Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.

BACKGROUND: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown. METHODS: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery. RESULTS: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis. CONCLUSIONS: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Adipose Derived Stromal Vascular Fraction and Mesenchymal Stem Cells Improve Angiogenesis in a Rat Hindlimb Ischaemia Model.

OBJECTIVE: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model. METHODS: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment. RESULTS: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups. CONCLUSION: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease.

Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model.

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Small extracellular vesicles derived from patients with persistent atrial fibrillation exacerbate arrhythmogenesis via miR-30a-5p.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles that contribute to the pathogenesis of atrial fibrillation (AF). Here, we investigated the role of sEVs derived from patients with persistent AF in the pathophysiology of AF. First, we evaluated the pathological effects of sEVs derived from the peripheral blood of patients with persistent AF (AF-sEVs). AF-sEVs treatment reduced cell viability, caused abnormal Ca2+ handling, induced reactive oxygen species (ROS) production and led to increased CaMKII activation of non-paced and paced atrial cardiomyocytes. Next, we analyzed the miRNA profile of AF-sEVs to investigate which components of AF-sEVs promote arrhythmias, and we selected six miRNAs that correlated with CaMKII activation. qRT-PCR experiment identified that miR-30a-5p was significantly down-regulated in AF-sEVs, paced cardiomyocytes, and atrial tissues of patients with persistent AF. CaMKII was predicted by bioinformatics analysis as a miR-30a-5p target gene and validated by a dual luciferase reporter; hence, we evaluated the effects of miR-30a-5p on paced cardiomyocytes and validated miR-30a-5p as a pro-arrhythmic signature of AF-sEVs. Consequently, AF-sEVs-loaded with miR-30a-5p attenuated pacing-induced Ca2+-handling abnormalities, whereas AF-sEVs-loaded with anti-miR-30a-5p reversed the change in paced cardiomyocytes. Taken together, the regulation of CaMKII by miR-30a-5p revealed that miR-30a-5p is a major mediator for AF-sEVs-mediated AF pathogenesis. Accordingly, these findings suggest that sEVs derived from patients with persistent AF exacerbate arrhythmogenesis via miR-30a-5p.

Clinical and Hemodynamic Outcomes in 121 Patients Who Underwent Perceval Sutureless Aortic Valve Implantation　- Early Results From a Single Korean Institution.

BACKGROUND: This study aimed to evaluate the early outcomes of Perceval sutureless valves in the Korean population and to introduce a modified technique of guiding suture placement during valve deployment.Methods and Results:From December 2014 to April 2019, 121 patients (mean age: 74.7±6.2 years; 53.7% female) received a Perceval sutureless aortic valve replacement. To prevent conduction system injury, the depth of guiding suture placement (1 mm below the nadir of the annulus) was modified. All patients underwent echocardiographic evaluation at discharge and 6-12 months postoperatively, with a mean follow up of 13.7±11.2 months. Concomitant surgeries, such as coronary artery bypass grafting, and other valvular surgeries, were performed in 45.5% of cases. The mean aortic cross-clamp times for isolated and minimal procedures were 32.8±7.9, and 41.2±8.0 min, respectively. The overall transvalvular mean gradients were 13.1±3.8 mmHg at discharge and 11.5±4.7 mmHg at the last follow up. After modifying the guiding suture placement, permanent pacemaker implantation risk decreased from 9.9% to 2.5%. Cardiac-related mortality was 0.8%, with no patient developing valvular or paravalvular aortic regurgitation, valve thrombosis, or endocarditis. CONCLUSIONS: Perceval valve implantation provided a significant cardiac-related survival benefit with excellent early hemodynamic and clinical outcomes. Further research is needed to determine whether adjusting the implantation depth, such as modification of the guiding suture technique, can reduce the risk of permanent pacemaker implantation.

Late open conversion after thoracic endovascular aortic repair.

