Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia.

Despite the significant progress made in recent years, clinical issues with small-diameter vascular grafts related to low mechanical strength, thrombosis, intimal hyperplasia, and insufficient endothelialization remain unresolved. This study aims to design and fabricate a core-shell fibrous small-diameter vascular graft by co-axial electrospinning process, which will mechanically and biologically meet the benchmarks for blood vessel replacement. The presented graft (PGHV) comprised polycaprolactone/gelatin (shell) loaded with heparin-VEGF and polycaprolactone (core). This study hypothesized that the shell structure of the fibers would allow rapid degradation to release heparin-VEGF, and the core would provide mechanical strength for long-term application. Physico-mechanical evaluation, in vitro biocompatibility, and hemocompatibility assays were performed to ensure safe in vivo applications. After 25 days, the PGHV group released 79.47 ± 1.54% of heparin and 86.25 ± 1.19% of VEGF, and degradation of the shell was observed but the core remained pristine. Both the control (PG) and PGHV groups demonstrated robust mechanical properties. The PGHV group showed excellent biocompatibility and hemocompatibility compared to the PG group. After four months of rat aorta implantation, PGHV exhibited smooth muscle cell regeneration and complete endothelialization with a patency rate of 100%. The novel core-shell structured graft could be pivotal in vascular tissue regeneration application.

Poly(l-lactide)/polycaprolactone based multifunctional coating to deliver paclitaxel/VEGF and control the degradation rate of magnesium alloy stent.

Despite significant advancements made in cardiovascular stents, restenosis, thrombosis, biocompatibility, and clinical complications remain a matter of concern. Herein, we report a biodegradable Mg alloy stent with a dual effect of the drug (Paclitaxel) and growth factor (VEGF) release. To mitigate the fast degradation of Mg alloy, inorganic and organic coatings were formed on the alloy surface. The optimized hierarchal sequence of the coating was the first layer consisting of magnesium fluoride, followed by poly(l-lactide) and hydroxyapatite coating, and finally sealed by a polycaprolactone layer (MgC). PLLA and HAp were used to increase the adhesion strength and biocompatibility of the coating. Paclitaxel and VEGF were loaded in the final PCL layer (Mg-C/PTX-VEGF). As compared to bare Mg alloy (28 % weight loss), our MgC system showed (3.1 % weight loss) successful decrease in the degradation rate. Further, the in vitro biocompatibility illustrated the highly biocompatible nature of our drug and growth factor-loaded system. The in vivo results displayed that the drug loading decreased the inflammation and neointimal hyperplasia as indicated by the α-SMA and CD-68 antibody staining. The growth factor helped in the endothelialization which was established by the FLKI and ICAM antibody staining of the tissue.

New disordered anyon phase of doped graphene zigzag nanoribbon.

We investigate interacting disordered zigzag nanoribbons at low doping, using the Hubbard model to treat electron interactions within the density matrix renormalization group and Hartree-Fock method. Extra electrons that are inserted into an interacting disordered zigzag nanoribbon divide into anyons. Furthermore, the fractional charges form a new disordered anyon phase with a highly distorted edge spin density wave, containing numerous localized magnetic moments residing on the zigzag edges, thereby displaying spin-charge separation and a strong non-local correlation between the opposite zigzag edges. We make the following new predictions, which can be experimentally tested: (1) In the low doping case and weak disorder regime, the soft gap in the tunneling density of states is replaced by a sharp peak at the midgap energy with two accompanying peaks. The [Formula: see text] fractional charges that reside on the boundary of the zigzag edges are responsible for these peaks. (2) We find that the midgap peak disappears as the doping concentration increases. The presence of [Formula: see text] fractional charges will be strongly supported by the detection of these peaks. Doped zigzag ribbons may also exhibit unusual transport, magnetic, and inter-edge tunneling properties.

Physico-mechanical and biological evaluation of heparin/VEGF-loaded electrospun polycaprolactone/decellularized rat aorta extracellular matrix for small-diameter vascular grafts.

