RIG-I contributes to the innate immune response after cerebral ischemia

BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia

Optical coherence tomography angiography in choroidal melanoma and nevus

Fariba Ghassemi,1,2 Reza Mirshahi,1,2 Kaveh Fadakar,1,2 Siamak Sabour3 1Retina & Vitreous Service, 2Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, 3Safety Promotion and Injury Prevention Research Centre, Department of Clinical Epidemiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Synopsis: In optical coherence tomography angiography, the choroidal vascular flow rate in choroidal melanoma is significantly lower than that in choroidal nevus.Objective: The objective of this study was to describe the choriocapillaris and retinal features imaged by optical coherence tomography angiography (OCTA) in eyes with choroidal nevus from small malignant choroidal melanoma.Methods: In this retrospective, noninvasive, observational study, 11 patients diagnosed with small choroidal mass (five with choroidal nevus and six with malignant melanoma) who underwent dilated fundus examination, ocular ultrasonography and OCTA images were compared.Results: In choroidal nevus of all patients, OCTA demonstrated a hyporeflective mass with no significant deformity of choroidal vasculature and an intact retinal pigment epithelium (RPE)–Bruch’s membrane complex. The flow void mass was surrounded by an intense vascular rim named as surface microvasculature (SMV) that had an approximately similar flow rate median of 63.68 mm2 (60.42–67.62 mm2), comparable with the median of the contralateral normal eye of 61.77 mm2 (60.42–64.53 mm2; P>0.09) for nevi. OCTA showed an obscured Bruch’s membrane–RPE–Bruch’s membrane complex and outer retinal layer in choroidal melanomas. Choriocapillaris flow rate over the melanomas was 55.73% (41.93%–60.82%), and the corresponding normal areas had a flow area of 62.75% (61.99%–63.10%; P=0.01). A flow rate difference between choroidal melanoma and nevus was significant (P=0.006). Axial and peripheral feeding vessels were more dilated and tortuous compared with benign nevi.Conclusion: Decreased flow rate of SMV of choroidal melanoma cases compared with nevi was a significant finding. Detection of characteristic vascular features of choroidal melanoma by OCTA could make OCTA an assuring diagnostic modality to differentiate malignant lesions. Keywords: melanoma, choroidal nevus, OCT, OCTA, uveal melanom

Practice patterns and influence of allograft nephrectomy in pediatric kidney re- transplantation: A pediatric nephrology research consortium study

IntroductionThere are no guidelines regarding management of failed pediatric renal transplants.Materials & MethodsWe performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016.ResultsFourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty- three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re- listing, donor source at re- transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post- graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re- transplant (18% vs 7%; P = .03) and multiple rejections in first year after re- transplant (7% vs 1%; P = .03).ConclusionsPractices pertaining to failed renal allografts are inconsistent- 40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re- transplant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169276/1/petr13974.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169276/2/petr13974_am.pd

A spatial clustering approach for stochastic fracture network modelling

Fracture network modelling plays an important role in many application areas in which the behaviour of a rock mass is of interest. These areas include mining, civil, petroleum, water and environmental engineering and geothermal systems modelling. The aim is to model the fractured rock to assess fluid flow or the stability of rock blocks. One important step in fracture network modelling is to estimate the number of fractures and the properties of individual fractures such as their size and orientation. Due to the lack of data and the complexity of the problem, there are significant uncertainties associated with fracture network modelling in practice. Our primary interest is the modelling of fracture networks in geothermal systems and, in this paper, we propose a general stochastic approach to fracture network modelling for this application. We focus on using the seismic point cloud detected during the fracture stimulation of a hot dry rock reservoir to create an enhanced geothermal system; these seismic points are the conditioning data in the modelling process. The seismic points can be used to estimate the geographical extent of the reservoir, the amount of fracturing and the detailed geometries of fractures within the reservoir. The objective is to determine a fracture model from the conditioning data by minimizing the sum of the distances of the points from the fitted fracture model. Fractures are represented as line segments connecting two points in two-dimensional applications or as ellipses in three-dimensional (3D) cases. The novelty of our model is twofold: (1) it comprises a comprehensive fracture modification scheme based on simulated annealing and (2) it introduces new spatial approaches, a goodness-of-fit measure for the fitted fracture model, a measure for fracture similarity and a clustering technique for proposing a locally optimal solution for fracture parameters. We use a simulated dataset to demonstrate the application of the proposed approach followed by a real 3D case study of the Habanero reservoir in the Cooper Basin, Australia. © 2013 Springer-Verlag Wien.S. Seifollahi, P. A. Dowd, C. Xu, A. Y. Fadaka

COVID-19 in pediatric kidney transplantation: a follow-up report of the Improving Renal Outcomes Collaborative

BackgroundWe report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).MethodsPatient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.ResultsFrom September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age &gt; 12&nbsp;years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19.ConclusionsDespite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in &lt; 1% of COVID-19-positive patients and in less than &lt; 0.1% of all transplant patients within the IROC cohort. A higher resolution version of the Graphical abstract is available as Supplementary information