Original Research Article Effect of Radiotherapy on Flexural Strength of Luting Cementsan In Vitro Study

Aim - The aim of this study was to evaluate changes in the flexural strength of luting cements due to radiotherapy. Methodology- Total of 90 rectangular specimens of 25×2×2 mm dimension were fabricated by utilizing the putty consistency polyvinyl siloxane rubber mould. They were grouped based on their type. Group A included 30 specimens made of zinc phosphate cement, Group B included 30 specimens fabricated using glass ionomer luting cement, and Group C consisted of 30 specimen’s fabricated using resin luting cement. Once the specimens were set, they were stored in distilled water between the experiments. After 24 hours, 15 from each group of the mentioned cements were subjected to irradiation fractionally upto 60 Gy by a Cobalt-60 external beam machine. Remaining specimens from each group were used as controls. After radiotherapy, the specimens were stored in distil water for 24 hours until performing the 3 point bend test. All the specimens were subjected to 3 point bend test on universal testing machine for checking flexural strength. Statistics- Kruskal Wallis Test followed by Mann Whitney test as post hoc analysis was used to compare the mean values of different parameters between three groups of Irradiated and controlled samples. The level of significance was set at P<0.05. Results- After exposure to fractional irradiation for 4 weeks, in the zinc phosphate luting cement (Group-A) and glass ionomer luting cement (Group-B), showed a slight decrease in flexural strength. The resin luting cement (Group-C) showed slight increase in flexural strength. Conclusion- Among all the groups, the resin luting cement showed a slight increase in flexural strength when compared to the other luting cement groups after fractional irradiatio

Clinical Factors Associated with C - Reactive Protein in Chronic Spinal Cord Injury

Study Design Cross-sectional study. Objectives: Determine clinical factors associated with plasma C-reactive protein (CRP) in persons with chronic spinal cord injury (SCI). Setting: Veterans Affairs Medical Center in Boston, MA. Methods: Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess total and regional body fat. Linear regression models were used to assess cross-sectional associations with plasma CRP. Results: In multivariable models, factors associated with a higher CRP included a greater BMI, urinary catheter use, a respiratory illness in the past week, and non-white race. Mean CRP also increased with decreasing mobility (motorized wheel chair >hand propelled wheel chair > walk with an assistive device > walk independently). Results were similar when adjusting for % android, gynoid, trunk, or total fat mass in place of BMI. Level and completeness of SCI was not associated with CRP in multivariable models. Conclusions: Clinical characteristics common in chronic SCI are associated with plasma CRP. These factors are more important than level and completeness of SCI and some are potentially modifiable

Splicing is an alternate oncogenic pathway activation mechanism in glioma

High-grade diffuse glioma (HGG) is the leading cause of brain tumour death. While the genetic drivers of HGG have been well described, targeting these has thus far had little impact on survival suggesting other mechanisms are at play. Here we interrogate the alternative splicing landscape of pediatric and adult HGG through multi-omic analyses, uncovering an increased splicing burden compared with normal brain. The rate of recurrent alternative splicing in cancer drivers exceeds their mutation rate, a pattern that is recapitulated in pan-cancer analyses, and is associated with worse prognosis in HGG. We investigate potential oncogenicity by interrogating cancer pathways affected by alternative splicing in HGG; spliced cancer drivers include members of the RAS/MAPK pathway. RAS suppressor neurofibromin 1 is differentially spliced to a less active isoform in >80% of HGG downstream from REST upregulation, activating the RAS/MAPK pathway and reducing glioblastoma patient survival. Overall, our results identify non-mutagenic mechanisms by which cancers activate oncogenic pathways which need to accounted for in personalized medicine approaches

SIRF: Synergistic Image Reconstruction Framework

The combination of positron emission tomography (PET) with magnetic resonance (MR) imaging opens the way to more accurate diagnosis and improved patient management. At present, the data acquired by PET-MR scanners are essentially processed separately, but the opportunity to improve accuracy of the tomographic reconstruction via synergy of the two imaging techniques is an active area of research. In this paper, we present Release 2.1.0 of the CCP-PETMR Synergistic Image Reconstruction Framework (SIRF) software suite, providing an open-source software platform for efficient implementation and validation of novel reconstruction algorithms. SIRF provides user-friendly Python and MATLAB interfaces built on top of C++ libraries. SIRF uses advanced PET and MR reconstruction software packages and tools. Currently, for PET this is Software for Tomographic Image Reconstruction (STIR); for MR, Gadgetron and ISMRMRD; and for image registration tools, NiftyReg. The software aims to be capable of reconstructing images from acquired scanner data, whilst being simple enough to be used for educational purposes

