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Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification., Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier)., Results: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems., Conclusions: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Background: Cricoid pressure (CP) is used to prevent pulmonary aspiration of regurgitated gastric contents and gastric insufflation during positive-pressure ventilation. However, CP impedes the successful insertion of laryngeal mask airway (LMA). Left paratracheal pressure (LPP), a maneuver of applying backward digital force at the lower left paratracheal level, was recently introduced as an alternative to CP. We assessed whether LPP is non-inferior to CP in successful LMA insertion on the first attempt in adult patients undergoing general anesthesia., Methods: In this non-inferiority randomized controlled trial, 108 patients undergoing general anesthesia were randomly allocated to receive either LPP or CP during LMA insertion. The primary outcome was the success rate of LMA insertion on the first attempt. The margin of non-inferiority was defined as 15%., Results: The success rate of LMA insertion on the first attempt was 68.5% (37/54) in the LPP group and 51.9% (28/54) in the CP group (P=0.077) with between-group difference of 16.7% (two-sided 95% CI, -1.9% to 35.2%). Time for successful device insertion was comparable in the two groups (P=0.355), whereas LMA insertion was easier in the LPP group than in the CP group (P=0.001). There was no significant difference between the two groups for change in antral cross-sectional area measured before and after mask ventilation (P=0.081). No serious complication was evident in any group., Conclusions: This randomized clinical trial demonstrated the non-inferiority of LPP over CP in the success rate of LMA insertion on the first attempt in adult patients undergoing general anesthesia.

This study aims to find out whether whole body vibration has an effect on the sprint ability to shorten the time of bobsled-skeleton athletes. Seventeen bobsled-skeleton athletes (male = 11, female = 6) were recruited from Korea Winter Olympics National Team. Participants were randomly assigned to either a sprint immediately after whole body vibration or a sprint without whole body vibration protocol during two separate visits by a period of 3 months. To evaluate the effects of the sprint ability, measurements were performed 60-m sprint recorded test. In males, at the 45m (p<0.05) significant faster sprint section record after WBV more than Non-WBV. In females, at the 15m (p<0.05), 30m (p<0.01), 45m (p<0.05), and 60m (p<0.05) significant faster sprint section record after WBV more than Non-WBV. In males, at the 30m (p<0.05), 45m (p<0.05), and 50m (p<0.05) significant faster sprint cumulative record after WBV more than Non-WBV. In females, at the 15m (p<0.05), 30m (p<0.05), 45m (p<0.01), 50m (p<0.01), and 60m (p<0.01) significant faster sprint cumulative record after WBV more than Non-WBV. This study indicated that significant faster after WBV more than Non-WBV in males and females bobsled-skeleton athletes., Competing Interests: The authors have declared that no competing interests exist.

Objective: A systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to determine the effectiveness and safety of drug coated balloon (DCB) angioplasty compared with uncoated plain balloon (PB) angioplasty in treating arteriovenous access stenosis., Methods: MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials were searched for RCTs comparing paclitaxel coated DCB and PB angioplasty for arteriovenous access stenosis. The last date of the literature search was 31 December 2020. Risk of bias of the retrieved studies was assessed with the Cochrane Collaboration tool for assessing risk of bias (RoB 2.0). The random effects model was used to estimate the risk of loss of target lesion patency (six and 12 months) and circuit patency (six and 12 months). Procedure related adverse events and mortality rate were also compared. Patency results were pooled using the time to event meta-analytical method and the quality of evidence was assessed according to the GRADE approach., Results: Sixteen eligible trials, including 1 682 lesions, were included in the quantitative analysis for the efficacy and safety of paclitaxel coated DCBs. DCBs were associated with a lower risk of loss of target lesion patency at six months (HR 0.53, 95% CI 0.42 - 0.66) and 12 months (HR 0.60, 95% CI 0.47 - 0.76), and were also associated with improved six and 12 month circuit patency. Overall quality of evidence was moderate to low. Procedural complications were rare, and the risk of death up to 12 months was similar between the two groups (OR 1.03, 95% CI 0.68 - 1.56)., Conclusion: Paclitaxel coated DCBs reduced the risk of loss of target lesion patency and circuit patency in arteriovenous access stenosis compared with PBs. Considering the heterogeneity of the included trials, there is a need to investigate optimal treatment regimens regarding drug dose and agent of the DCB and the treatment procedure., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure < 60 mmHg during surgery. The factors predictive of perioperative HI were determined using both univariate and multivariate analyses. Intraoperative HI occurred in 79 (69.3%) patients. In multivariate analysis, α-adrenergic receptor blocker duration (days) (odds ratio, 1.015; 95% confidence interval, 1.001-1.029) was a predictor for intraoperative HI. Postoperative hypotension occurred in 36 (31.6%) patients. Higher urine epinephrine levels, and greater preoperative highest heart rate (HR) were predictive factors for postoperative hypotension in PPGL patients. Caution should be taken in perioperative management for PPGL, especially with long duration of α-adrenergic receptor blocker use, higher urine epinephrine levels, and greater preoperative highest HR., (© 2021. The Author(s).)

Theoretical/computational description of excited state molecular dynamics is nowadays a crucial tool for understanding light-matter interactions in many materials. Here we present an open-source Python-based nonadiabatic molecular dynamics program package, namely PyUNIxMD, to deal with mixed quantum-classical dynamics for correlated electron-nuclear propagation. The PyUNIxMD provides many interfaces for quantum chemical calculation methods with commercial and noncommercial ab initio and semiempirical quantum chemistry programs. In addition, the PyUNIxMD offers many nonadiabatic molecular dynamics algorithms such as fewest-switch surface hopping and its derivatives as well as decoherence-induced surface hopping based on the exact factorization (DISH-XF) and coupled-trajectory mixed quantum-classical dynamics (CTMQC) for general purposes. Detailed structures and flows of PyUNIxMD are explained for the further implementations by developers. We perform a nonadiabatic molecular dynamics simulation for a molecular motor system as a simple demonstration., (© 2021 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.)

