Predicting glucocorticoid effectiveness in thyroid eye disease: combined value from serological lipid metabolism and an orbital MRI parameter.

Purpose: The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED). Methods: This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances. Results: Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031). Conclusion: Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.

Insight into the mechanisms of neuroendocrine toxicity induced by 6:2FTCA via thyroid hormone disruption.

6:2 fluorotonic carboxylic acid (6:2 FTCA), a novel substitute for perfluorooctanoic acid (PFOA), is being used gradually in industrial production such as coatings or processing aids, and its detection rate in the aqueous environment is increasing year by year, posing a potential safety risk to aquatic systems and public health. However, limited information is available on the effects and mechanism of 6:2 FTCA. Therefore, this study was conducted to understand better the neuroendocrine effects of early exposure to 6:2 FTCA and the underlying mechanisms on zebrafish. In this study, zebrafish embryos were treated to varied doses of 6:2 FTCA (0, 0.08 µg/mL, 0.8 µg/mL and 8 µg/mL) at 4 h post-fertilization (hpf) for a duration of six days, which exhibited a pronounced inhibition of early growth and induced a disorganized swim pattern characterized by reduced total swim distance and average swim speed. Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRß). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes. Our findings indicated that 6:2 FTCA acts as a thyroid endocrine disruptor and can induce neuroendocrine toxic effects. Furthermore, our results show that targeting TRß may be a potentially therapeutic strategy for 6:2 FTCA-induced neuroendocrine disrupting effects.

Potential value of guard-wire technology in the interventional treatment for ostial coronary lesions.

BACKGROUND: To explore potential value of guard-wire technology during percutaneous coronary intervention (PCI) in patients with ostial coronary lesions. METHODS: Patients, who underwent PCI, were collected between October 2011 and March 2017. Of the 141 patients, 63 (44.7%) have ostial lesions, and 78 (55.3%) have distal bifurcation sites. They were divided into group A (n = 71) and group B (n = 70). Group A received PCI after guard-wire technology. Group B were given balloon dilation and stent after placing guide wire through target lesion vessel. X-ray exposure time, contrast agent dosage, total PCI duration, pressure incarceration times, cases of malignant arrhythmia and cases of failed PCI of all patients were analyzed, respectively. RESULTS: The general clinical characteristics includes patients age, sex ratio, the proportion of complications, smoking ratio and left ventricular ejection fraction of both groups was not significantly different. X-ray exposure time, contrast agent dosage, PCI total time, stent positioning time, pressure infestation frequency, arrhythmia frequency and complication number of group B were higher than those of group A. There is no case of malignant arrhythmia and case of failed PCI in group A, while there were five malignant arrhythmia and four failed PCI in group B. Contrast agent dosage and cases of failed PCI increased in group B compared with group A. CONCLUSION: The guard wire technology is safer and more feasible to patients with ostial coronary lesions who underwent PCI.

Regional Mapping of Flow and Wall Characteristics of Intracranial Aneurysms.

The evolution of intracranial aneurysms (IAs) is thought to be driven by progressive wall degradation in response to abnormal hemodynamics. Previous studies focused on the relationship between global hemodynamics and wall properties. However, hemodynamics, wall structure and mechanical properties of cerebral aneurysms can be non-uniform across the aneurysm wall. Therefore, the aim of this work is to introduce a methodology for mapping local hemodynamics to local wall structure in resected aneurysm specimens. This methodology combines image-based computational fluid dynamics, tissue resection, micro-CT imaging of resected specimens mounted on 3D-printed aneurysm models, alignment to 3D vascular models, multi-photon microscopy of the wall, and regional mapping of hemodynamics and wall properties. This approach employs a new 3D virtual marking tool for surgeons to delineate the location of the resected specimen directly on the 3D model, while in the surgical suite. The case of a middle cerebral artery aneurysm is used to illustrate the application of this methodology to the assessment of the relationship between local wall shear stress and local wall properties including collagen fiber organization and wall geometry. This methodology can similarly be used to study the relationship between local intramural stresses and local wall structure.

Diversity in the Strength and Structure of Unruptured Cerebral Aneurysms.

Intracranial aneurysms are pathological enlargements of brain arteries that are believed to arise from progressive wall degeneration and remodeling. Earlier work using classical histological approaches identified variability in cerebral aneurysm mural content, ranging from layered walls with intact endothelium and aligned smooth muscle cells, to thin, hypocellular walls. Here, we take advantage of recent advances in multiphoton microscopy, to provide novel results for collagen fiber architecture in 15 human aneurysm domes without staining or fixation as well as in 12 control cerebral arteries. For all aneurysm samples, the elastic lamina was absent and the abluminal collagen fibers had similar diameters to control arteries. In contrast, the collagen fibers on the luminal side showed great variability in both diameter and architecture ranging from dense fiber layers to sparse fiber constructs suggestive of ineffective remodeling efforts. The mechanical integrity of eight aneurysm samples was assessed using uniaxial experiments, revealing two sub-classes (i) vulnerable unruptured aneurysms (low failure stress and failure pressure), and (ii) strong unruptured aneurysms (high failure stress and failure pressure). These results suggest a need to refine the end-point of risk assessment studies that currently do not distinguish risk levels among unruptured aneurysms. We propose that a measure of wall integrity that identifies this vulnerable wall subpopulation will be useful for interpreting future biological and structural data.

Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model.

The objective of this study was to evaluate the long-term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into "neoarteries" (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues.

A theoretical and non-destructive experimental approach for direct inclusion of measured collagen orientation and recruitment into mechanical models of the artery wall.

Gradual collagen recruitment has been hypothesized as the underlying mechanism for the mechanical stiffening with increasing stress in arteries. In this work, we investigated this hypothesis in eight rabbit carotid arteries by directly measuring the distribution of collagen recruitment stretch under increasing circumferential loading using a custom uniaxial (UA) extension device combined with a multi-photon microscope (MPM). This approach allowed simultaneous mechanical testing and imaging of collagen fibers without traditional destructive fixation methods. Fiber recruitment was quantified from 3D rendered MPM images, and fiber orientation was measured in projected stacks of images. Collagen recruitment was observed to initiate at a finite strain, corresponding to a sharp increase in the measured mechanical stiffness, confirming the previous hypothesis and motivating the development of a new constitutive model to capture this response. Previous constitutive equations for the arterial wall have modeled the collagen contribution with either abrupt recruitment at zero strain, abrupt recruitment at finite strain or as gradual recruitment beginning at infinitesimal strain. Based on our experimental data, a new combined constitutive model was presented in which fiber recruitment begins at a finite strain with activation stretch represented by a probability distribution function. By directly including this recruitment data, the collagen contribution was modeled using a simple Neo-Hookean equation. As a result, only two phenomenological material constants were required from the fit to the stress stretch data. Three other models for the arterial wall were then compared with these results. The approach taken here was successful in combining stress-strain analysis with simultaneous microstructural imaging of collagen recruitment and orientation, providing a new approach by which underlying fiber architecture may be quantified and included in constitutive equations.