Search

Loss-of-function variant in the gene encoding the KCNQ4 potassium channel causes autosomal dominant nonsyndromic hearing loss (DFNA2), and no effective pharmacotherapeutics have been developed to reverse channel activity impairment. Phosphatidylinositol 4,5-bisphosphate (PIP2), an obligatory phospholipid for maintaining KCNQ channel activity, confers differential pharmacological sensitivity of channels to KCNQ openers. Through whole-exome sequencing of DFNA2 families, we identified three novel KCNQ4 variants related to diverse auditory phenotypes in the proximal C-terminus (p.Arg331Gln), the C-terminus of the S6 segment (p.Gly319Asp), and the pore region (p.Ala271_Asp272del). Potassium currents in HEK293T cells expressing each KCNQ4 variant were recorded by patch-clamp, and functional recovery by PIP2 expression or KCNQ openers was examined. In the homomeric expression setting, the three novel KCNQ4 mutant proteins lost conductance and were unresponsive to KCNQ openers or PIP2 expression. Loss of p.Arg331Gln conductance was slightly restored by a tandem concatemer channel (WT-p.R331Q), and increased PIP2 expression further increased the concatemer current to the level of the WT channel. Strikingly, an impaired homomeric p.Gly319Asp channel exhibited hyperactivity when a concatemer (WT-p.G319D), with a negative shift in the voltage dependence of activation. Correspondingly, a KCNQ inhibitor and chelation of PIP2 effectively downregulated the hyperactive WT-p.G319D concatemer channel. Conversely, the pore-region variant (p.Ala271_Asp272del) was nonrescuable under any condition. Collectively, these novel KCNQ4 variants may constitute therapeutic targets that can be manipulated by the PIP2 level and KCNQ-regulating drugs under the physiological context of heterozygous expression. Our research contributes to the establishment of a genotype/mechanism-based therapeutic portfolio for DFNA2., Hearing loss: genetically tailored treatment strategy for congenital deafness People with a certain type of inherited hearing loss may stand to benefit from a personalized, genetically tailored treatment strategy. A research team from South Korea led by Byung Yoon Choi from Seoul National University College of Medicine identified three new mutations in KCNQ4, a gene that encodes a potassium channel protein found in the inner ear, that can cause congenital deafness. Strikingly, the authors identified the first hyperactive KCNQ4 variant. They inserted these gene variants into human cells in culture, and found that drugs known to affect the activity of this channel protein had different effects on different mutations. Impairments caused by two of the variants were prevented by drug treatment; the third variant proved resistant to the same therapeutic approach. The authors propose further validating the therapeutic responsiveness of different KCNQ4 variants in genetically engineered mice.

BackgroundDown-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study.MethodsBased on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ‘SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.ResultsLOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.ConclusionsLOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation.

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the homeodomain of LMX1A in a subject with congenital severe-to-profound deafness through Exome sequencing, we performed luciferase assay to evaluate transcriptional activity of all LMX1A variants reported in the literature including p.Arg199Gly. Resultantly, p.Arg199Gly manifesting the most severe NSHL showed the biggest reduction of transcriptional activity in contrast with moderately reduced activity of p.Cys97Ser and p.Val241Leu associated with less severe progressive NSHL, proposing a genotype-phenotype correlation. Further, our dominant LMX1A variant exerted pathogenic effects via haploinsufficiency rather than dominant-negative effect. Collectively, we provide a potential genotype-phenotype correlation of LMX1A variants as well as the pathogenic mechanism of LMX1A-related NSHL.

The purposes of this study were to evaluate the nutritional status and dietary habits of the elderly using the nutrition quotient for the elderly (NQ-E) and to analyze the differences in the NQ-E according to their levels of oral health.The survey was administered to 123 elderly people receiving congregate meal services in Seoul. The questionnaire comprised 3 domains: oral health status, general characteristics, and the NQ-E for the elderly.The respondents were divided into 2 groups based on the average score of their levels of oral health (the group with high oral health scores: 4.42 points and the group with low oral health scores: 2.89 points). As a result of evaluating nutritional status using the NQ-E, it was found that the average NQ-E score was 58.7 points, with 46.0 points in the balance domain, 47.0 points in the diversity domain, 72.9 points in the moderation domain, and 61.8 points in the dietary behavior domain. The NQ-E score (62.3 points) of the group with high oral health scores is significantly higher than the NQ-E score (54.7 points) of the group with low oral health scores (Overall, several dietary areas needed improvement in general. Those with poor oral health conditions urgently needed to improve related factors to minimize the risk of increasing imbalanced nutrition and comorbidities due to insufficient nutrition and undesirable eating habits.