Complicated urinary tract infection (UTI) is a symptomatic urinary infection accompanied by functional or structural abnormalities of the genitourinary tract. Benign prostatic hyperplasia (BPH) is a major cause of lower urinary tract obstruction in male patients, and bladder outlet obstruction (BOO) secondary to BPH can lead to UTIs in men. However, no evidence has clearly shown that UTI in the aging male population is associated with either post-void residual urine or BOO. Screening for the presence of bacteriuria is recommended prior to any procedure manipulating the urinary tract, and imaging studies of the upper urinary tract are recommended to identify underlying abnormalities. Recurrent or persistent UTI in men with BPH is an indication for surgical treatment. Asymptomatic bacteriuria should be screened for and treated before transurethral resection of the prostate (TURP). In addition, antibiotic prophylaxis reduced the risk of UTI in patients undergoing TURP. The choice of specific antimicrobial for prophylaxis should be based on local pathogen prevalence and individual antibiotic susceptibility. Patients with severe systemic infections require hospitalization, and empirical therapy should include an intravenous antimicrobial regimen. Further prospective studies are needed to refine the treatment process for complicated UTI in patients diagnosed with BPH., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Endoscopic ultrasound (EUS)-guided sampling has been widely used for pathologic diagnosis of pancreatic lesions and intra-abdominal lymphadenopathy. However, its effectiveness for diagnostic decision making in indeterminate radiological diagnosis has not been well determined., Materials and Methods: From March 2012 to October 2015, 98 consecutive patients who underwent EUS-guided FNA for solid intra-abdominal lesions were retrospectively analyzed (100 procedures). The purpose of EUS-guided sampling was classified as (1) confirmation of a high-confidence radiological diagnosis (High-confidence group) or (2) decision making in the differential diagnostic dilemma for indeterminate radiological diagnosis (Indeterminate group). The accuracies of EUS-guided sampling according to the purpose were analyzed and then compared., Results: Of the 100 procedures, 22 procedures (22%) came under the Indeterminate group, whereas 78 came under the High-confidence group. The accuracies did not differ between the Indeterminate and the High-confidence groups (86.4% vs. 88.5%, p = 1.000). Clinical conditions that required EUS-guided sampling for indeterminate radiological diagnosis were (1) pancreatic cancer vs. benign disease ( n = 8; e.g., pancreatic cancer vs. mass-forming pancreatitis), (2) recurrence of previous/pre-existing cancer vs. benign disease ( n = 5; e.g., recurrent gastric cancer vs. reactive lymph node), (3) pathologic differentiation of presumed malignancy ( n = 6; e.g., lymphadenopathies in the previous history of esophageal cancer and colon cancer), or (4) miscellaneous ( n = 3; e.g., tuberculous lymphadenopathy vs. other condition)., Conclusions: EUS-guided sampling demonstrated an accuracy of 86.4% in the clinical setting of indeterminate radiological diagnosis, which was not different from that of the confirmation of high-confidence diagnosis.

We present a detailed study of the decoherence correction to surface hopping that was recently derived from the exact factorization approach. Ab initio multiple spawning calculations that use the same initial conditions and the same electronic structure method are used as a reference for three molecules: ethylene, the methaniminium cation, and fulvene, for which nonadiabatic dynamics follows a photoexcitation. A comparison with the Granucci-Persico energy-based decoherence correction and the augmented fewest-switches surface-hopping scheme shows that the three decoherence-corrected methods operate on individual trajectories in a qualitatively different way, but the results averaged over trajectories are similar for these systems.

Background and objectives: NELL-1 is a competent growth factor and it reported to target cells committed to the osteochondral lineage. The secreted, osteoinductive glycoproteins are reported to rheostatically control skeletal ossification. This study was performed to determine the effects of NELL-1 on spheroid morphology and cell viability and the promotion of osteogenic differentiation of stem cell spheroids. Materials and Methods: Cultures of stem cell spheroids of gingiva-derived stem cells were grown in the presence of NELL-1 at concentrations of 1, 10, 100, and 500 ng/mL. Evaluations of cell morphology were performed using a microscope, and cell viability was assessed using a two-color assay and Cell Counting Kit-8. Evaluation of the activity of alkaline phosphatase and calcium deposition assays involved anthraquinone dye assay to determine the level of osteogenic differentiation of cell spheroids treated with NELL-1. Real-time quantitative polymerase chain reaction (qPCR) was used to evaluate the expressions of RUNX2 , BSP , OCN , COL 1 A1 , and β- actin mRNAs. Results: The applied stem cells produced well-formed spheroids, and the addition of NELL-1 at tested concentrations did not show any apparent changes in spheroid shape. There were no significant changes in diameter with addition of NELL-1 at 0, 1, 10, 100, and 500 ng/mL concentrations. The quantitative cell viability results derived on Days 1, 3, and 7 did not show significant disparities among groups ( p > 0.05). There was statistically higher alkaline phosphatase activity in the 10 ng/mL group compared with the unloaded control on Day 7 ( p < 0.05). A significant increase in anthraquinone dye staining was observed with the addition of NELL-1, and the highest value was noted at 10 ng/mL ( p < 0.05). qPCR results demonstrated that the mRNA expression levels of RUNX2 and BSP were significantly increased when NELL-1 was added to the culture. Conclusions: Based on these findings, we conclude that NELL-1 can be applied for increased osteogenic differentiation of stem cell spheroids.