SIRF: Synergistic Image Reconstruction Framework

The combination of positron emission tomography (PET) with magnetic resonance (MR) imaging opens the way to more accurate diagnosis and improved patient management. At present, the data acquired by PET-MR scanners are essentially processed separately, but the opportunity to improve accuracy of the tomographic reconstruction via synergy of the two imaging techniques is an active area of research. In this paper, we present Release 2.1.0 of the CCP-PETMR Synergistic Image Reconstruction Framework (SIRF) software suite, providing an open-source software platform for efficient implementation and validation of novel reconstruction algorithms. SIRF provides user-friendly Python and MATLAB interfaces built on top of C++ libraries. SIRF uses advanced PET and MR reconstruction software packages and tools. Currently, for PET this is Software for Tomographic Image Reconstruction (STIR); for MR, Gadgetron and ISMRMRD; and for image registration tools, NiftyReg. The software aims to be capable of reconstructing images from acquired scanner data, whilst being simple enough to be used for educational purposes. The most recent version of the software can be downloaded from http://www.ccppetmr.ac.uk/downloads and https://github.com/CCPPETMR/. Program summary: Program Title: Synergistic Image Reconstruction Framework (SIRF) Program Files DOI: http://dx.doi.org/10.17632/s45f5jh55j.1 Licensing provisions: GPLv3 and Apache-2.0 Programming languages: C++, C, Python, MATLAB Nature of problem: In current practice, data acquired by PET-MR scanners are processed separately. Methods for improving the accuracy of the tomographic reconstruction using the synergy of the two imaging techniques are actively being investigated by the PET-MR research and development community, however, practical application is heavily reliant on software. Open-source software available to the PET-MR community – such as the PET package (STIR) (Thielemans et al., 2012) and the MR package Gadgetron (Hansen and Sørensen, 2013) – provide a basis for new synergistic PET-MR software. However, these two software packages are independent and have very different software architectures. They are mostly written in C++ but many researchers in the PET-MR community are more familiar with script-style languages, such as Python and MATLAB, which enable rapid prototyping of novel reconstruction algorithms. In the current situation it is difficult for researchers to exploit any synergy between PET and MR data. Furthermore, techniques from one field cannot easily be applied in the other. Solution method: In SIRF, the bulk of computation is performed by available advanced open-source reconstruction and registration software (currently STIR, Gadgetron and NiftyReg) that can use multithreading and GPUs. The SIRF C++ code provides a thin layer on top of these existing libraries. The SIRF layer has unified data-containers and access mechanisms. This C++ layer provides the basis for a simple and intuitive Python and MATLAB interface, enabling users to quickly develop and test their reconstruction algorithms using these scripting languages only. At the same time, advanced users proficient in C++ can directly utilise wider SIRF functionality via the SIRF C++ libraries that we provide

Infant head growth in male siblings of children with and without autism spectrum disorders

Previous research has indicated that children with autism exhibit accelerated head growth (HG) in infancy, although the timing of acceleration varies between studies. We examined infant HG trajectory as a candidate autism endophenotype by studying sibling pairs. We retrospectively obtained serial head orbitofrontal circumference measurements of: a) 48 sibling pairs in which one (n = 28) or both (n = 20) sibs were affected by an autism spectrum disorder (ASD); and b) 85 control male sibling pairs. Rate of HG of ASD subjects was slightly accelerated compared to controls, but the magnitude of difference was below the limit of reliability of standard measurement methods. Sibling intra class correlation for rate of HG was highly statistically significant; the magnitude was significantly stronger among autism-affected families (ICC = .63) than among controls (ICC = .26), p < .01. Infant HG trajectory appears familial—possibly endophenotypic—but was not a reliable marker of autism risk among siblings of ASD probands in this sample

Open‐label, clinical trial extension:Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis

SummaryBackgroundSeladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory and anti‐pruritic effects.AimsTo evaluate the long‐term safety and efficacy of seladelpar in patients with PBC.MethodsIn an open‐label, international, long‐term extension study, patients with PBC completing seladelpar lead‐in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non‐alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years.ResultsThere were no serious treatment‐related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] &lt;1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2.ConclusionsSeladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16.</jats:sec

Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis

BACKGROUND: Seladelpar is a potent and selective peroxisome proliferator-activated receptor-δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti-cholestatic, anti-inflammatory and anti-pruritic effects. AIMS: To evaluate the long-term safety and efficacy of seladelpar in patients with PBC. METHODS: In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. RESULTS: There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. CONCLUSIONS: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year