Variant prioritization of exome sequencing (ES) data for molecular diagnosis of sensorineural hearing loss (SNHL) with extreme etiologic heterogeneity poses a significant challenge. This study used an automated variant prioritization system (“EVIDENCE”) to analyze SNHL patient data and assess its diagnostic accuracy. We performed ES of 263 probands manifesting mild to moderate or higher degrees of SNHL. Candidate variants were classified according to the 2015 American College of Medical Genetics guidelines, and we compared the accuracy, call rates, and efficiency of variant prioritizations performed manually by humans or using EVIDENCE. In our in silico panel, 21 synthetic cases were successfully analyzed by EVIDENCE. In our cohort, the ES diagnostic yield for SNHL by manual analysis was 50.19% (132/263) and 50.95% (134/263) by EVIDENCE. EVIDENCE processed ES data 24-fold faster than humans, and the concordant call rate between humans and EVIDENCE was 97.72% (257/263). Additionally, EVIDENCE outperformed human accuracy, especially at discovering causative variants of rare syndromic deafness, whereas flexible interpretations that required predefined specific genotype–phenotype correlations were possible only by manual prioritization. The automated variant prioritization system remarkably facilitated the molecular diagnosis of hearing loss with high accuracy and efficiency, fostering the popularization of molecular genetic diagnosis of SNHL.

A systems-level understanding of cytokine-mediated, intertissue signaling is one of the keys to developing fundamental insight into the links between aging and inflammation. Here, we employed Drosophila, a routine model for analysis of cytokine signaling pathways in higher animals, to identify a receptor for the growth-blocking peptide (GBP) cytokine. Having previously established that the phospholipase C/Ca2+ signaling pathway mediates innate immune responses to GBP, we conducted a dsRNA library screen for genes that modulate Ca2+ mobilization in Drosophila S3 cells. A hitherto orphan G protein coupled receptor, Methuselah-like receptor-10 (Mthl10), was a significant hit. Secondary screening confirmed specific binding of fluorophore-tagged GBP to both S3 cells and recombinant Mthl10-ectodomain. We discovered that the metabolic, immunological, and stress-protecting roles of GBP all interconnect through Mthl10. This we established by Mthl10 knockdown in three fly model systems: in hemocyte-like Drosophila S2 cells, Mthl10 knockdown decreases GBP-mediated innate immune responses; in larvae, Mthl10 knockdown decreases expression of antimicrobial peptides in response to low temperature; in adult flies, Mthl10 knockdown increases mortality rate following infection with Micrococcus luteus and reduces GBP-mediated secretion of insulin-like peptides. We further report that organismal fitness pays a price for the utilization of Mthl10 to integrate all of these various homeostatic attributes of GBP: We found that elevated GBP expression reduces lifespan. Conversely, Mthl10 knockdown extended lifespan. We describe how our data offer opportunities for further molecular interrogation of yin and yang between homeostasis and longevity.

The purpose of this study was to evaluate the service quality attributes of Korean restaurants by North American and Chinese residents in Korea based on the Kano model. This survey was performed from September to December 2010. The subjects consisted of 135 Nort h Americans and 165 Chinese in Seoul. The service quality attributes of Korean restaurants were composed of twenty three items in the categories of ‘food quality’, ‘employee's service quality’, ‘sanitation quality’, ‘facility quality’, and ‘convenience quality'. For North Americans, there were five ‘attractive quality’ items, eleven ‘one-dimensional quality’ items and six ‘indifferent quality’ items, and one item had the same frequency on both ‘attractive quality’ and ‘one-dimensional quality'. For the Chinese, there were twelve ‘attractive quality’ items, and ten ‘one-dimensional quality’ items, and one item had the same frequency on ‘attractive quality’ and ‘one-dimensional quality'. According to the customer satisfaction coefficient developed by Timko, ‘taste of the ‘food (0.80)’ for North Americans and ‘freshness of the ingredients (0.94)’ for Chinese were highest scores in the ‘Better coefficient'. On the other h and, within the ‘Worse coefficient’, ‘sanitation of the food’ had the lowest score for both North Americans (-0.89) and Chinese (-0.90).Key words: Korean restaurant, service quality, North American, Chinese, Kano model

The purposes of this study were to investigate the effects of university foodservice quality attributes on Chinese students' satisfaction, as well as the mediating effects of perceived value on the relationship between foodservice quality attributes and satisfaction. A total of 250 university students in Daejeon were surveyed, and 216 responses were returned. Excluding responses with significant missing data, 196 responses were used for data analysis. The reasons for using university foodservice were ‘meal plan’ (37.8%) and ‘time saving’ (22.4%), whereas the reasons for not using university foodservice were ‘untasty food’ (33.2%) and ‘limited menu selection’ (27.6%). Results confirm that enhanced performance of food quality, service quality, sanitation, and convenience had favorable effects on per-ceived value and satisfaction. Further, perceived value had a significant positive influence on satisfaction. In analyzing the mediating role, the effect of foodservice quality attributes on satisfaction was partially mediated by perceived value.

