Entropic comparison of Landau-Zener and Demkov interactions in the phase space of a quadrupole billiard.

We investigate two types of avoided crossings in a chaotic billiard within the framework of information theory. The Shannon entropy in the phase space for the Landau-Zener interaction increases as the center of the avoided crossing is approached, whereas for the Demkov interaction, the Shannon entropy decreases as the center of avoided crossing is passed by with an increase in the deformation parameter. This feature can provide a new indicator for scar formation. In addition, it is found that the Fisher information of the Landau-Zener interaction is significantly larger than that of the Demkov interaction.

Isothermal anisotropic magnetoresistance in antiferromagnetic metallic IrMn.

Antiferromagnetic spintronics is an emerging field; antiferromagnets can improve the functionalities of ferromagnets with higher response times, and having the information shielded against external magnetic field. Moreover, a large list of aniferromagnetic semiconductors and metals with Néel temperatures above room temperature exists. In the present manuscript, we persevere in the quest for the limits of how large can anisotropic magnetoresistance be in antiferromagnetic materials with very large spin-orbit coupling. We selected IrMn as a prime example of first-class moment (Mn) and spin-orbit (Ir) combination. Isothermal magnetotransport measurements in an antiferromagnetic-metal(IrMn)/ferromagnetic-insulator thin film bilayer have been performed. The metal/insulator structure with magnetic coupling between both layers allows the measurement of the modulation of the transport properties exclusively in the antiferromagnetic layer. Anisotropic magnetoresistance as large as 0.15% has been found, which is much larger than that for a bare IrMn layer. Interestingly, it has been observed that anisotropic magnetoresistance is strongly influenced by the field cooling conditions, signaling the dependence of the found response on the formation of domains at the magnetic ordering temperature.

Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting.

Pigs are an attractive animal model to study the progression of cancer because of their anatomical and physiological similarities to human. However, the use of pig models for cancer research has been limited by availability of genetically engineered pigs which can recapitulate human cancer progression. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9 systems were used to target RUNX3, a known tumour suppressor gene, to generate a pig model that can induce gastric cancer in human. First, RUNX3 knockout cell lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells were used as donor cells for somatic cell nuclear transfer, followed by embryo transfer. We successfully obtained four live RUNX3 knockout piglets from two surrogates. The piglets showed the lack of RUNX3 protein in their internal organ system. Our results demonstrate that the CRISPR/Cas9 system is effective in inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can be useful resources for human cancer research and to develop novel cancer therapies.

Potential association of VAMP5 polymorphisms with total colonic aganglionosis in Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a congenital bowel disease caused by the absence of nerve cells in portions of the intestine. Our recent genome-wide association study has identified a variant (rs1254900) of vesicle-associated membrane protein 5 (VAMP5) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. In addition, VAMP5 is a member of the VAMP/synaptobrevin protein complex, which participates in nerve signal transduction by regulating the vesicular fusion of the neurotransmitter in synaptic transmission. METHODS: A total of 11 single nucleotide polymorphisms (SNPs), including those in the functionally important coding region, were selected on the basis of linkage disequilibrium and genotyped in 187 HSCR patients and 283 unaffected controls by using a TaqMan assay. Logistic analysis was conducted to investigate the possible association between VAMP5 SNPs and the risk of HSCR. KEY RESULTS: Genetic variants of VAMP5 showed increased association signals in the TCA subgroup of HSCR patients (minimum p = 9.69 × 10(-5) , OR = 3.93 at rs10206961) compared to other subgroups, even after Bonferroni correction (pcorr = 0.002). In haplotype analysis, three haplotypes (BL1_ht1, BL2_ht1, and BL2_ht2) were associated with the risk of TCA (minimum pcorr = 0.005). In additional combined analysis after imputation based on our previous GWAS, five SNPs still retained significant associations with the TCA subtype (minimum pcorr = 0.006 at rs10206961). CONCLUSIONS & INFERENCES: Considering that differential genetic effects on the development of the enteric nervous system, our results suggest that VAMP5 may be associated with the TCA of HSCR. However, further replications and functional evaluations are required.

