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Xanthine Oxidase-Induced Inflamed Replies within The respiratory system Epithelial Tissues: An overview within Immunopathology associated with COVID-19.
Oxides and carbides enriched surface improved the microhardness of the re-solidified layer from 320 HV to 727 HV. Surface topology reveals nano-porosity (50-200 nm) which enhances osseointegration due to the absorption of proteins especially collagen to the surface.Ni-Ti stents fatigue strength assessment requires a multi-factorial complex integration of applied loads, material and design and is of increasing interest. In this work, a coupled experimental-numerical method for the multi-axial fatigue strength assessment is proposed and verified for two different stent geometries that resemble commercial products. Particular attention was paid to the identification of the material fatigue limit curve. The common approach for the Ni-Ti stents fatigue assessment based on the von Mises yield criterion was proven unsuitable for a realistic fatigue strength assessment. On the other hand, critical plane-based criteria were more representative of the experimental outcomes regardless of stent design.Currently, Periodontal ligament (PDL) is considered as a viscoelastic solid biomaterial. However, we observed the steady-state rheological behavior of PDL through long time loading experiments, and suggested the theoretical definition of PDL as a viscoelastic fluid biomaterial. PDL specimens were prepared from the middle area of the mandibular central incisors in pigs. Dynamic force loading with frequencies of 0 (static load), 2, 5, and 10 Hz and amplitudes of 0.01, 0.02, and 0.03 MPa was adopted. The shear strain-time curve at the equilibrium position of PDL was obtained by a dynamic shear creep experiment. The results showed that the shear strain increased exponentially at first and then inclined toward an oblique line. The results showed that the PDL has viscoelastic fluid characteristics, independent of frequency and amplitude. The shear strain decreased with an increase in frequency and amplitude. To further analyze the viscoelastic characteristics of PDL, a 50000-s static shear creep experiment was re-designed. PDL exhibited viscoelastic fluid biomaterial characteristics according to the three aspects of the algebraic fitting, geometric characteristics, and physical results. For the first time, a viscoelastic fluid constitutive model was established to characterize the mechanical properties of PDL with high fitting accuracy. Furthermore, the shear viscosity coefficient of the dynamic load was larger than that of the static load, increasing with an increase in frequency and amplitude; compared with the static force, the dynamic force improved the viscosity of PDL, enhancing its function of fixing teeth, and introducing the new medical knowledge of "No tooth extraction after a meal."Mechanotransduction, the encoding of local mechanical stresses and strains at sensory endings into neural action potentials at the viscera, plays a critical role in evoking visceral pain, e.g., in the distal colon and rectum (colorectum). The wall of the colorectum is structurally heterogeneous, including two major composites the inner consists of muscular and submucosal layers, and the outer consists of circular muscular, intermuscular, longitudinal muscular, and serosal layers. In fact the colorectum presents biomechanical heterogenity across both the longitudinal and through-thickness directions thus highlighting the differential roles of sensory nerve endings within different regions of the colorectum in visceral mechanotransduction. We determined constitutive models and model parameters for individual layers of the colorectum from three longitudinal locations (colonic, intermediate, and distal) using nonlinear optimization to fit our experimental results from biaxial extension tests on layer-separated co constitutive modeling of biaxial extension tests of colon tissues from mice. Our constitutive models and modeling framework facilitate analyses of both fundamental questions (e.g., the impact of organ/tissue biomechanics on mechanotransduction of the sensory nerve endings, structure-function relationships, and growth and remodeling in health and disease) and specific applications (e.g., device design, minimally invasive surgery, and biomedical research).Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.Multi-scale finite element analysis is performed to ascertain the effect of geometrical changes at multiple structural scales on the mechanical properties of cortical bone. Finite element models are developed, with reference to experimental data from existing literature, to account for bone's viscoelastic behaviour and anisotropic structure from the most fundamental level of bone consisting of mineralised collagen fibrils, up to the macroscopic level consisting of osteons and the Haversian canals. A statistical approach is incorporated to perform sensitivity analyses on the effects of different geometrical parameters on the effective material properties of cortical bone at each length scale. Numerical results indicate that there is an exponential correlation between the mineral volume fraction and the effective stiffness constants at each length scale. This contributes to the exponential behaviour of the instantaneous moduli describing cortical bone's two-phase stress relaxation process a fast and slow response relaxation behaviour. Results indicate that the fast response relaxation time is independent of bone's structural anisotropy, whilst being dependent on variations in the global mineral volume fraction between length scales. However, the slow response relaxation time is independent of the changes in mineral volume fraction. It is also observed that the slow response relaxation time varies with bone's anisotropic structure, and therefore, contributes to the anisotropic properties of bone.
Pre-therapeutic UGT1A1 genotyping is not yet routinely performed in most hospitals in patients starting irinotecan chemotherapy. The aim of this position paper was to evaluate the available evidence and to assess the potential value of genotyping of UGT1A1∗28 and UGT1A1*6 in patients before starting treatment with irinotecan to reduce the risk of severe toxicity.