Diabetes currently affects 9.3% of the U.S. population totaling $245 billion annually in U.S. direct and indirect healthcare costs. Current therapies for diabetes are limited in their ability to control blood glucose and/or enhance insulin sensitivity. Therefore, innovative and efficacious therapies for diabetes are urgently needed. Herein we describe a fluorescent insulin reporter system (preproinsulin-mCherry, PPI-mCherry) that tracks live-cell insulin dynamics and secretion in pancreatic β-cells with utility for high-content assessment of real-time insulin dynamics. Additionally, we report a new modality for sensing insulin granule packaging in conventional high-throughput screening (HTS), using a hybrid cell-based fluorescence polarization (FP)/internal FRET biosensor using the PPI-mCherry reporter system. We observed that bafilomycin, a vacuolar H(+) ATPase inhibitor and inhibitor of insulin granule formation, significantly increased mCherry FP in INS-1 cells with PPI-mCherry. Partial least squares regression analysis demonstrated that an increase of FP by bafilomycin is significantly correlated with a decrease in granularity of PPI-mCherry signal in the cells. The increased FP by bafilomycin is due to inhibition of self-Förster resonant energy transfer (homo-FRET) caused by the increased mCherry intermolecular distance. FP substantially decreases when insulin is tightly packaged in the granules, and the homo-FRET decreases when insulin granule packaging is inhibited, resulting in increased FP. We performed pilot HTS of 1782 FDA-approved small molecules and natural products from Prestwick and Enzo chemical libraries resulting in an overall Z'-factor of 0.52 ± 0.03, indicating the suitability of this biosensor for HTS. This novel biosensor enables live-cell assessment of protein-protein interaction/protein aggregation in live cells and is compatible with conventional FP plate readers.

The purpose of this study was to investigate workers’ perception on the quality improvement of Korean restaurants for the globa lization of Korean food. A total of 342 workers at Korean restaurants in Seoul and Gyeonggi province were surveyed using a self-administ rated questionnaire. Excluding responses with significant missing data, 250 responses were used for data analysis. In terms of the improvement of service quality attributes, the ‘sanitation management (4.51)’ category received the highest score, followed by ‘service skill (3.93)’, ‘menu development (3.90)’, ‘serving method (3.88)’, ‘facility and ambiance (3.84)’, and ‘food taste (3.40)’. There were significant differences of workers’ perception on the improvement of service quality which were ‘menu development ( p

Obesity and insulin resistance are primary risk factors for Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is generally exhibited by non-progressive simple steatosis. However, a significant subset of patient's progress to nonalcoholic steatohepatitis (NASH) that is defined by the presence of steatosis, inflammation and hepatocyte injury with fibrosis. Unfortunately, there are no approved therapies for NAFLD or NASH and therefore therapeutic approaches are urgently needed. Niclosamide is an U.S. Food and Drug Administration (FDA)-approved anthelmintic drug that mediates its effect by uncoupling oxidative phosphorylation. Niclosamide and its salt forms, Niclosamide Ethanolamine (NEN), and Niclosamide Piperazine (NPP) have shown efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism. While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed. Unfortunately, niclosamide has very poor water solubility, leading to low oral bioavailability. This, in addition to mitochondrial uncoupling activity and potential genotoxicity have reduced enthusiasm for its clinical use. More recently, salt forms of niclosamide, NEN and NPP, have demonstrated improved oral bioavailability while retaining activity. This suggests that development of safer more effective niclosamide derivatives for the treatment of NAFLD and Type 2 Diabetes may be possible. Herein we explored the ability of a series of N-substituted phenylbenzamide derivatives of the niclosamide salicylanilide chemotype to attenuate hepatic steatosis using a novel phenotypic in vitro model of fatty liver and the high fat diet-fed mouse model of diet induced obesity. These studies identified novel compounds with improved pre-clinical properties that attenuate hepatic steatosis in vitro and in vivo. These compounds with improved drug properties may be useful in alleviating symptoms and protection against disease progression in patients with metabolic syndrome and NAFLD.

Invertebrates are productive models for understanding basic molecular principles that link cytokine-mediated inflammatory pathways to aging in humans. Here, we use a high-throughput dsRNA screen to determine that the multifunctional Drosophila cytokine, GBP, is a ligand for the hitherto orphan GPCR, Mthl10. Through genetic manipulation of the GBP/Mthl10 axis in larvae and adult flies, we are able to demonstrate how organismal longevity is interconnected to immunological, metabolic, and stress-protective responses. Our results provide a molecular basis for hypothesizing that a successful defense against environmental insults—be they pathogenic inflammation or noninfective challenges—will ultimately reduce lifespan.

