Implementation of computer simulation to assess flow diversion treatment outcomes: systematic review and meta-analysis.

INTRODUCTION: Despite a decade of research into virtual stent deployment and the post-stenting aneurysmal hemodynamics, the hemodynamic factors which correlate with successful treatment remain inconclusive. We aimed to examine the differences in various post-treatment hemodynamic parameters between successfully and unsuccessfully treated cases, and to quantify the additional flow diversion achievable through stent compaction or insertion of a second stent. METHODS: A systematic review and meta-analysis were performed on eligible studies published from 2000 to 2019. We first classified cases according to treatment success (aneurysm occlusion) and then calculated the pooled standardized mean differences (SMD) of each available parameter to examine their association with clinical outcomes. Any additional flow diversion arising from the two common strategies for improving the stent wire density was quantified by pooling the results of such studies. RESULTS: We found that differences in the aneurysmal inflow rate (SMD -6.05, 95% CI -10.87 to -1.23, p=0.01) and energy loss (SMD -5.28, 95% CI -7.09 to -3.46, p<0.001) between the successfully and unsuccessfully treated groups were indicative of statistical significance, in contrast to wall shear stress (p=0.37), intra-aneurysmal average velocity (p=0.09), vortex core-line length (p=0.46), and shear rate (p=0.09). Compacting a single stent could achieve additional flow diversion comparable to that by dual-stent implantation. CONCLUSIONS: Inflow rate and energy loss have shown promise as identifiers to discriminate between successful and unsuccessful treatment, pending future research into their diagnostic performance to establish optimal cut-off values.

A novel method to eliminate the influence of absorbed lipids on the characterization of ultra-high molecular weight polyethylene using Fourier-transform infrared spectroscopy.

BACKGROUND: Fourier-transform infrared spectroscopy (FTIR) is one of the standard methods to analyze ultra-high molecular weight polyethylene (UHMWPE) in orthopedic implants. For retrieved components, lipid extraction using an organic solvent prior to the measurement is necessary to eliminate the influence of lipids absorbed in vivo. However, its influence on the measurement has not been substantially investigated. OBJECTIVE: To investigate the influence of lipid extraction on the FTIR analysis of UHMWPE and to develop a novel method to obtain reliable results without inconvenient lipid extraction. METHODS: FTIR analysis was repeatedly performed on UHMWPE specimens from retrieved components before and after lipid extraction under various conditions. A method to calculate the extent of influence of the absorbed lipids from the FTIR spectra was developed using a peak separation technique. RESULTS: An elevated temperature was necessary for lipid extraction; however, it had the potential to influence the results if the conditions were not properly controlled. The results obtained using the peak separation technique coincided with those obtained after lipid extraction. CONCLUSION: The use of the peak separation technique enables the efficient acquisition of reliable results without the need for lipid extraction.

Selective cesium removal from radioactive liquid waste by crown ether immobilized new class conjugate adsorbent.

Conjugate materials can provide chemical functionality, enabling an assembly of the ligand complexation ability to metal ions that are important for applications, such as separation and removal devices. In this study, we developed ligand immobilized conjugate adsorbent for selective cesium (Cs) removal from wastewater. The adsorbent was synthesized by direct immobilization of dibenzo-24-crown-8 ether onto inorganic mesoporous silica. The effective parameters such as solution pH, contact time, initial Cs concentration and ionic strength of Na and K ion concentrations were evaluated and optimized systematically. This adsorbent was exhibited the high surface area-to-volume ratios and uniformly shaped pores in case cavities, and its active sites kept open functionality to taking up Cs. The obtained results revealed that adsorbent had higher selectivity toward Cs even in the presence of a high concentration of Na and K and this is probably due to the Cs-π interaction of the benzene ring. The proposed adsorbent was successfully applied for radioactive Cs removal to be used as the potential candidate in Fukushima nuclear wastewater treatment. The adsorbed Cs was eluted with suitable eluent and simultaneously regenerated into the initial form for the next removal operation after rinsing with water. The adsorbent retained functionality despite several cycles during sorption-elution-regeneration operations.

Brazilian propolis inhibits the differentiation of Th17 cells by inhibition of interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3.

Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. It has been reported to show immunomodulatory activity. Previously, we reported the protective effect of Brazilian propolis ethanolic extract against the pathogenesis of collagen-induced arthritis (CIA), an experimental animal model of rheumatoid arthritis (RA). Moreover, we found that the protective effect against CIA was involved in suppression of the production of interleukin-17 (IL-17) in CIA mice. In the present study, we demonstrated for the first time that propolis inhibited IL-6 plus transforming growth factor-ß induced Th17 differentiation in vitro. Propolis also suppressed the IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a cytokine-activated essential transcription factor in Th17 development, concomitantly with the enhanced suppressor of cytokine signaling 3 expression involved in the downregulation of STAT3 phosphorylation. These data suggest that the suppressive effect of propolis on Th17 differentiation might be useful for controlling unbalanced cytokine networks in autoimmune diseases.

Determination of soluble tumor necrosis factor-α receptor type I (TNFRI) and II (TNFRII) in the urine of healthy Japanese subjects.

We determined the urinary soluble tumor necrosis factor-α receptor type I (sTNFRI) and type II (sTNFRII) levels in healthy Japanese individuals to establish a reference value by means of specific ELISA. It was found that there were no significant differences between the urine sTNFRI and sTNFRII levels of children and adults. To demonstrate the usefulness of the reference value for children, we measured the urine sTNFRI and sTNFRII levels of children with diarrhea positive (D+) hemolytic uremic syndrome (HUS) as a preliminary study. The urine sTNFRI and sTNFRII levels of the patients with HUS were markedly higher than those of healthy children from the onset of D + HUS. Our reliable reference value for healthy children will allow us to discriminate between normal and pathological conditions in future studies.

Determination of age-related changes in human vascular endothelial growth factor in the serum and urine of healthy subjects.

Vascular endothelial growth factor (VEGF) is an important regulator of endothelial cells and a key promoter of angiogenesis in physiological and pathophysiological conditions. A large number of studies dealing with body fluid measurement of VEGF for diagnostic and therapeutic monitoring have been reported. Neither the age-related profile of serum and urine VEGF levels nor the correlation between serum and urinary VEGF levels has been sufficiently investigated. In the present study, we determined the VEGF levels of the serum and urine of healthy Japanese subjects using an enzyme-linked immunosorbent assay (ELISA). The serum VEGF level of children (0-14 years old) was significantly higher than that of adults (over 15 years old) (p < 0.05). On the other hand, there was no significant difference between the urine VEGF levels of children and adults. Thus, it is recommended that when the serum VEGF levels of patients are evaluated, they should be compared with those of age-matched controls. The VEGF level of the serum was not statistically correlated with that of the urine (p = 0.800). Fundamental VEGF values for body fluids of healthy subjects are necessary for the rigorous assessment of health and illness.

Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading.

This study evaluated the possibility of differentiation from embryonic stem (ES) cells to vascular wall cells by physical (mechanical) stress loading in vitro. A cell mixture containing Flk1-positive cells (ca. 30%) derived from murine ES cells was added to a compliant microporous tube made of segmented polyurethane. The compliance of the tube was close to that of the human artery [the stiffness parameter (beta) = 57.2 (n = 5, SD < 5%)]. The luminal surface of the tube was fully covered with the cells by preincubation for two days in the presence of vascular endothelial growth factor (VEGF). After 2 days of additional incubation without VEGF under static conditions, layering of the grown cells, mostly smooth muscle actin (SMA)-positive cells, was observed only on the luminal surface of the tube. The cells were flat, polygonal, and randomly oriented. On the other hand, after a 2-day incubation under a weak pulsatile flow simulating the human venous systems [wall shear stress (WSS) from -0.98 to 2.2 dyn/cm(2); circumferential strain (CS) 4.6-9.6 x 10(4) dyn/cm(2)] without VEGF, cells in the superficial layer were regularly oriented in the direction of the pulsatile flow. The oriented cells exhibited endothelial-like appearance, indicating that they were platelet endothelial cell adhesion molecule 1 (PECAM1)-positive. In addition, the cells growing into the interstices in the deeper layer showed smooth muscle-like appearance, indicating that they were SMA-positive. Differentiation to two different cell types and segregation of incorporated ES cells may be simultaneously encouraged by the combination of WSS and CS. It is expected that the monobloc building of hierarchically structured hybrid vascular prostheses composed of several vascular wall cell types is possible by physically synchronized differentiation of ES cells.

Development of sutureless vascular connecting system for easy implantation of small-caliber artificial grafts.