OBJECTIVE: With the increasing use of endovascular aortic repair, open repair after aortic stent grafting is of increasing interest. We retrospectively reviewed cases of late open conversion for complications after thoracic endovascular aortic repair (TEVAR). METHODS: TEVAR due to aortic aneurysm and dissection was performed in 538 patients between 1994 and 2017. A total of 33 patients, including 4 patients referred from other centers, required late conversion to open repair; 14 (42.4%) patients required circulatory arrest for aortic arch involvement. The mean interval to open conversion after TEVAR was 33.9 months (range, 1-123 months). Demographics of the patients, reason for conversion, surgical techniques, surgical outcomes, and survival were reviewed. RESULTS: Indications for late open conversion included type I endoleak (14), stent graft-induced new entry intimal tear (6), retrograde type A dissection (4), stent migration and fracture (3), stent graft infection (3), sac enlargement without endoleak (1), aortopulmonary fistula (1), and stent implantation failure (1). Hospital mortality was 9.1% (3/33). All occurred in the patients with arch involvement. The patients had several major morbidities; six patients (18.1%) had pulmonary complications, two (6.1%) suffered a stroke, one (3.0%) experienced paraplegia, and one (3.0%) had renal failure. Overall survival rates at 1 year, 5 years, and 10 years were 84.5% ± 6.4%, 74.5% ± 8.7%, and 67.1% ± 10.1%, respectively. The arch involvement group (48.1% ± 15.7%) had significantly worse 10-year survival than the no arch involvement group (86.1% ± 9.4%; P = .048). CONCLUSIONS: Despite the complexity of TEVAR, open conversion due to late complications can be performed successfully with acceptable results. However, cases involving the aortic arch have relatively worse outcomes. Lifelong surveillance is mandatory, and early decision-making about open conversion before the development of a complicated aortic arch lesion is suggested to achieve better outcomes.

Late complications after hybrid aortic arch repair.

OBJECTIVE: Although hybrid arch repair has gained widespread application as an alternative option for high-risk patients, concerns about its long-term durability remain an important issue. The aim of this study was to investigate late complications after hybrid arch repair. METHODS: From January 2002 to December 2017, hybrid arch repair was performed in 65 patients with aortic arch disease (median age, 66.1 years; range, 41-86 years). Hybrid arch repair was defined as debranching involving at least one supra-aortic vessel bypass and simultaneous or staged endovascular thoracic stent grafting. We retrospectively analyzed late complications including reintervention, open conversion, and aortic-related death. The median follow-up period was 60.1 months (range, 1-170 months). RESULTS: The in-hospital mortality rate was 6% (4/65). Except for early death (n = 4) and early open conversion (n = 2), late complications were observed in 25 patients (25/59 [42%]). The median time interval between the initial procedure and late complication was 36.6 months (range, 1-92 months). Late complications included delayed type I endoleak (n = 8), distal stent-induced new entry (n = 3), stent migration (n = 3), retrograde type A dissection (n = 2), aortopulmonary fistula (n = 2), aortoesophageal fistula (n = 1), stent fracture (n = 1), infection (n = 1), and sudden death (n = 4). Six of these patients (10%) underwent late open conversion. The overall survival rates at 3 years and 6 years were 71.1 ± 7.4% and 57.2 ± 11.3%, respectively. The aortic event-free rates at 3 years and 6 years were 52.1 ± 7.3% and 39.4 ± 10.3%, respectively. CONCLUSIONS: Late complications in hybrid arch repair occurred in a substantial proportion of patients during midterm follow-up. Regardless of zone type, the incidence of late complications was relatively high. This study suggests that timely reintervention and open conversion are important for rescuing patients, but repeated reinterventions and conservative strategies are not recommended. Aggressive management and life-long surveillance after hybrid arch repair are mandatory for better outcomes.

Effects of a Proximal Seal System on Neurologic Outcomes of Off-Pump Coronary Artery Bypass Grafting.

