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Biotin is an essential coenzyme involved in various metabolic processes across all known organisms, with biotinylation being crucial for the activity of carboxylases. BirA from Haemophilus influenzae is a bifunctional protein that acts as a biotin protein ligase and a transcriptional repressor. This study reveals the crystal structures of Hin BirA in both its apo- and holo-(biotinyl-5'-AMP bound) forms. As a class II BirA, it consists of three domains: N-terminal DNA binding domain, central catalytic domain, and C-terminal SH3-like domain. The structural analysis shows that the biotin-binding loop forms an ordered structure upon biotinyl-5'-AMP binding. This facilitates its interaction with the ligand and promotes protein dimerization. Comparative studies with other BirA homologs from different organisms indicate that the residues responsible for binding biotinyl-5'-AMP are highly conserved. This study also utilized AlphaFold2 to model the potential heterodimeric interaction between Hin BirA and biotin carboxyl carrier protein, thereby providing insights into the structural basis for biotinylation. These findings enhance our understanding of the structural and functional characteristics of Hin BirA, highlighting its potential as a target for novel antibiotics that disrupt the bacterial biotin synthesis pathways., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Rooted in economics market strategies, preference signaling was introduced to the Plastic Surgery Common Application (PSCA) in 2022 for integrated plastic surgery residency applicants. This study surveyed program and applicant experience with preference signaling and assessed how preference signals influenced likelihood of interview invitations., Design: Two online surveys were designed and distributed to all program directors and 2022-2023 applicants to integrated plastic surgery. Opinions regarding the utility of preference signaling were solicited, and the influence of preference signals on likelihood of interview offers was assessed., Setting: All integrated plastic surgery programs., Participants: All 88 program directors and 2022-2023 applicants to integrated plastic surgery., Results: A total of 45 programs and 99 applicants completed the survey (response rates, 54.2% and 34.2%, respectively). Overall, 79.6% of applicants and 68.9% of programs reported that preference signals were a useful addition to the application cycle. Programs reported that 41.4% of students who sent preference signals received interview offers, compared to 84.6% of home students, 64.8% of away rotators, and 7.1% of other applicants; overall, students who signaled were 5.8 times more likely to receive an interview offer compared to students who were not home students and did not rotate or signal. After multivariable adjustment, programs with higher Doximity rankings, numbers of away rotators, and numbers of integrated residents per year received more preference signals (all p < 0.05)., Conclusions: Applicants and programs report that preference signaling was a useful addition to the integrated plastic surgery application cycle. Sending preference signals resulted in a higher likelihood of interview offers among nonrotators. Preference signaling may be a useful tool to reduce congestion in the integrated plastic surgery application cycle., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Anaerobic digestion (AD) is a biological process that employs anaerobic microorganisms to degrade organic material, yielding biogas and biofertilizers. Understanding quorum sensing (QS) signaling in mixed microbial systems provides valuable insights into microbial behavior and functions. This review aims to examine recent studies on the roles of QS and QQ in the AD processes. A QS signal molecule, N-acyl homoserine lactone (AHL), induce the production of extraceluller polymers, promoting biofilm formation and bacterial aggregation, thereby the efficiency of AD process. QS-assisted granule formation fosters syntrophy between acetogens and methanogens, leading to increased organic removal and methane production. Specific AHLs were shown to be correlated with the abundance of hydrolytic bacteria and acidogens, further benefiting methane production. QQ was shown to effectively control membrane fouling in anaerobic membrane bioreactors, yet its impact on methane productivity remains unclear. This review shed lights on the existing literature gaps regarding the mechanisms of QS and QQ in AD systems, which will play a vital role in advancing AD applications in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pseudomonas aeruginosa is an opportunistic pathogen with significant public health implications due to its multi-drug resistance (MDR). Among the mechanisms that mediate MDR, the NalC protein, a member of the TetR family of transcriptional regulators, modulates the mexAB-oprM operon, thus facilitating the efflux pump system. The resistance-nodulation-division (RND) family of multidrug efflux pumps plays a crucial role in expelling a broad spectrum of antimicrobial compounds, serving as a key adaptive mechanism. Structural analyses revealed that NalC adopts a modular architecture consisting