Although a large number of genetic variants have been identified to be associated with common diseases through genome-wide association studies, there still exits limitations in explaining the missing heritability. One approach to solving this missing heritability problem is to investigate gene-gene interactions, rather than a single-locus approach. For gene-gene interaction analysis, the multifactor dimensionality reduction (MDR) method has been widely applied, since the constructive induction algorithm of MDR efficiently reduces high-order dimensions into one dimension by classifying multi-level genotypes into high- and low-risk groups. The MDR method has been extended to various phenotypes and has been improved to provide a significance test for gene-gene interactions. In this paper, we propose a simple method, called accelerated failure time (AFT) UM-MDR, in which the idea of a unified model-based MDR is extended to the survival phenotype by incorporating AFT-MDR into the classification step. The proposed AFT UM-MDR method is compared with AFT-MDR through simulation studies, and a short discussion is given.
Classification ; Genome-Wide Association Study ; Genotype ; Methods* ; Multifactor Dimensionality Reduction* ; Phenotype

Background: Tibial tuberosity transposition (TTT) causes caudalization of the patellar ligament insertion in canine medial patellar luxation, which can lead to increases in patellofemoral contact pressure. Objectives: The purpose of this study is to confirm the effect of patellofemoral contact mechanics after craniolateral and caudolateral transposition of tibial tuberosity in normal canine hindlimbs. Methods: Craniolateral and caudolateral transposition of tibial tuberosity was performed in 5 specimens, respectively. The pressure was measured in the specimen before TTT, and then in the same specimen after TTT. In this process, data was obtained in 10 specimens. The measurement results were output as visualization data through the manufacturer's software and numerical data through spreadsheet. Based on these 2 data and the anatomical structure of the patellofemoral joint (PFJ) surface, whole measurement area was analysed by dividing into medial, lateral and central area. Results: In craniolateralization of tibial tuberosity, total, medial, central contact pressure was decreased and lateral contact pressure was not statistically changed lateral contact pressure than normal PFJ. In caudolateralization of tibial tuberosity, total, lateral contact pressure was increased and medial contact pressure was not statistically changed than normal PFJ. Although not statistically significant changed, central contact pressure in caudolateralization of tibial tuberosity was increased in all 5 specimens. Conclusions These results imply that traditional TTT, prone to caudal shift of patellar tendon, can increase retropatellar pressure may lead to various complications and diseases of the stifle joint.

Purpose: To report a case of transient total occlusive attack of the ophthalmic artery with asymptomatic patent foramen ovale.Case summary: A 31‐year‐old female presented with worsening of intermittent visual loss in her right eye from the previous day. The visual acuity in the right eye was reduced to 0.04 at her first visual examination. In the doctor’s room, her visual acuity in the right eye improved to 1.0 at first; however, after several minutes, it decreased to no light perception. A relative afferent pupillary defect was observed. Following that, fluorescein angiography was performed, and visual acuity improved and worsened repeatedly; corresponding intermittent perfusion and occlusion of the ophthalmic artery were observed during the examination. Further evaluation was performed to determine the cause of intermittent occlusion of the ophthalmic artery; patent foramen ovale was diagnosed. Transient ophthalmic artery occlusion was presumed to have occurred owing to embolism by the patent foramen ovale. Aspirin was used as a prophylaxis. Since then, there have been no recurring symptoms of visual impairment. Conclusions Patients with ophthalmic diseases such as ophthalmic artery occlusion, retinal artery occlusion, and amaurosis fugax, especially young people, require a thorough assessment to identify potential causes of embolism.