A novel sutureless vascular connecting system, an assembly with a delivery rod, an introducing sheath, and a connecting device, was developed for easy implantation of small-caliber vascular grafts less than 2 mm in internal diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm, wall thickness 65 microm, pore diameter 400 microm, pore-to-pore distance 500 microm) was designed to serve as a connecting device. The feasibility of the system was tested using two types of preliminary animal experiments. One animal model consisted of graft implantation into the rat abdominal aorta (1.5 mm in diameter). The connecting device was inserted into the proximal and distal ends of the aorta through the introducing sheath by pushing the delivery rod with the connecting device placed over it. Subsequently, the aortic segments were inserted into both ends of model grafts made of segmented polyurethane (1.8 mm in internal diameter) and were fixed with banding silk threads from the exterior. The procedure was completed within 20 min without requiring specialized microsurgery techniques. Blood leakage and obstruction did not occur. The second model consisted of an end-to-end anastomosis between rabbit common carotid arteries (2 mm in diameter), which was performed within several minutes of blood flow interruption. Scanning electron microscopy demonstrated that the luminal surface of the device was fully covered with endothelial cells (ECs) after 1 week as a result of transluminal ingrowth of native ECs through the micropores in the device. This endothelialization may prevent early thrombus-induced occlusion. This simple and "easy-to-learn" technique will promote the development of small-caliber arterial grafts, and furthermore, it may have potential for clinical application.

Anthropometric, lifestyle and biomarker assessment of Japanese non-professional ultra-marathon runners.

BACKGROUND: Anthropometric characteristics, lifestyle, and baseline biological markers of Japanese non-professional ultra-marathon runners have not been fully assessed. METHODS: We evaluated anthropometric characteristics, lifestyle, and baseline biological markers of 180 Japanese amateur ultra-marathon runners (144 males [mean age: 50.5 +/- 9.4 (standard deviation) years] and 36 females [48.9 +/- 6.9]), and compared them with those of participants in a community heath check-up program and with the figures in the literature. We furthermore evaluated baseline blood indices according to monthly running distance with analysis of variance adjusted for age, body mass index, smoking and alcohol drinking habits. RESULTS: The ultra-marathon runners demonstrated more favorable values for body mass index and bone density, and the proportion of smoking, and undertaking physical activity (for both sexes), eating breakfast (for males), and having daily bowel movements (for females), while greater proportion of alcohol drinking habit (for both sexes), than the comparison group. Average monthly running distances and standard deviations (km) were 257.2 +/- 128.9 for males and 209.0 +/- 86.2 for females. Male runners possessed beneficial markers, including lowered triglyceride and elevated high-density lipoprotein cholesterol, and their values showed hockey-stick (or inverse hockey-stick) patterns depending on their monthly running distance. Some subjects running more than 300 km/month exhibited signs of an over-reaching/training syndrome, including somewhat lowered hemoglobin, ferritin and white blood cell count, and elevated creatine kinase and lactate dehydrogenase. CONCLUSIONS: Together with a desirable lifestyle, Japanese non-professional ultra-marathon runners with vigorous exercise habit demonstrated a preferable health status according to biological indices.

Denaturing high performance liquid chromatography analysis of the DPYD gene in patients with lethal 5-fluorouracil toxicity.

Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency is a pharmacogenetic syndrome with possible fatal outcome following 5-fluorouracil (5-FU) treatment. Several studies examining the molecular basis for DPD deficiency have identified over 30 sequence variations in the DPYD gene (which codes for the DPD enzyme). Our laboratory has recently developed and validated a denaturing high performance liquid chromatography method capable of identifying both known and unknown sequence variations in the DPYD gene. In the present study, we used this denaturing high performance liquid chromatography approach to examine the DPYD genotype of three patients who experienced lethal toxicity after administration of 5-FU. DPD enzyme activity could only be measured in one patient before death and demonstrated that lethal toxicity can occur in a partially DPD-deficient individual. Multiple heterozygous sequence variations (both known and unknown) were detected in all three patients including the novel variants 545T>A, M182K and 2329G>T, A777S. We conclude that (a) lethal toxicity can occur in partially DPD-deficient individuals after administration of 5-FU and is not exclusive to profoundly DPD-deficient individuals as suggested previously, (b) the complicated heterozygote genotype seen in these patients, combined with DPD deficiency being an autosomal codominant inherited syndrome, precludes the use of simple genotyping assays that identify only one or two mutations as a method for identifying DPD-deficient individuals; and (c) these multiple heterozygote genotypes (which are more difficult to accurately characterize) may be responsible for some of the conflicting reports which suggests a lack of correlation between phenotype and genotype.