Although the continuous development of small-diameter vascular grafts (SDVGs) (D < 5 mm) continues, most vascular grafts are made from synthetic polymers, which lead to serious complications from arteriosclerosis, thrombosis, and vascular ischemia. Here, to address these shortcomings, we combine synthetic polymers with natural decellularized small-diameter vessels and loaded with growth factor. We fabricated vascular grafts by electrospinning polycaprolactone (PCL) to decellularized rat aorta matrix (ECM) followed by heparin and vascular endothelial growth factor (VEGF) loading. In- vitro studies showed that PCL/ECM/VEGF vascular grafts, showed excellent hemocompatibility and biocompatibility properties. The vascular grafts implanted into the rat aorta revealed that the PCL/ECM/VEGF grafts promotes endothelial cells and smooth-muscle cells infiltration with a rate of FLK-1, ICAM1, and a-SMA distribution higher than that of the PCL and PCL/ECM vascular grafts at 2 weeks and 4 weeks after implantation. The PCL/ECM/VEGF vascular graft should be considered for potential small-diameter vascular grafts in clinical fields.

LGI1 governs neuritin-mediated resilience to chronic stress.

Depression is accompanied by neuronal atrophy and decreased neuroplasticity. Leucine-rich glioma-inactivated protein 1 (LGI1), a metastasis suppressor, plays an important role in the development of CNS synapses. We found that LGI1 expression was reduced in the hippocampi of mice that underwent chronic unpredictable stress (CUS), and could be rescued by the antidepressant, fluoxetine. Recombinant soluble neuritin, an endogenous protein previously implicated in antidepressant-like behaviors, elevated hippocampal LGI1 expression in a manner dependent on histone deacetylase 5 (HDAC5) phosphorylation. Accordingly, Nrn1 flox/flox ;Pomc-cre (Nrn1 cOE) mice, which conditionally overexpress neuritin, displayed increases in hippocampal LGI1 level under CUS and exhibited resilience to CUS that were blocked by hippocampal depletion of LGI1. Interestingly, neuritin-mediated LGI1 expression was inhibited by HNMPA-(AM)3, an insulin receptor inhibitor, as was neuritin-mediated HDAC5 phosphorylation. We thus establish hippocampal LGI1 as an effector of neurite outgrowth and stress resilience, and suggest that HDAC5-LGI1 plays a critical role in ameliorating pathological depression.

Expression of AMP-activated protein kinase/ten-eleven translocation 2 and their clinical relevance in colorectal cancer.

Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.

Wound outcomes and factors associated with wound healing after first-time femoropopliteal artery intervention in patients with ischemic tissue loss.

BACKGROUND/OBJECTIVE: This study's goal is to describe wound outcomes at 2 years following intervention for atherosclerotic femoropopliteal lesions in patients with ischemic tissue loss. METHODS: A retrospective review of 135 first-time endovascular procedures for chronic femoropopliteal atherosclerotic lesions related to ischemic tissue loss was performed. The final wound outcomes were categorized according to the initial wound healing, recurrence and the need of major/minor amputation. RESULTS: At 2-years of follow up, 76 limbs (56.3%) showed complete wound healing without recurrence, however, wound development occurred at other sites on the same foot following complete primary healing in 11 limbs (8.1%). Tolerable wounds persisted or wounds recurred at the same site in 30 limbs (22.2%), and 18 limbs (13.3%) needed major amputations. Independent factors that prevented wound healing without recurrence at 2 years were renal insufficiency (HR = 0.225, 95% C.I. = 0.091-0.556, p = 0.001), ankle pressure < 50 mmHg or flat forefoot PVR (HR = 0.328, 95% C.I. = 0.124-0.867, p = 0.025) and functional performance < 4 metabolic equivalents (MET) (HR = 0.150, 95% C.I. = 0.063-0.360, p < 0.001). CONCLUSION: Wound outcome classifications showed detailed information regarding clinical outcomes in patients with ischemic tissue loss. Renal insufficiency, ischemia grade 3 and poor functional performance were independent risk factors that prevented wound healing.

Effect of Opt-out System for Organ Donation After Brain Death on Ethical Legitimacy and Potential Efficacy in a Mathematical Model.

