of audiovisual simultaneity. Two hypotheses were proposed and examined: (1) the red-impairment hypothesis: visual processing speed deteriorates when viewing a red background because the magnocellular system is inhibited by red light; and (2) the blue-enhancement hypothesis: the detection of both visual and auditory signals is enhanced when viewing a blue background because it stimulates the blue-light sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs), which trigger a higher alert state. Participants were exposed to different backgrounds while performing an audiovisual simultaneity judgment (SJ) task: a flash and a beep were presented at pre-designated stimulus onset asynchronies (SOAs) and participants judged whether or not the two stimuli were presented simultaneously. Experiment 1 demonstrated a shift of the point of subjective simultaneity (PSS) toward the visual-leading condition in the red compared to the blue background when the flash was presented in the periphery. In Experiment 2, the stimulation of ipRGCs was specifically manipulated to test the blue-enhancement hypothesis. The results showed no support for this hypothesis, perhaps due to top-down cortical modulations. Taken together, the shift of PSS toward the visual-leading condition in the red background was attributed to impaired visual processing speed with respect to auditory processing speed, caused by the inhibition of the magnocellular system under red light.

Identifying Features that Enhance Older Adults' Acceptance of Robots: A Mixed Methods Study.

BACKGROUND: With global aging, robots are considered a promising solution for handling the shortage of aged care and companionships. However, these technologies would serve little purpose if their intended users do not accept them. While the socioemotional selectivity theory predicts that older adults would accept robots that offer emotionally meaningful relationships, selective optimization with compensation model predicts that older adults would accept robots that compensate for their functional losses. OBJECTIVE: The present study aims to understand older adults' expectations for robots and to compare older adults' acceptance ratings for 2 existing robots: one of them is a more human-like and more service-oriented robot and the other one is a more animal-like and more companion-oriented robot. METHODS: A mixed methods study was conducted with 33 healthy, community-dwelling Taiwanese older adults (age range: 59-82 years). Participants first completed a semi-structured interview regarding their ideal robot. After receiving information about the 2 existing robots, they then completed the Unified Theory of Acceptance and Use of Technology questionnaires to report their pre-implementation acceptance of the 2 robots. RESULTS: Interviews were transcribed for conventional content analysis with satisfactory inter-rater reliability. From the interview data, a collection of older adults' ideal robot characteristics emerged with highlights of humanlike qualities. From the questionnaire data, respondents showed a higher level of acceptance toward the more service-oriented robot than the more companion-oriented robot in terms of attitude, perceived adaptiveness, and perceived usefulness. From the mixed methods analyses, the finding that older adults had a higher level of positive attitude towards the more service-oriented robot than the more companion-oriented robot was predicted by higher expectation or preference for robots with more service-related functions. CONCLUSION: This study identified older adults' preference toward more functional and humanlike robots. Our findings provide practical suggestions for future robot designs that target the older population.

Patients with chronic periodontitis are more likely to develop upper urinary tract stone: a nation-wide population-based eight-year follow up study.

BACKGROUND: The purpose of this study was to investigate the relationship between chronic periodontitis (CP) and upper urinary tract stone (UUTS) in Taiwan by using a population-based data set. METHODS: A total of 16,292 CP patients and 48,876 randomly-selected controls without chronic periodontitis were selected from the National research database and studied retrospectively. Subjects selected have not been diagnosed with UUTS previously. These subjects were prospectively followed for at least eight years. Cox regression models were used to explore the connection between risk factors and the development of UUTS. RESULTS: The CP patients have a greater chance of developing UUTS compared to controls (1761/16292, 10.8% vs. 4775/48876, 9.8%, p-values < 0.001). Conditioned logistic regression suggested CP increases the risk of UUTS development (HR 1.14, 95% CI [1.08-1.20], p < 0.001). After respective adjustment for age, gender, hypertension and diabetes, results showed that CP still increases the risk of developing UUTS (HR 1.14, 95% CI [1.08-1.20], p < 0.001). CONCLUSION: By using a population-based database with a minimum eight 8 follow-up of CP in Taiwan, we discovered patients with CP are more likely to develop UUTS.