Despite widespread interest in the amphiphilic polymeric micelles for drug delivery systems, it is highly desirable to achieve high loading capacity and high efficiency to reduce the side effects of therapeutic agents while maximizing their efficacy. Here, we present a novel hydrophobic epoxide monomer, cyclohexyloxy ethyl glycidyl ether (CHGE), containing an acetal group as a pH-responsive cleavable linkage. A series of its homopolymers, poly(cyclohexyloxy ethyl glycidyl ether)s (PCHGEs), and block copolymers, poly(ethylene glycol)- block -poly(cyclohexyloxy ethyl glycidyl ether)s ( m PEG- b -PCHGE), were synthesized via anionic ring-opening polymerization in a controlled manner. Subsequently, the self-assembled polymeric micelles of m PEG- b -PCHGE demonstrated high loading capacity, excellent stability in biological media, tunable release efficiency, and high cell viability. Importantly, quantum mechanical calculations performed by considering prolonged hydrolysis of the acetal group in CHGE indicated that the CHGE monomer had higher hydrophobicity than three other functional epoxide monomer analogues developed. Furthermore, the preferential cellular uptake and in vivo therapeutic efficacy confirmed the enhanced stability and the pH-responsive degradation of the amphiphilic block copolymer micelles. This study provides a new platform for the development of versatile smart polymeric drug delivery systems with high loading efficiency and tailorable release profiles.

Background: Preventing emergence cough after nasal surgery is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil to prevent emergence cough after propofol anesthesia for nasal surgery when remifentanil was or was not combined with dexmedetomidine., Methods: Forty-seven patients with propofol-remifentanil anesthesia for nasal surgery were randomly assigned to a dexmedetomidine group (Group D, n = 23) or a saline group (Group S, n = 24). Group D and Group S were infused with dexmedetomidine (0.5 μg/kg) and saline, respectively, for 10 min before the completion of surgery. A predetermined Ce of remifentanil was infused until extubation. Remifentanil Ce to prevent cough in 50 and 95% of patients (EC 50 and EC 95 ) was estimated using modified Dixon's up-and-down method and isotonic regression. Hemodynamic and recovery parameters were recorded., Results: The EC 50 of remifentanil Ce was significantly lower in Group D than in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC 95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67-2.78) ng/mL] than in Group S [3.16 (3.06-3.18) ng/mL]. Emergence and recovery variables did not differ between the two groups., Conclusion: The remifentanil EC 50 to prevent cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 μg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted to prevent emergence cough when used in combination with dexmedetomidine., Trial Registration: ClinicalTrials.gov ( NCT03622502 , August 9, 2018).

Objective: Tracheal intubation using a direct laryngoscope is difficult to teach. The McGrath videolaryngoscope, a Macintosh-like device with a camera, can be used as a direct laryngoscope to educate novices under supervision using the screen. We compared the effect on Macintosh laryngoscopy skills following training with a McGrath videolaryngoscope as a direct versus indirect laryngoscope., Methods: Thirty-seven participants were randomized into direct and indirect groups according to the training method using a McGrath videolaryngoscope. Participants attempted Macintosh direct laryngoscopy in normal and difficult airway scenarios. The primary endpoint was the intubation time, and the rate of successful intubation, dental trauma, and difficulty were secondary outcomes., Results: The intubation time after education decreased significantly in both groups and was significantly shorter in the direct group than in the indirect group across time. The difficulty degree in the direct group was lower than that in the indirect group across time; however, the rate of dental trauma was not significantly different., Conclusion: Both direct and indirect laryngoscopy using a McGrath videolaryngoscope improved the performance of Macintosh direct laryngoscopy in novices, while direct laryngoscopy using a McGrath videolaryngoscope demonstrated better educational effects than indirect laryngoscopy.Registered at ClinicalTrials.gov (NCT03471975).

This study investigated the prevalence of depression and levels of physical fitness in high school students during the coronavirus disease 2019 (COVID-19) pandemic. One hundred fifty participants were divided into four groups according to the number of days that they felt depressed due to the COVID-19 during the last 7 days: no-depression group (NDG, n=17), some-depression group (SDG, n=32), occasional-depression group (ODG, n=81), and most-depression group (MDG, n=20). Shuttle run for endurance capacity and standing long jump for muscle power were selected to estimate the states of type I and type II muscle fibers, respectively. This study found that the Center for Epidemiologic Studies Depression Scale score of MDG was significantly higher than those of other three groups. In addition, ODG and MDG showed the lowest interest in their school studies compared with other groups. Endurance capacity showed a significant difference among groups, whereas muscle power showed no significant difference among groups. In conclusion, this study suggests that higher levels of depression reflect a greater lack of interest in life and academics. Furthermore, lower endurance capacity appears to be associated with more severe levels of depression. This highlights the importance of maintaining type I muscle fibers through regular aerobic exercise., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2021 Korean Society of Exercise Rehabilitation.)

