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Background and purpose: Anosognosia refers to a deficit of self‐awareness or impaired insight for cognitive and behavioral problems. Cognitive anosognosia was explored in de novo patients with Parkinson's disease (PD) and its relationship to cognitive function and neuropsychiatric symptoms was investigated. Methods: The cross‐sectional study enrolled 340 drug‐naïve patients with PD. According to the presence of mild cognitive impairment (MCI) and subjective cognitive complaint, patients were classified as patients with cognitive anosognosia (PD‐CA, n = 74), with normal cognitive recognition (PD‐NR, n = 184) or with cognitive underestimation (PD‐CU, n = 82). After controlling for covariates, cognitive performance and neuropsychiatric symptoms were compared between the PD groups. Results: Cognitive anosognosia was found in 21.8% of patients with de novo PD. The PD‐CA group showed poorer performance in all cognitive domains except for attention. Amongst PD patients with MCI, those with cognitive anosognosia showed lower composite z‐scores in the Stroop color reading test than those without. The Beck Depression Inventory score in the PD‐NR group was lower than that in the PD‐CU group and higher than that in the PD‐CA group. The Cognitive Complaints Interview score mediated the association between cognitive anosognosia and Beck Depression Inventory score. Conclusions: Cognitive anosognosia in PD was associated with greater frontal dysfunction and lower depression. Since cognitive anosognosia has a harmful impact on PD patients and their caregivers due to overestimation of their abilities in everyday life, early identification of cognitive anosognosia in PD is important in management and prognosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co‐occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. Methods: The cross‐sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. Results: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. Conclusions: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-assisted siRNA treatment was accomplished with a nanofibrous matrix for suicidal gene therapy of diabetic ulcers. We fabricated a MMP-responsive nanofibrous matrix to control release of small interfering RNA (siRNA) in response to a high concentration of MMPs in diabetic ulcers. For MMP-responsive release of siRNA, linear polyethyleneimine (LPEI) was chemically conjugated on the surface of the nanofibrous matrix via a MMP-cleavable linker. To control the abnormally elevated MMP-2 expression in diabetic ulcers, MMP-2 siRNA was electrostatically incorporated into LPEI-immobilized nanofibrous meshes with various nitrogen/phosphate (N/P) ratios. The release profiles of siRNA and LPEI were monitored to confirm that MMP responsiveness of the matrix and MMP-2 significantly increased the release of both siRNA and LPEI for 72 h. The released fractions were transfected to dermal fibroblasts. Quantitative reverse transcription (qRT)-PCR for endogenous MMP-2 expression confirmed that the gene-silencing effects of siRNA were dependent on the charge ratio of LPEI to siRNA on the mesh. Diabetic animals with dorsal burns were treated with siRNA-incorporated nanofibrous mesh for 7days. siRNA-incorporated nanofibrous meshes dramatically increased the MMP-2 gene-silencing effects of the siRNA and neo-collagen accumulation at the wound sites. RT-PCR also confirmed the highest expression levels of the keratinocyte-specific markers and the lowest expression levels of MMP-2 in the nanofibrous mesh-treated groups, suggesting that wound recovery is restored to normal levels. The wound recovery rates of diabetic ulcers were significantly increased when siRNA-incorporated nanofibrous meshes were administered. Thus, the suicidal treatment with the MMP-2 siRNA-decorated nanofibrous mesh is expected to improve prognosis of diabetic ulcers with reduced side effects. [ABSTRACT FROM AUTHOR]

Background and purpose: As a major antioxidant, uric acid (UA) is known to be associated with the clinical progression of Parkinson's disease (PD). This study investigated whether baseline UA levels are associated with the risk for levodopa‐induced dyskinesia (LID) in PD in a sex‐dependent manner. Methods: In all, 152 patients with de novo PD (78 males and 74 females) who were followed up for >2 years were enrolled. The effect of baseline serum UA levels on LID‐free survival was assessed by Cox regression, separately for sex, whilst being adjusted for potential confounding factors. The optimal UA level cut‐off value to determine the high‐risk group for LID was set using Contal and O'Quigley's method. Results: Levodopa‐induced dyskinesia developed in 23 (29.5%) male patients and 30 (40.5%) female patients. Cox regression showed a significant interaction between UA level and sex. Higher UA levels were associated with a higher risk for LID in male PD patients (hazard ratio 1.380; 95% confidence interval 1.038–1.835; P = 0.027), although this relationship was not observed in female PD patients. The optimal UA level cut‐off for LID in male PD was 7.2 mg/dl, and the high UA group had a 5.7‐fold higher risk of developing LID than the low UA group. Conclusions: Contrary to a presumptive beneficial role of UA, the present study demonstrated that higher UA levels are associated with increased risk of LID occurrence in male patients with PD, suggesting a sex‐dependent role of UA in LID. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with de novo Parkinson's disease (PD). Methods: In all, 167 de novo PD patients who underwent 18F‐fluorinated N‐3‐fluoropropyl‐2‐beta‐carboxymethoxy‐3‐beta‐(4‐iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex‐dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR). Results: The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD (r = −0.156, P = 0.045), and this association was more prominent in male PD patients (r = −0.422, P < 0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side (r = 0.312, P = 0.005) and the less affected side (r = 0.312, P = 0.005) only in male PD patients. Conclusions: The present study demonstrated the potentially close sex‐specific relationship between the serum UA levels and the anterior–posterior gradient of DAT patterns, suggesting a sex‐specific protective effect of UA on nigrostriatal dopaminergic neurons in de novo PD. [ABSTRACT FROM AUTHOR]