Severe aortic atherosclerosis is a risk factor for stroke during coronary artery bypass grafting (CABG). The purpose of this study was to evaluate the incidence of postoperative neurologic complications after off-pump CABG (OPCAB) with a proximal seal system (Heartstring).From January 2011 to December 2014, 729 patients underwent isolated OPCAB. The cohort was divided into two groups (Heartstring [HS] and aortic no-touch [NT]). The severity of aortic atherosclerosis (Katz grade) was evaluated by intraoperative epiaortic ultrasonography (EUS). The primary endpoints were postoperative neurologic complications (early stroke and minor events (delirium, transient ischemic attack, and syncope) ), and the secondary endpoints were late major adverse cardiac and cerebrovascular events (MACCEs) and death.The mean age of all patients was 65.1 ± 9.5 years, and a severe Katz grade (IV or V) was demonstrated to be an independent risk factor of long-term mortality (HR 3.53; 95% CI 1.06-11.75; P = 0.04) and MACCEs (HR 2.41; 95% CI 1.19-4.92; P = 0.02), but no significant differences were found for early stroke (0.9% versus 1.7%; P = 0.53) and minor neurologic complications (14.6% versus 9.9%; P = 0.05) between the groups regardless of the Katz grade. The 5-year overall survival rate did not differ significantly between the groups (90.9% versus 87.6%; P = 0.61).Although a higher Katz grade was identified as an independent risk factor of death and MACCEs, the HS group was not inferior in terms of neurologic complications regardless of the Katz grade. Therefore, the Heartstring system might be safely and efficiently used with EUS to decrease the incidence of neurologic complications.

Effect of Recurrent Mitral Regurgitation After Mitral Valve Repair in Patients With Degenerative Mitral Regurgitation.

BACKGROUND: This study investigated the consequences of recurrent mitral regurgitation (MR) after mitral valve (MV) repair in patients with degenerative MR and risk factors for recurrence.Methods and Results:From January 1990 to December 2015, 792 patients underwent MV repair due to degenerative MR. Recurrent MR was defined as moderate-to-severe MR on follow-up echocardiography. Mean follow-up duration was 8.71±5.58 years. During the follow-up period, MR recurred in 133 (16.8%) patients, and the MR recurrence-free rate at 20 years was 77.5±2.0%. In the recurrence group, the degree of MR decreased in 8 (6.0%) patients and was aggravated in 46 (34.6%) patients. Recurrent MR was associated with increased mortality and adverse left ventricular (LV) remodeling. Independent risk factors for MR recurrence were MV repair performed before 2000, preoperative atrial fibrillation, high LV end-diastolic dimension (LVEDD), prolapse of the isolated anterior leaflet or multiple segments, and absence of ring annuloplasty. Predictors of MR progression were high LVEDD and repair without artificial chordae implantation. CONCLUSIONS: Recurrent MR after MV repair in patients with degenerative MR showed a tendency to progress and was associated with increased mortality and adverse LV remodeling. Early referral for MV repair before development of atrial fibrillation and LV enlargement may reduce the risk of MR recurrence. Moreover, artificial chordae implantation and ring annuloplasty may assure the long-term durability of MV repair.

Predictors and Clinical Impacts of Aggravated Left Ventricular Diastolic Dysfunction After Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: To determine the predictors of aggravated left ventricular diastolic dysfunction (LVDD) in patients undergoing off-pump coronary artery bypass grafting (OPCAB) and to compare late outcomes according to the aggravated LVDD. METHODS AND RESULTS: OPCAB was performed in 1,101 patients (2001-2013). LVDD was classified as normal, mild, moderate or severe. Patients were divided into 2 groups: non-aggravated LVDD (group I) and aggravated LVDD (group II). The primary endpoint was aggravation of LVDD. The secondary endpoint was late mortality and morbidity such as major adverse cardiac and cerebrovascular events (MACCE) related to LVDD aggravation postoperatively. There were 894 patients in group I and 207 in group II. Multivariate analysis revealed that preoperative peripheral artery obstructive disease (PAOD) (P=0.04), renal failure (P<0.01), and A' velocity (P<0.01) anticipated aggravated LVDD. The Cox hazards model revealed that aggravated LVDD was a poor prognostic factor for MACCE (P<0.01) and overall survival (P<0.01). The Kaplan-Meier survival curve showed that aggravated LVDD was related to poor late outcomes (freedom from MACCE, P=0.01; overall survival, P<0.01). CONCLUSIONS: Aggravated LVDD significantly affects late clinical outcomes after OPCAB and preoperative PAOD, renal failure, and A' velocity might be predictors. (Circ J 2016; 80: 1937-1945).

