Rationale and design of the ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) trial

BackgroundCoronary CT angiography (CTA) has emerged as an effective noninvasive method for direct visualization of the coronary arteries, with high diagnostic performance compared with invasive coronary angiography (ICA). However, coronary CTA is prone to artifacts, including coronary motion, which may reduce its diagnostic performance. Intracycle motion compensation algorithms (MCAs) from a combination of software and hardware techniques now allow for correction of coronary motion, but the diagnostic performance of MCAs compared with traditional coronary CTA reconstruction methods remains unexplored.MethodsViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) is a prospective international multicenter trial of 218 patients which is designed to evaluate the performance of MCAs for the diagnosis of anatomically obstructive coronary artery disease (CAD) compared with an ICA reference standard, on a per-patient, per-vessel, and per-segment basis. Patients enrolled into ViCTORY will undergo investigational coronary CTA and clinically indicated ICA and will not receive heart rate-lowering medications before coronary CTA. Coronary CTA images will be reconstructed by conventional standard methods as well as by MCAs. Blinded core laboratory interpretation will be performed for coronary CTA and ICA in an intent-to-diagnose fashion.ResultsThe primary end point of ViCTORY is the per-patient diagnostic accuracy of MCAs for the diagnosis of anatomically obstructive CAD compared with ICA. Secondary end points will include other per-patient, per-vessel, and per-segment diagnostic performance characteristics, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Other key secondary end points will include diagnostic interpretability, image quality, the upper heart rate threshold of utility of MCAs, and the additive value of MCAs to traditionally reconstructed coronary CTA.ConclusionViCTORY will determine whether MCAs improve the diagnosis of obstructive CAD in patients undergoing coronary CTA who are not receiving heart rate-lowering medications.     

A Combination of Constitutive Damage Model and Artificial Neural Networks to Characterize the Mechanical Properties of the Healthy and Atherosclerotic Human Coronary Arteries

It has been indicated that the content and structure of the elastin and collagen of the arterial wall can subject to a significant alteration due to the atherosclerosis. Consequently, a high tissue stiffness, stress, and even damage/rupture are triggered in the arterial wall. Although many studies so far have been conducted to quantify the mechanical properties of the coronary arteries, none of them consider the role of collagen damage of the healthy and atherosclerotic human coronary arterial walls. Recently, a fiber family‐based constitutive equation was proposed to capture the anisotropic mechanical response of the healthy and atherosclerotic human coronary arteries via both the histostructural and uniaxial data. In this study, experimental mechanical measurements along with histological data of the healthy and atherosclerotic arterial walls were employed to determine the constitutive damage parameters and remodeling of the collagen fibers. To do this, the preconditioned arterial tissues were excised from human cadavers within 5‐h postmortem, and the mean angle of their collagen fibers was precisely determined. Thereafter, a group of quasistatic axial and circumferential loadings were applied to the arterial walls, and the constrained nonlinear minimization method was employed to identify the arterial parameters according to the axial and circumferential extension data. The remodeling of the collagen fibers during the tensile test was also predicted via Artificial Neural Networks algorithm. Regardless of loading direction, the results presented a noteworthy load‐bearing capability and stiffness of the atherosclerotic arteries compared to the healthy ones (P < 0.005). Theoretical fiber angles were found to be consistent with the experimental histological data with less than 2 and 5° difference for the healthy and atherosclerotic arterial walls, respectively. The pseudoelastic damage model data were also compared with that of the experimental data, and interestingly, the arterial mechanical behavior for both the primary loading (up to the elastic region) and the discontinuous softening (up to the ultimate stress) was well addressed. The proposed model predicted well the mechanical response of the arterial tissue considering the damage of collagen fibers for both the healthy and atherosclerotic arterial walls.     

