Uric acid and the cardio-renal effects of SGLT2 inhibitors

Sodium/glucose co‐transporter‐2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed in part to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo‐glomerular functions as well as reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardio‐renal risk. Chronically raised circulating uric acid concentrations are associated with increased risk of hypertension, CV disease and chronic kidney disease (CKD). The extent to which uric acid contributes to these conditions either as a cause or aggravating factor remains unclear, but interventions that reduce urate production or increase urate excretion in hyperuricaemic patients have consistently improved cardio‐renal prognoses. Uric acid concentrations are often raised in type 2 diabetes, contributing to the ‘metabolic syndrome’ of CV risk. Treating type 2 diabetes with an SGLT2 inhibitor increases uric acid excretion, reduces circulating uric acid and improves parameters of CV and renal function. This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes. SGLT2 inhibition might also be useful in the treatment of gout and gouty arthritis, especially when co‐existent with diabetes

Personality Factors Predicting Smartphone Addiction Predisposition: Behavioral Inhibition and Activation Systems, Impulsivity, and Self-control

The purpose of this study was to identify personality factor-associated predictors of smartphone addiction predisposition (SAP). Participants were 2,573 men and 2,281 women (n = 4,854) aged 20-49 years (Mean +/- SD: 33.47 +/- 7.52); participants completed the following questionnaires: the Korean Smartphone Addiction Proneness Scale (K-SAPS) for adults, the Behavioral Inhibition System/Behavioral Activation System questionnaire (BIS/BAS), the Dickman Dysfunctional Impulsivity Instrument (DDII), and the Brief Self-Control Scale (BSCS). In addition, participants reported their demographic information and smartphone usage pattern (weekday or weekend average usage hours and main use). We analyzed the data in three steps: (1) identifying predictors with logistic regression, (2) deriving causal relationships between SAP and its predictors using a Bayesian belief network (BN), and (3) computing optimal cut-off points for the identified predictors using the Youden index. Identified predictors of SAP were as follows: gender (female), weekend average usage hours, and scores on BAS-Drive, BAS-Reward Responsiveness, DDII, and BSCS. Female gender and scores on BAS-Drive and BSCS directly increased SAP. BAS-Reward Responsiveness and DDII indirectly increased SAP. We found that SAP was defined with maximal sensitivity as follows: weekend average usage hours > 4.45, BAS-Drive > 10.0, BAS-Reward Responsiveness > 13.8, DDII > 4.5, and BSCS > 37.4. This study raises the possibility that personality factors contribute to SAP. And, we calculated cut-off points for key predictors. These findings may assist clinicians screening for SAP using cut-off points, and further the understanding of SA risk factors.111413Ysciescopu

Is lymphovascular invasion a powerful predictor for biochemical recurrence in pT3 N0 prostate cancer?: Results from the K-CaP database

To assess the impact of lymphovascular invasion (LVI) on the risk of biochemical recurrence (BCR) in pT3 N0 prostate cancer, clinical data were extracted from 1,622 patients with pT3 N0 prostate cancer from the K-CaP database. Patients with neoadjuvant androgen deprivation therapy (n = 325) or insufficient pathologic or follow-up data (n = 87) were excluded. The primary endpoint was the oncologic importance of LVI, and the secondary endpoint was the hierarchical relationships for estimating BCR between the evaluated variables. LVI was noted in 260 patients (21.5%) and was significantly associated with other adverse clinicopathologic features. In the multivariate Cox regression analysis, LVI was significantly associated with an increased risk of BCR after adjusting for known prognostic factors. In the Bayesian belief network analysis, LVI and pathologic Gleason score were found to be first-degree associates of BCR, whereas prostate-specific antigen (PSA) level, seminal vesicle invasion, perineural invasion, and high-grade prostatic intraepithelial neoplasia were considered second-degree associates. In the random survival forest, pathologic Gleason score, LVI, and PSA level were three most important variables in determining BCR of patients with pT3 N0 prostate cancer. In conclusion, LVI is one of the most powerful adverse prognostic factors for BCR in patients with pT3 N0 prostate cancer.1132Ysciescopu

C5 Extract Induces Apoptosis in B16F10 Murine Melanoma Cells through Extrinsic and Intrinsic Apoptotic Pathways and Sub-G1 Phase Arrest