of distinct domains involved in ligand recognition and transcriptional regulation. The N-terminal domain of NalC contains a DNA-binding helix-turn-helix motif, which interacts with specific DNA sequences in the PA3720-armR operon region. This interaction initiates the transcriptional activation of the efflux pump system. On the other hand, the C-terminal domain of NalC exhibits a highly dynamic structure and is implicated in ligand sensing and signal transduction. Our findings suggest potential binding sites for small molecules that could act as allosteric modulators, thereby providing new avenues for the development of therapeutic strategies targeting MDR Pseudomonas aeruginosa., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: It is unclear whether the poor outcome of patients with severe vancomycin-resistant enterococci (VRE) infection is attributable to vancomycin resistance or to Enterococcus faecium (Efm), which predominates among VRE., Methods: Retrospective study of a prospectively identified cohort from nationwide surveillance. A cohort of consecutive, nonduplicate episodes of monomicrobial bloodstream infections (BSIs) caused by Efm in 2016 was selected. The primary outcome was all-cause, 30-day, in-hospital mortality. Inverse probability weighting was applied using the propensity score for vancomycin-resistant Efm (VREfm) BSI., Results: A total of 241 Efm BSI episodes were included, of which 59 (24.5%) were VREfm. Patients with VREfm BSI were younger but had similar comorbidities to those with vancomycin-sensitive Efm (VSEfm) BSI. Multivariable logistic regression revealed that younger age, previous piperacillin-tazobactam use, and steroid use were significant risk factors for VREfm BSI, but 30-day in-hospital mortality did not differ significantly between groups (35.6% and 23.6% for VREfm and VSEfm, respectively; odds ratio, 1.79; 95% confidence interval, 0.95-3.37; P = 0.101). However, Cox regression with inverse probability weighting revealed that vancomycin resistance was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.18; 95% confidence interval, 1.03-4.62; P = 0.041)., Conclusion: In patients with Efm BSI, vancomycin resistance was independently associated with mortality., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Aims: The Akt/mammalian target of rapamycin (mTOR) pathway in macrophages converges inflammatory and metabolic signals from multiple receptors to regulate a cell's survival, metabolism and activation. Although mesenchymal stromal cells (MSCs) are well known to modulate macrophage activation, the effects of MSCs on the Akt/mTOR pathway in macrophages have not been elucidated., Methods: We herein investigated whether MSCs affect the Akt/mTOR complex 1 (mTORC1) pathway to regulate macrophage polarization., Results: Results showed that human bone marrow-derived MSCs induced activation of Akt and its downstream mTORC1 signaling in THP-1-differentiated macrophages in a p62/sequestosome 1-independent manner. Inhibition of Akt or mTORC1 attenuated the effects of MSCs on the suppression of tumor necrosis factor-α and interleukin-12 production and the promotion of interleukin-10 and tumor growth factor-β1 in macrophages stimulated by lipopolysaccharide/ATP. Conversely, activation of Akt or mTORC1 reproduced and potentiated MSC effects on macrophage cytokine production. MSCs with cyclooxygenase-2 knockdown, however, failed to activate the Akt/mTORC1 signaling in macrophages and were less effective in the modulation of macrophage cytokine production than control MSCs., Conclusions: These data demonstrate that MSCs control THP-1-differentiated macrophage activation at least partly through upregulation of the Akt/mTORC1 signaling in a cyclooxygenase-2-dependent manner., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation., Methods: Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients., Results: A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33-34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05-0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group., Discussion: Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Diminished immune response to coronavirus disease 2019 (COVID-19) vaccines and breakthrough infection (BI) is a major concern for solid organ transplant recipients. Humoral and cellular immune responses of kidney transplant (KT) recipients after a third COVID-19 vaccination were investigated compared to matched health care workers. Anti-severe acute respiratory syndrome coronavirus 2 spike protein antibody and severe acute respiratory syndrome coronavirus 2 specific interferon-gamma releasing assay (IGRA) were assessed. A total of 38 KT recipients, including 20 BI and 18 noninfection, were evaluated. In the KT BI group, antibody titers were significantly increased (median 5 to 724, binding antibody units/mL (P = 0.002) after the third vaccination, but IGRA responses were negligible. After BI, antibody titers increased (median 11 355 binding antibody unit/mL; P < 0.001) and there was a significant increase of IGRA responses to spike proteins (Spike 1 -Nil, median 0.05 to 0.41 IU/mL; P = 0.009). Antibody titers and IGRA responses were significantly higher in the BI than in the noninfection group after 