OBJECTIVES: We aimed to compare the possible outcomes of the current (opt-in) system and an opt-out system for organ donation in South Korea using a mathematical model. MATERIALS AND METHODS: A structured questionnaire was used to investigate the decision on organ donation and family consent after brain death under the current system and an opt-out system. The survey was conducted in August 2018 by means of a voluntary survey of 100 opposite-sex married couples. RESULTS: Sixty-three percent of participants wished to self-donate their organs after brain death: 69.5% were positive and 30.5% were negative regarding the implementation of the opt-out system. Among 200 participants, the total number of possible donors increased from 110 (55.0%) in the current system to 139 (69.5%) in the opt-out system. Positive autonomy was defined as obtainment of consent from the donor and the spouse, and negative autonomy was defined as concordaence of refusal between the donor and the spouse. Comparisons between the systems showed that the rate of autonomy increased from 57.0% in the current system to 61.5% in the opt-out system. Although the achievement of positive autonomy increased from 59.5% in the current system to 74.6% in the opt-out system, the achievement of negative autonomy decreased from 52.7% in the current system to 39.2% in the opt-out system. CONCLUSIONS: An opt-out system can increase the number of organ donors; however, achievement of negative autonomy can decrease.

The Effect of Severe Femoropopliteal Arterial Calcification on the Treatment Outcome of Femoropopliteal Intervention in Patients with Ischemic Tissue Loss.

PURPOSE: We investigated the effect of severe calcification of the femoropopliteal artery on intervention outcomes in patients with ischemic tissue loss. MATERIALS AND METHODS: A retrospective review of the first endovascular treatment of the femoropopliteal artery for ischemic tissue loss between May 2010 and February 2018 was performed. The calcification of femoropopliteal lesions was estimated by the Compliance 360° score, and lesions with a score of 4 were defined as severe calcification lesions. RESULTS: Overall, 135 first femoropopliteal endovascular procedures on 135 limbs from 112 patients were included in this study. Among the 135 limbs that received treatement of the femoropopliteal arteries, 74 limbs had Trans-Atlantic Inter Society Consensus (TASC) A or B lesions and 61 limbs had TASC C or D lesions. Among 61 cases of TASC C or D lesions, 21 limbs (34.4%) had severe calcification; there was no statistically significant difference in limb salvage (P=0.75), and amputation-free survival (P=0.11) based on the degree of calcification. However, the survival rate in TASC C or D lesions was significantly different between the two groups (non-severe calcification group vs severe calcification group at 1-year, 2-years, and 3-years: 88.6%, 79.7%, and 61.0% vs 70.0%, 56.0%, and 28.0%, respectively, P=0.01). In multivariate analysis of influencing factors for poor survival in TASC C or D using the Cox proportional hazards model, severe calcification (hazard ratio, 2.362; 95% confidence interval, 1.035-5.391; P=0.041) was a statistically significant risk factor. CONCLUSION: Severe femoropopliteal artery calcification was associated with poor survival, especially in TASC C or D lesions.

Magnetic field induced quantum phases in a tensor network study of Kitaev magnets.

Recent discovery of the half quantized thermal Hall conductivity in [Formula: see text]-RuCl[Formula: see text], a candidate material for the Kitaev spin liquid, suggests the presence of a highly entangled quantum state in external magnetic fields. This field induced phase appears between the low field zig-zag magnetic order and the high field polarized state. Motivated by this experiment, we study possible field induced quantum phases in theoretical models of the Kitaev magnets, using the two dimensional tensor network approach or infinite tensor product states. We find various quantum ground states in addition to the chiral Kitaev spin liquid occupying a small area in the phase diagram. They form a band of emergent quantum phases in an intermediate window of external magnetic fields, somewhat reminiscent of the experiment. We discuss the implications of these results in view of the experiment and previous theoretical studies.

The effect of a mandatory choice systemfor organ donation after brain death onethical legitimacy and potential efficacyin a mathematical model.

Background: The "mandatory choice" system is an organ donation system that forces individuals to clearly express their choice about organ donation. Although this system is widely practiced in western countries, it has not yet been implemented in many Asian countries. This study aimed to compare the possible outcomes of a mandatory choice system and the current system in Korea. Methods: A mathematical model was used to predict outcomes under each system. A structured questionnaire assuming two systems (current opt-in and mandatory choice) was developed to investigate participants' decisions on organ donation and the family's consent after brain death in each system. Participants who enrolled in this survey were 100 couples (200 people). Results: The total number of donors decreased slightly from 102 (51.0%) in the current opt-in system to 93 (46.5%) in the mandatory choice system. The rate of achieving autonomy was increased from 62.5% (125/200) in the current system to 68.0% (136/200) in the mandatory choice system. The achievement of negative autonomy was relatively higher in the mandatory choice system (73.6% [67/91] vs. 63.2% [55/87]). Conclusions: The mandatory choice system can supplement the weak ethical point of the current system by increasing the achievement of autonomy.