The metamaterial structure composed of cubic high dielectric resonators periodically arrayed in a low dielectric substrate is analysed and a flat metamaterial lens is used to improve the gain of a rectangular patch antenna. A dielectric slab is also discussed and compared with the metamaterial lens. Experimental results show that the proposed metamaterial flat lens can improve the gain of a patch antenna remarkably at both the first and the third resonant mode. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we reported that the stress associated with chronic isolation was associated with increased β-amyloid (Aβ) plaque deposition and memory deficits in the Tg2576 transgenic animal model of Alzheimer''s disease (AD) [Dong H, Goico B, Martin M, Csernansky CA, Bertchume A, Csernansky JG (2004) Effects of isolation stress on hippocampal neurogenesis, memory, and amyloid plaque deposition in APP (Tg2576) mutant mice. Neuroscience 127:601–609]. In this study, we investigated the potential mechanisms of stress-accelerated Aβ plaque deposition in this Tg2576 mice by examining the relationship between plasma corticosterone levels, expression of glucocorticoid receptor (GR) and corticotropin-releasing factor receptor-1 (CRFR1) in the brain, brain tissue Aβ levels and Aβ plaque deposition during isolation or group housing from weaning (i.e. 3 weeks of age) until 27 weeks of age. We found that isolation housing significantly increased plasma corticosterone levels as compared with group-housing in both Tg+ mice (which contain and overexpress human amyloid precursor protein (hAPP) gene) and Tg− mice (which do not contain hAPP gene as control). Also, isolated, but not group-housed animals showed increases in the expression of GR in the cortex. Furthermore, the expression of CRFR1 was increased in isolated Tg+ mice, but decreased in isolated Tg− mice in both cortex and hippocampus. Changes in the components of hypothalamic–pituitary–adrenal (HPA) axis were accompanied by increases in brain tissue Aβ levels and Aβ plaque deposition in the hippocampus and overlying cortex in isolated Tg+ mice. These results suggest that isolation stress increases corticosterone levels and GR and CRFR1 expression in conjunction with increases in brain tissue Aβ levels and Aβ plaque deposition in the Tg2576 mouse model of AD. [Copyright &y& Elsevier]

Sedimentological and micropaleontological characteristics of core sediments from the outer shelf of the Korea Strait, which connects the northern East China Sea and the East Sea (Sea of Japan), were investigated to elucidate the paleoceanographic environment, especially the timing of the Kuroshio inflow, since the last glacial maximum. The core sediments, containing continuous records of the last 15,000 years, are characterized by a relatively high mud content (more than 50%, on average) and well-developed tide-influenced sedimentary structures. Their mineralogy suggests that the material originated from the paleo-Nakdong River system, which extended across the shelf of the Korea Strait during low sea-level periods. Planktonic foraminifers reveal a series of well-defined changes in paleoceanographic conditions during the late Pleistocene–Holocene. Down-core variations in the abundance of four foraminiferal assemblages, i.e., cold, coastal, tropical–subtropical, and Kuroshio water groups comprising characteristic planktonic species, suggest the occurrence of a distinct paleoenvironmental change in the surface water at 7,000 years b.p., i.e., from 15,000 to 7,000 years b.p., the area was influenced by coastal waters whereas since ca. 7,000 years b.p., it has been under the influence of open-sea water related to the Kuroshio Current flow, associated with both higher temperature and higher salinity. In particular, Pulleniatina obliquiloculata increased markedly in abundance at this time, documenting the inflow of the Kuroshio into the study area. These data indicate that the coastal water stage terminated at ca. 7,000 years b.p. when the warm Kuroshio and its major branch, the Tsushima Current, began to flow into the East Sea, as is the case today. The intrusion of the Tsushima Current through the Korea Strait after ca. 7,000 years b.p. resulted in abrupt changes in sedimentation rates and a dramatic increase in abundance of the Kuroshio indicator species, P. obliquiloculata. [ABSTRACT FROM AUTHOR]

Background and purpose: To clarify whether subtyping of amnestic and non‐amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes. Methods: We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting‐state functional connectivity between the patients with de‐novo PD with amnestic MCI (PD‐aMCI) (n = 50) and non‐amnestic MCI (PD‐naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de‐novo PD‐aMCI (n = 125) and PD‐naMCI (n = 61). Results: The demographic data showed that scores in memory domains were lower in the PD‐aMCI group compared with the PD‐naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD‐aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD‐aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD‐naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD‐aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD‐naMCI (P = 0.022). In addition, the PD‐aMCI group had a higher risk of dementia conversion than the PD‐naMCI group. Conclusions: This study suggests that the designation of PD‐MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis. [ABSTRACT FROM AUTHOR]

Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin β3 is another potential target for combination treatment with SAIT301. Suppression of integrin β3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin β3 are resistant to crizotinib treatment, suggesting that FGFR and integrin β3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti-cancer treatment have been sought from natural resources. Here, we have investigated anti-proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the de novo sphingolipid pathway, and its mechanism in B16F10 melanoma cells. We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate levels were analysed by HPLC. Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21 was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate in myriocin-treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells. Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21, followed by inhibition of cyclin B1 and cdc2, resulting in G/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism-based therapy for this type of skin cancer. [ABSTRACT FROM AUTHOR]

Seven of 18 elk on a deer farm were found by the official Rose-Bengal agglutination test (RBT) and tube agglutination test to be brucellosis reactors/suspects. Evaluation with the competitive ELISA (C-ELISA) and the fluorescence polarization assay (FPA) tests revealed that six and five sera were positive respectively. The seven reactors/ suspects were slaughtered and their blood and tissues were collected. Brucella species could be isolated from three of the slaughtered animals, with nine isolates being obtained from the popliteal, supramammary and submandibular lymph nodes, vaginal discharge, mammary tissue and spleen. Brucella genus-specific PCR based on 16S rRNA and AMOS-PCR, which is specific for differential Brucella species, revealed that all nine isolates were Brucella abortus. These nine were further confirmed to be B. abortus biovar 1 by classical biotyping scheme assays. This is the first report of an outbreak of brucellosis in domestic elk in Korea. Our observations suggest that deer should be included in the routine Brucella surveillance programme for the effective control and prevention of brucellosis in Korea. [ABSTRACT FROM AUTHOR]

A Vero cell attenuated porcine epidemic diarrhea virus (PEDV) strain, DR13, was distinguished from wild-type PEDV using restriction enzyme fragment length polymorphism (RFLP). Cell attenuated DR13 was orally or intramuscularly (IM) administered to late-term pregnant sows, and mortality resulting from the highly virulent PEDV challenge was investigated in passively immunized suckling piglets of the two different groups. The mortality rate of the oral group (13%) was lower than that of the IM group (60%). In particular, the concentration of IgA against PEDV was higher in piglets of sows in the oral group, compared to the IM group. The attenuated DR 13 virus remained safe, even after three backpassages in piglets. The findings of this study support the theory that the Vero cell attenuated DR 13 virus may be applied as an oral vaccine for inducing specific immunity in late-term pregnant sows with a high margin of protection against PEDV infection. [ABSTRACT FROM AUTHOR]

Acupuncture is useful in treating the nausea and vomiting related to chemotherapy, adult postoperative surgery pain and postoperative dental pain. We obtained single-photon emission computed tomography (SPECT) brain perfusion images of six patients with middle cerebral artery occlusion obtained before and after acupuncture and compared the changes in regional cerebral blood flow (rCBF) to those in normal control. Images were obtained before and after acupuncture at six traditional acupoints (LI 4, 10, 11, 15 and 16 and TE5) in the affected arm. The baseline image was subtracted from the postacupuncture image, to produce a subtraction image displaying only voxels with values >2 SD from the mean and those voxels were coregistered to the baseline SPECT or T2-weighted MRI. Similar images were obtained before and after acupuncture of eight normal volunteers. Statistical parametric mapping with a threshold of P =0.001 and a corrected P of 0.05 was performed for group comparison between postacupuncture and baseline SPECT. Focally increased CBF was seen in all patients especially in the hypoperfused zone surrounding the ischaemic lesion, the ipsilateral or contralateral sensorimotor area, or both. Normal subjects showed increased rCBF mainly in the parahippocampal gyrus, premotor area, frontal and temporal areas bilaterally and ipsilateral globus pallidus. Acupuncture stimulation after stroke patients appears to activate perilesional or use-dependent reorganised sites and might be a way of looking at brain reorganisation. [ABSTRACT FROM AUTHOR]

The article accounts an outbreak and the immediate control of Streptococcus equi subspecies zooepidemicus-induced hemorrhagic pneumonia in a research dog colony at the College of Veterinary Medicine, Seoul National University in South Korea. The dogs developed acute clinical signs that included a moist cough, depression, anorexia, fever and nasal discharge, which immediately died two to 12 hours after. Immediate control by prompt fluid and antibiotic therapy has resolved the problem.

The article presents a clinical case report which describes a case of lymphohistiocytic encephalomyelitis associated with Akabane virus in calves with neurological disorders in South Korea. The case involves eight calves, ranging from three days to four months, showing neurological signs such as hypersensitivity, tremor, locomotor ataxia, and lameness. Gross pathology shows that the lymphohistiocytic encephalomyelitis in calves was caused by Akabane virus infection.