Latent Feature Lasso.

The latent feature model (LFM), proposed in (Griffiths & Ghahramani, 2005), but possibly with earlier origins, is a generalization of a mixture model, where each instance is generated not from a single latent class but from a combination of latent features. Thus, each instance has an associated latent binary feature incidence vector indicating the presence or absence of a feature. Due to its combinatorial nature, inference of LFMs is considerably intractable, and accordingly, most of the attention has focused on nonparametric LFMs, with priors such as the Indian Buffet Process (IBP) on infinite binary matrices. Recent efforts to tackle this complexity either still have computational complexity that is exponential, or sample complexity that is high-order polynomial w.r.t. the number of latent features. In this paper, we address this outstanding problem of tractable estimation of LFMs via a novel atomic-norm regularization, which gives an algorithm with polynomial run-time and sample complexity without impractical assumptions on the data distribution.

Switching to the Rubber Hand.

Inducing the rubber hand illusion (RHI) requires that participants look at an imitation hand while it is stroked in synchrony with their occluded biological hand. Previous explanations of the RHI have emphasized multisensory integration, and excluded higher cognitive functions. We investigated the relationship between the RHI and higher cognitive functions by experimentally testing task switch (as measured by switch cost) and mind wandering (as measured by SART score); we also included a questionnaire for attentional control that comprises two subscales, attention-shift and attention-focus. To assess experience of RHI, the Botvinick and Cohen (1998) questionnaire was used and illusion onset time was recorded. Our results indicate that rapidity of onset reliably indicates illusion strength. Regression analysis revealed that participants evincing less switch cost and higher attention-shift scores had faster RHI onset times, and that those with higher attention-shift scores experienced the RHI more vividly. These results suggest that the multi-sensory hypothesis is not sufficient to explain the illusion: higher cognitive functions should be taken into account when explaining variation in the experience of ownership for the rubber hand.

Preservation of epithelial progenitor cells from collagenase-digested oral mucosa during ex vivo cultivation.

To avoid xenogeneic infection, we report a novel protocol for producing animal-derived component-free oral mucosal epithelial cells (OMECs) sheet for transplantation, in which collagenase was used to replace dispase II/trypsin-EDTA for digesting oral mucosal tissue, and human platelet-derived PLTMax to replace fetal bovine serum. The resulting epithelial aggregates were expanded on de-epithelialized amniotic membranes without 3T3 feeder cells, and serum-free EpiLife was used to reduce contamination by submucosal mesenchymal cells. The OMEC sheets thus generated showed similar positive keratin 3/76-positive and keratin 8-negative staining patterns compared with those generated by the original protocol. Colony formation efficiency assay, BrdU label retention assay, and p63 and p75NTR immunostaining results indicated that higher proliferative potentials and more progenitor cells were preserved by the modified protocol. TaqMan array analysis revealed that the transcription of integrin-linked kinase (ILK) was up-regulated along with an increase in ß-catenin signaling and its downstream cell cycle modulators, cyclin D1 and p27KIP1. Furthermore, ILK silencing led to the inhibition of nuclear ß-catenin accumulation, suppressed p63 expression, and reduced the expression of cyclin D1 and p27KIP1; these observations suggest that ILK/ß-catenin pathway may be involved in cell proliferation regulation during the ex vivo expansion of OMECs for transplantation purposes.

The Association between Sleep Duration and Hypertension in Non-obese Premenopausal Women in Korea.