6 months. Immune responses were stronger in the health care worker than in the KT cohort, but the gap became narrower after BI. In conclusion, KT recipients who experienced BI after 3 COVID-19 vaccinations acquired augmented humoral and cellular immune responses., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups., Methods: We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey., Results: We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND 50 , 2367.74 [95% CI, 1970.03-2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88-2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16-470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND 50 , 872.01 [95% CI, 685.33-1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78-434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05-296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group., Discussion: Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia., Methods: We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups., Results: Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494)., Conclusion: We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b + Ly6C + and CD11b + Ly6G + myeloid cells, not Foxp3 + regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Objective: Step 1 will transition to a pass/fail system in 2022. This study aimed to characterize the effects of this change on integrated plastic surgery program directors' selection criteria and assess whether Step 2 Clinical Knowledge (CK) can replace Step 1 as an application selection metric., Design: Online survey that was administered to a collaborative group of ten plastic surgery program directors collecting USMLE Step 1, Step 2 CK, In-Service, and written board scores for 3 years of graduated integrated residents., Setting: Ten academic integrated plastic surgery programs., Participants: Data from 80 graduated integrated plastic surgery residents., Results: Across 80 included integrated residents, mean (SD) Step 1 score was 247 (13), Step 2 CK was 249 (13), PGY1-6 In-Service percentiles varied from 45 to 53 percentile, and written board pass rate was 98.3%. Both Step 1 and Step 2 CK correlated highly with In-Service percentiles (both p < 0.001), with Step 2 CK scores correlating similarly with In-Service performance compared to Step 1 (rho 0.359 vs. 0.355, respectively). Across applicant characteristics, program directors reported the highest relative increase in Step 2 CK importance after Step 1 transitions to pass/fail., Conclusions: Step 2 CK correlates similarly with plastic surgery In-Service performance compared to Step 1. While Step scores do not necessarily correlate with residency performance, Step 2 CK may also be used as an application screening metric for programs seeking objective data to differentiate plastic surgery applicants., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

We investigated the vibrational density of states of sodium carboxymethyl starch (CM-starch) by terahertz (THz) time-domain spectroscopy. The CM-starch showed a broad peak at ∼3 THz. The structure of the peak was similar to those corresponding to glucose-based polymer glasses possessing hydrogen bonds. The boson peak (BP) appeared at 1.16 THz at the lowest temperature and disappeared because of the existence of excess wing at higher temperatures. However, based on our novel BP frequency determination method using the inflection point of the extinction coefficient, the BP frequency showed almost no dependence on temperature. Further, the chain length dependence of the BP frequency of the glucose-based glasses showed that the BP frequency of the polymer glass was slightly lower than that of the monomer glass. The power law behaviour of the absorption coefficient suggested the existence of fractons, and the fractal dimension was estimated to be 2.33., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Positron emission tomography greatly advanced our understanding on the underlying neural mechanisms of movement disorders. PET with flurodeoxyglucose (FDG) is especially useful as it depicts regional metabolic activity level that can predict patients' symptoms. Multivariate pattern analysis has been used to determine and quantify the co-varying brain networks associated with specific clinical traits of neurodegenerative disease. The result is a biomarker, useful for diagnosis, treatments, and follow up studies. Parkinsonian traits and parkinsonisms are associated with specific spatial pattern of metabolic abnormality useful for differential diagnosis. This approach has also been used for monitoring disease progression and novel treatment responses mostly in Parkinson's disease. In this book chapter, we, illustrate and discuss the significance of the brain networks associated with disease and their modification with neuroplastic changes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: We implemented a stratified risk analysis to predict the development of active tuberculosis (TB) in liver transplantation (LT) recipients based on IGRA and chest images in a TB-endemic area., Methods: In this retrospective cohort study, LT recipients who tested for IGRA between May 2008 and December 2017 were included. Chest images compatible with old TB