Degenerative Calcification of Pericardial Bioprostheses: Comparison of Five Implantation Methods in a Rabbit Model.

BACKGROUND AND AIM OF THE STUDY: The degenerative calcification of bioprosthetic heart valves remains a clinical challenge, especially among young adults and children. Animal models that are based on subcutaneous and intramuscular implantation and are typically used to assess interventions to prevent bioprosthetic heart valve calcification do not reflect actual hemodynamic stress and lack direct blood contact. Thus, the study aim was to investigate bioprosthesis calcification at different implantation sites. METHODS: The calcification degrees of five valve implantation methods, namely subcutaneous, intramuscular and intravenous implantation, and arterial and venous patch angioplasty, were simultaneously investigated in 10 New Zealand White rabbits. RESULTS: Ultrasonography and computed tomography images showed vascular patency to be well maintained in all implanted vessels. Histologically, cellular infiltrates around the implant and within the collagen fibers were only found in the intravenous implantation group, which also had the highest calcium level among the methods. CONCLUSION: The present study was the first to compare the degree of calcification after applying five implantation methods simultaneously in one animal species. The rabbit intravenous implantation model, which involved direct contact with blood factors, is expected to serve as a useful animal model for research into the prevention of bioprosthetic heart valve degeneration.

Anomalous Origin of Right Coronary Artery from Left Coronary Sinus: Surgical Management and Clinical Result.

BACKGROUND: Anomalous aortic origin of coronary artery is a rare congenital condition in which the coronary artery arises from the opposite sinus of Valsalva. Although many patients are asymptomatic at the time of presentation or diagnosis, surgical correction is recommended due to the risk of ischemic sudden death. We describe seven cases of right coronary artery (RCA) arising from the left sinus of Valsalva, causing the hypoperfusion through RCA. PATIENTS AND METHODS: All patients underwent preoperative coronary angiography, echocardiography, and cardiac stress test (treadmill test [TMT], n = 4; technetium-99m sestamibi [MIBI], n = 3). In four patients, coronary computed tomography (CT) was performed. On the basis of preoperative test results, unroofing of the coronary artery (n = 3) or off-pump coronary artery bypass (OPCAB; n = 4; patients with coronary arterial occlusive disease) was performed. In two patients, intraoperative flow meter was performed and showed the improvement of flow rate through RCA. RESULTS: Postoperative CT angiography after OPCAB confirmed good graft patency (n = 4); CT angiography after unroofing demonstrated widely patent neo-orifice (n = 3). All patients underwent postoperative cardiac stress tests including TMT and MIBI, which revealed no evidence of ischemia. All patients were asymptomatic and returned to normal activities (mean follow-up, 41 months; 32-49 months). CONCLUSION: The appropriate surgical procedure based on specific anatomical details, perioperative evaluation, and follow-up by focusing on the ischemia may lead to successful surgical outcomes of this coronary anomaly.

