Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.

BACKGROUND/AIMS: Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. METHODS: We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. RESULTS: We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. CONCLUSION: Treatment with VKA predisposes to the development of calciphylaxis.TFH is funded by the Cambridge BRC and NIHR.This is the accepted manuscript for a paper published in Nephron Clinical Practice, Vol. 129, No. 3, 2015, DOI:10.1159/00037144

An analysis of effectiveness of parliamentary questions in the Queensland Parliament

Parliamentary questions are an integral part of most Westminster parliamentary systems, serving as\ud a major form of legislative oversight and constituency service (Glassman 2008). There are two\ud types of parliamentary questions, ‘questions without notice’ and ‘questions on notice’. Questions\ud without notice are asked and answered orally during ‘Question Time’. Questions on notice are\ud asked in writing and the relevant minister provides the answer in writing. Parliamentary questions\ud provide a mechanism to seek the accountability of the executive on the floor of the House and\ud barely ‘any aspect of the executive department’s powers and activities can be shielded from\ud questions’ (Crick 1964: 237). In terms of media coverage, this practice is the most widely reported\ud legislative device. Therefore, to a casual observer, the working of parliament is synonymous with\ud Question Time

Pixel-Based Soil Loss Estimation and Prioritization of North-Western Himalayan Catchment Based on Revised Universal Soil Loss Equation (RUSLE)

Land degradation is a noteworthy environmental risk causing water quality issues, reservoir siltation, and loss of valuable arable lands, all of which negate sustainable development. Analysis of the effect of land use changes on erosion rate and sediment yield is particularly useful to identify critical areas and define catchment-area treatment plans. This study utilized remote sensing and geographical information system/science (GIS) techniques combined with the Revised Universal Soil Loss Equation (RUSLE) on a pixel basis to estimate soil loss over space and time and prioritized areas for action. The methodology was applied to the Sutlej catchment from the perspective of sedimentation of the Bhakra reservoir, which is leading to the loss of active storage capacity and performance and of the safety and efficiency of many existing hydroelectric projects in the Sutlej and its tributaries that drain the Himalayas. Soil loss estimation using RUSLE was first calibrated using data from three sites, and the calibrated model was then used to estimate catchment soil loss for 21 years (1995–2015). The number of land use/land cover (LULC) classes as 14 and the C factor as 0.63 for agriculture land were optimized using the observed data for the Sutlej catchment. Further, the linkage between soil erosivity and annual precipitation was also established. It was concluded that extensive control treatment would be necessary from the soil and water conservation point of view. Structures like check dams, terraces, bunds, and diversion drains in the upstream can overcome the issue of fragmentation of soil in the Sutlej catchment

Molecular Properties of Drugs Handled by Kidney OATs and Liver OATPs Revealed by Chemoinformatics and Machine Learning: Implications for Kidney and Liver Disease

In patients with liver or kidney disease, it is especially important to consider the routes of metabolism and elimination of small-molecule pharmaceuticals. Once in the blood, numerous drugs are taken up by the liver for metabolism and/or biliary elimination, or by the kidney for renal elimination. Many common drugs are organic anions. The major liver uptake transporters for organic anion drugs are organic anion transporter polypeptides (OATP1B1 or SLCO1B1; OATP1B3 or SLCO1B3), whereas in the kidney they are organic anion transporters (OAT1 or SLC22A6; OAT3 or SLC22A8). Since these particular OATPs are overwhelmingly found in the liver but not the kidney, and these OATs are overwhelmingly found in the kidney but not liver, it is possible to use chemoinformatics, machine learning (ML) and deep learning to analyze liver OATP-transported drugs versus kidney OAT-transported drugs. Our analysis of >30 quantitative physicochemical properties of OATP- and OAT-interacting drugs revealed eight properties that in combination, indicate a high propensity for interaction with “liver” transporters versus “kidney” ones based on machine learning (e.g., random forest, k-nearest neighbors) and deep-learning classification algorithms. Liver OATPs preferred drugs with greater hydrophobicity, higher complexity, and more ringed structures whereas kidney OATs preferred more polar drugs with more carboxyl groups. The results provide a strong molecular basis for tissue-specific targeting strategies, understanding drug–drug interactions as well as drug–metabolite interactions, and suggest a strategy for how drugs with comparable efficacy might be chosen in chronic liver or kidney disease (CKD) to minimize toxicity

Human Cadaveric Donor Cornea Derived Extra Cellular Matrix Microparticles for Minimally Invasive Healing/Regeneration of Corneal Wounds

Biological materials derived from extracellular matrix (ECM) proteins have garnered interest as their composition is very similar to that of native tissue. Herein, we report the use of human cornea derived decellularized ECM (dECM) microparticles dispersed in human fibrin sealant as an accessible therapeutic alternative for corneal anterior stromal reconstruction. dECM microparticles had good particle size distribution (≤10 µm) and retained the majority of corneal ECM components found in native tissue. Fibrin–dECM hydrogels exhibited compressive modulus of 70.83 ± 9.17 kPa matching that of native tissue, maximum burst pressure of 34.3 ± 3.7 kPa, and demonstrated a short crosslinking time of ~17 min. The fibrin–dECM hydrogels were found to be biodegradable, cytocompatible, non-mutagenic, non-sensitive, non-irritant, and supported the growth and maintained the phenotype of encapsulated human corneal stem cells (hCSCs) in vitro. In a rabbit model of anterior lamellar keratectomy, fibrin–dECM bio-adhesives promoted corneal re-epithelialization within 14 days, induced stromal tissue repair, and displayed integration with corneal tissues in vivo. Overall, our results suggest that the incorporation of cornea tissue-derived ECM microparticles in fibrin hydrogels is non-toxic, safe, and shows tremendous promise as a minimally invasive therapeutic approach for the treatment of superficial corneal epithelial wounds and anterior stromal injuries