This study used multicenter data to compare the oncological safety of transduodenal ampullectomy (TDA) with that of pylorus-preserving pancreatoduodenectomy (PPPD) in early ampulla of Vater (AoV) cancer. Data for patients who underwent surgical resection for AoV cancer (pTis-T2 stage) from January 2000 to September 2019 were collected from 15 institutions. The clinicopathologic characteristics and survival outcomes were compared between the PPPD and TDA groups. A total of 486 patients were enrolled (PPPD, 418; TDA, 68). The oncologic behavior in the PPPD group was more aggressive than that in the TDA group at all T stages: larger tumor size ( p = 0.034), advanced T stage ( p < 0.001), aggressive cell differentiation ( p < 0.001), and more lymphovascular invasion ( p = 0.002). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the two groups when considering all T stages or only the Tis+T1 group. Among T1 patients, PPPD produced significantly better DFS (PPPD vs. TDA, 84.8% vs. 66.6%, p = 0.040) and superior OS (PPPD vs. TDA, 89.1% vs. 68.0%, p = 0.056) than TDA. Lymph node dissection (LND) in the TDA group did not affect DFS or OS (TDA + LND vs. TDA-only, DFS, p = 0.784; OS, p = 0.870). In conclusion, PPPD should be the standard procedure for early AoV cancer.

Insulin-like growth factor 2 (IGF-2) is a growth factor that is involved in various functions of cells, including stem cells. The effects of IGF-2 on the cellular viability and osteogenic differentiation of stem cell spheroids were investigated in the present study. Stem cell spheroids were formed using concave microwells in the presence of IGF-2 at final concentrations of 0, 10 and 100 ng/ml. Cellular viability was measured qualitatively using a microscope and quantitatively using an assay kit based on water-soluble tetrazolium salt. The level of alkaline phosphatase activity, and an anthraquinone dye assay for calcium deposit evaluation, were used to assess osteogenic differentiation. A quantitative PCR analysis was conducted to evaluate the expression of Runx2 and Col1. Spheroid formation was noticed on day 1 in the microwells, and the spheroidal shape was maintained up to day 7. The cell viability assay values for IGF-2 at 0, 10 and 100 ng/ml at day 1 were 0.193±0.002, 0.191±0.002 and 0.201±0.006, respectively (P>0.05). The absorbance values at 405 nm for the alkaline phosphatase activity assays on day 21 were 0.221±0.006, 0.375±0.010 and 0.280±0.015 for IGF-2 at 0, 10 and 100 ng/ml, respectively. There were significantly higher values for IGF-2 in the 10 and 100 ng/ml groups when compared with the control (P<0.05). Significantly higher Alizarin red staining was noted for IGF-2 in the 10 ng/ml group when compared with the unloaded control at day 21 (P<0.05). Quantitative PCR revealed that mRNA levels of Runx2 and Col1 were significantly higher at 100 ng/ml on day 7. Conclusively, the present study demonstrated that the application of IGF-2 increased alkaline phosphatase activity, Alizarin red staining, and Runx2 and Col1 expression of stem cell spheroids., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Min et al.)

Purpose: Native arteriovenous fistula (AVF) is the first choice for hemodialysis access; however, the maturation failure rate remains high. Hence, balloon-assisted maturation (BAM) is increasingly being used to overcome maturation failure. This study evaluated the outcomes of BAM and compared the differences between radial-cephalic (RC) and brachial-cephalic (BC) AVF., Materials and Methods: Between January 2013 and December 2017, 1,622 new AVFs were created. BAM was considered if the AVF did not satisfy the criteria for hemodynamic maturation (6-mm diameter and 500-mL/min flow rate within 8 weeks after the operation)., Results: Of the 1,622 AVFs, BAM was performed in 142 patients (8.75%). There were 92 RC and 50 BC AVFs. Multivariate analyses revealed that ipsilateral central vein catheter history was the sole risk factor for maturation failure after BAM. Oneyear functional primary patency (FPP) and functional secondary patency (FSP) in RC AVFs were higher than those in BC AVFs without statistical significance (FPP, RC vs. BC: 70.9% vs. 50.9%, P=0.099; FSP, 95.5% vs. 81.1%, P=0.146). Further, based on the multivariate analysis, the independent risk factors for FPP in the RC and BC AVFs were the number of BAMs (odds ratio [OR], 3.05; 95% confidence interval [CI], 1.11-8.37; P=0.03) and age (OR, 1.04; 95% CI, 1.00-1.07; P=0.04), respectively., Conclusion: BAM is a relatively good salvage method with tolerable patency. However, the risk factors for patency and the outcomes of BAM differ between RC and BC AVFs.

Purpose: The aim of this study was to analyze changes in stump length over time in patients with saphenous vein incompetence treated with cyanoacrylate closure (CAC) or radiofrequency ablation (RFA)., Materials and Methods: We retrospectively analyzed data collected from patients with saphenous vein incompetence who underwent either CAC or RFA at Seoul National University Hospital between November 2015 and December 2018. The stump lengths were measured using duplex ultrasonography (DUS) within 1 month and 6 months after treatment. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) score were used to assess clinical outcomes., Results: A total of 97 veins (64 great saphenous veins and 33 small saphenous veins) were analyzed. The stump length was not significantly different between the two groups at <1 month (P=0.311). However, the stump length in the CAC group was significantly longer than that in the RFA group at 6 months (P=0.004). At 6 months, the mean change in stump length was 1.41±2.28 cm in the CAC group and 0.51±0.54 cm in the RFA group (P=0.006). The VCSSs and AVVQ scores significantly improved after both procedures but were not significantly different between the two groups., Conclusion: DUS at 6 months after treatment showed that the stump length in the CAC group increased more than that in the RFA group. No other factors affected the changes in stump length.