The literature was selected and assessed based on five pre-specified criteria 1) the level of evidence for associations between UGT1A1 polymorphisms and irinotecan-induced severe toxicity, 2) clinical validity and utility of pre-therapeutic genotyping of UGT1A1, 3) safety and tolerability of irinotecan in carriers of UGT1A1 polymorphisms, 4) availability of specific dose recommendations for irinotecan in carriers of UGT1A1 polymorphisms, 5) evidence of cost benefits of pre-therapeutic genotyping of UGT1A1.

On all five criteria, study results were favourable for pre-therapeutic genotyping of UGT1A1. A high level of evidence (level I) was found for a higher incidence of irinotecan-induced severe toxicity in homozygous carriers of UGT1A1*28 or UGT1A1*6. The clinical validity and utility of this genetic test proved to be acceptable. Dose-finding studies showed a lower maximum tolerated dose in homozygous variant allele carriers, and most of the drug labels and guidelines recommend a dose reduction of 25-30% in these patients. In addition, pre-therapeutic genotyping of UGT1A1 is likely to save costs.

Pre-therapeutic genotyping of UGT1A1 in patients initiating treatment with irinotecan improves patient safety, is likely to be cost-saving, and should, therefore, become standard of care.
Pre-therapeutic genotyping of UGT1A1 in patients initiating treatment with irinotecan improves patient safety, is likely to be cost-saving, and should, therefore, become standard of care.Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been largely applied for early clinical testing. In this review, we discuss some repurposed anticancer drugs for the treatment of COVID-19, which are under investigation in clinical trials or proposed for the clinical testing.
Stratification of hepatoblastoma (HB) patients is based on clinical and imaging characteristics obtained at the time of diagnosis. We aim to integrate biomarkers into a tool that accurately predicts survival of HB patients.

We retrospectively analysed 174 HB patients for the presence of four biomarkers and explored their prognostic potential by correlating with overall survival (OS) and event-free survival (EFS).

Mutations of CTNNB1, NFE2L2and TERT were found in 135 (78%), 10 (6%)and 10 (6%) patients, respectively, and the adverse C2 subtype of the 16-gene signature in 63 (36%) patients. C2-patients had more frequent metastatic disease, higher alpha-fetoprotein levels, non-fetal histologyand significantly worse 3-year OS (68% versus 95%) and EFS (63% versus 87%) than C1-patients. Patients carrying a NFE2L2 mutation had a significantly worse 3-year OS (57% versus 88%) than NFE2L2 wild-type patients and were more likely to have vessel invasive growth and non-fetal histology. TERT mutations were almost exclusively found in older patients, whereas CTNNB1 mutations showed no association with any clinical feature or outcome. In a multivariable analysis, the C2 subtype remained a significant predictor of poor outcome with hazard ratios of 6.202 and 3.611 for OS and EFS, respectively. When added to the Children's Hepatic tumors International Collaboration risk stratification, the presence of the C2 subtype identified a group of high-risk patients with a very poor outcome.

We propose a new stratification system based on the combination of clinical factors and the 16-gene signature, which may facilitate a risk-adapted management of HB patients.
We propose a new stratification system based on the combination of clinical factors and the 16-gene signature, which may facilitate a risk-adapted management of HB patients.
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