Background and purpose
Studies on cortical involvement and its relationship with cognitive function in patients with neuromyelitis optica spectrum disorder (NMOSD) remain scarce. The objective of ...this study was to compare cortical thickness on magnetic resonance imaging (MRI) between patients with NMOSD and multiple sclerosis (MS) and to investigate its relationship with clinical features and cognitive function.
Methods
This observational clinical imaging study of 91 patients with NMOSD, 52 patients with MS and 44 healthy controls was conducted from 1 December 2013 to 30 April 2015 at the institutional referral center. Three tesla MRI of the brain and neuropsychological tests were performed. Cortical thickness was measured using three‐dimensional surface‐based analysis.
Results
Both sets of patients exhibited cortical thinning throughout the entire brain cortex. Patients with MS showed a significantly greater reduction in cortical thickness over broad regions of the bilateral frontal and parieto‐temporal cortices and the left precuneus compared to those with NMOSD. Memory functions in patients with MS were correlated with broad regional cortical thinning, whereas no significant associations were observed between cortical thickness and cognitive function in patients with NMOSD.
Conclusions
Widespread cortical thinning was observed in patients with NMOSD and MS, but the extent of cortical thinning was greater in patients with MS. The more severe cortical atrophy may contribute to memory impairment in patients with MS but not in those with NMOSD. These results provide in vivo evidence that the severity and clinical relevance of cortical thinning differ between NMOSD and MS.
The topotactic phase transition in SrCoO
(x = 2.5-3.0) makes it possible to reversibly transit between the two distinct phases, i.e. the brownmillerite SrCoO
that is a room-temperature ...antiferromagnetic insulator (AFM-I) and the perovskite SrCoO
that is a ferromagnetic metal (FM-M), owing to their multiple valence states. For the intermediate x values, the two distinct phases are expected to strongly compete with each other. With oxidation of SrCoO
, however, it has been conjectured that the magnetic transition is decoupled to the electronic phase transition, i.e., the AFM-to-FM transition occurs before the insulator-to-metal transition (IMT), which is still controversial. Here, we bridge the gap between the two-phase transitions by density-functional theory calculations combined with optical spectroscopy. We confirm that the IMT actually occurs concomitantly with the FM transition near the oxygen content x = 2.75. Strong charge-spin coupling drives the concurrent IMT and AFM-to-FM transition, which fosters the near room-T magnetic transition characteristic. Ultimately, our study demonstrates that SrCoO
is an intriguingly rare candidate for inducing coupled magnetic and electronic transition via fast and reversible redox reactions.
Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC).
Eligibility criteria included advanced nccRCC except ...for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR).
Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3–19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2–8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7–23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4–42.9 months). Toxicity profiles were commensurate with prior reports.
Sunitinib has promising activity in patients with nccRCC (NCT01219751).
Summary
The wide geographic spread of Eurasian Goose/Guangdong lineage highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses by wild birds is of great concern. In December 2014, an H5N8 HPAI ...clade 2.3.4.4 Group A (2.3.4.4A) virus was introduced to North America. Long‐distance migratory wild aquatic birds between East Asia and North America, such as Northern Pintail (Anas acuta), were strongly suspected of being a source of intercontinental transmission. In this study, we evaluated the pathogenicity, infectivity and transmissibility of an H5N8 HPAI clade 2.3.4.4A virus in Northern Pintails and compared the results to that of an H5N1 HPAI clade 2.3.2.1 virus. All of Northern Pintails infected with either H5N1 or H5N8 virus lacked clinical signs and mortality, but the H5N8 clade 2.3.4.4 virus was more efficient at replicating within and transmitting between Northern Pintails than the H5N1 clade 2.3.2.1 virus. The H5N8‐infected birds shed high titre of viruses from oropharynx and cloaca, which in the field supported virus transmission and spread. This study highlights the role of wild waterfowl in the intercontinental spread of some HPAI viruses. Migratory aquatic birds should be carefully monitored for the early detection of H5 clade 2.3.4.4 and other HPAI viruses.