This study investigated the knowledge, attitude, and behavior of 280 University students towards nutrition labels. The purpose of the study was to examine knowledge, attitudes, and behaviors of university students regarding nutrition labeling, and whether body mass index (BMI) with nutrition labeling was associated with knowledge, attitudes, and behaviors. Descriptive statistics analyzed knowledge, attitudes, and behaviors of university students regarding food labeling. The ANOVA and χ 2 analysis was evaluated and assessed for its relationship with BMI. Pearson's correlation coefficient analysis examined relationships between knowledge, attitudes, and behaviors. More than 90 percent of answers relating to 11 nutritional knowledge questions were correct. Only 30% of participants answered correctly regarding questions about plan source oil and cholesterol content. Attitudes and behaviors of nutrition labels were significantly higher among participants who were obese (p

This study was conducted to investigate the current use and the demand for processed rice food products by full-time and working housewives in a metropolitan area. Out of 330 questionnaires distributed, 300 were analyzed(90.9% response rate). It was revealed that more than half of the respondents(54.0%) had used processed rice food products, regardless of their occupation. Most respondents stated that they used rice food products because of the variety of the products, digestibility and the taste. The development necessity for processed rice food products was analyzed, showing that rice cake(3.86), rice sauce(3.64), and rice cookie(3.89) had the highest score in each category. The average demand for education and promotion of rice food products was 3.89; among 7 items, menu recipe using rice flour was highly demanded(4.18) by the respondents. Approximately 43.0% of the respondents agreed that the internet is the most effective method for learning about rice flour cooking, and the respondents who have used processed rice food products(59.5%) were more likely to attend education programs compared to housewives who have not used processed rice food products (44.5%)(p

The purpose of this study was to investigate the perceptions of the foodservice industry workers in regard to the use of seasonings and sweeteners in the restaurants. Questionnaires were distributed to 902 foodservice workers of various restaurants. Participants were questioned on their perceptions of both natural and artificial seasonings & sweeteners. Furthermore, they were asked to respond to questions regarding the need of public education and information about the use of seasonings and sweeteners, along with the demographic information. The results showed that 65.7% of respondents used both the artificial seasoning and artificial sweeteners, while 9.9% of respondents used only natural seasonings and sweeteners. The restaurant employees answered that they have tried to reduce the use of artificial seasonings and sweeteners(3.69/5 point). Some of the respondents reported that they have tried to increase the used of natural seasonings and sweeteners(3.54/5 point). There were significant differences in the respondents' perceptions and attitudes on the seasonings and sweeteners by the restaurant type(p

The purposes of this study were to investigate students' perception on importance and performance of service quality of university foodservice, and to examine Importance-Performance Analysis(IPA) of foodservice quality for male and female students. A total of 500 university students in Daejeon were surveyed and 432 responses were returned. Excluding responses with significant missing data, 412 responses were used for data analysis. In terms of importance of service quality attributes, 'sanitation(4.74)' category received the highest score, followed by 'food(4.36)', 'service(4.22)', 'convenience(4.01)', 'menu(3.90)' and 'atmosphere(3.73)'. In terms of performance, the highest service quality attribute was associated with 'convenience(3.30)', followed by 'service(3.06)', 'sanitation(2.95)', 'food(2.88)', 'atmosphere(2.79)' and 'menu(2.68)'. As the results of IPA, 'staff's kindness', 'overall quality of service', 'taste of the food', 'freshness of the food', 'overall quality of the food', and 'cleanliness of the facility' fell into the Quadrant IV(Focus here) for female students. On the other hand, male students' IPA grid illustrated that 'taste of the food', 'freshness of the food', 'nutrition of the food', 'sanitation of the food', and 'sanitation of the utensils' fell into Quadrant IV(Focus here).

Objective To determine the incidence, etiology, and concurrent ophthalmic findings in small breed dogs that presented with cataracts. Animal studied Five hundred and sixty-one small breed dogs (942 eyes) were presented to the Veterinary Medical Teaching Hospital of Seoul National University between July 2002 and December 2007 with cataract. Procedure The medical records of small breed dogs with cataract were reviewed. The reason for presentation, cataract duration, bilaterality, breed, gender, age, vision, etiology, stage of cataract development, concurrent ophthalmic findings, IOP, ocular ultrasonography findings, and scotopic electroretinography (ERG) findings were investigated. Results The most frequently presented breeds were the Miniature/Toy Poodle (n = 112, 20.0%), Yorkshire Terrier (n = 110, 19.6%), and Shih Tzu (n = 95, 16.9%). The Miniature/Toy Poodle showed a significantly higher odds ratio for cataract formation (2.6). The proportion of female cataract patients was significantly higher than that of male cataract patients in the overall population (P

Objective To evaluate motility of silicone orbital implants and corneoscleral prostheses, with and without use of a motility coupling post (MCP) in dogs. Animals studied Eighteen mixed-breed dogs. Procedures The motility of an orbital silicone implant and corneoscleral prosthesis after enucleation (n = 6), evisceration (n = 6), or use of a MCP with evisceration (n = 6) in dogs were compared. One eye from each dog had surgery whereas the opposite eye was used as a control. Clinical evaluations were performed three times a week. Histopathology of the orbital tissues was performed 8 and 12 weeks after surgery. Results Implant motility in dogs with evisceration (vertical movement [VM] 8.04 ± 2.13; horizontal movement [HM] 11 ± 3.05) and evisceration with MCP (VM 9.61 ± 1.59); HM was significantly greater than the enucleation group (VM 0.51 ± 0.5; HM 1.22 ± 0.68) (P

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.

