A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Synthesis of core-shell copper-graphite submicronic particles and carbon nano-onions by spark discharges in liquid hydrocarbons.

Spark discharge in hydrocarbon liquids is considered a promising method for the synthesis of various nanomaterials, including nanocomposites. In this study, copper-carbon particles were synthesized by generating spark discharges between two Cu electrodes immersed in heptane, cyclohexane, or toluene. The synthesized particles were characterized using scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction. Overall, two families of particles were observed: Cu particles (diameter < 10 nm) embedded in a carbon matrix and submicrometric Cu particles encapsulated in a carbon shell. The obtained results indicate that the size distribution of the Cu nanoparticles and the degree of graphitization of the carbon matrix depend on the liquid. Indeed, discharges in heptane lead to Cu particles with diameters of 2-6 nm embedded in a carbon matrix of low graphitization degree, while discharges in toluene result in particles with diameters of 2-14 nm embedded in carbon matrix of high graphitization degree. Based on the obtained experimental results, it is proposed that the Cu nanoparticles are produced in the plasma core where Cu (evaporated from the electrode surface) and carbonaceous species (decomposition of the liquid) are present. When the plasma hits the electrode surface, hot (thousands of Kelvin) Cu particles are ejected from the electrode, and they propagate in the liquid. The propagation of the hot particles in the liquid results in the local evaporation of this liquid, which leads to the formation of a C-shell around each Cu particle. In few cases where the shape of the Cu particle is not spherical, carbon nanoonions are detected between the C-shell and the Cu core. These nanoonions are supposedly formed under the effect of the fluid vortices generated close to the particle surfaces when these latter are ejected into the liquid.

Role of transient receptor potential vanilloid type 1 in the trigeminal ganglion and brain stem following dental pulp inflammation.

AIM: To verify whether experimentally induced pulpitis activates the expression of transient receptor potential vanilloid type 1 (TRPV1) and c-Fos, both peripherally and centrally. METHODOLOGY: Acute pulpitis was induced in Sprague-Dawley rats via pulp exposure and application of complete Freund's adjuvant (CFA; n = 13). Saline-treated (n = 13) rats and rats that did not undergo tooth preparation (n = 13) served as control groups. Three days post-CFA or post-saline application, face grooming activity was recorded, and the rats were then euthanized to allow for immunohistochemical analysis of the trigeminal ganglion (TG) and spinal trigeminal nucleus. anova with Student's t-test for post-hoc analysis was used to quantify the differences in behavioural tests and immunohistochemical labelling (c-Fos and TRPV1) in TG amongst groups. Kruskal-Wallis test with Dunnett's test for post-hoc analysis was used to compare immunohistochemical labelling (c-Fos and TRPV1) in the brainstem amongst groups. RESULTS: Histological evidence of severe pulp inflammation was found, and there was a significant increase in pain-like behaviour (P < 0.05) in CFA-treated animals. C-Fos labelling and TRPV1 immunoreactivity in the TG were significantly higher (both P < 0.05) in the CFA group than in the control groups. In the spinal trigeminal nucleus, the immunoreactivity for c-Fos was absent in the intermediate region (trigeminal subnucleus interpolaris) in all animals, with comparable expression of TRPV1 amongst all groups. In contrast, neurons in the trigeminal subnucleus caudalis (TSC) exhibited significant c-Fos immunoreactivity in the CFA group (P = 0.0063). The expression of TRPV1 did not differ amongst the three groups, but the superficial laminae of the TSC exhibited significantly greater expression of TRPV1 than did the deep layers (P = 0.0014). CONCLUSIONS: Following acute pulp inflammation, the TRPV1 channel was significantly involved in nociceptive signal processing in the peripheral nervous system, but not in the CNS. Because pulpitis induced some neuronal activation at the brainstem levels, further studies are needed to identify additional transducers that mediate signal transmission from pulpal afferents to their central targets.

Soliton fractional charge of disordered graphene nanoribbon.

We investigate the properties of the gap-edge states of half-filled interacting disordered zigzag graphene nanoribbons, and find that the midgap states can display a quantized fractional charge of 1/2. These gap-edge states can be represented by topological kinks with their site probability distribution divided between the left and right zigzag edges with different chiralities. In addition, there are numerous spin-split gap-edge states, similar to those in a Mott-Anderson insulator.

Microscopic hematuria is a risk factor of incident chronic kidney disease in the Korean general population: a community-based prospective cohort study.