A
bstract
The Reactor Experiment for Neutrino Oscillation (RENO) experiment has been taking data using two identical liquid scintillator detectors since August 2011. The experiment has observed the ...disappearance of reactor neutrinos in their interactions with free protons, followed by neutron capture on hydrogen (n-H). Based on 1500 live days of data taken with 16.8 GW
th
reactors at the Hanbit Nuclear Power Plant in Korea, the near (far) detector observes 567690 (90747) electron antineutrino candidate events with the n-H data. This provides an independent measurement of neutrino mixing angle
θ
13
and a consistency check on the validity of the result obtained from the data with neutron capture on Gadolinium (n-Gd). Furthermore, it provides an important cross-check on the systematic uncertainties of the n-Gd measurement. Based on a rate-only analysis, we obtain sin
2
2
θ
13
= 0
.
086 ± 0
.
008(stat
.
) ± 0
.
014(syst
.
). The combination of this result with that of n-Gd is also reported.
The spatiotemporal variations of surface air pollutants (O3, NO2, SO2, CO, and PM10) with four land-use types, residence (R), commerce (C), industry (I) and greenbelt (G), have been investigated at ...283 stations in South Korea during 2002-2013, using routinely observed data. The volatile organic compound (VOC) data at nine photochemical pollutant monitoring stations available since 2007 were utilized in order to examine their effect on the ozone chemistry. The land-use types, set by the Korean government, were generally consistent with the satellite-derived land covers and with the previous result showing anti-correlation between O3 and NO2 in diverse urban areas. The relationship between the two pollutants in the Seoul Metropolitan Area (SMA) residence land-use areas was substantially different from that outside of the SMA, probably due to the local differences in vehicle emissions. The highest concentrations of air pollutants in the diurnal, weekly, and annual cycles were found in industry for SO2 and PMPM10, in commerce for NO2 and CO, and in greenbelt for O3. The concentrations of air pollutants, except for O3, were generally higher in big cities during weekdays, while O3 showed its peak in suburban areas or small cities during weekends. The weekly cycle and trends of O3 were significantly out of phase with those of NO2, particularly in the residential and commercial areas, suggesting that vehicle emission was a major source in those areas. The ratios of VOCs to NO2 for each of the land-use types were in the order of I (10.2) > C (8.7) > G (3.9) > R (3.6), suggesting that most areas in South Korea were likely to be VOC-limited for ozone chemistry. The pollutants (NO2, SO2, CO, and PMPM10 except for O3 have decreased, most likely due to the effective government control. The total oxidant values (OX = O3 + NO2) with the land-use types were analyzed for the local and regional (or background) contributions of O3, respectively, and the order of OX (ppb) was C (57.4) > R (53.6) > I (50.7) > G (45.4), indicating the greenbelt observation was close to the background.
Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer ...metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased β-catenin expression at the post-translational level through induction of MUC1, which was physically associated with β-catenin. Indeed, the association between β-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of β-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through β-catenin stabilization.
Summary
Background
Nasal polyposis is a multi‐factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) ...accumulation are involved in the pathogenesis of nasal polyposis.
Objective
The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)‐β1‐induced myofibroblast differentiation and ECM accumulation in nasal polyp‐derived fibroblasts (NPDFs).
Methods
Nasal polyp‐derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF‐β1‐induced NPDFs. Expression levels of HDAC2, α‐smooth muscle actin (SMA), TGF‐β1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT‐PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT‐PCR and western blot. The epigenetic effect on α‐SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67‐positive cell staining and cytotoxicity was assessed by 3‐(4,5‐ dimethylthiazol‐2yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay.
Results
The expression levels of HDAC2, α‐SMA and TGF‐β1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α‐SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α‐SMA gene promoter in TGF‐β1‐induced NPDFs. TSA inhibited TGF‐β1‐induced Smad 2/3 and rescued TGF‐β1‐suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF‐β1‐induced NPDFs and has no cytotoxic effect in NPDFs.
Conclusions and Clinical Relevance
These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.
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