Hiccup-like segmental myoclonus in thoracic compressive myelopathy: a case report.

STUDY DESIGN: A case report. OBJECTIVES: This study discusses a case of spinal segmental myoclonus caused by thoracic myelopathy, mimicking hiccup spasms. Spinal myoclonus caused by thoracic myelopathy is extremely rare. It can be misdiagnosed as chronic intractable hiccups due to similar clinical manifestations. SETTING: Korea University Anam Hospital, Seoul, Republic of Korea. METHODS: A 42-year-old man presented with a history of involuntary jerky movement of the upper abdominal wall muscles that had been continuing for over 3 years. A neurological examination, brain computed tomography and electroencephalogram did not reveal a cause of the symptoms. Electromyography was performed on the abdominal muscles and the findings revealed were compatible with spinal myoclonus. The spinal myoclonus had started in the abdominal muscles, with a spinal magnetic resonance imaging revealing a disc protrusion compressing the anterior spinal cord. RESULTS: The cause of the spinal myoclonus was determined to be spinal myelopathy due to mild T7 disc protrusion. The patient refused surgical or invasive interventions and was conservatively treated with clonazepam. The symptoms were reported to be less frequent following the treatment. CONCLUSION: Compressive myelopathy developed from disc protrusion may cause spinal myoclonus mimicking as hiccup spasms.

Comparison of MR imaging findings between extraligamentous and subligamentous disk herniations in the lumbar spine.

BACKGROUND AND PURPOSE: The method of treating an HIVD in the lumbar spine may depend on the integrity of the PLL. The purpose of this study was to analyze and compare the MR imaging findings of extraligamentous and subligamentous HIVDs in the lumbar spine. MATERIAL AND METHODS: One hundred seventeen patients (M/F = 71:46; mean age, 47 years; age range, 15-79 years) underwent lumbar spine MR imaging and disk surgery (extraligamentous/subligamentous = 66:51) from May 2003 to November 2006. Two radiologists in consensus retrospectively reviewed all MR images, focusing on 10 criteria. RESULTS: The following 5 criteria are suggestive of extraligamentous HIVD in the lumbar spine: 1) spinal canal compromised for more than half its dimension, 2) internal signal difference in the HIVD, 3) an ill-defined margin of the HIVD, 4) disruption of the continuous low-signal-intensity line covering the HIVD, and 5) the presence of an internal dark line in the HIVD (P < .05). When we combined these 5 MR imaging criteria, the sensitivity, specificity, accuracy, and odds ratio were 77.3%, 74.5%, 76.1%, and 9.93 (P < .0001). CONCLUSIONS: Our proposed 5 MR imaging criteria will be helpful in differentiating extraligamentous and subligamentous HIVDs in the lumbar spine.

Inhibition of swine leukocyte antigen-I presentation in transgenic mini-pig cell lines by expressing human cytomegalovirus US6.

Xenotransplantation using porcine organs may resolve the chronic shortage of donor organs for clinical transplantation if significant immunologic barriers can be overcome. A xenograft can be rejected by T cells, especially CD8(+) cytotoxic T lymphocytes (CTL)-mediated responses, as these cells show cytotoxicity against xenografts by recognition of swine leukocyte antigen (SLA)-I. Peptide translocation is inhibited by the endoplasmic reticulum-resident human cytomegalovirus (HCMV) glycoprotein unique short (US) 6, due to alterations of the transporter associated with antigen processing loading onto MHC class I for antigen presentation to CD8(+) CTL. In this study we transfected the US6 gene into minipig fetal fibroblasts establishing three US6 clonal cell lines. Flow cytometry analysis of US6 clonal cell lines demonstrated a substantial reduction in SLA-I expression. The level of SLA-I expression in US6 clones was decreased to 56.3% compared with the control 42.7%. In CTL assays, the rate of CD8(+) CTL-mediated cytotoxicity was significantly reduced to 35.2% ± 11.7% compared with the control, 79.9% ± 6.5%, (P < .01). These results suggested that HCMV viral protein US6 suppresses the presentation of SLA-I on pig fetal fibroblast cells. This strategy might be used in transgenic pig production to protect porcine organs from CTL-mediated immune rejection.