BACKGROUND: Although asymptomatic microscopic hematuria (MH) is a common finding in clinical practice, its long-term outcome remains unknown. AIM: This study evaluated the clinical implication of MH in the general population using a large-scale long-term longitudinal cohort database. METHODS: This study included 8719 participants from the Korean Genome and Epidemiology Study between 2001 and 2014. MH was defined as ≥5 red blood cells per high-power field in random urinalysis without evidence of pyuria. The primary study outcome measure was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate <60 ml min-1⋅1.73⋅m-2. RESULTS: During a median follow-up of 11.7 years, CKD occurred in 677 (7.8%) subjects. In Cox regression after adjustment for multiple confounders, subjects with MH had a significantly higher risk of incident CKD than those without [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.12-1.87; P = 0.005]. Isolated MH without proteinuria was also a risk factor of incident CKD (HR 1.37, 95% CI 1.04-1.79; P = 0.023) and the risk was further increased in MH with concomitant proteinuria (HR 5.41, 95% CI 2.54-11.49; P < 0.001). In propensity score matching analysis after excluding subjects with proteinuria, multi-variable stratified Cox regression analysis revealed that subjects with isolated MH had a significantly higher risk of incident CKD than those without (HR 1.83, 95% CI 1.14-2.94; P = 0.012). CONCLUSION: The presence of MH is associated with an increased risk of incident CKD in the general population. Therefore, attentive follow-up is warranted in persons with MH for early detection of CKD.

Value of unenhanced MRI with diffusion-weighted imaging for detection of primary small (≤20 mm) solid pancreatic tumours and prediction of pancreatic ductal adenocarcinoma.

AIM: To determine the diagnostic performance of unenhanced magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI; NonMRI) for the detection of primary small (≤20 mm) pancreatic solid tumours and prediction of pancreatic ductal adenocarcinoma (PDAC) in comparison with pancreatic computed tomography (CT; PanCT) and pancreatic MRI with magnetic resonance cholangiopancreatography (PanMRI). METHODS AND MATERIALS: The institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 126 patients who underwent PanCT and PanMRI, including 94 small (≤20 mm) pancreatic tumours (51 PDACs, 34 neuroendocrine tumours [NETs], nine solid pseudopapillary tumours [SPTs]), and 32 patients with a normal pancreas, comprised the study population. Two observers assessed three sets of images: PanCT, PanMRI and NonMRI (T1- and T2-weighted images and DWI). Receiver operating characteristic curve analysis and diagnostic accuracy using the area under the receiver operating characteristic curve (Az) were used for statistical analysis. RESULTS: On NonMRI and PanMRI, all of tumours except one NET were detected, but eight tumours (six NETs, one PDAC, one SPT) were not detected on PanCT (p<0.01). For prediction of PDAC, the Az value of the NonMRI (0.884 for observer 1; 0.930 for observer 2) was comparable with PanCT (0.922; 0.924; p>0.05), and inferior to PanMRI (0.930; 0.977; p<0.05), but all of 51 PDACs were considered as probable or definite PDAC on NonMRI by both observers. CONCLUSION: NonMRI showed better performance than PanCT, and competitive performance to PanMRI for the detection of primary small solid pancreatic tumours, and showed reasonable sensitivity for prediction of PDACs compared with PanCT and PanMRI.

Safety and efficacy of medium-sized particle embolisation for skull-base meningioma.

AIM: To determine the effectiveness and safety of preoperative tumour embolisation for skull-base meningiomas via external carotid artery (ECA) feeders using medium-sized (150-250 µm) polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: This study included 114 consecutive patients with skull-base meningiomas who underwent preoperative tumour embolisation using medium-sized PVA particles from January 2004 to December 2013. Tumours were categorised according to feeding artery as follows: type 1, tumour staining at ECA angiography only; type 2, tumour staining at both the ECA and internal carotid artery (ICA) angiography; or type 3, little or no tumour staining at ECA angiography. The effectiveness was based on the percent reduction in the enhanced area: >75% was considered effective, 25-75% was considered partially effective, and <25% was considered ineffective. RESULTS: Tumour embolisation was performed in patients with dominant feeding vessels originating from the ECA. Procedural-related complications occurred in two (1.8%) patients. Post-procedural MRI images were available for 51 patients, which revealed effective embolisation in only 13 (25.5%) patients. Identification of an ICA feeding vessel was associated with ineffective embolisation (p=0.011). Effective embolisation was associated with low estimated blood loss during surgery. CONCLUSION: ECA embolisation using medium-sized PVA is ineffective in patients in whom a definitive ICA feeding vessel was identified, even if preprocedural angiography showed that the dominant feeder originated from the ECA. When the risks of surgical morbidity and mortality are expected to be high, ICA feeder embolisation should also be considered.