Purpose: To investigate the anti-cancer activities of C5 extract (C5E), a new herbal preparation from Korea, on B16F10 cells.Methods: The anti-proliferative effects of C5E were assessed by culturing B16F10 cells in the presence or absence of C5E. Cell cycle progression was analyzed by PI staining using flow cytometry. The quantities of apoptosis-inducing proteins were measured by Western blot.Results: C5E inhibited the proliferation of B16F10 cells but not human keratinocytes. C5E induced S phase arrest by interfering with cell regulatory factors such as cyclins B1, D1, D3, and E, and cyclindependent kinase 2, in B16F10 cells. Furthermore, immunoblot analysis confirmed that treatment with C5E induced apoptosis and cleaved caspase-3, poly (ADP-ribose) polymerase, via extrinsic pathway, whereas Bcl-2 expression was down-regulated. In addition, the suppression of cell proliferation by C5E is through down-regulation of p-Akt, up-regulation of phosphatase and tensin homolog protein expression via phosphoinositol 3 kinase survival signaling pathways in B16F10 cells. The combined cytotoxic effects of C5E and vinblastine generated 10 % increase in activity in contrast to the sum of the inhibitory effects of the individual agents.Conclusion: C5E shows promising anti-cancer activity and can be a useful adjuvant with vinblastine in combination therapeutic treatment of skin cancer.Keywords: Melanoma, Apoptosis, Anti-cancer, p53, Vinblastine, Cell cycle arrest, Caspas

Accessibility-based reranking in multimedia search engines

Traditional multimedia search engines retrieve results based mostly on the query submitted by the user, or using a log of previous searches to provide personalized results, while not considering the accessibility of the results for users with vision or other types of impairments. In this paper, a novel approach is presented which incorporates the accessibility of images for users with various vision impairments, such as color blindness, cataract and glaucoma, in order to rerank the results of an image search engine. The accessibility of individual images is measured through the use of vision simulation filters. Multi-objective optimization techniques utilizing the image accessibility scores are used to handle users with multiple vision impairments, while the impairment profile of a specific user is used to select one from the Pareto-optimal solutions. The proposed approach has been tested with two image datasets, using both simulated and real impaired users, and the results verify its applicability. Although the proposed method has been used for vision accessibility-based reranking, it can also be extended for other types of personalization context

Unassisted photoelectrochemical water splitting exceeding 7% solar to hydrogen conversion efficiency using photon recycling

Various tandem cell configurations have been reported for highly efficient and spontaneous hydrogen production from photoelectrochemical solar water splitting. However, there is a contradiction between two main requirements of a front photoelectrode in a tandem cell configuration, namely, high transparency and high photocurrent density. Here we demonstrate a simple yet highly effective method to overcome this contradiction by incorporating a hybrid conductive distributed Bragg reflector on the back side of the transparent conducting substrate for the front photoelectrochemical electrode, which functions as both an optical filter and a conductive counter-electrode of the rear dye-sensitized solar cell. The hybrid conductive distributed Bragg reflectors were designed to be transparent to the long-wavelength part of the incident solar spectrum (lambda>500 nm) for the rear solar cell, while reflecting the short-wavelength photons (lambda<500 nm) which can then be absorbed by the front photoelectrochemical electrode for enhanced photocurrent generation.114129Ysciescopu

Prolonged gastroparesis after corrective surgery for Wilkie's syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Wilkie's syndrome, a rare cause of intestinal obstruction, is related to anatomical and mechanical factors associated with the reduction of retroperitoneal fat padding. The diagnostic challenges of identifying vascular constriction between the aorta and superior mesenteric artery have been answered by advances in the field of computed tomography. Despite diagnostic confusion with intestinal dysmotility syndrome, conservative therapy with nutritional supplementation is the initial approach and duodenojejunostomy is favoured if non-surgical treatment fails.</p> <p>Case presentation</p> <p>We present a case of a 49-year-old woman with Wilkie's syndrome with persistent symptoms of gastroparesis for 15 months following corrective surgery.</p> <p>Conclusion</p> <p>Open and laparoscopic duodenojejunostomy have been described as the best surgical treatment options for Wilkie's syndrome, but further work needs to be done for patients with refractory symptoms of gastroparesis after these corrective surgeries.</p

Monitoring iron chelation effect in hearts of thalassaemia patients with improved sensitivity using reduced transverse relaxation rate (RR2)

Posters - Myocardial Viability: Human Models: No. 3660Accurate MRI characterization of myocardial iron is needed to improve the diagnosis and management of thalassaemia patients with transfusional iron overload. This study aimed to demonstrate that a new transverse relaxation index, the reduced R2 (RR2) that is estimated from non-monoexponential multi-echo CPMG signal decay and sensitive to ferritin iron, could detect the myocardial iron changes immediately following 1-week iron chelation suspension in thalassaemia patients at 3T.postprin

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p