Thermal-transport studies of kagomé antiferromagnets.

Searching for the ground state of a kagomé Heisenberg antiferromagnet (KHA) has been one of the central issues of condensed-matter physics, because the KHA is expected to host spin-liquid phases with exotic elementary excitations. Here, we show our longitudinal ([Formula: see text]) and transverse ([Formula: see text]) thermal conductivities measurements of the two kagomé materials, volborthite and Ca kapellasite. Although magnetic orders appear at temperatures much lower than the antiferromagnetic energy scale in both materials, the nature of spin liquids can be captured above the transition temperatures. The temperature and field dependence of [Formula: see text] is analyzed by spin and phonon contributions, and large sample variations of the spin contribution are found in volborthite. Clear changes in [Formula: see text] are observed at the multiple magnetic transitions in volborthite, showing different magnetic thermal conduction in different magnetic structures. These magnetic contributions are not clearly observed in low-[Formula: see text] crystals of volborthite, and are almost absent in Ca kapellasite, showing the high sensitivity of the magnetic excitation in [Formula: see text] to the defects in crystals. On the other hand, a clear thermal Hall signal has been observed in the lowest-[Formula: see text] crystal of volborthite and in Ca kapellasite. Remarkably, both the temperature dependence and the magnitude of [Formula: see text] of volborthite are found to be very similar to those of Ca kapellasite, despite of about an order of magnitude difference in [Formula: see text] We find that [Formula: see text] of both compounds is well reproduced, both qualitatively and quantitatively, by spin excitations described by the Schwinger-boson mean-field theory applied to KHA with the Dzyaloshinskii-Moriya interaction. This excellent agreement demonstrates not only that the thermal Hall effect in these kagomé antiferromagnets is caused by spins in the spin liquid phase, but also that the elementary excitations of this spin liquid phase are well described by the bosonic spin excitations.

Survey for the Opinion of Medical Students and Medical Staff on a Financial Incentive System for Deceased Organ Donation in an Asian Country.

BACKGROUND: Financial incentives for deceased organ donation are associated with many controversial ethical issues. This study examines the perspectives of medical students and staff members on financial incentives for the families of brain-dead organ donors. METHODOLOGY: A structured survey form was used between December 7, 2017 and January 28, 2018 to elicit opinions on financial incentives for the families of brain-dead organ donors. Forty-three medical staff members and 81 medical students participated in the survey voluntarily. The opinions on the financial incentive system and the relationship between willingness to give information about organ donation to families and a financial incentive system were assessed. RESULTS: The majority of the participants (81.4%) had positive thoughts on organ donation. More than half of the participants (60.5%) thought that the financial incentive system did not erode the ethical purity of organ donation. As charge doctors, most respondents (84.6%) were willing to give information about organ donation to family members in the presence of financial incentives. However, the percentage decreased significantly to 60.5% when financial incentive was no longer factored into consideration (P < .001). LIMITATION: The study population is small, and the participants are not representative of the general population. CONCLUSION: The opinions of medical students and medical staff on financial incentives for deceased organ donation were generally positive. Financial incentives proved to be a potential influencing factor as an option of organ donation to be given to families.

Gapless Kitaev Spin Liquid to Classical String Gas through Tensor Networks.

We provide a framework for understanding the gapless Kitaev spin liquid (KSL) in the language of the tensor network (TN). Without introducing a Majorana fermion, most of the features of the KSL, including the symmetries, gauge structure, criticality, and vortex freeness, are explained in a compact TN representation. Our construction reveals a hidden string gas structure of the KSL. With only two variational parameters to adjust, we obtain an accurate KSL Ansatz with the bond dimension D=8 in a compact form, where the energy is about 0.007% higher than the exact one.

Arterial Aneurysmal Degeneration With Venous Varicosity Following Ligation of an Arteriovenous Fistula in a Kidney Transplant Recipient.