Clinical relevance of the apparent diffusion coefficient value of metastatic bone tumours on diffusion-weighted MRI images: differences according to the types of primary tumour, the affected bones, and clinical factors.

AIM: To evaluate whether the apparent diffusion coefficient (ADC) of metastatic bone tumours on diffusion-weighted magnetic resonance imaging (MRI) images differs according to the type of primary cancer, the affected bone, and clinical factors. MATERIALS AND METHODS: For this retrospective study, two radiologists reviewed MRI images, including ADC maps, of 67 patients (M:F=38:29; median age, 48 years) who were diagnosed with bone metastasis by means of histological or clinical confirmation. The primary tumours included 29 lung adenocarcinomas, 15 invasive ductal adenocarcinomas of the breast, 13 hepatocellular carcinomas, six prostatic carcinomas, and four renal cell carcinomas. ADC values of the metastatic tumour were compared according to the type of primary malignancy, the affected bone, and the age and sex of the patient using Kruskal-Wallis and Mann-Whitney U-tests with Bonferroni correction. In addition, pre-contrast CT images were available in 38 of 67 patients; a subanalysis of the CT radiodensity and ADC values were performed with Spearman correlation. RESULTS: The mean, standard deviation, and minimum and maximum values of the ADC of metastatic bone tumours did not differ significantly according to type of primary malignancy, the affected bone, or clinical variables (p>0.1). The ADC value was not significantly correlated with CT radiodensity (p=0.24). Intra- and interobserver agreements for the mean ADC values were excellent (intra-observer: p=0.98; interobserver: p=0.98). CONCLUSIONS: Assessment of the ADC value of metastatic bone tumours is not reliable for differentiation of the type of primary cancer.

CR6-interacting factor 1 is a key regulator in Aß-induced mitochondrial disruption and pathogenesis of Alzheimer's disease.

Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-ß (Aß), yet the pathways between Aß and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aß-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aß undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aß. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aß-treated cells. Conversely, Crif1 overexpression prevented Aß-induced mitochondrial dysfunction and cell death. Finally, we show that Aß-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aß-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD.

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice.

Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies.

Meigs' syndrome with elevated serum CA 125 level in a case of ovarian fibrothecoma.

Meigs' syndrome is the association of benign ovarian tumor, pleural effusion, and ascites. Meigs' syndrome with marked elevated CA 125 is a rare clinical entity and only 42 cases have been reported. Although there is difficulty in discerning the diagnosis of Meigs' syndrome from that of an ovarian malignancy, it should be considered in the differential diagnosis in postmenopausal patients with an ovarian mass, hydrothorax, ascites, and elevated CA 125. In this report, the authors present the case of a 52-year-old postmenopausal woman with ovarian fibrothecoma, pleural effusion, ascites, and elevated CA 125 (319.2 IU/ml). Exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy was performed, and the pathologic diagnosis was ovarian fibrothecoma. After the surgery, the pleural effusion disappeared spontaneously and the CA 125 became normal. The authors also summarized other cases of Meigs' syndrome with elevated CA 125, and reviewed the mechanism of elevation of CA 125, ascites, and pleural effusion.

The association between asymptomatic coronary artery disease and CHADS2 and CHA2 DS2 -VASc scores in patients with stroke.

BACKGROUND AND PURPOSE: CHADS2 and CHA2 DS2 -VASc scores are measurement tools that stratify thromboembolic risk in patients with non-valvular atrial fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and ischaemic heart disease. Patients with higher CHADS2 and CHA2 DS2 -VASc scores are more likely to have had an akinetic/hypokinetic left ventricular segment or a recent myocardial infarction, all of which are associated with coronary artery disease (CAD). Most of the CHADS2 score components are also risk factors for atherosclerosis. Thus, CHADS2 and CHA2 DS2 -VASc scores may be predictive of CAD. METHODS: In all, 1733 consecutive patients with acute ischaemic stroke who underwent multi-slice computed tomography coronary angiography were enrolled. The association of CHADS2 and CHA2 DS2 -VASc scores with the presence and severity of CAD was investigated. RESULTS: Of the 1733 patients, 1220 patients (70.4%) had any degree of CAD and 576 (33.3%) had significant CAD (≥ 50% stenosis in at least one coronary artery). As the CHADS2 and CHA2 DS2 -VASc scores increased, the presence of CAD also increased (P < 0.001). The severity of CAD was correlated with CHADS2 score (Spearman coefficient 0.229, P < 0.001) and CHA2 DS2 -VASc score (Spearman coefficient 0.261, P < 0.001). In multivariate analysis, after adjusting for confounding factors, CHADS2 and CHA2 DS2 -VASc scores ≥2 were independently associated with CAD. The CHA2 DS2 -VASc score was a better predictor of the presence of CAD than the CHADS2 score on area under the curve analysis. CONCLUSION: CHADS2 and CHA2 DS2 -VASc scores were predictive of the presence and severity of CAD in patients with stroke. When a patient has high CHADS2 or CHA2 DS2 -VASc scores, physicians should consider coronary artery evaluation.