BACKGROUND: Previous studies have revealed that sleep duration is linked to both obesity and hypertension. Here, we evaluated the association between sleep duration and hypertension in obese and non-obese premenopausal women using representative national survey data from the Korean population. METHODS: A total of 4,748 subjects over 20 years of age from the Korean National Health and Nutrition Examination Survey from 2010 to 2012 were included. To control for risk factors, multivariable logistic regression was used to calculate the adjusted odds ratios and 95% confidence intervals of hypertension across the following sleep duration categories: <6, 6-8, and >8 h/d. RESULTS: Among the participants, 367 subjects (7.7%) had hypertension. Their mean sleep duration was 7 hours. In the non-obese subjects, after controlling for potential confounding variables, the odds ratio for hypertension was 1.86 fold greater in those with a sleep duration of <6 hours (odds ratio, 1.79; 95% confidence interval, 1.05 to 3.03) as compared to those who slept for 6.8 hours. However, there was no association between sleep duration and the risk of hypertension in obese subjects. Long sleep duration (over 8 h/d) was not associated with hypertension in either the non-obese or the obese subjects in this study. CONCLUSION: Short sleep duration (less than 6 h/d) may be a significant risk factor for hypertension in non-obese premenopausal women. However, there is no association between sleep duration and the risk of hypertension in obese women.

Epithelial-myoepithelial carcinoma of the nasopharynx: A case report and review of the literature.

An 80-year-old female with complaints of right-sided nose blockage and occasional epistaxis for several months was referred to Sanggye Paik Hospital (Seoul, Korea). Nasal examination revealed a hemorrhagic mass protruding towards the right posterior nasal cavity, for which the patient was subjected to excisional biopsy. The pathological diagnosis was epithelial-myoepithelial carcinoma, as immunohistochemical analysis revealed that the inner cells stained positive for cytokeratin 7, an epithelial cell marker, whereas the outer cells stained positive for smooth muscle actin and P63, consistent with a myoepithelial phenotype. The patient received concurrent chemoradiation therapy followed by systemic chemotherapy. Following the achievement of a partial response, the patient's treatment course was uneventful. Follow-up at 24 months revealed a stable status at partial response, with no subsequent progression.

Lysophosphatidic acid induces YAP-promoted proliferation of human corneal endothelial cells via PI3K and ROCK pathways.

The first two authors contributed equally to this work.Silence of p120-catenin has shown promise in inducing proliferation in human corneal endothelial cells (HCECs), but there is concern regarding off-target effects in potential clinical applications. We aimed to develop ex vivo expansion of HCECs using natural compounds, and we hypothesized that lysophosphatidic acid (LPA) can unlock the mitotic block in contact-inhibited HCECs via enhancing nuclear translocation of yes-associated protein (YAP). Firstly, we verified that exogenous YAP could induce cell proliferation in contact-inhibited HCEC monolayers and postconfluent B4G12 cells. In B4G12 cells, enhanced cyclin D1 expression, reduced p27(KIP1)/p21(CIP1) levels, and the G1/S transition were detected upon transfection with YAP. Secondly, we confirmed that LPA induced nuclear expression of YAP and promoted cell proliferation. Moreover, PI3K and ROCK, but not ERK or p38, were required for LPA-induced YAP nuclear translocation. Finally, cells treated with LPA or transfected with YAP remained hexagonal in shape, in addition to unchanged expression of ZO-1, Na/K-ATPase, and smooth muscle actin (SMA), suggestive of a preserved phenotype, without endothelial-mesenchymal transition. Collectively, our findings indicate an innovative strategy for ex vivo cultivation of HCECs for transplantation and cell therapy.

A transient auditory signal shifts the perceived offset position of a moving visual object.

Information received from different sensory modalities profoundly influences human perception. For example, changes in the auditory flutter rate induce changes in the apparent flicker rate of a flashing light (Shipley, 1964). In the present study, we investigated whether auditory information would affect the perceived offset position of a moving object. In Experiment 1, a visual object moved toward the center of the computer screen and disappeared abruptly. A transient auditory signal was presented at different times relative to the moment when the object disappeared. The results showed that if the auditory signal was presented before the abrupt offset of the moving object, the perceived final position was shifted backward, implying that the perceived visual offset position was affected by the transient auditory information. In Experiment 2, we presented the transient auditory signal to either the left or the right ear. The results showed that the perceived visual offset shifted backward more strongly when the auditory signal was presented to the same side from which the moving object originated. In Experiment 3, we found that the perceived timing of the visual offset was not affected by the spatial relation between the auditory signal and the visual offset. The present results are interpreted as indicating that an auditory signal may influence the offset position of a moving object through both spatial and temporal processes.

Depth modulation of the attentional repulsion effect.