Purpose: The purpose of this study was to investigate the recurrence factors of choledocholithiasis after common bile duct (CBD) exploration., Methods: From January 2000 to December 2018, we retrospectively reviewed 253 patients who underwent CBD exploration surgery. We excluded 100 cases who had residual stone, combined major surgery, or follow-up loss after surgery. Total of 153 patients were included, and we investigated the recurrence factors of choledocholithiasis. Various variables such as patients' demographics, gallstones, preoperative endoscopic treatment, and laboratory data were analyzed to find factors related to recurrent choledocholithiasis., Results: The median follow-up period was 20.6 months (range 4.7-219 months), and 27 patients (17.6%) had experienced recurrent choledocholithiasis. Univariate analysis showed that the following variables were associated with recurrence of choledocholithiasis; preoperative leukocytosis (white blood cell ≥ 11,000/µL), open procedure, T tube insertion, long hospital duration, and long operation time. Logistic regression multivariate analysis identified preoperative leukocytosis (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.21-9.73; p = 0.021), open procedure (OR, 5.54; 95% CI, 4.73-6.35; p = 0.037), and T-tube insertion (OR, 2.82; 95% CI, 1.04-7.65; p = 0.042) as independent predictors of recurrent choledocholithiasis., Conclusion: Because of delayed recurrence of choledocholithiasis, it is recommended to continue follow-up of patients after CBD exploration surgery. Laparoscopic surgery was observed to be associated with a reduction in recurrence. The preoperative leukocytosis and clinical conditions in which open surgery is performed could be associated with recurrence of choledocholithiasis. However, further study is necessary to validate the result., Competing Interests: All authors have no conflicts of interest to declare., (Copyright © 2021 The Journal of Minimally Invasive Surgery. All rights reserved.)

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6-25.5%] and 16.0% [11.5-23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = - 0.067, P = .527; dosing adherence, ρ = - 0.098, P = .352; timing adherence, ρ = - 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism. [BMB Reports 2021; 54(3): 170-175].

Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE 2 , interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κ B activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF- κ B activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Ju-Mi Hong et al.)

We present a machine learning-assisted excited state molecular dynamics (ML-ESMD) based on the ensemble density functional theory framework. Since we represent a diabatic Hamiltonian in terms of generalized valence bond ansatz within the state-interaction state-averaged spin-restricted ensemble-referenced Kohn-Sham (SI-SA-REKS) method, we can avoid singularities near conical intersections, which are crucial in excited state molecular dynamics simulations. We train the diabatic Hamiltonian elements and their analytical gradients with the SchNet architecture to construct machine learning models, while the phase freedom of off-diagonal elements of the Hamiltonian is cured by introducing the phase-less loss function. Our machine learning models show reasonable accuracy with mean absolute errors of ∼0.1 kcal/mol and ∼0.5 kcal/mol/Å for the diabatic Hamiltonian elements and their gradients, respectively, for penta-2,4-dieniminium cation. Moreover, by exploiting the diabatic representation, our models can predict correct conical intersection structures and their topologies. In addition, our ML-ESMD simulations give almost identical result with a direct dynamics at the same level of theory.

Purpose: Tumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS)., Methods: We retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm])., Results: This study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes ( p =0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097-1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013-1.086; p =0.007), HER2 (HR, 1.069; 95% CI, 1.014-1.126; p =0.013), and TNBC (HR, 1.038; 95% CI, 1.01-1.067; p =0.008)., Conclusion: The incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

We hypothesized that deep neuromuscular blockade (NMB) with low-pressure pneumoperitoneum (PP) would improve respiratory mechanics and reduce biotrauma compared to moderate NMB with high-pressure PP in a steep Trendelenburg position. Seventy-four women undergoing robotic gynecologic surgery were randomly assigned to two equal groups. Moderate NMB group was maintained with a train of four count of 1-2 and PP at 12 mmHg. Deep NMB group was maintained with a post-tetanic count of 1-2 and PP at 8 mmHg. Inflammatory cytokines were measured at baseline, at the end of PP, and 24 h after surgery. Interleukin-6 increased significantly from baseline at the end of PP and 24 h after the surgery in moderate NMB group but not in deep NMB group (P group*time  = 0.036). The peak inspiratory, driving, and mean airway pressures were significantly higher in moderate NMB group than in deep NMB group at 15 min and 60 min after PP (P group*time  = 0.002, 0.003, and 0.048, respectively). In conclusion, deep NMB with low-pressure PP significantly suppressed the increase in interleukin-6 developed after PP, by significantly improving the respiratory mechanics compared to moderate NMB with high-pressure PP during robotic surgery.

The incidence of laparoscopy-related shoulder pain reaches 90% in women. We evaluated the effect of lidocaine patch 5% on the shoulder pain after laparoscopic cholecystectomy (LC) in female patients. Total 63 female patients were randomly allocated to patch group (n = 31) and control group (n = 32). Patch group received lidocaine patch 5% and dressing retention tape on both shoulder, and control group received only dressing retention tape. Abdominal and shoulder pains were evaluated with rating on numeric rating scale (0 = no pain and 10 = the worst pain) at baseline and at 30 min, 6 h, 24 h, and 48 h after surgery. There were no significant differences in patient characteristics and operation details. The overall incidence of shoulder pain was significantly lower in patch group than in control group (42% vs. 78%, P = 0.005). The severity of shoulder pain also was significantly reduced in patch group compared to control group at 24 h and 48 h after surgery (P = 0.01 and P = 0.015, respectively). Complications related to lidocaine patch were not found except nausea. Lidocaine patch 5% reduced the incidence and severity of postoperative shoulder pain in female patients undergoing LC without complications.

