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 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}.
An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting ...of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.
Summary
Background
Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify ...the pathogenesis of asthma by systemic review.
Objective
We applied a 1H‐NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers.
Method
A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H‐NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target‐profiling procedure.
Results
Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O‐phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects).
Conclusion & Clinical Relevance
These data showed that 1H‐NMR‐based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.
This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy.
An open, randomized, comparative study was conducted. ...Subjects with painful symmetric neuropathy in the lower limbs and mean pain-intensity score > or = 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36-item Short Form Health Survey, average pain intensity and sleep disturbance.
One hundred and sixty-three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 +/- 1.6; gabapentin 6.3 +/- 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A -3.1 +/- 2.0; gabapentin -2.7 +/- 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores.
This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
Summary
What is known and objective
Higher rate of statin‐related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin‐related aminotransferase elevation for those who ...show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated.
Methods
Post‐statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin‐related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors.
Results and discussion
The progression rate to abnormal AST/ALT values >×3 the upper normal limit (UNL) was significantly higher (2·4–16% vs. 0·3–1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study.
What is new and conclusion
It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.
The progression rate to abnormal AST/ALT values (>×3 the UNL) was significantly higher in subjects with borderline (>×1, but ≤ ×3 of UNL) compared to normal AST/ALT values at baseline. It is advisable to regularly monitor AST/ALT levels in patients with AST/ALT increases >×1, but ≤×3 of UNL.
Background
Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM ...patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns.
Methods
A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K‐means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State‐Trait Anxiety Inventor and Social Support Scale.
Results
Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome.
Conclusions
We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms.
Significance
FM patients can be clustered into four distinct subgroups based on clinically measurable variables – pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.
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