Shifts of attention can cause mislocalisation of visual objects. Abriefcue that attracts attention can cause a shift in the perceived location of a subsequently presented visual object--specifically, moving it away from the focus of attention (attentional repulsion). In the present study we investigated whether depth would influence the magnitude of attentional repulsion by presenting peripheral visual cues in different depth planes from the target or fixation. In experiment 1 the results showed that the magnitude of the attentional repulsion was larger when the cue was presented at the depth plane farther away from the target and fixation. In experiment 2 we presented the fixation point in the same depth plane as the nearest cues and found larger repulsion effects when the cues were presented in depth planes farther away from the fixation. In experiment 3 no depth modulation was observed when the fixation was presented in the same depth plane with the farthest cues. Taken together, when the cues were presented in the depth plane farther away from the fixation, the magnitude of the attentional repulsion effect increased. It is speculated that the residual coarser spatial representation in the space farther from the fixation plane or the enhanced attentional process for the space closer than the fixation may be responsible for the larger attentional repulsion effect.

Mislocalization of visual stimuli: independent effects of static and dynamic attention.

Shifts of visual attention cause systematic distortions of the perceived locations of visual objects around the focus of attention. In the attention repulsion effect, the perceived location of a visual target is shifted away from an attention-attracting cue when the cue is presented before the target. Recently it has been found that, if the visual cue is presented after the target, the perceived location of the target shifts toward the location of the following cue. One unanswered question is whether a single mechanism underlies both attentional repulsion and attraction effects. We presented participants with two disks at diagonal locations as visual cues and two vertical lines as targets. Participants were asked to perform a forced-choice task to judge targets' positions. The present study examined whether the magnitude of the repulsion effect and the attraction effect would differ (Experiment 1), whether the two effects would interact (Experiment 2), and whether the location or the dynamic shift of attentional focus would determine the distortions effects (Experiment 3). The results showed that the effect size of the attraction effect was slightly larger than the repulsion effect and the preceding and following cues have independent influences on the perceived positions. The repulsion effect was caused by the location of attnetion and the attraction effect was due to the dynamic shift of attentional focus, suggesting that the underlying mechanisms for the retrospective attraction effect might be different from those for the repulsion effect.

Developing constructs for psychopathology research: research domain criteria.

There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions.

Gluteal and Thigh Compartment Syndrome due to Rhabdomyolysis Following Prolonged Immobilization: A Case Report / 대한신장학회지

Compartment syndrome is rarely associated with non-traumatic rhabdomyolysis. We report the case of a 23-year-old man who developed compartment syndrome associated with rhabdomyolysis caused by prolonged immobilization after antidepressive drug overdose. Elevation of serum creatine phosphokinase and myoglobinuria indicated rhabdomyolysis. Painful swelling of the right buttock and thigh and right lower limb paralysis with sensory and motor deficit were suggestive of gluteal and thigh compartment syndrome with the complication of sciatic nerve injury. The patient received an immediate fasciotomy, medical treatment and rehabilitation. At five months after initial treatment, the patient could walk independently with nearly full recovery of his right lower limb function.

KR-31831, a new synthetic anti-ischemic agent, inhibits in vivo and in vitro angiogenesis.

Angiogenesis is considered to be an integral process to the growth and spread of solid tumors. Anti-angiogenesis therapy recently has been found to be one of the most promising anti-cancer therapeutic strategies. In this study, we provide several lines of evidences showing that KR-31831, a new benzopyran derivative, has anti-angiogenic activities. KR-31831 inhibited the proliferation, migration, invasion and tube formation of bovine aortic endothelial cells (BAECs), and suppressed the release of matrix metalloproteinase-2 (MMP-2) of BAECs. KR-31831 also inhibited in vivo angiogenesis in mouse Matrigel plug assay. Furthermore, the mRNA expressions of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-2 (FGFR-2), and vascular endothelial growth factor receptor-2 (VEGFR-2) were decreased by KR-31831. Taken together, these results suggest that KR-31831 acts as a novel angiogenesis inhibitor and might be useful for treating hypervascularized cancers.