Platelet-rich fibrin (PRF) gel modified by a carbodiimide crosslinker for tissue regeneration

Platelet-rich fibrin (PRF) as a rich source of effective growth factors has been used as a scaffold in tissue regeneration. It is known that PRF exhibits rapid degradability against enzymes, which should be decreased using crosslinking agents to reduce the release rate of growth factors and increase the effectiveness of tissue regeneration. In this study, a carbodiimide crosslinker with different concentrations (0.01%, 0.05%, 1%, and 2%) was used to modify and improve the properties of PRF gel. The crosslinked gels were evaluated with analyses such as SEM, swelling, degradability, mechanical strength, release test, cytotoxicity, and cell adhesion. The results showed that with increasing crosslinker concentration, the morphology of the fiber structure changes drastically, the swelling rate decreases from 300% (control) to 160% for the crosslinked gel, the degradation time for the control sample increases from 8 days to more than two weeks for the crosslinked gel, and the Young''s modulus increases from 0.15 MPa (control) to 0.61 MPa for the crosslinked samples. Growth factors also showed lower release with increasing crosslinking ratio. Cytotoxicity assays demonstrated that by increasing the crosslinker concentration to 1% w/v, no cytotoxicity was observed. Cellular studies with DAPI staining showed that the cells penetrated well into the gels and were well distributed, especially in gels with lower crosslinker concentrations. In addition, the modified PRF gel can be used as a scaffold for tissue regeneration.

1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) as a crosslinker can improve the physical and mechanical properties of PRF gel by forming covalent bonds.     

Neuregulin‐1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury

Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro‐ and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin‐1 (Nrg‐1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg‐1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically‐relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg‐1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin‐10 and arginase‐1 expression. We also found a decrease in proinflammatory factors including IL‐1β, TNF‐α, matrix metalloproteinases (MMP‐2 and 9) and nitric oxide after injury. In addition, Nrg‐1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg‐1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg‐1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll‐like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg‐1 treatment with the therapeutic dosage of 1.5 μg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg‐1 in acute SCI and suggest a positive immunomodulatory role for Nrg‐1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.     

Cetyltrimethyl ammonium bromide effect on highly electrocatalysis of methanol oxidation based on nickel particles electrodeposited into poly (m-toluidine) film on the carbon paste electrode

In this work, m-toluidine is electropolymerized at the surface of carbon paste electrode using consecutive cyclic voltammetry in 20 mM monomer aqueous solution in the presence of 6 mM cetyltrimethyl ammonium bromide (CTAB) as surfactant. Then transition metal of nickel is incorporated into the polymer by electrodepositing of Ni (II) from 1.5 M NiSO₄ acidic solution using chronoamperometry technique (−1.0 V versus Ag|AgCl|KCl (3 M) for 15 min). In alkaline medium (i.e. NaOH 0.1 M) a good redox behavior of Ni (III)/Ni (II) couple at the surface of Ni/poly (m-toluidine) modified carbon paste electrode (Ni/PMT/MCPE) in the absence and presence of CTAB (Ni/CTAB-PMT/MCPE) can be observed. Electrocatalytic oxidation of methanol has been studied on Ni/PMT/MCPE and Ni/CTAB-PMT/MCPE. The results show that CTAB significantly enhances the catalytic efficiency of nickel particles on the oxidation of methanol in aqueous alkaline media. Moreover, the effects of various parameters such as concentration of CTAB, concentration of methanol, electrodepositing time, film thickness and monomer concentration on the electrooxidation of methanol as well as long-term stability of the Ni/CTAB-PMT/MCPE have also been investigated. This polymeric modified electrode can oxidize the methanol with high current density (over 40 mA cm⁻²).     

The vagus nerve modulates CD4+ T cell activity

The vagus nerve has a counter-inflammatory role in a number of model systems. While the majority of these anti-inflammatory effects have been ascribed to the activation of nicotinic receptors on macrophages, little is known about the role of the vagus in modulating the activity of other cells involved in inflammatory responses. Here, we demonstrate that following subdiaphragmatic vagotomy of mice CD4⁺ T cells from the spleen proliferated at a higher rate and produced more pro-inflammatory cytokines, including TNF and IFN-γ, upon in vitro stimulation. Cell responses were restored to control levels following the administration of nicotine and the treatment of non-vagotomized animals with a nicotinic receptor antagonist could mimic the effect of vagotomy. Our results suggest that vagal input constitutively down-regulates T cell function through action at nicotinic receptors and the role of the vagus in regulating immune responses is more extensive than previously demonstrated.