Interictal metabolic changes in episodic migraine: a voxel-based FDG-PET study.

Whereas there are many H(2)(15)O-positron emission tomography (PET) studies demonstrating neuronal activation during acute migraine attacks, little information is available on the interictal (headache-free period) glucose metabolic changes in migraine. We therefore conducted voxel-based statistical parametric mapping analysis of (18)F-fluorodeoxyglucose-PET to evaluate interictal metabolic differences between 20 episodic migraine patients (four with aura; three men; mean age 34.0 +/- 6.4 years) and 20 control subjects. Separate correlation analyses were performed to delineate a possible relationship between regional glucose metabolism and disease duration or lifetime headache frequency in migraine patients. Group comparison showed that migraine patients had significant hypometabolism in several regions known to be involved in central pain processing, such as bilateral insula, bilateral anterior and posterior cingulate cortex, left premotor and prefrontal cortex, and left primary somatosensory cortex (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Correlation analyses showed that regional metabolism of the insula and anterior cingulate cortex had significant negative correlations with disease duration and lifetime headache frequency (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Our findings of progressive glucose hypometabolism in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time lead to metabolic abnormalities of selective brain regions belonging to the central pain matrix.

The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction.

OBJECTIVE: The effects of granulocyte-colony stimulating factor (G-CSF) on endothelial function are unknown. Therefore, we investigated the effects of G-CSF on endothelial function. METHODS: 76 patients participating in the MAGIC-Cell-3-DES trial were enrolled. These were patients with acute myocardial infarction (AMI) or old MI (OMI) who underwent percutaneous coronary intervention (PCI), and were prospectively randomised into a G-CSF group (G-CSF (10 microg/kg/day) injection for 3 days after PCI) or a control group. Additionally, 20 healthy volunteers were also enrolled. These subjects were categorised into five groups: AMI-control (n = 18), AMI-G-CSF (18), OMI-control (20), OMI-G-CSF (20) and healthy-G-CSF (20). Baseline flow-mediated dilation (FMD) of the brachial artery and serum inflammatory biomarkers were performed on day 1, and repeated on day 4 in all groups. G-CSF was injected for 3 days between days 1 and 4 in the AMI-G-CSF, OMI-G-CSF and healthy-G-CSF groups. RESULTS: In both the healthy-G-CSF and OMI-G-CSF groups, G-CSF increased serum high sensitivity C-reactive protein (hsCRP) (0.3 (0.5) mg/l vs 6.1 (3.5) mg/l and 5.6 (3.8) mg/l vs 13.0 (7.7) mg/l, baseline vs post-G-CSF in the healthy and OMI-G-CSF groups, respectively, p<0.001). In the AMI-G-CSF group, G-CSF hindered the decline of hsCRP during the recovery phase, resulting in a relative increase in hsCRP. However, in all three groups, G-CSF did not significantly alter FMD. CONCLUSION: Despite an associated increase in systemic inflammation, G-CSF treatment does not lead to acute impairment of brachial artery endothelial function in either healthy subjects or patients with MI.

Usefulness of a photophobia questionnaire in patients with migraine.