lesions were considered as positive images. LT recipients were divided into six groups: LT recipients with history of treated TB, image (+)/IGRA (+), image (+)/IGRA (-), image (-)/IGRA (+), image (-)/IGRA (-) and LTBI treated. The Cox regression model was used to analyze risk groups., Results: Among the 717 eligible LT recipients included in this study, 21 patients developed active TB. Incidence rates of TB were 2,261, 724, and 119 cases/100,000 person-years in the 1st, 2nd, and ≥ 3rd year after transplantation, respectively. History of treated TB (HR 18.92; 95% CI 4.10-87.25) and image (+)/IGRA (+) (HR 10.86; 95% CI 2.75-42.89) were independent risk factors for developing active TB. IGRA (+) with a negative image was not a risk factor., Conclusions: Our findings suggested that both IGRA and chest images should be considered to identify risk groups for LTBI treatment., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Endovascular treatment (EVT) is less effective for intracranial atherosclerosis-induced emergent large vessel occlusion. Extracranial-intracranial (EC-IC) bypass surgery is a possible treatment option to augment cerebral blood flow in the perfusion defect area. We compared the efficacy and safety of EC-IC bypass surgery with those of EVT and maximal medical treatment for acute ischemic stroke., Methods: The data from 39 patients, for whom vessel revascularization had failed despite mechanical thrombectomy, were retrospectively analyzed. Of the 39 patients, 22 had undergone percutaneous transluminal angioplasty or intracranial stenting (PTA/S), 10 had undergone emergency EC-IC bypass surgery within 24 hours of symptom onset, and 7 had received maximal medical treatment (MMT) only. The patency, perfusion status, and postoperative infarct volume were evaluated. The clinical outcomes were assessed at 6 months postoperatively using the modified Rankin scale., Results: The mean reperfusion time was significantly longer for the EC-IC bypass group (14.9 hours) compared with that in the PTA/S group (4.1 hours) and MMT group (7.5 hours; P < 0.05). The postoperative infarct volume on diffusion-weighted magnetic resonance imaging was significantly lower in the emergency EC-IC bypass group (11.3 cm 3 ) than in the MMT group (68.0 cm 3 ) but was not significantly different from that of the PTA/S group (14.0 cm 3 ; P < 0.05). The proportion of patients with a modified Rankin scale score of 0-2 at 6 months after surgery was significantly higher in the EC-IC bypass group (80%) than in the PTA/S (59%) and MMT (14%) groups (P < 0.05)., Conclusions: Emergency EC-IC bypass surgery is an effective and safe treatment option for intracranial atherosclerosis-induced acute ischemic stroke for which EVT is inadequate., (Copyright © 2021. Published by Elsevier Inc.)

Alterations in sialylation of terminal residues of glycoproteins have been implicated in forming tumor-associated glycans. ST6GALNAC transfers sialyl moiety to N-acetylgalactosamine residue via α2,6 linkage. Although the oncogenic characteristics of ST6GALNACI or II have been demonstrated in various cancer cells, the impact of ST6GALNACIII on tumor progression remains undefined. In this study, we evaluated the effect of ST6GALNACIII knockdown on the growth of A549 non-small cell lung cancer cells. ST6GALNACIII depletion resulted in significant retardation in growth of A549 cells under various culture conditions, including collagen-supported 3D culture and anchorage-independent soft agar culture conditions. Liquid chromatography with tandem mass spectrometry revealed that two glycopeptides of transferrin receptor protein 1 (TFR1) containing N-acetylhexosamine-sialic acid were not detected in ST6GALNACIII-depleted A549 cells compared with control cells. Subsequent lectin binding assay, western blotting, and real-time RT-PCR indicated that TFR1 sialylation was not significantly changed, but TFR1 protein and mRNA expressions were decreased after ST6GALNACIII knockdown. However, cell growth retardation by ST6GALNACIII knockdown was partially rescued by TFR1 overexpression. Additionally, TFR1 mRNA degradation was accelerated following ST6GALNACIII knockdown with concomitant reduction in mRNA levels of iron regulatory protein 1 and 2, the upstream regulators of TFR1 mRNA stability. Therefore, our results indicated an important role of ST6GALNACIII in promoting A549 cell growth through quantitative regulation of TFR1 expression and provided therapeutic implications for ST6GALNACIII targeting in tumor growth suppression in vivo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Carotid web (CaW) is reported as one of the causes of cryptogenic strokes. However, its pathophysiology is not known, which makes clinicians debate CaW treatment. The current study presents the mechanism of ischemic stroke in CaW and finds a potential indicator for ischemic stroke in CaW., Methods: Computational fluid dynamics (CFD) was applied to computer-aided artificial human CaW models to investigate the correlation between stenosis rate and CaW angle. The CFD results were compared with stroke or symptomatic CaW including adequate reported images for anatomic analysis of the stenosis rate and CaW angle., Results: The CFD result of the CaW models