Although surgical resection has been an important alternative treatment for patients with intractable epilepsy related to focal cortical dysplasia (FCD), the prognostic relevance of the degree of ...pathologic severity is controversial and there has been only limited information regarding the prognostic factors involved in the surgical treatment of refractory epilepsy in patients with FCD.
We undertook the present study to assess whether the pathologic subtypes of FCD affect surgical outcomes in patients with drug-resistant epilepsy. We also studied the prognostic roles of clinical factors and various diagnostic modalities in the surgical treatment.
A total of 166 consecutive patients were included. By univariate analysis, incomplete resection of epileptogenic area (p < 0.001), mild pathologic features (p = 0.01), and the presence of secondary tonic clonic seizures (2GTCS) (p = 0.05) were associated with poor surgical outcomes. There was a strong tendency for patients with severe pathologic features to have MRI abnormalities (p < 0.001). Incomplete resection of epileptogenic area (p < 0.001) and mild pathologic features (p = 0.02) were poor independent outcome predictors on multivariate analysis. The results of MRI, scalp EEG, fluorodeoxyglucose-PET, and ictal SPECT were not associated with surgical outcomes.
Our study shows that there is a strong tendency for patients with severe pathologic features to have MRI abnormalities, and patients with incomplete resection, mild pathologic features, or the presence of secondary tonic clonic seizures have a high chance of a poorer surgical outcome.
Aims
We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin‐mediated activation of endothelial nitric oxide synthase (eNOS) and angiogenesis.
...Methods
Fluo‐8 NW assay was for Ca2+ detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis.
Results
In endothelial cells (ECs), treatment with simvastatin time‐dependently increased intracellular level of Ca2+. Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin‐mediated elevation of intracellular Ca2+ in ECs or TRPV1‐transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin‐induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin‐elicited increase in the formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex. In mice, Matrigel plug assay showed that simvastatin‐evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin‐activated TRPV1‐Ca2+ signalling and in the consequent NO production and angiogenesis as evidence by that re‐expression of TRPA1 further augmented simvastatin‐elicited Ca2+ influx in TRPV1‐expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin‐induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice.
Conclusion
Simvastatin‐induced Ca2+ influx may through the activation of TRPV1–TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1–CaMKII–AMPK–eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs.
Aims/hypothesis We recently reported associations of some persistent organic pollutants (POPs) with both prevalence of type 2 diabetes and insulin resistance in a US population with background ...exposure to POPs. Restricted to non-diabetic participants, we now investigate the relationship between POPs and the metabolic syndrome, a prediabetic state. Materials and methods Cross-sectional associations were investigated in 721 non-diabetic participants aged >=20 years. Nineteen POPs in five subclasses were selected because they were detectable in >=60% of participants. Results Among five POPs subclasses, organochlorine (OC) pesticides were most strongly and consistently associated with metabolic syndrome: adjusted odds ratios (ORs) of 1.0, 1.5, 2.3 and 5.3 across OC pesticide quartiles (p for trend <0.01). Dioxin-like polychlorinated biphenyls (PCBs) were also positively associated with adjusted ORs of 1.0, 1.1, 2.2 and 2.1 (p for trend = 0.01). However, non-dioxin-like PCBs showed an inverted U-shaped association with adjusted ORs of 1.0, 1.3, 1.8 and 1.0 (p for quadratic term <0.01). Associations of specific POPs varied across five components of the metabolic syndrome. OC pesticides were positively and significantly associated with four of the five components, especially elevated triacylglycerol and high fasting glucose, but not high blood pressure. PCBs were significantly associated with waist circumference, triacylglycerol and impaired fasting glucose. Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans showed small but significant associations only with high blood pressure. Conclusions/interpretation This study suggests that the prevalence of a cluster of cardiovascular risk factors relates to background exposure to a mixture of POPs, several of which are also related to the prevalence of diabetes. POPs associated differentially with different components of the metabolic syndrome.
Extratropical cyclones are identified and compared using data from four recent reanalyses for the winter periods in both hemispheres. Results show the largest differences occur between the older ...lower resolution 25-yr Japanese Reanalysis (JRA-25) when compared with the newer high resolution reanalyses, particularly in the Southern Hemisphere (SH). Spatial differences between the newest reanalyses are small in both hemispheres and generally not significant except in some common regions associated with cyclogenesis close to orography. Differences in the cyclone maximum intensitites are generally related to spatial resolution except in the NASA Modern Era Retrospective-Analysis for Research and Applications (NASA MERRA), which has larger intensities for several different measures. Matching storms between reanalyses shows the number matched between the ECMWF Interim Re-Analysis (ERA-Interim) and the other reanalyses is similar in the Northern Hemisphere (NH). In the SH the number matched between JRA-25 and ERA-Interim is lower than in the NH; however, for NASA MERRA and the NCEP Climate Forecast System Reanalysis (NCEP CFSR), the number matched is similar to the NH. The mean separation of the identically same cyclones is typically less than 2° geodesic in both hemispheres for the latest reanalyses, whereas JRA-25 compared with the other reanalyses has a broader distribution in the SH, indicating greater uncertainty. The instantaneous intensity differences for matched storms shows narrow distributions for pressure, while for winds and vorticity the distributions are much broader, indicating larger uncertainty typical of smaller-scale fields. Composite cyclone diagnostics show that cyclones are very similar between the reanalyses, with differences being related to the intensities, consistent with the intensity results. Overall, results show NH cyclones correspond well between reanalyses, with a significant improvement in the SH for the latest reanalyses, indicating a convergence between reanalyses for cyclone properties.
Aim
To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)‐induced insulin‐deficient mice (STZ mice).
Methods
...Nine‐week‐old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.
Results
The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.
Conclusions
Our results show that LY2405319 reduces blood glucose levels in insulin‐deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.
We study the robustness properties of multiplex networks consisting of multiple layers of distinct types of links, focusing on the role of correlations between degrees of a node in different layers. ...We use generating function formalism to address various notions of the network robustness relevant to multiplex networks, such as the resilience of ordinary and mutual connectivity under random or targeted node removals, as well as the biconnectivity. We found that correlated coupling can affect the structural robustness of multiplex networks in diverse fashion. For example, for maximally correlated duplex networks, all pairs of nodes in the giant component are connected via at least two independent paths and network structure is highly resilient to random failure. In contrast, anticorrelated duplex networks are on one hand robust against targeted attack on high-degree nodes, but on the other hand they can be vulnerable to random failure.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
Abstract
Background
In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be ...improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes.
Methods
Patients with low cT3–4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response.
Results
More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease.
Conclusion
Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.
Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.
This multicentre retrospective cohort study, including 1216 patients with low cT3–4 rectal cancer, demonstrated that internal iliac lateral lymph node enlargement is associated with an increased rate of lateral local recurrence, whereas obturator nodes are associated with more advanced disease resulting in increased distant metastasis and reduced cancer-specific survival rates. Lateral lymph node dissection improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.
We conducted a 24‐week, multicentre, double‐blind, randomized study with a 28‐week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add‐on to metformin in patients ...with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were −0.85 ± 0.70% (p < 0.0001) for anagliptin and −0.83 ± 0.61% (p < 0.0001) for sitagliptin, with a mean difference of −0.02% (95% confidence interval of difference, −0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non‐inferiority of the efficacy of anagliptin to sitagliptin as an add‐on therapy was established with regard to efficacy and safety.
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