Preoperative coronary angiography within one day of valve surgery is not associated with postoperative acute kidney injury in patients with preserved renal function.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Associations between the time interval (TI) from preoperative coronary angiography (CAG) to cardiac surgery have been investigated, although with conflicting results. METHODS: We evaluated data collected from a retrospective review of consecutive patients who underwent preoperative CAG and heart valve surgery at our institution between September 2008 and February 2013. A total of 426 patients met the study criteria. Patients were divided into two groups according to the length of time between preoperative CAG and valve surgery: within one day (group A) or longer than one day (group B). Logistic regression was applied to analyze the relationships between TI and postoperative AKI. RESULTS: Of 426 patients, 140 (33%) underwent CAG on preoperative day 1, while 286 (67%) underwent CAG on preoperative day 2 or sooner. AKI occurred in 19 (13.6%) patients in group A and in 35 (12.2%) patients in group B (p = 0.70). CAG on preoperative day 1 was not associated an increased risk of AKI relative to CAG on preoperative day 2 or sooner (p = 0.49; odds ratio, 1.26; 95% CI, 0.66 to 2.41). CONCLUSIONS: Preoperative CAG within one day of elective heart valve surgery is not associated with an increase in postoperative AKI in patients with normal renal function.

Posttreatment platelet reactivity on clopidogrel is associated with the risk of adverse events after off-pump coronary artery bypass.

BACKGROUND: Dual antiplatelet therapy with aspirin and clopidogrel is currently recommended in off-pump coronary artery bypass (OPCAB). However, no data exist concerning platelet reactivity on clopidogrel after OPCAB. The aim of this study was to assess the relationship between platelet reactivity and late major adverse cardiovascular events (MACEs) after OPCAB. METHODS: In this prospective, single-center, observational study, on-clopidogrel platelet reactivity was measured using a point-of-care assay (VerifyNow system; Accumetrics Inc, San Diego, CA) in 859 patients who underwent OPCAB with 1 or more vein grafts. The primary end point was late MACEs (30 days-1 year) including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. Receiver operating characteristic curve analysis was used to estimate the cutoff value of P2Y12 reaction units (PRUs) for MACEs. RESULTS: The optimal cutoff value for posttreatment reactivity for the incidence of late MACEs was ≥188 PRU (area under the curve 0.72, 95% CI 0.68-0.75, P = .002). The incidence of late MACEs was significantly higher in the high platelet reactivity (HPR; ≥188 PRU) group than in the low platelet reactivity (<188 PRU) group (3.6% vs. 1.4%, P = .040). Kaplan-Meier analysis revealed 1-year MACE-free survival rates of 98.4% ± 0.5% and 95.9% ± 1.3% in the low platelet reactivity and HPR groups, respectively (P = .034). According to a Cox regression hazard model, HPR was an independent risk factor for late MACE-free survival (hazard ratio 3.51, 95% CI 1.27-9.69, P = .015). CONCLUSION: High residual platelet reactivity after clopidogrel administration is strongly associated with 1-year MACE-free survival. Routine measurement of platelet reactivity and thorough monitoring of patients with HPR after OPCAB are warranted.

Sequence variability in the HC-Pro coding regions of Korean soybean mosaic virus isolates is associated with differences in RNA silencing suppression.

Soybean mosaic virus (SMV), a member of the family Potyviridae, is an important viral pathogen affecting soybean production in Korea. Variations in helper component proteinase (HC-Pro) sequences and the pathogenicity of SMV samples from seven Korean provinces were compared with those of previously characterized SMV isolates from China, Korea and the United States. Phylogenetic analysis separated 16 new Korean SMV isolates into two groups. Fourteen of the new Korean SMV samples belonged to group II and were very similar to U.S. strain SMV G7 and Chinese isolate C14. One isolate in group II, A297-13, differed at three amino acid positions (L54F, N286D, D369N) in the HC-Pro coding sequence from severe isolates and SMV 413, showed very weak silencing suppressor activity, and produced only mild symptoms in soybean. To test the role of each amino acid substitution in RNA silencing and viral RNA accumulation, a series of point mutations was constructed. Substitution of N for D at position 286 in HC-Pro of SMV A297-12 significantly reduced silencing suppression activity. When the mutant HC-Pro of A297-13 was introduced into an infectious clone of SMV 413, accumulation of viral RNA was reduced to less than 3 % of the level of SMV 413 containing HC-Pro of A297-12 at 10 days post-inoculation (dpi) but increased to 40 % of SMV 413(HC-Pro A297-12) at 40 dpi. At 50 dpi RNA accumulation of SMV 413(HC-Pro A297-13) was similar to that of SMV 413(HC-Pro A297-12). However, at 50 dpi, the D at position 286 of HC-Pro in SMV 413(HC-Pro A297-13) was found to have reverted to N. The results showed that 1) a naturally occurring mutation in HC-Pro significantly reduced silencing suppression activity and accumulation of transgene and viral RNAs, and 2) that there was strong selection for revision to wild type when the mutation was introduced into an infectious clone of SMV.