BACKGROUND The flexibility of the long flexometallic tube makes insertion of the flexible reinforced laryngeal mask airway (f-LMA) difficult. We compared the usefulness of rigid lightwand-guided f-LMA insertion with standard digital manipulation. MATERIAL AND METHODS Fifty-four patients (aged 19-70 years) were randomly divided into a control group (digital manipulation technique) or the lightwand group (lightwand-guided insertion technique). The insertion profiles, oropharyngeal leak pressure (OLP), peak inspiratory pressure (PIP), expiratory tidal volume, and ventilatory score were measured in patients with neutral, extension, rotation, flexion, and re-neutral head-neck positions in turn. RESULTS The success rate and ease of insertion did not differ between groups, but the insertion time was longer in the lightwand group. The fiberoptic laryngeal view was significantly better in the lightwand group than in the control group. However, the OLP, PIP, expiratory tidal volume, and ventilatory scores were not significantly different between groups according to head-neck positions. The extension posture was associated with a significant negative effect on ventilation, but ventilation returned to initial levels with the other postures. CONCLUSIONS Lightwand-guided f-LMA insertion showed a better fiberoptic laryngeal view than standard digital manipulation, but no improvement in the ventilatory state was observed due to position. Therefore, lightwand-guided insertion could facilitate correct placement of the f-LMA, but it has limited clinical usefulness.

Background: The effects of renal transplantation in patients with augmentation cystoplasty are still controversial. We retrospectively analyzed nine patients who underwent renal transplantation after augmentation cystoplasty., Methods: A total of nine patients who underwent augmentation cystoplasty prior to renal transplantation between January 1990 and May 2020 were reviewed. Basic information on augmentation cystoplasty, transplant procedures, and long-term outcomes of renal transplantation were analyzed., Results: The bowel segments utilized for augmentation cystoplasty were the stomach in two patients (one patient needed revision using the ileum), the ileum in four patients, the ileocolic pouch in one patient, the sigmoid in one patient, and the ureter in one patient. All the cystoplasties were performed prior to renal transplantation. The mean follow-up period after transplantation was 161 months (range, 2-341 months). Two patients had an episode of acute rejection each; however, their graft functions were well-maintained. Five patients had recurrent urinary tract infections, and three of these patients progressed to allograft failure. One patient died from bladder cancer with a functioning graft. Five of nine patients showed well-maintained graft function., Conclusions: Renal transplantation after bladder augmentation surgery is a major operation requiring a high level of surgical skill. Based on our long-term experiences, we recommend diligent postoperative monitoring for urinary tract infections, optimal catheter use, and use of appropriate antibiotic prophylaxis to avoid severe complications., Competing Interests: Conflict of Interest Sangil Min is an editorial board member of the journal but did not involve in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (Copyright © 2020 The Korean Society for Transplantation.)

Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogenic, angiogenic and chemoattractant, and is one of the most abundant growth factors in platelet-derived products. The goal of the present study was to examine the effects of PDGF-BB on cellular morphology and cellular viability using 3D stem cell cultures. On day 1, spheroids formed well in silicon-elastomer-based concave microwells. The addition of 10 or 100 ng/ml PDGF-BB did not affect the morphology of the cell spheroids. During longer periods of incubation, the cell spheroids maintained their shape without noticeable alterations. The majority of cells in the spheroids exhibited green fluorescence when analyzed using a live/dead assay, indicative of live cells. On day 1, the Cell Counting Kit-8 (CCK-8) assay values for PDGF-BB at 0, 10 and 100 ng/ml were 0.241±0.003, 0.227±0.001 and 0.241±0.004, respectively; on day 3, the CCK-8 assay values for PDGF-BB were 0.233±0.005, 0.278±0.001 and 0.194±0.003, respectively; and on day 7, they were 0.248±0.014, 0.293±0.031 and 0.346±0.034, respectively. The 100 ng/ml group showed significantly higher values compared with the control group on day 7. Together, the results of the present study showed that the addition of 10 and 100 ng/ml PDGF-BB increased cellular viability, suggesting that PDGF-BB may be usable in cell therapy., (Copyright: © Paek et al.)

The aim of the present study was to determine the anti-inflammatory effect of an extracts isolated from the lichen. Amandinea sp. was collected from the Antarctic and extracted with methanol. The basic screening of the anti-inflammatory property of the extracts was done using the NO assay. The extracts showed very little cytotoxicity, and reduced NO production in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the extracts inhibited LPS-induced release of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α), and inflammatory mediators inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The extracts also reduced the cytosolic p-IκB-α level and the level of the nuclear factor p65. We examined the anti-inflammatory effects of the extracts using zebrafish in vivo. The extracts reduced the amount of reactive oxygen species (ROS) in LPS-induced zebrafish larvae and inhibited the mRNA expression of inflammatory cytokines and mediators in a tail-cutting induced model. These results are similar to those obtained in vitro with RAW 264.7 cells. Collectively, the data suggest that the extracts may contain one of more compounds with anti-inflammatory effects. Further studies are required to identify the candidate compound/s and to understand the mechanism of action of the extract., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bone morphogenetic protein 2 (BMP-2) is a growth factor that is used to induce osteogenic differentiation in stem cells. The present study assessed the effects of BMP-2 on stem cell spheroid morphology, viability and osteogenic differentiation. Stem cell spheres were constructed and treated with BMP-2 at predetermined concentrations (0-100 ng/ml) using concave microwells. Cell viability was qualitatively and quantitatively analyzed via microscopy and a water-soluble tetrazolium salt assay kit, respectively. Alkaline phosphatase activity was assessed and an anthraquinone dye for calcium deposit evaluation was performed to determine osteogenic differentiation. The expressions of (runt-related transcription factor 2) and collagen 1 were also determined via quantitative PCR. Spherical shapes were formed using concave microwells on day 1, which were maintained up to day 21. On day 1, the relative cell viability of 0, 10 and 100 ng/ml BMP-2 treated cells was 100.0±1.9, 97.3±4.4 and 101.3±2.6%, respectively. Significantly higher values for alkaline phosphatase activity were determined in the 100 ng/ml treated group when compared with the control group. Additionally, Runx2 mRNA levels were significantly higher in the 100 ng/ml BMP-2 group compared with the control group, as determined via quantitative PCR. The results of the present study indicated that BMP-2 enhanced the differentiation of stem cell spheres, which was demonstrated by increased alkaline phosphatase activity and Runx2 expression., (Copyright: © Min et al.)