The optimal dark adaptation time of electroretinograms (ERG's) performed on conscious dogs were determined using a commercially available ERG unit with a contact lens electrode and a built-in light source (LED-electrode). The ERG recordings were performed on nine healthy Miniature Schnauzer dogs. The bilateral ERG's at seven different dark adaptation tim es at an intensity of 2.5 cdㆍs/m² was performed. Signal averaging (4 flashes of light stimuli) was adopted to reduce electrophysiologic noise. As the dark adaptation time increased, a significant increase in the mean a-wave amplitudes was observed in comparison to base-line levels up to 10 min (p < 0.05). Thereafter, no significant differences in amplitude oc- cured over the dark adaptation time. Moreover, at this time the mean amplitude was 60.30 ± 18.47 µV. However, no significant changes were observed for the implicit times of the a-wave. The implicit times and amplitude of the b-wave increased significantly up to 20 min of dark adap- tation (p < 0.05). Beyond this time, the mean b-wave am- plitudes was 132.92 ± 17.79 µV. The results of the present study demonstrate that, the optimal dark adaptation time when performing ERG's, should be at least 20 min in con- scious Miniature Schnauzer dogs.

Previous studies have indicated that the sulfated polysaccharide heparin has anti-inflammatory effects. However, the mechanistic basis for these effects has not been fully elucidated.NCI-H292 (mucoepidermoid) and HBE-1 (normal) human bronchial epithelial cells were treated with LPS alone or in the presence of high-molecular-weight (HMW) fully sulfated heparin or desulfated HMW heparin. Cells were harvested to examine the phosphorylation levels of ERK1/2, p38, and NF-kB p65 and COX-2 protein expression by Western blot and gene expression of both COX-2 and CXCL-8 by TaqMan qRT-PCR.Heparin is known to exert an influence on receptor-mediated signaling through its ability to both potentiate and inhibit the receptor-ligand interaction, depending upon its concentration. In H292 cells, fully-sulfated HMW heparin significantly reduced LPS-induced gene expression of both COX-2 and CXCL-8 for up to 48 hours, while desulfated heparin had little to no significant suppressive effect on signaling or on COX-2 gene or protein expression. Desulfated heparin, initially ineffective at preventing LPS-induced CXCL8 up-regulation, reduced CXCL8 transcription at 24 hours. In contrast, in normal HBE-1 cells, fully sulfated heparin significantly suppressed only ERK signaling, COX-2 gene expression at 12 hours, and CXCL-8 gene expression at 6 and 12 hours, while desulfated heparin had no significant effects on LPS-stimulated signaling or on gene or protein expression. Sulfation determines heparin's influence and may reflect the moderating role of GAG sulfation in lung injury and health.Heparin's anti-inflammatory effects result from its nonspecific suppression of signaling and gene expression and are determined by its sulfation.

The medical records of 23 dogs that underwent medial canthoplasty for treatment of epiphora were reviewed. The most prevalent breed encountered was the shih tzu. Other affected breeds included the Pekingese, Maltese, toy poodle, and pug. All dogs had epiphora associated with medial canthal trichiasis and/or entropion. Other ocular abnormalities included conjunctivitis, keratitis, pigmentary keratitis, corneal ulceration, globe prolapse, and nasal fold trichiasis. After medial canthoplasty, the epiphora resolved in all dogs.

In pharmaceutical companies and research institutes, many toxicity tests are performed with laboratory animals. This study was performed to produce reference data for eye toxicity tests and to investigate the ophthalmic diseases of 408 ICR mice and 119 BALB/c mice, which are commonly used as subjects in toxicity tests. The experimental animals without clinical disorders were selected regardless of sex. The ophthalmic diseases were examined by using special ophthalmic instruments: direct ophthalmoscope, indirect ophthalmoscope, slit-lamp biomicroscope and focal illuminator. The most prevalent ocular variation within normal limits was hyaloid vessel remnant (ICR mice, 28.2%; BALB/c mice, 31.9%) and the incidence gradually decreased with age. The ocular diseases found in ICR mice were retinal degeneration (9.8%), corneal scar (4.2%), focal cataract (2.2%), anisocoria (1.2%), corneal ulcer (0.2%) and uveitis (0.2%). In BALB/c mice, corneal scar (9.2%), focal cataract (1.7%) and corneal ulcer (0.8%) were the ocular diseases found.