Endophytic fungi from Lycium chinense Mill and characterization of two new Korean records of Colletotrichum.

Chinese boxthorn or matrimony vine (Lycium chinense Mill) is found primarily in southeastern Europe and Asia, including Korea. The dried ripe fruits are commonly used as oriental medicinal purposes. Endophytic fungi were isolated from surface sterilized tissues and fruits of the medicinal plant in 2013 to identify the new or unreported species in Korea. Among 14 isolates, 10 morphospecies were selected for molecular identification with the internal transcribed spacer (ITS) gene. Phylogenetic analysis revealed that all isolates belonged to Ascomycota including the genera Acremonium, Colletotrichum, Cochliobolus, Fusarium, Hypocrea and Nemania. Two Colletotrichum species were identified at the species level, using three genes including internal transcribed spacer (ITS), glycerol-3-phosphate dehydrogenase (GAPDH) and Actin (ACT) for PCR and molecular data analysis along with morphological observations. The fungal isolates, CNU122031 and CNU122032 were identified as Colletotrichum fructicola and C. brevisporum, respectively. Morphological observations also well supported the molecular identification. C. brevisporum is represented unrecorded species in Korea and C. fructicola is the first record from the host plant.

Effects of some pesticides on development of Ascaris suum eggs.

To evaluate the effects of pesticides to parasite eggs, Ascaris suum eggs were incubated with 5 different pesticides (1:1,500-1:2,000 dilutions of 2% emamectin benzoate, 5% spinetoram, 5% indoxacarb, 1% deltamethrin, and 5% flufenoxuron; all v/v) at 20℃ for 6 weeks, and microscopically evaluated the egg survival and development on a weekly basis. The survival rate of A. suum eggs incubated in normal saline (control eggs) was 90±3% at 6 weeks. However, the survival rates of eggs treated with pesticides were 75-85% at this time, thus significantly lower than the control value. Larval development in control eggs commenced at 3 weeks, and 73±3% of eggs had internal larvae at 6 weeks. Larvae were evident in pesticide-treated eggs at 3-4 weeks, and the proportions of eggs carrying larvae at 6 weeks (36±3%-54±3%) were significantly lower than that of the control group. Thus, pesticides tested at levels similar to those used in agricultural practices exhibited low-level ovicidal activity and delayed embryogenesis of A. suum eggs, although some differences were evident among the tested pesticides.

Sustained drug release behavior of captopril-incorporated chitosan/carboxymethyl cellulose biomaterials for antihypertensive therapy.