Objective: Vascular surgeons can be useful in non-vascular surgery cases, especially in oncology where complete resection is important. Such activity has been quantified at least locally, but maybe not adequately reported in a systematic manner, or studied prospectively. This study aimed to describe the roles of vascular surgeons in oncovascular surgery (OVS) and non-vascular surgery (NVS), and to analyse the yearly trends of consult surgery, early mortality and morbidity and risk factors for poor outcomes., Methods: This study was a five year retrospective review of the role of vascular surgeons in various settings at a tertiary hospital. Electronic medical records and images were reviewed retrospectively. Between January 2014 and December 2018, the vascular surgery registry data of Seoul National University Hospital were reviewed for OVS or NVS assisted by vascular surgeons and operations primarily done by vascular surgeons. Demographic data, clinical characteristics, operative data, vascular related data and operative outcomes were collected. The operations were classified into primary surgery or consult surgery. Consult procedures were divided into planned or unplanned surgery., Results: Of 564 cases, vascular surgeons performed 74 OVS as primary surgery, and retroperitoneal tumour was the most frequent diagnosis (n = 34). There were 490 intra-operative requests for a vascular surgeon's assistance, of which 109 were emergency calls. Total intra-operative consultations increased by 115.9% over five years, and the proportion of unplanned operations also increased. Unplanned assistance was most commonly requested for bleeding, whereas node dissection was the most common reason for planned surgery. The mortality rate was not different between the planned and unplanned surgery groups, but the latter showed worse outcomes in total operating time, length of hospital stay, post-operative consultations, and post-operative vascular related complications., Conclusion: Vascular surgeons have an essential role to play in the modern practice of cancer surgery. Oncovascular surgery enables gross resection of a tumour even in the presence of major vessel invasion. Emergency unplanned surgery had worse outcomes; therefore, pre-operative vascular consultation and multidisciplinary management are highly recommended for better patient outcomes., Competing Interests: Conflict of interest None., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC., Methods: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers., Results: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002)., Conclusions: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.

Purpose: The optimal treatment for in-stent restenosis (ISR) of the superficial femoral artery (SFA) is still in debate. This study aimed to evaluate the safety and effectiveness of directional atherectomy (DA) as a primary treatment modality for ISR in SFA., Materials and Methods: A retrospective single-center analysis was conducted. In total, 617 stents were deployed in 242 limbs for SFA diseases during the study period. ISR was identified in 29 limbs (12.0%); 14 limbs were treated with DA and 15 limbs with balloon angioplasty (BAP) alone. Technical success rate, target lesion revascularization (TLR) and patency rates (PRs) at 12 months, and any complications were evaluated., Results: DA group included complete occlusions in 50% of patients and BAP group included in 40%. Mean improvement in the ankle-brachial index was 0.29 and 0.32, respectively (P=0.638). Technical success was achieved in all patients. The procedural success rates were 85.7% and 73.3%, respectively (P=0.651). There was no significant difference regarding residual stenosis, distal embolization, or flow-limiting dissection. Primary PRs at 1 year were 85.7% and 73.3%, secondary PRs were 100.0% and 93.3%, and TLR rates were 14.3% and 20.0% (P=0.411, 0.326, and 0.684, respectively)., Conclusion: Short-term outcomes after DA for ISR were not different from those after BAP but showed a tendency of better primary PR and TLR. Larger multicenter prospective studies are needed to define the role of DA in ISR treatment.

Fibroblast growth factors (FGFs) are growth factors that were initially identified as proteins that stimulate fibroblast proliferation. The aim of the present study was to examine the effects of FGF-4 on the morphology, cellular viability and osteogenic differentiation of stem cell spheroids. Stem cell spheroids were generated using concave microwells in the presence of FGF-4 at concentrations of 0, 50, 100 and 200 ng/ml. Cellular viability was qualitatively assessed by a fluorometric live/dead assay using a microscope and quantitatively determined by using Cell Counting Kit-8. Furthermore, alkaline phosphatase activity and calcium deposition were determined to assess osteogenic differentiation. Reverse transcription-quantitative PCR (RT-qPCR) was performed to evaluate the mRNA expression levels of Runt-related transcription factor 2 (RUNX2) and bone γ-carboxyglutamate protein (BGLAP). Spheroidal shapes were achieved in the microwells on day 1 and a significant increase in the spheroid diameter was observed in the 200 ng/ml FGF-4 group compared with the control group on day 1 (P<0.05). The results regarding viability using Cell Counting Kit-8 in the presence of FGF-4 at 50, 100 and 200 ng/ml at day 1 were 98.0±2.5, 106.2±17.6 and 99.5±6.0%, respectively, when normalized to the control group (P>0.05). Furthermore, the alkaline phosphatase activity was significantly elevated in the 200 ng/ml group, when compared with the control group. The RT-qPCR results demonstrated that the mRNA expression levels of RUNX2 and BGLAP were significantly increased at 200 ng/ml. Therefore, the present results suggested that the application of FGF-4 maintained cellular viability while enhancing the osteogenic differentiation of stem cell spheroids, at least partially by regulating RUNX2 and BGLAP expression levels., (Copyright: © Son et al.)