Vitamin D-binding protein interacts with Aß and suppresses Aß-mediated pathology.

The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aß), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aß aggregation in vitro. DBP also prevented Aß-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aß-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aß into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aß by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.

Low ankle-brachial index is a predictive factor for initial severity of acute ischaemic stroke.

BACKGROUND: A low ankle-brachial index (ABI) is predictive of peripheral arterial disease (PAD). For unknown reasons, patients with PAD demonstrate higher vascular mortality during follow-up than do those without. Initial stroke severity is a strong predictor of long-term outcome and may be different between patients with and without PAD. Thus, we investigated whether a low ABI was associated with severe stroke presentation. METHODS: We enrolled 1147 first-ever ischaemic stroke patients who underwent ABI measurements during hospitalization. Patients were categorized into the normal (≥ 0.90) or the abnormal (<0.90) ABI group. Baseline characteristics and initial National Institutes of Health Stroke Scale (NIHSS) scores were compared between the groups. We further analysed components of the NIHSS subscales in these groups. RESULTS: Ankle-brachial index was abnormal in 85 (7.4%) patients. Mean initial NIHSS score was higher in the abnormal ABI group (6.61 ± 6.56) than in the normal ABI group (4.36 ± 4.90) (P = 0.003). A low ABI was independently associated with higher NIHSS score in a multivariate analysis. In the abnormal ABI group, leg weakness was more severe than it was in the normal ABI group, and the contribution of leg weakness to the initial NIHSS score was higher. CONCLUSIONS: Patients with low ABI values presented with more severe ischaemic stroke. Contribution of pre-existing PAD to leg weakness may play a role in the initial severity of stroke in patients with PAD. Our findings suggest that poor clinical outcomes in patients with PAD may be partially explained by their increased likelihood for severe stroke.

Use of a handheld, computerized device as a decision support tool for stroke classification.

BACKGROUND: The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification has been widely used to determine etiology of ischemic stroke. However, interrater reliability is known to be modest. The complexity of abstraction and the interpretation of various clinical and laboratory data might limit the accuracy of the TOAST classification. In this study, we developed a computerized clinical decision support system for stroke classification that can be used in a handheld device and tested whether this system can improve diagnostic accuracy and reliability. METHODS: Based on the TOAST classification, a logical algorithm was developed and implemented on a handheld device, named iTOAST. After answering six questions using the touch interface, the stroke subtype result is displayed on the screen. Four neurology residents were randomly assigned to classify stroke subtypes using iTOAST or the conventional method (cTOAST). Using a crossover design, they classified the stroke subtypes of 70 patients. The standard subtypes were determined by three stroke experts. Correlated kappa coefficients using iTOAST compared with cTOAST were determined. RESULTS: The kappa (SE) value of iTOAST [0.790 (0.041), 95% CI: 0.707-0.870] was higher than that of cTOAST [0.692 (0.046), 95% CI: 0.600-0.782] (P<0.001). Neither sequence (P=0.857) nor period effect (P=0.999) was observed. CONCLUSIONS: The stroke classification tool using a handheld, computerized device was easy, accurate, and reliable over the conventional method. It may have additional benefit because a handheld, computerized device is accessible anytime and anywhere.

Stroke mechanism in patients with non-valvular atrial fibrillation according to the CHADS2 and CHA2 DS2 -VASc scores.