Captopril (CTP) is an oral drug widely used to treat high blood pressure and congestive heart failure. In this study, CTP-incorporated biomaterials for antihypertensive therapy were synthesized from chitosan, carboxymethyl cellulose, and plasticizers. The physicochemical properties of the prepared biomaterials were characterized using FE-SEM, FT-IR analysis, and physical properties. CTP release experiments were carried out in buffer solutions at various pH values and temperatures. Results indicated that above 99.0 % of CTP was released within 180 min. Optimization of the experimental conditions for CTP release was analyzed by using response surface methodology (RSM). Results of CTP release through artificial skin indicated that CTP was continuously released above 95.0 % from the prepared biomaterials for 36.0 h. The CTP release mechanisms into a buffer and through artificial skin followed pseudo-Fickian diffusion mechanism and non-Fickian diffusion mechanisms, respectively. Moreover, angiotensin-converting enzyme (ACE) inhibition (related to cardiovascular disease) via the released CTP clearly reveals that the prepared biomaterials have a high potential as a transdermal drug delivery agent in antihypertensive therapy.

Long-term Outcomes of Mitral Valve Repair for Atrial Functional Mitral Regurgitation.

BACKGROUND: Atrial functional mitral regurgitation (AFMR), defined by normal left ventricular function, enlarged left atrium, and a dilated mitral valve annulus, has been a concept discussed for >10 years. However, there are still no established guidelines for its treatment in the American College of Cardiology/American Heart Association recommendations. This study aimed to determine the long-term outcomes of mitral annuloplasty as a treatment for AFMR. METHODS: We analyzed 1435 patients who underwent mitral valve repair at our institution between 2005 and 2020, with 162 classified as having AFMR. Exclusion criteria for AFMR were established based on preoperative echocardiography and operative notes. The primary outcome was overall mortality, and the secondary outcome was MR recurrence, which was defined as moderate or greater mitral regurgitation observed on echocardiography during the follow-up period, analyzed using our hospital's medical records and data from the National Statistical Office. RESULTS: The median follow-up duration for the entire patient cohort was 6.1 years (interquartile range, 3.2-11.2 years). Patients had a 5-year survival rate of 86% and a 10-year survival rate of 73%, with freedom from MR recurrence rates of 89% and 80% at 5 and 10 years, respectively. Although all 162 patients had moderate or greater MR before surgery, most experienced trivial or mild MR after mitral valve repair throughout the follow-up period. CONCLUSIONS: In summary, mitral valve repair effectively treats patients with AFMR, addressing survival and mitigating MR recurrence.

Hybrid endovascular repair for aortic arch pathology: intermediate outcomes and complications: a retrospective analysis.

OBJECTIVES: To evaluate the outcomes of hybrid endovascular repair for aortic arch pathology. METHODS: This study was a retrospective analysis involving patients who underwent hybrid endovascular repair for aortic arch pathologies. RESULTS: Twenty-one patients (16 men; mean age, 64.7 ± 16.2 years) with aortic arch pathologies were treated by hybrid endovascular repair. The indications for treatment included increased aneurysm size in 16 cases (71.4%), rupture or impending aneurysmal rupture in 5 cases (23.8%), and rapid growth of aortic dissection (≥ 10 mm/y) in 1 case (4.8%). Supra-aortic vessel transposition and stent-graft implantation were achieved in all cases. Two types of stent-graft was used, as follows: the Seal thoracic stent-graft in 14 patients (66.7%); and the Valiant stent grafts in 7 patients (33.3%). Perioperative complications affected 5 patients (23.8%), as follows: bleeding (n = 4, 19.0%); stroke (n = 3, 14.3%); renal failure (n = 2, 9.5%); vascular injury (n = 1, 4.8%), and respiratory failure (n = 1, 4.8%). Two patients died within 30 days (9.5%). Technical success was achieved in 15 patients (71.5%). Early endoleaks were noted in 4 patients (19.0%). One patient died during follow-up (mean, 21.3 ± 11.6 months) due to a de novo intramural hematoma. Persistent early endoleaks were noted in 4 patients (19.0%); 2 of the 4 patients were successfully managed with implantation of additional stent-grafts. No late onset endoleaks were noted. The death-free survival and reintervention-free survival rates during follow-up were 85.7% and 90.5%, respectively. CONCLUSION: Hybrid treatment with supra-aortic vessel transposition and endovascular repair may be an option in frail patients in who open procedures is too risky.