shows that the velocity decreases and the turbulence generation of blood flow increases in the area under CaW (AuCaW). In AuCaW, turbulence intensity (TI) is high in the high stenosis rate and small angle conditions. Moreover, TI remained high in the AuCaW throughout the cardiac cycles. The analysis of 67 anatomic figures appeared in 36 articles merged with CFD results, and a CaW scoring system was introduced for clinicians to determine patients with CaW with a high risk of ischemic stroke., Conclusions: This study is believed to be the first to apply TI to CaW. Because most ischemic strokes in CaW occurred at a high stenosis rate and small angle, TI may be used as a potential indicator of ischemic stroke in CaW. Furthermore, TI is easily used in the daily clinical field by applying CaW scores., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bottom ash (BA) management is often implemented through its co-disposal with municipal solid waste (MSW) in landfills. However, BA co-disposal may lead to heavy metal leaching in landfills. In this study, the effect of BA co-disposal on heavy metal leaching behavior under different scenarios, specifically, MSW, low BA co-disposal (BA&#95;L), high BA co-disposal (BA&#95;H), and BA monofill were investigated. The heavy metal concentrations in the leachate decreased in landfills over time. The leached metals primarily included Zn, Cu, Mn, Pb, Cr, and Cd. The discharge concentration ratio of heavy metals in the leachates exhibited the following decreasing order: MSW, BA&#95;L, BA&#95;H, and BA. In particular, the discharge concentration ratio of Cu in the MSW, BA&#95;L, BA&#95;H, and BA cases ranged from 7.1 × 10 -3 to 8.8 × 10 -1 (mean = 3.0 ×10 -1 ), 2.8 × 10 -4 to 2.0 × 10 -1 (mean = 5.4 ×10 -2 ), 9.1 × 10 -5 to 3.0 × 10 -2 (mean = 5.9 ×10 -3 ), and 4.4 × 10 -4 to 7.9 × 10 -3 (mean = 1.8 ×10 -3 ), respectively. Moreover, the leaching of the heavy metals could be attributed to waste contents, properties of the heavy metals, and leachate characteristics, such as the pH, chemical oxygen demand (COD), alkalinity, and Cl - content. The presented findings can help clarify the leaching characteristics of heavy metals in BA co-disposal landfills, thereby facilitating the optimization of practical landfills., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hypertrophic scars are devastating outcomes of severe burn injuries, producing physical and mental burdens. Adequate treatment is of benefit to relieve these burdens. Laser therapy has shown scar reducing effects. In this study, we compared outcomes after combination of two different lasers or single laser treatment to treat severe hypertrophic burn scars., Methods: Forty patients with hypertrophic burn scars were included in one of two therapeutic groups: continuous wave CO 2 laser and fractional ablative CO 2 laser group (group 1, n = 20) or fractional ablative CO 2 laser alone group (group 2, n = 20). Hypertrophic scars were evaluated by the observer-rated Vancouver Scar Scale (VSS) before and after treatment and by patient-completed questionnaires after treatment. Comparative analyses were performed before and after treatment, and time-dependent improvement was also analyzed., Results: Forty patients (54 hypertrophic scars) completed the laser treatment protocols. Group 1 exhibited significantly more improvement in VSS vascularity, pliability, and height indices than group 2 (p < 0.05). Time-dependent analysis of total VSS scores suggested that group 1 experienced more improvement during a shorter treatment period (p < 0.05). For patient-reported outcomes, group 1 noted better grades than group 2 in four indices, namely scar appearance, scar thickness, pain, and pruritus (p < 0.05)., Conclusion: Effective scar reduction was achieved using combination laser treatment, with significant improvement in multiple observer- and patient-reported outcomes. The shorter treatment period of the combination method can be a merit, as prolonged hypertrophic scars may increase morbidity. Nonetheless, cautious treatment protocols are necessary to avoid undesirable sequelae related to laser application., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Background: Highly displaced Hangman's fracture is a very rare and extremely unstable fracture of the C2 axis. Combined anteroposterior or posterior long-segment fusion surgery is typically performed for the treatment of highly displaced Hangman's fracture. However, these kinds of surgeries increase the risk of complications, loss of motion, and hospital costs., Objective: We sought to investigate the surgical outcomes of anterior C2-3 fusion surgery alone for highly displaced Hangman's fractures with severe angulation of C2-3 by more than 30° and discoligamentous injury., Methods: A total of five patients (four men and one woman) were included in this study with a mean age of 40.4 years (range, 26-70 years). The mean follow-up period after surgery was 37.2 months (range, 12-96 months). The fracture characteristics, treatment methods, and outcomes were retrospectively analyzed., Results: All five patients had type II Hangman's fractures (according to the Levine and Edwards classification scheme). None of the included patients had neurologic