Purpose: To evaluate the diagnostic value of retinal nerve fiber layer-to-disc ratio (RDR) compared to established parameters including retinal nerve fiber layer thickness (RNFLT), Bruch membrane opening-minimum rim width (BMO-MRW), and Bruch membrane opening-minimum rim area (BMO-MRA) for differentiating between open angle glaucoma (OAG) and nonarteritic anterior ischemic optic neuropathy (NAION). Methods: This retrospective study included 23 optic disc size-matched normal control eyes and 23 OAG and NAION eyes matched according to global RNFLT. The RDR, RNFLT, BMO-MRW, and BMO-MRA were analyzed; the diagnostic capabilities of these parameters were compared using the area under the receiver operating characteristic curve (AUC). Results: The global BMO-MRW and total BMO-MRA were lower in the OAG group than in the other two groups (all p < 0.001). RDR was greatest in the OAG group, followed by the healthy and NAION groups (p < 0.001). Between the OAG and NAION groups, the AUCs for temporal inferior BMO-MRW, total BMO-MRA, and RDR were 0.987, 0.996, and 1.000, respectively; these were greater than the temporal inferior RNFLT (0.811; p = 0.005, p = 0.006, and p = 0.006, respectively). Conclusions RDR could be one of the useful parameters for differential diagnosis in OAG and NAION.

BACKGROUND: Microencapsulation of islet cells has been studied for the treatment of type I diabetes to protect islets from immune attack by recipient cells during islet transplantation. In this study, we established optimal preparation conditions for islet microcapsules with good morphology and cell viability by employing an electrostatic droplet generator. METHODS: To obtain good quality islet microcapsules, various parameters such as the inner diameter of the electrostatic droplet generator nozzle, concentrations and infusion rates of alginate, electrostatic strength, and calcium chloride concentrations were tested. The size and shape of the capsules and cell viability were examined by light microscopy, and insulin secretion from the cells was determined by an ELISA analysis. RESULTS: The optimal preparation conditions for microencapsulation were a 0.35 mm inner nozzle diameter, a 1.75% alginate concentration, a 20 mL/hr alginate infusion rate, a 5 kV electrostatic potential, and a 75 mM calcium chloride. Under these conditions, over 90% of the capsules had a proper size (300~350 micrometer) and shape, and cell viability was 91%. Cell viability was maintained at greater than 80% even after the capsules were cultured for 2 weeks. However, glucose-induced insulin secretion of encapsulated islet cells was reduced by 85% compared to that of nonencapsulated cells. CONCLUSIONS: The results showed that an encapsulation technique using an electrostatic droplet generator is useful for making islet microcapsules with good morphology and cell viability. This technique is necessary to study microencapsulation using primary islets, enhancing glucose-induced insulin secretion, and to perform a functional evaluation of encapsulated islets in vivo in the near future.
Alginates ; Calcium Chloride ; Capsules ; Cell Survival ; Drug Compounding ; Enzyme-Linked Immunosorbent Assay ; Glucuronic Acid ; Hexuronic Acids ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Light ; Microscopy

No abstract available.
Caves ; Esophageal and Gastric Varices ; Portal Vein

Xenotransplantation of porcine organs has the potential to overcome the acute shortage of human tissues and organs for human transplantation. Swine represents an ideal source of such organs owing to their anatomical and physiological similarities to human besides their plentiful supply. However, this procedure is also associated with a number of safety issues related to zoonotic infections. Among such zoonotically important pathogens, porcine endogenous viruses (PERVs) represent the most concerned virus as they persist asymptomatically and show germline transmission in pigs. They belong to gamma retroviruses and are of three types viruses: A, B and C. In the present study, PCR based cloning was performed with chromosomal DNA extracted from miniature pigs to analyze the envelope gene of PERVs. Amplified PCR fragments of about 1.5 Kb, covering the partial env gene, were cloned into pCR2.1-TOPO vectors and sequenced. A total of 51 env clones were obtained from two miniature pigs, types M149 and T1111. Phylogenetic analysis of these genes revealed the presence of only PERV type A and B in the proportion of 45% and 55%, respectively. Among these, 9 clones had the correct open reading frame: eight were PERV type A and one PERV type B. Since both these PERV types are polytropic and have the capacity to infect human cells, our data raise a concern that proviral PERVs might have the potential to generate infectious viruses during or after xenotransplantation in humans.
Clone Cells ; Cloning, Molecular* ; Cloning, Organism ; DNA ; Genes, env ; Humans ; Methods ; Open Reading Frames ; Polymerase Chain Reaction ; Retroviridae ; Swine* ; Transplantation, Heterologous ; Zoonoses