To compare the antiangiogenic effects of tetraarsenic oxide (As4O6) with those of diarsenic oxide (As2O3) in the rat cornea, rat cornea micropocket assay was conducted to induce angiogenesis by implantation of the pellet contained 1.0 ng of nerve growth factor (NGF). Ten of thirty eyes of Sprague-Dawley rats were randomly assigned to one of three groups, namely, control group (no medication), As2O3 group (50 mg/kg As2O3, PO, s.i.d.), and As4O6 group (50 mg/kg As4O6, PO, s.i.d.). After implantation, the number of new vessels, vessel length and clock hour of neovascularization were examined under the microscope from day 3 to day 7. The area of neovascularization was calculated using a mathematical formula. Although new vessels in control and As2O3 groups were first noticed at day 3, whereas those of As4O6 group were first observed on day 5. The number, length, clock hour of neovascularization and areas of the vessels in As4O6 group showed more significant inhibition than those of control and As2O3 groups from day 5 (P

To determine whether celecoxib (CXB) can be released from incubated intraocular lenses (IOLs) sufficiently to inhibit lens epithelial cell (LEC) growth in an ex vivo model of posterior capsule opacification (PCO).LEC growth was evaluated for 14 days in canine lens capsules (LCs) that had been exposed to media containing 20 μM CXB for 1-5 days. After the incubation of hydrophilic and hydrophobic IOLs in CXB solution, the determination of the in vitro release of CXB from the IOLs was performed for up to 28 days. The incubated and nonincubated IOLs were evaluated in the ex vivo model of PCO, and the rate of LEC growth was evaluated over 28 days.The treatment of LCs with 20 μM CXB for 4 and 5 days completely inhibited LEC growth. LEC repopulation did not occur after the removal of CXB. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels theoretically sufficient to inhibit PCO. LCs in the ex vivo model of PCO treated with acrylic IOLs incubated in CXB had significantly suppressed LEC ingrowth compared with untreated and IOL-only LCs.A 4-day treatment of LCs with a concentration of 20 μM CXB may effectively prevent PCO. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels sufficient to inhibit LEC growth in the ex vivo model of PCO. Further studies are needed to determine whether CXB-incubated IOLs can effectively prevent the development of PCO in vivo.

The aim of this study was to determine the most effective light intensity for flash electroretinogram (ERG) examination in conscious dogs using ERG equipment with a contact lens electrode with a built-in LED light source. ERG was performed on the bilateral eyes of ten clinically healthy Miniature Schnauzers at 6 different intensities (0.025, 0.079, 0.25, 0.79, 2.5 and 7.9 cd·s/m 2 ) after dark adaptation for 20 min. With the increase in stimulus intensity, the most significant increase in a and b-wave amplitudes were observed at 2.5 cd·s/m 2 (p

Objective To examine the feasibility and accuracy of a handheld rebound tonometer, TonoVet®, and to compare the intraocular pressure (IOP) readings of the TonoVet® with those of an applanation tonometer, TonoPen XL®, in normal Eurasian Eagle owls. Animals studied Ten clinically normal Eurasian Eagle owls (20 eyes). Procedures Complete ocular examinations, using slit-lamp biomicroscopy and indirect ophthalmoscopy, were conducted on each raptor. The IOP was measured bilaterally using a rebound tonometer followed by a topical anesthetic agent after 1 min. The TonoPen XL® tonometer was applied in both eyes 30 s following topical anesthesia. Results The mean ± SD IOP obtained by rebound tonometer was 10.45 ± 1.64 mmHg (range 7–14 mmHg), and by applanation tonometer was 9.35 ± 1.81 mmHg (range 6–12 mmHg). There was a significant difference (P = 0.001) in the IOP obtained from both tonometers. The linear regression equation describing the relationship between both devices was y = 0.669x + 4.194 (x = TonoPen XL® and y = TonoVet®). The determination coefficient (r2) was r2 = 0.550. Conclusions The results suggest that readings from the rebound tonometer significantly overestimated those from the applanation tonometer and that the rebound tonometer was tolerated well because of the rapid and minimal stress-inducing method of tonometry in the Eurasian Eagle owls, even without topical anesthesia. Further studies comparing TonoVet® with manometric measurements may be necessary to employ rebound tonometer for routine clinical use in Eurasian Eagle owls.