The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria-targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self-assemble into spherical micelles directed to mitochondria. Self-assembly of the photosensitizer resulted in a higher photostability by preventing free rotation of the indoline ring of the indocyanine moiety. The mitochondria targeting capability of the photosensitizer allowed it to utilize intramitochondrial oxygen. We found that the mitochondria-targeted photosensitizer localized to mitochondria and induced apoptosis of cancer cells both normoxic and hypoxic conditions through generation of ROS. The micellar self-assemblies of the photosensitizer were further confirmed to selectively localize to tumor tissues in a xenograft tumor mouse model through passive targeting and showed efficient tumor growth inhibition., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The aim of this study was to compare tracheal intubation performance regarding the time to intubation, glottic view, difficulty, and dental click, by novices using McGrath videolaryngoscope (VL), Pentax Airway Scope (AWS) and Macintosh laryngoscope in normal and cervical immobilized manikin models., Methods: Thirty-five anesthesia nurses without previous intubation experience were recruited. Participants performed endotracheal intubation in a manikin model at two simulated neck positions (normal and fixed neck via cervical immobilization), using three different devices three times each. Performance parameters included intubation time, success rate of intubation, Cormack Lehane laryngoscope grading, dental click, and subjective difficulty score., Results: Intubation time and success rate during first attempt were not significantly different between the 3 groups in normal airway manikin. In the cervical immobilized manikin, the intubation time was shorter (p = 0.012), and the success rate with the first attempt was significantly higher (p < 0.001) when using McGrath VL and Pentax AWS compared with Macintosh laryngoscope. Both VLs showed less difficulty score (p < 0.001) and more Cormack Lehane grade I (p < 0.001) in both scenarios. The incidence of dental clicks was higher with Macintosh laryngoscope compared with McGrath VL in cervical immobilized airway (p < 0.001)., Conclusions: McGrath VL and Pentax AWS did not show clinically significant decrease in intubation time, however, they achieved higher first attempt success rate, easier intubation and better glottis view compared with Macintosh laryngoscope by novices in a cervical immobilized manikin model. McGrath VL may reduce the risk of dental injury compared with Macintosh laryngoscope in cervical immobilized scenario., Trial Registration: ClinicalTrials.gov (NCT03161730), May 22, 2017 https://clinicaltrials.gov/ct2/hom.

Background and objectives: Morinda citrifolia (Noni) has been widely used in herbal remedies to treat and prevent various kinds of diseases. We conducted this study to evaluate the effects of Noni extract on the maintenance of morphology, the improvement of cellular viability, and the enhancement of osteogenesis of stem cell spheroids. Materials and Methods: We cultured stem cell spheroids made with gingiva-derived stem cells in the presence of Noni extract at concentrations of 10, 100 and 200 ng/mL. We performed analysis of the cell morphology and changes in the cellular viability. We conducted alkaline phosphatase activity assays using a kit, and mineralization assays using an anthraquinone dye to evaluate the osteogenesis of stem cell spheroids with the addition of Noni extract. Results: The applied cells formed spheroids well, and the addition of Noni at 10, 100 and 200 ng/mL concentrations did not produce significant morphological changes. The quantitative values for cellular viability on Day 3 showed that the absorbance values at 450 nm were 0.314 ± 0.013, 0.318 ± 0.008, 0.304 ± 0.000 and 0.300 ± 0.011 for Noni at 0, 10, 100 and 200 ng/mL concentrations, respectively. The results of alkaline phosphatase activity with absorbance values at 405 nm were 0.189 ± 0.019, 0.174 ± 0.023, 0.192 ± 0.014 and 0.210 ± 0.062 for Noni at 0, 10, 100 and 200 ng/mL concentrations, respectively, on Day 4. There were significantly higher values of Alizarin Red S staining for Noni in the 10, 100 and 200 ng/mL groups, with the highest value at 100 ng/mL when compared with the unloaded control on Day 14. Conclusions: Based on these findings, we concluded that Noni extract might be applied for the enhanced osteogenic differentiation of stem cell spheroids.

Background: Brachio-basilic/brachial transposition arteriovenous fistula has emerged as one of the autologous arteriovenous fistula options. However, there have not been many reports on the outcomes of basilic or brachial elevation of arteriovenous fistula compared with those of conventional transposition. We evaluated the efficacy of modified brachio-basilic and brachio-brachial arteriovenous fistula creation with short-segment elevation preserving the axillary area., Methods: From March 2016 to August 2018, medical records of the patients who underwent short-segment elevation of brachio-basilic or brachio-brachial arteriovenous fistula in the upper arm (sBAE or sBRE) were reviewed retrospectively., Results: Of the 51 patients, 37 underwent sBAE and 14 underwent sBRE. Maturation failure occurred in two patients (3.92%), who underwent sBAE. Stenosis was the most common complication, which developed in 13 patients (25.5%), and there was no significant difference between the sBAE and the sBRE. In the 51 patients, cumulative primary patency rates at 6 and 12 months were 88.3% and 69.1%, respectively. Assisted primary patency rates at 6 and 12 months were 97.8% and 90.7%, respectively. Secondary patency rates at 6 and 12 months were both 100%. There were no significant differences between the sBAE and the sBRE in 1-year primary patency (79.1% vs. 46.7%; P = 0.20), assisted primary patency (91.6% vs. 88.1%; P = 0.36), and secondary patency rates (100% vs. 100%)., Conclusions: Brachio-basilic/brachial arteriovenous fistula with short-segment elevation preserving the axilla showed excellent 1-year patency rate, easier cannulation, and other future advantages, and therefore, is a logical modification of conventional transposition of arteriovenous fistula., (Copyright © 2020 Elsevier Inc. All rights reserved.)