Xenotransplantation of porcine organs has the potential to overcome the acute shortage of human tissues and organs for human transplantation. Swine represents an ideal source of such organs owing to their anatomical and physiological similarities to human besides their plentiful supply. However, this procedure is also associated with a number of safety issues related to zoonotic infections. Among such zoonotically important pathogens, porcine endogenous viruses (PERVs) represent the most concerned virus as they persist asymptomatically and show germline transmission in pigs. They belong to gamma retroviruses and are of three types viruses: A, B and C. In the present study, PCR based cloning was performed with chromosomal DNA extracted from miniature pigs to analyze the envelope gene of PERVs. Amplified PCR fragments of about 1.5 Kb, covering the partial env gene, were cloned into pCR2.1-TOPO vectors and sequenced. A total of 51 env clones were obtained from two miniature pigs, types M149 and T1111. Phylogenetic analysis of these genes revealed the presence of only PERV type A and B in the proportion of 45% and 55%, respectively. Among these, 9 clones had the correct open reading frame: eight were PERV type A and one PERV type B. Since both these PERV types are polytropic and have the capacity to infect human cells, our data raise a concern that proviral PERVs might have the potential to generate infectious viruses during or after xenotransplantation in humans.
Clone Cells ; Cloning, Molecular* ; Cloning, Organism ; DNA ; Genes, env ; Humans ; Methods ; Open Reading Frames ; Polymerase Chain Reaction ; Retroviridae ; Swine* ; Transplantation, Heterologous ; Zoonoses

Purpose: To report a case of orbital apex syndrome and central retinal vein occlusion after blow-out fracture repair.Case summary: A 22-year-old man who underwent emergency re-operation in a department of plastic surgery due to pain, decreased visual acuity, and ophthalmoplegia in all direction after orbital blow-out fracture repair was referred to ophthalmologist on postoperative day 2 and there was no improvement in symptoms. He showed severe complications, including optic neuropathy and ophthalmoplegia in all direction, central retinal vein occlusion, and outer retinal disruption caused by orbital apex hemorrhage. Although we were concerned that it was too late, we started high dose steroid intravenous pulse treatment and the visual acuity, ophthalmoplegia, and retinal findings were improved. However, the optic atrophy and visual field defect did not. Conclusions After a complicated blow-out fracture repair in other department, if a patient shows severely decreased visual acuity or ocular movement limitation, a thorough and immediate ophthalmologic examination is recommended. During ophthalmologic examination, meticulous examination of the entire eye, including the retina, is required, in addition to general orbital complications. A relatively good prognosis can be expected through accurate cause analysis and appropriate treatment for the confirmed abnormal findings.

Background: Postoperative pain is affected by preoperative depression. If the risk of postoperative pain associated with depression can be predicted preoperatively, anesthesiologists and/or surgeons can better manage it with personalized care. The objective of this study was to determine the efficacy of Patient Health Questionnaire-2 (PHQ-2) depression screening tool as a predictor of postoperative pain. Methods: A total of 50 patients scheduled for elective laparoscopic cholecystectomy with an American Society of Anesthesiologists grade of 1 or 2 were enrolled. They answered the PHQ-2, which consists of two questions, under the supervision of a researcher on the day before the surgery. The numerical rating scale (NRS) scores were assessed at post-anesthesia care unit (PACU), at 24, and 48 postoperative hours, and the amount of intravenous patient-controlled analgesia (IV-PCA) administered was documented at 24, 48, and 72 postoperative hours. At 72 h, the IV-PCA device was removed and the final dosage was recorded. Results: The NRS score in PACU was not significantly associated with the PHQ-2 score (correlation coefficients: 0.13 [P = 0.367]). However, the use of analgesics after surgery was higher in patients with PHQ-2 score of 3 or more (correlation coefficients: 0.33 [P = 0.018]). Conclusions We observed a correlation between the PHQ-2 score and postoperative pain. Therefore, PHQ-2 could be useful as a screening test for preoperative depression. Particularly, when 3 points were used as the cut-off score, the PHQ-2 score was associated with the dosage of analgesics, and the analgesic demand could be expected to be high with higher PHQ-2 scores.