The purpose of this study was to investigate spontaneous eye disease in New Zealand White (NZW) rabbits, which are commonly used for toxicity tests, and to provide reference materials for pharmaceutical companies and research centers. A total of 586 NZW rabbits were randomly chosen without sex preference and were examined using ocular equipment, including a direct ophthalmoscope, an indirect ophthalmoscope, a slit-lamp biomicroscope, a focal illuminator, and a fundus camera. This study showed that the incidence rate of temporary cataracts, regarded as a change within normal variation, was 0.5% in the NZW rabbits. Regarding abnormal ophthalmic disease, blepharitis was the most commonly observed ocular disease. Other findings included cataract, conjunctivitis, choroidal hypoplasia, keratitis, corneal scarring, eyelid laceration, posterior synechiae, uveitis, dacryocystitis, and persistent pupillary membrane. In total, the incidence rate of ophthalmic diseases was 9.6%. Based on sex and age distributions, females had more ocular diseases than males, and rabbits were less susceptible to eye diseases as they got older. In this study, photographs were taken to document findings, such as normal fundus, normal variations, ophthalmic disease, and histopathologic examination.

A 4-month-old female maltese dog was admitted to Veterinary Medical Teaching Hospital of Seoul National University for evaluation of abnormal color of bilateral irises. This patient had the photophobia in the light and exhibited the complete absence of pigment resulting in white hair, pink muzzle, eyelids and foot-pads. Central zone of the irises were yellow in color influenced by tapetal reflex, and peripheral zone were pale blue. The iridal capillaries were transparented on the irises. Ophthalmoscopic examination revealed a yellow tapetal fundus but no pigment in the nontapetal fundus.

A mongrel male dog of three years old was referred to the Seoul National University Veterinary Teaching Hospital following a one month history of glaucoma. On ophthalmic examination, hyphema, glaucoma, uveitis, iridal mass, and loss of vision were noted in the right eye. Ultrasonography and computed tomography revealed a mass with involvement of the entire uvea. Radiographic evaluation did not reveal any evidence of distant metastasis. The right eye was surgically removed because of the high likelihood of neoplasia. A histologic diagnosis of malignant uveal melanoma was made.

Our society is aging rapidly, and the number of elderly people who are in charge of purchasing and preparing foods at home is increasing. However, most the elderly have difficulty managing nutrition and food safety by themselves. The purpose of this study was to develop the necessary knowledge, through focus group interview and Delphi technique to establish a food safety and nutrition education program. The diet and educational needs of the elderly were surveyed through FGI. The education topics were decided by the Delphi technique. The education program consisted of a five week program, and the topics taught were ‘Dietary Change for Healthy Life’, ‘Prevention of Food Poisoning in Everyday Life’, ‘Safe Food Handling for my Health’, ‘Healthy Dietary Life to Prevent Chronic Disease’, and ‘Safety! Nutrition! Healthy Dietary Life’. This education program was designed to decrease the perceived barriers, and to increase the perceived interests and the sense of self-efficacy. Education program materials, lesson plans, slides, handouts, videos, leaflets, and booklets were developed. Based on the results, the contents of the food safety guideline leaflets for the elderly were decided as the following: (1) wash your hands in the correct way; (2) select safe food; (3) cook foods safely; (4) keep foods safely; (5) keep kitchen utensils clean. In conclusion, if advanced education programs are implemented and delivered continuously in locations such as health centers and community welfare centers, those will contribute significantly to enhance the perception of food safety and to change the desirable dietary behavior of the elderly. (Korean J Community Nutr 17(2) : 167~181, 2012)

This study was performed to develop a children’s dietary life safety index required by the Special Act on Safety Management of Children’s Dietary Life enacted in 2009. An analytical hierarchy process was used to obtain initial weights of dietary life safety evaluation indicators. The Delphi method was applied to develop the weights along with 98 food and nutrition professionals. Three representative policy indicators, nine strategy indicators, 11 main evaluation indicators, and 20 detailed evaluation indicators were selected for the children’s dietary life safety assessment. Three policy indicators and nine strategy indicators were the following: children’s food safety indicator (support level of children’ safety, safety management level of children’s favorite foods, and safety management level of institutional food service), children’s nutrition safety indicator (management level of missing meals and obesity, nutrition management level of children’s favorite foods, and nutrition management level of institutional food service), and children’s perception and practice level indicator (“Dietary Life Law” perception level, perception, and practice level for dietary life safety management, perception, and practice level for nutrition management). Weights of 40%, 40%, and 20% were given for the three representative policy indicators. The relative importance of nine strategic indicators, which were determined by the Delphi method is as follows: For children’s food safety, support level of children’s safety, safety management level of children’s favorite foods, and safety management level of institutional food service were given weights of 12%, 9%, and 19%, respectively. For children’s nutrition safety, the missing meals and obesity management level, nutrition management level of children’s favorite foods, and the nutrition management level of institutional food service were given weights of 13%, 11%, and 16%, respectively. The “Dietary Life Law” perception level, perception and practice level of dietary life safety management, and perception and practice level of nutrition management were given weights of 4%, 7%, and 9%, respectively. (Ko