BACKGROUND AND PURPOSE: The CHADS(2) and CHA(2) DS(2) -VASc scores are useful to stratify embolic risks in patients with non-valvular atrial fibrillation (NVAF) and to identify patients eligible for anticoagulation. Although the risk of stoke increases in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores, it is uncertain why the stroke rate increases in them. Concomitant potential cardiac sources of embolism (PCSE) may be more frequent in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores because stroke risks increase when concomitant PCSE is present in Atrial fibrillation (AF). On the other hand, atherothrombosis may be the cause when considering that most components of the CHADS(2) and CHA(2) DS(2) -VASc scores are risk factors for atherosclerosis. METHODS: Amongst 5493 stroke patients who were prospectively registered with the stroke registry for 11years, 860 consecutive patients with NVAF were included for this study. We investigated the mechanisms of stroke according to the CHADS(2) /CHA(2) DS(2) -VASc score in stroke patients with NVAF. RESULTS: Amongst 860 patients, concomitant PCSE were found in 334 patients (38.8%). The number of PCSE increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). Of individual PCSE, akinetic left ventricular segment, hypokinetic left ventricular segment and myocardial infarction <4weeks were associated with the CHADS(2) /CHA(2) DS(2) -VASc score. The presence of possible atherothrombotic mechanism, in addition to AF, was suggested in 27.3%. The proportion of patients with concomitant presence of possible atherothrombosis was increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). CONCLUSIONS: Increased frequency of concomitant PCSE and that of the atherothrombotic mechanism may explain the high risk of stroke in patients with higher CHADS(2) /CHA(2) DS(2) -VASc score.

Early neurological outcomes according to CHADS2 score in stroke patients with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: A higher CHADS(2) score or CHA(2)DS(2)-VASc score is associated with an increased risk of ischaemic stroke in patients with non-valvular atrial fibrillation (NVAF). However, there are no data regarding early neurological outcomes after stroke according to the risk levels. METHODS: In this study, a total of 649 stroke patients with NVAF were enrolled and categorized into three groups: low-risk (CHADS(2) score of 0-1), moderate-risk (CHADS(2) score 2-3), or high-risk group (CHADS(2) score ≥4). CHA(2)DS(2)-VASc score was divided into four groups including 0-1, 2-3, 4-5, and ≥6. We investigated whether there were differences in initial stroke severity, early neurological outcome, and infarct size according to CHADS(2) score or CHA(2)DS(2)-VASc score in stroke patients with NVAF. RESULTS: The initial National Institutes of Health Stroke Scale (NIHSS) score was highest in high-risk group [9.5, interquartile range (IQR) 4-18], followed by moderate-risk (8, IQR 2-17) and low-risk group (6, IQR 2-15) (P=0.012). Likewise, initial stroke severity increased in a positive fashion with increasing the CHA(2)DS(2)-VASc score. During hospitalization, those in the high-risk group or higher CHA(2)DS(2)-VASc score had less improvement in their NIHSS score. Furthermore, early neurological deterioration (END) developed more frequently as CHADS(2) score or CHA(2)DS(2)-VASc score increased. Multivariate analysis showed being in the high-risk group was independently associated with END (OR 2.129, 95% CI 1.013-4.477). CONCLUSIONS: Our data indicate that patients with NVAF and higher CHADS(2) score or CHA(2)DS(2)-VASc score are more likely to develop severe stroke and a worse clinical course is expected in these patients after stroke presentation.

Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the potential for manipulation of their connective tissue turnover.

Epinephrine-induced MMP expression is different between skeletal fibroblasts and myoblasts.

Skeletal fibroblasts and myoblasts are among the cell types currently being considered in cell therapy for ischaemic heart disease. To investigate whether the expression of the tissue-remodelling proteolytic enzymes matrix metalloproteinases (MMPs) and the cellular energy regulator AMP-activated protein kinase (AMPK) is comparable between the two cell lines in response to epinephrine treatment, mouse skeletal fibroblasts (NOR-10) and myoblasts (C2C12) were treated with or without a low (11 nmol·l(-1) ) or high (55 nmol·l(-1) ) dose of epinephrine for 2 or 6 h. Cellular MMP-3 expression was increased by the high-dose epinephrine at both treatment periods in both cell lines. Cellular MMP-2 and MMP-13 expressions were amplified by the 2- or 6-h epinephrine incubation in fibroblasts. However, in myoblasts, such an increase was only seen at the longer treatment time. An elevated AMPKα expression was observed after a 2-h presence of epinephrine in both cell lines, which matches temporally with the early increased cellular MMP-2 and MMP-13 expression in fibroblasts. Activity of secreted MMP-2 increased only after 6-h epinephrine treatment in both cell types. Our data suggest that skeletal fibroblasts respond earlier to epinephrine application in terms of endogenous synthesis of the proteolytic and the energy homeostasis enzymes, whereas such response occurs later and to a milder dose of the beta adrenergic agonist in myoblasts.