Uncoupling Protein-2 Mediates DPP-4 Inhibitor-Induced Restoration of Endothelial Function in Hypertension Through Reducing Oxidative Stress

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Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

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Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats

Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.published_or_final_versio

Rectification of electronic heat current by a hybrid thermal diode

We report the realization of an ultra-efficient low-temperature hybrid heat current rectifier, thermal counterpart of the well-known electric diode. Our design is based on a tunnel junction between two different elements: a normal metal and a superconducting island. Electronic heat current asymmetry in the structure arises from large mismatch between the thermal properties of these two. We demonstrate experimentally temperature differences exceeding $60$ mK between the forward and reverse thermal bias configurations. Our device offers a remarkably large heat rectification ratio up to $\sim 140$ and allows its prompt implementation in true solid-state thermal nanocircuits and general-purpose electronic applications requiring energy harvesting or thermal management and isolation at the nanoscale.Comment: 8 pages, 6 color figure

Accuracy of magnetic resonance studies in the detection of chondral and labral lesions in femoroacetabular impingement : systematic review and meta-analysis

Background: Several types of Magnetic resonance imaging (MRI) are commonly used in imaging of femoroacetabular impingement (FAI), however till now there are no clear protocols and recommendations for each type. The aim of this meta-analysis is to detect the accuracy of conventional magnetic resonance imaging (cMRI), direct magnetic resonance arthrography (dMRA) and indirect magnetic resonance arthrography (iMRA) in the diagnosis of chondral and labral lesions in femoroacetabular impingement (FAI). Methods: A literature search was finalized on the 17th of May 2016 to collect all studies identifying the accuracy of cMRI, dMRA and iMRA in diagnosing chondral and labral lesions associated with FAI using surgical results (arthroscopic or open) as a reference test. Pooled sensitivity and specificity with 95% confidence intervals using a random-effects meta-analysis for MRI, dMRA and iMRA were calculated also area under receiver operating characteristic (ROC) curve (AUC) was retrieved whenever possible where AUC is equivocal to diagnostic accuracy. Results: The search yielded 192 publications which were reviewed according inclusion and exclusion criteria then 21 studies fulfilled the eligibility criteria for the qualitative analysis with a total number of 828 cases, lastly 12 studies were included in the quantitative meta-analysis. Meta-analysis showed that as regard labral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.864, 0.833 and 0.88 and for dMRA were 0.91, 0.58 and 0.92. While in chondral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.76, 0.72 and 0.75 and for dMRA were 0.75, 0.79 and 0.83, while for iMRA were sensitivity of 0.722 and specificity of 0.917. Conclusions: The present meta-analysis showed that the diagnostic test accuracy was superior for dMRA when compared with cMRI for detection of labral and chondral lesions. The diagnostic test accuracy was superior for labral lesions when compared with chondral lesions in both cMRI and dMRA. Promising results are obtained concerning iMRA but further studies still needed to fully assess its diagnostic accuracy

The addition of a pH-sensitive gel improves microemulsion stability for the targeted removal of colonic ammonia

<p>Abstract</p> <p>Background</p> <p>We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA).</p> <p>Methods</p> <p>MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA.</p> <p>Results</p> <p>MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine.</p> <p>Conclusions</p> <p>MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.</p

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

A new context-based method for restoring occluded text in natural scene images

Text recognition from natural scene images is an active research area because of its important real world applications, including multimedia search and retrieval, and scene understanding through computer vision. It is often the case that portions of text in images are missed due to occlusion with objects in the background. Therefore, this paper presents a method for restoring occluded text to improve text recognition performance. The proposed method uses the GOOGLE Vision API for obtaining labels for input images. We propose to use PixelLink-E2E methods for detecting text and obtaining recognition results. Using these results, the proposed method generates candidate words based on distance measures employing lexicons created through natural scene text recognition. We extract the semantic similarity between labels and recognition results, which results in a Global Context Score (GCS). Next, we use the Natural Language Processing (NLP) system known as BERT for extracting semantics between candidate words, which results in a Local Context Score (LCS). Global and local context scores are then fused for estimating the ranking for each candidate word. The word that gets the highest ranking is taken as the correction for text which is occluded in the image. Experimental results on a dataset assembled from standard natural scene datasets and our resources show that our approach helps to improve the text recognition performance significantly

Comparative reliability and diagnostic performance of conventional 3T magnetic resonance imaging and 1.5T magnetic resonance arthrography for the evaluation of internal derangement of the hip

Objective; To compare the diagnostic accuracy of conventional 3T MRI against 1.5T MR arthrography (MRA) in patients with clinical femoroacetabular impingement (FAI). Methods; Sixty-eight consecutive patients with clinical FAI underwent both 1.5T MRA and 3T MRI. Imaging was prospectively analysed by two musculoskeletal radiologists, blinded to patient outcomes and scored for internal derangement including labral and cartilage abnormality. Interobserver variation was assessed by kappa analysis. Thirty-nine patients subsequently underwent hip arthroscopy and surgical results and radiology findings were analysed. Results; Both readers had higher sensitivities for detecting labral tears with 3T MRI compared to 1.5T MRA (not statistically significant p=0.07). For acetabular cartilage defect both readers had higher statistically significant sensitivities using 3T MRI compared to 1.5T MRA (p=0.02). Both readers had a slightly higher sensitivity for detecting delamination with 1.5T MRA compared to 3T MRI, but these differences were not statistically significant (p=0.66). Interobserver agreement was substantial to perfect agreement for all parameters except the identification of delamination (3T MRI showed moderate agreement and 1.5T MRA substantial agreement). Conclusion; Conventional 3T MRI may be at least equivalent to 1.5T MRA in detecting acetabular labrum and possibly superior to 1.5T MRA in detecting cartilage defects in patients with suspected FAI

Effects of Macromolecular Crowding on Protein Conformational Changes

Many protein functions can be directly linked to conformational changes. Inside cells, the equilibria and transition rates between different conformations may be affected by macromolecular crowding. We have recently developed a new approach for modeling crowding effects, which enables an atomistic representation of “test” proteins. Here this approach is applied to study how crowding affects the equilibria and transition rates between open and closed conformations of seven proteins: yeast protein disulfide isomerase (yPDI), adenylate kinase (AdK), orotidine phosphate decarboxylase (ODCase), Trp repressor (TrpR), hemoglobin, DNA β-glucosyltransferase, and Ap4A hydrolase. For each protein, molecular dynamics simulations of the open and closed states are separately run. Representative open and closed conformations are then used to calculate the crowding-induced changes in chemical potential for the two states. The difference in chemical-potential change between the two states finally predicts the effects of crowding on the population ratio of the two states. Crowding is found to reduce the open population to various extents. In the presence of crowders with a 15 Å radius and occupying 35% of volume, the open-to-closed population ratios of yPDI, AdK, ODCase and TrpR are reduced by 79%, 78%, 62% and 55%, respectively. The reductions for the remaining three proteins are 20–44%. As expected, the four proteins experiencing the stronger crowding effects are those with larger conformational changes between open and closed states (e.g., as measured by the change in radius of gyration). Larger proteins also tend to experience stronger crowding effects than smaller ones [e.g., comparing yPDI (480 residues) and TrpR (98 residues)]. The potentials of mean force along the open-closed reaction coordinate of apo and ligand-bound ODCase are altered by crowding, suggesting that transition rates are also affected. These quantitative results and qualitative trends will serve as valuable guides for expected crowding effects on protein conformation changes inside cells