The purposes of this study were to investigate one portion size of menus served and to evaluate nutrient intake of lunch at three elderly care facility food services located in Seoul. A weighed plate method was employed to measure plate wastes and consumption of the menus served. Yield factors were calculated from cooking experiments based on standardized recipes, and were used to evaluate nutrient intake. One hundred elderly participated in this study for measuring plate waste and were asked to complete questionnaire. Nutrient analyses for the served and consumed meal were performed using CAN program. The yield factors of rice dishes after cooking are 2.4 regardless of rice dish types, 1.58 for thick soups, 0.60 to 0.70 for meat dishes, and 1.0 to 1.25 branched vegetable. Average consumption quantity of dishes were 235.97 g for rice, 248.53 g for soup, 72.83 g for meat dishes, 39.80 g for vegetables and 28.36 g for Kimchi. On average the food waste rate is 14.0%, indicating the second highest plate waste percentage of Kimchi (26.2%), and meat/fish dish (17.3%). The evaluation results of NAR (Nutrition Adequacy Ratio) showed that iron (0.12), calcium (0.64), riboflavin (0.80), and folic acid (0.97) were less than 1.0 in both male and female elderly groups, indicating significant differences of NAR among three facilities. Compared to the 1/3 Dietary Reference Intake (DRIs) for the elderly groups, nutrient intake analysis demonstrated that calcium (100%) and iron (100%), followed by riboflavin, vitamin A, and Vitamin B6 did not met of the 1/3 EAR (Estimated Average Requirement). For the nutritious meal management, a professional dietitian should be placed at the elderly care center to develop standardized recipes in consideration of yield factors and the elderly’s health and nutrition status. (Korean J Nutr 2009; 42(7): 650 ~ 663)

Objective—To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp. Sample Population—Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation). Procedures—Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU (28). Aqueous humor and serum were also evaluated for anti-Leptospira antibody titers from clinically normal horses (n = 12), horses with non-ERU inflammation (17), and horses with confirmed chronic ERU (24). Results—Bacterial DNA was not detected in aqueous humor or vitreous humor of horses with ERU or clinically normal horses. No significant difference was found in titers of anti-Leptospira antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse with ERU and 1 horse with non-ERU inflammation, had definitive intraocular production of antibodies against Leptospira organisms. Conclusions and Clinical Relevance—In horses from the southeastern United States, Leptospira organisms may have helped initiate ERU in some, but the continued presence of the organisms did not play a direct role in the pathogenesis of this recurrent disease.

This study evaluated the surgical outcome and complications of phacoemulsification and the implantation of an acryl foldable intraocular lens (IOL) with a squared edge in dogs with cataracts. Thirty-two eyes from 26 dogs were examined. The mean follow up period was 75.9 days ranging from 23 to 226 days. The complications after phacoemulsification were posterior capsular opacity (PCO) around the IOL (n = 11), ocular hypertension (n = 4), focal posterior synechia (n = 4), hyphema (n = 3) and corneal ulcer (n = 2). The complications associated with the IOL were decenteration of the optic (n = 2) and ventral haptic displacement (n = 1). Most cases of PCO were found only around the margin of the IOL, and all eyes had vision during the observation period. In conclusion, the implantation of an acryl-foldable lens with a squared edge at the time of phacoemulsification is an effective method for preserving the central visual field of dogs with cataract.

This study was performed to compare the effect of intratesticular (IT) injection of xylazine/ketamine combination for canine castration with those of intramuscular (IM) or intravenous (IV) injection. Xylazine and ketamine was administered simultaneously via intratesticularly (IT group), intramuscularly (IM group) or intravenously (IV group) at doses of 2 and 10 mg/kg, respectively. Pain response at the time of injection, mean induction time, mean arousal time, mean walking time and cardiopulmonary function during anesthesia were monitored after the xylazine and ketamine administration. In IV and IM groups, heart rates were significantly decreased 30 and 45 min after xylazine and ketamine administration, respectively (p < 0.05). Respiratory rates were significantly decreased in the IV group (p < 0.05). In the IT group, there was no significant changes in heart and respiratory rates. The occurrence of cardiac arrhythmias was less severe in IT group compared with those in IM and IV groups. The route of administration did not affect rectal temperature. Mean induction time was significantly (p < 0.05) longer in IT group than in IM and IV groups. On the contrary, mean arousal time and mean walking time were shortened in IT group. Clinical signs related to pain response at the time of injection and vomiting were less observed in IT group than in IM group, and head shaking was less shown in IT group than in IM and IV groups during recovery period. These results indicated that intratesticular injection of xylazine/ketamine for castration has several advantages such as less inhibition of cardiopulmonary function and fast recovery from anesthesia without severe complications, and would be an effective anesthetic method for castration in small animal practice.