Late occurrence of arterial aneurysms following ligation of a hemodialysis arteriovenous fistula (AVF) is rare. Here, we report the case of 51-year-old male patient with an AVF in which arterial aneurysms developed. The patient had undergone left arm radiocephalic (RC) AVF creation for hemodialysis in 2000. He had received a living related donor kidney transplantation from his father in the same year. His RC AVF was ligated in 2009. However, his arm continued to gradually grow in size even after ligation and he visited a hospital for acute pain and erythema around the left elbow in 2017. Since his renal allograft function had been deteriorating, duplex ultrasonography was performed. It revealed 2 giant aneurysms in the distal brachial artery and proximal radial artery with diameters of 3.0 and 2.8 cm, respectively. The superficial veins of the left upper arm showed varicosity and had multifocal thrombi. Microfistula between the artery and vein was revealed by contrast-enhanced ultrasonography and the contrast agent microbubbles flowed from the artery toward the superficial veins. The aneurysms were resected and the arteries were reconstructed with great saphenous vein. There were no perioperative complications and the patient was discharged on postoperative day 3. No complications in the arm or bypass conduit have occurred at 6 months after the surgery.

Spin Thermal Hall Conductivity of a Kagome Antiferromagnet.

A clear thermal Hall signal (κ_{xy}) was observed in the spin-liquid phase of the S=1/2 kagome antiferromagnet Ca kapellasite [CaCu_{3}(OH)_{6}Cl_{2}·0.6H_{2}O]. We found that κ_{xy} is well reproduced, both qualitatively and quantitatively, using the Schwinger-boson mean-field theory with the Dzyaloshinskii-Moriya interaction of D/J∼0.1. In particular, κ_{xy} values of Ca kapellasite and those of another kagome antiferromagnet, volborthite, converge to one single curve in simulations modeled using Schwinger bosons, indicating a common temperature dependence of κ_{xy} for the spins of a kagome antiferromagnet.

Ultrasound-Guided Direct Needle Engagement for Flush-Occluded Superficial Femoral Artery.

Flush ostial occlusion of the superficial femoral artery (SFA) is challenging for endovascular treatment. Neither ipsilateral nor contralateral access is easy. The drawback of ipsilateral common femoral artery (CFA) access is that the CFA is too short for catheter manipulation and sheath engagement. Contralateral retrograde CFA access could have merit, but it has the drawback of poor pushability and torquability in the manipulation of devices. The most challenging part of flush ostial occlusion is the difficulty of wire engagement into the SFA orifice. We describe a case of successful treatment of a flush-occluded long SFA lesion using ultrasound-guided direct ipsilateral ostial access.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer.

[This corrects the article on p. 19 in vol. 94, PMID: 29333422.].

Epigenetic inactivation of RUNX3 in colorectal cancer.

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

The ethanol extract of Aquilariae Lignum ameliorates hippocampal oxidative stress in a repeated restraint stress mouse model.

BACKGROUND: Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. METHODS: Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10). For 11 consecutive days, each group was orally administered with distilled water, ALE (20 or 80 mg/kg) or N-acetylcysteine (NAC; 100 mg/kg), and then all mice (except unstressed group) were subjected to restraint stress for 6 h. On the final day, brain tissues and sera were isolated, and stress hormones and hippocampal oxidative alterations were examined. We also treated lipopolysaccharide (LPS, 1 µg/mL)-stimulated BV2 microglial cells with ALE (1 and 5 µg/mL) or NAC (10 µM) to investigate the pharmacological mechanism. RESULTS: Restraint stress considerably increased the serum levels of corticosterone and adrenaline and the hippocampal levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). ALE administration significantly attenuated the above abnormalities. ALE also significantly normalized the stress-induced activation of astrocytes and microglial cells in the hippocampus as well as the elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The in vitro assay outcome supplemented ALE could dramatically block NF-κB activation in microglia. The anti-oxidative stress effects of ALE were supported by the results of antioxidant components, 4-hydroxynonenal (4-HNE), NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS) and NFE2L2 (Nrf2) in the hippocampal tissues. CONCLUSIONS: We firstly demonstrated the neuroprotective potentials of A. Lignum against hippocampal oxidative injury in repeated restraint stress. The corresponding mechanisms might involve modulations in the release of ROS, pro-inflammatory cytokines and stress hormones.