Photophobia is an important criterion for the diagnosis of migraine. However, several Asian epidemiological surveys about migraine have shown lesser prevalence of photophobia than that of Western studies. This discrepancy is probably caused by underestimation of photophobia due to inappropriate questioning of patients by physicians. To investigate this issue, we developed a questionnaire about photophobia and evaluated its usefulness in 103 patients with migraine. In phase 1 of the study, we found good repeatability of the questionnaire with a 0.826 kappa coefficient. In phase 2, the prevalence of photophobia from interviews and that from the questionnaire were compared. The prevalence of interview-documented photophobia was 51.5% and of questionnaire-documented photophobia 82.5% (P < 0.001). In phase 3, we attempted to make a short-form questionnaire with the same detection power of the questionnaire study. Two short-form questionnaires were identified as a useful method for detecting photophobia. The prevalence of photophobia could be underreported via interview, especially in Asian migraineurs. Using this questionnaire to test for photophobia, the diagnostic rate of photophobia and migraine could be improved.

The relationship of pain and health-related quality of life in Korean patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder. Increasing attention has been focused on the pain and health-related quality of life (HrQOL) in patients with PD. Objective - To evaluate the relationship between pain and the HrQOL in patients with PD. METHODS: Eighty-two patients with PD were included and classified into two groups according to the presence of pain. The Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS), the Modified Somatic Perception Questionnaire (MSPQ), the Zung Depression Inventory--Self-rating Depression Scale (SDS), the Visual Analogue Scale and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were administered. The factors influencing the pain, HrQOL and parkinsonian manifestations were evaluated. RESULTS: The PD with pain group had higher UPDRS part III scores, lower SF-36 scores, higher SDS scores and higher MSPQ scores than the PD without pain group. The presence of pain, high Hoehn and Yahr stage, advanced age and somatic perception were the factors that had a negative effect on the physical component of the HrQOL. Depression and somatic perception were the most important predictive factors for the mental component of the HrQOL. Depression and poor parkinsonian motor abilities were the leading factors contributing to pain. CONCLUSION: Pain and depression were major detrimental factors affecting the physical and mental aspects of the HrQOL respectively. Therefore, the treatment of pain and depression can be important to improve the HrQOL.

Regional grey matter changes in patients with migraine: a voxel-based morphometry study.

We used voxel-based morphometry (VBM) to compare grey matter volume (GMV) between 20 migraine patients (five with aura and 15 without aura) with normal conventional magnetic resonance imaging findings and 33 healthy controls matched for age and sex. A separate analysis was also performed to delineate a possible correlation between the GMV changes and the headache duration or lifetime headache frequency. When compared with controls, migraine patients had significant GMV reductions in the bilateral insula, motor/premotor, prefrontal, cingulate cortex, right posterior parietal cortex, and orbitofrontal cortex (P < 0.001, uncorrected for multiple comparisons at a voxel level; corrected P < 0.05 after small volume corrections). All regions of the GMV changes were negatively correlated with headache duration and lifetime headache frequency (P < 0.05, Pearson's correlation test). We found evidence for structural grey matter changes in patients with migraine. Our findings of progressive GMV reductions in relation to increasing headache duration and increasing headache frequency suggest that repeated migraine attacks over time result in selective damage to several brain regions involved in central pain processing.

Value of diagnostic lumbar selective nerve root block: a prospective controlled study.

BACKGROUND AND PURPOSE: Although diagnostic lumbar selective nerve root blocks are often used to confirm the pain-generating nerve root level, the reported accuracy of these blocks has been variable and their usefulness is controversial. The purpose of this study was to evaluate the accuracy of diagnostic lumbar selective nerve root blocks to analyze potential causes of false results in a prospective, controlled, single-blinded manner. MATERIALS AND METHODS: A total of 105 block anesthetics were performed under fluoroscopic guidance in 47 consecutive patients with pure radiculopathy from a single confirmed level: 47 blocks were performed at the symptomatic level, and 58 were performed at the adjacent asymptomatic "control" level. Contrast and local anesthetics were injected, and spot radiographs were taken in all cases. We calculated the diagnostic value of the block anesthetics using concordance with the injected level. We analyzed the potential causes of false results using spot radiographs. RESULTS: On the basis of a definition of a positive block as 70% pain relief, determined by receiver-operator characteristic (ROC) analysis, diagnostic lumbar selective nerve root block anesthetics had a sensitivity of 57%, a specificity of 86%, an accuracy of 73%, a positive predictive value of 77%, and a negative predictive value of 71%. False-negatives were due to the following causes identifiable on spot radiographs: insufficient infiltration, insufficient passage of the injectate, and intraepineural injections. On the other hand, false-positives resulted from overflow of the injectate from the injected asymptomatic level into either the epidural space or symptomatic level. CONCLUSION: The accuracy of diagnostic lumbar selective nerve root blocks is only moderate. To improve the accuracy, great care should be taken to avoid inadequate blocks and overflow, and to precisely interpret spot radiographs.

