Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
The Reactor Experiment for Neutrino Oscillation (RENO) has been taking electron antineutrino (ν¯e) data from the reactors in Yonggwang, Korea, using two identical detectors since August 2011. Using ...roughly 500 live days of data through January 2013 we observe 290 775 (31 514) reactor ν¯e candidate events with 2.8% (4.9%) background in the near (far) detector. The observed visible positron spectra from the reactor ν¯e events in both detectors show a discrepancy around 5 MeV with regard to the prediction from the current reactor ν¯e model. Based on a far-to-near ratio measurement using the spectral and rate information, we have obtained sin22θ13=0.082±0.009(stat.)±0.006(syst.) and |Δmee2|=2.62−0.23+0.21(stat.)−0.13+0.12(syst.)×10−3 eV2.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
To determine the immediate and long-term therapeutic efficacies of Gufoni and head-shaking maneuvers in apogeotropic type of benign paroxysmal positional vertigo involving the horizontal semicircular ...canal (HC-BPPV), a randomized, prospective, sham-controlled study was conducted.
In 10 nationwide dizziness clinics in Korea, 157 consecutive patients (95 women, age range: 18-89 years, mean age ± SD = 59.9 ± 13.6) with apogeotropic HC-BPPV were randomized to Gufoni (n = 52), head-shaking (n = 54), or sham maneuver (n = 51). For Gufoni maneuver, patients underwent ipsilesional side-lying and upward head-turn for migration of the debris toward the vestibule. Immediate responses were determined within 1 hour after a maximum of 2 trials of each maneuver and in the following day. The patients also had weekly follow-ups for 1 month after the initial maneuver.
After a maximum of 2 maneuvers on the initial visit day, Gufoni (38/52, 73.1%) and head-shaking (33/53, 62.3%) maneuvers showed better responses than the sham maneuver (17/49, 34.7%). The cumulative therapeutic effects were also better with Gufoni (p < 0.001) and head-shaking (p = 0.026) maneuvers compared with the sham maneuver. However, therapeutic efficacies did not differ between the Gufoni and head-shaking groups in terms of both immediate (p = 0.129) and long-term (p = 0.239) outcomes.
Using a prospective randomized trial, we demonstrated that the Gufoni and head-shaking maneuvers are effective in treating apogeotropic HC-BPPV.
This study provides Class II evidence that Gufoni and head-shaking maneuvers are effective in treating apogeotropic horizontal BPPV up to 1 month after initial treatment.
NCT00810641.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
(
) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate
promoter methylation status changes with DWI and DSC PWI ...features in patients with recurrent glioblastoma after standard treatment.
Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the
promoter methylation status for the initial and recurrent tumors: 2 groups whose
promoter methylation status remained, group methylated (
= 13) or group unmethylated (
= 18), and 1 group whose
promoter methylation status changed from methylated to unmethylated (
= 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The
test and Mann-Whitney
test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups.
Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all
< .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (
< .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594.
promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the
promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.
MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18–22 nucleotides) have received little ...attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.
The usefulness of pharmacokinetic parameters for glioma grading has been reported based on the perfusion data from parts of entire-tumor volumes. However, the perfusion values may not reflect the ...entire-tumor characteristics. Our aim was to investigate the feasibility of glioma grading by using histogram analyses of pharmacokinetic parameters including the volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue from T1-weighted dynamic contrast-enhanced perfusion MR imaging.
Twenty-eight patients (14 men, 14 women; mean age, 49.75 years; age range, 25-72 years) with histopathologically confirmed gliomas (World Health Organization grade II, n = 7; grade III, n = 8; grade IV, n = 13) were examined before surgery or biopsy with conventional MR imaging and T1-weighted dynamic contrast-enhanced perfusion MR imaging at 3T. Volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue were calculated from the entire-tumor volume. Histogram analyses from these parameters were correlated with glioma grades. The parameters with the best percentile from cumulative histograms were identified by analysis of the area under the curve of the receiver operating characteristic analysis and were compared by using multivariable stepwise logistic regression analysis for distinguishing high- from low-grade gliomas.
All parametric values increased with increasing glioma grade. There were significant differences among the 3 grades in all parameters (P < .01). For the differentiation of high- and low-grade gliomas, the highest area under the curve values were found at the 98th percentile of the volume transfer constant (area under the curve, 0.912; cutoff value, 0.277), the 90th percentile of extravascular extracellular space volume per unit volume of tissue (area under the curve, 0.939; cutoff value, 19.70), and the 84th percentile of blood plasma volume per unit volume of tissue (area under the curve, 0.769; cutoff value, 11.71). The 98th percentile volume transfer constant value was the only variable that could be used to independently differentiate high- and low-grade gliomas in multivariable stepwise logistic regression analysis.
Histogram analysis of pharmacokinetic parameters from whole-tumor volume data can be a useful method for glioma grading. The 98th percentile value of the volume transfer constant was the most significant measure.
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