Morphologic and histologic comparisons between in vivo and nuclear transfer derived porcine embryos.

Nuclear transfer (NT) is an inefficient but invaluable tool of the biotechnology industry. This study looked at abnormalities associated with peri-implantation NT porcine embryos. Four experimental groups were examined: nonpregnant animals, in vivo pregnant animals, NT recipients, and manipulation control embryos (MC). Embryos (Day 10, 12, or 14) were evaluated for embryonic disc diameter, gross morphology, nucleoli density, and mitotic figure index. Day 12 (P < or = 0.03) and Day 14 (P < or = 0.01) NT embryos had increased numbers of nucleoli, and Day 14 NT embryos had an increased (P < or = 0.03) mitotic index compared to in vivo and MC embryos. In vivo produced Day 14 embryos had increased (P < or = 0.01) disk diameters when compared to other embryos except for MC Day 14, which also showed increases (P < or = 0.01) in disk diameter except when compared to in vivo produced Day 12 and Day 14 embryos. In vivo produced Day 12 had greater (P < or = 0.03) disk diameters when compared to NT and MC embryos except for MC Day 14, and in vivo produced Day 14 embryos, which had a significantly increased (P < or = 0.01) disk diameter. In vivo produced Day 14 embryos were morphologically more advanced (P < or = 0.01) than Day 14 NT and MC counterparts. NT embryos develop at a slower rate than their in vivo produced counterparts. The increase in nucleoli and mitotic index of NT embryos suggest the cell cycle may be affected or the NT embryos are employing other means to compensate for slow development. The techniques used during NT also appear to compromise embryo development.

Association of endothelial constitutive nitric oxide synthase gene polymorphism with acute coronary syndrome in Koreans.

OBJECTIVE: To examine the effects of two polymorphisms of the endothelial constitutive nitric oxide synthase (ecNOS) gene, 4a/4b(A:B) located in intron 4 and Glu298Asp(G:T) located in exon 7, on the development of acute coronary syndromes (ACS). METHODS: 164 patients with ACS and 142 control participants were investigated for genotype and conventional risk factors. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Genotype and allele frequencies of the A:B polymorphism in the ACS group (0.15:0.85 for AA+AB:BB, 0.09:0.91 for A:B) differed from those in the control group (0.26:0.74 for AA+AB:BB, 0.15:0.85 for A:B). However, genotype and allele frequencies of the G:T polymorphism in the ACS group (0.22:0.78 for TT+TG:GG, 0.11:0.89 for T:G) were similar to those in the control group (0.17:0.83 for TT+TG:GG, 0.09:0.91 for T:G). Multiple logistic regression analysis showed that the non-BB (AA+AB) and the non-BB+GG genotypes were significant protective factors against ACS (odds ratios 0.49 and 0.34, 95% confidence intervals 0.26 to 0.93 and 0.14 to 0.83, respectively). In addition, linear association analysis showed that the percentage of ACS patients was significantly lower in the genotype group non-BB+GG than in the genotype group BB+non-GG (39.6% v 62.7%, p = 0.01). CONCLUSIONS: The non-BB genotype of the ecNOS 4a/4b gene polymorphism is a protective factor against the development of ACS. The GG genotype of the ecNOS Glu298Asp polymorphism exerts a benefit in addition to the non-BB genotype in the Korean population.

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans.

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.