deficit or other spine injury but all patients had complete C2-3 discoligamentous injury. Before surgery, all patients successfully achieved closed reduction by skull traction, followed by C2-3 anterior decompression and fusion (ACDF) with plating. For interbody grafting, three patients received a polyetheretherketone (PEEK) cage filled with an autogenous cancellous iliac bone graft and two received autogenous tricortical iliac bone grafts. Severe angulation (39.2° vs. 3.0°, P < 0.001) and severe displacement (76.1% vs. 4.0%, P < 0.001) of C2-3 were both significantly corrected after surgery. All patients had achieved solid fusion at last follow-up. In terms of clinical outcomes, the mean neck pain visual analog scale score was significantly improved (8.6 points vs. 1.8 points, P < 0.001). The mean neck disability index value was also significantly improved (45.4 points vs. 13.0 points, P < 0.01). According to Odom's criteria, all patients achieved satisfactory outcomes. No major complications occurred. One patient complained of dysphagia, but recovered after three months with conservative treatment., Conclusions: Preoperative closed reduction and anterior C2-3 fusion surgery alone should be considered as a less-invasive and useful surgical option for highly displaced Hangman's fracture with severe angulation of C2-3, which is an extremely unstable fracture of the C2 axis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Co-disposal of bottom ash (BA) with municipal solid waste (MSW) in landfills is commonly used for BA management. However, BA co-disposal may cause clogging of geotextiles in MSW landfills. This study investigated the effect of different BA co-disposal ratios on geotextile clogging, including MSW, low ash co-disposed (BA&#95;L), high ash co-disposed (BA&#95;H) landfills, and BA mono-fill. Results showed that the BA&#95;L group increased the geotextile clogging by 0.1-0.6 times, compared to that in the MSW landfill. In contrast, the geotextile clogging of the BA&#95;H and BA groups was reduced than that in the MSW landfill. The clogging was in a dynamic process during the experimental period in all the conditions, including chemical clogging and bio-clogging. Moreover, bio-clogging was the main contributor to the geotextile clogging, accounting for 64-83% of the total clogging mass. The BA co-disposal affected the leachate characteristics, such as pH, calcium concentration, and alkalinity, resulting in chemical clogging. When pH was above 7.0, calcium concentration and alkalinity were limiting factors for the calcium carbonate formation. In terms of the bio-clogging, the microbial analysis indicated that different BA co-disposal ratios influenced the diversity and structure of microbial community. These findings could help clarify the effect of BA co-disposal on geotextile clogging, thus useful to landfill operation in practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The double microcatheter technique (DMT) is a common technique for treating intracranial aneurysms with endovascular coiling. The DMT is usually performed with 6 Fr guiding catheters. However, to the best of our knowledge, this technique using 5 Fr guiding catheters has not been reported. We report a DMT using a 5 Fr guiding catheter and the thoughts and tenets to make this possible., Methods: An 84-year-old woman had presented with a subarachnoid hemorrhage caused by rupture of a broad-necked aneurysm on the origin of the left posterior inferior cerebellar artery. We decided to use the DMT for coil embolization. However, because of the tortuous and calcified vessels from the femoral artery to the vertebral artery (VA), placement of a 6 Fr guiding catheter within the left VA failed. Therefore, we changed the guiding catheter to a 5 Fr Chaperon guiding catheter, which has the largest inner diameter of the 5 Fr guiding catheters. It was successfully navigated to the left VA, and we performed the DMT using Headway Duo and Prowler 10 microcatheters. Coil embolization was successfully completed without any complications., Results: DMT using a 5 Fr guiding catheter can be performed if the sum of the largest outer diameters of the 2 microcatheters is less than the inner diameter of the 5 Fr guiding catheter., Conclusions: The DMT using a 5 Fr guiding catheter can be performed if the sum of the outer diameters of the 2 microcatheters is less than the inner diameter of the 5 Fr guiding catheter. This technique could be a safe and effective option for treatment of broad-necked aneurysms, especially in the case of an elderly patient with tortuous vasculature or posterior circulation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A subset of patients with COVID-19 require intensive respiratory care and tracheostomy. Several guidelines on tracheostomy procedures and care of tracheostomized patients have been introduced. In addition to these guidelines, further details of the procedure and perioperative care would be helpful. The purpose of this study is to describe our experience and tracheostomy protocol for patients with MERS or COVID-19., Materials and Methods: Thirteen patients with MERS were admitted to the ICU, 9 (69.2%) of whom underwent surgical tracheostomy. During the COVID-19 outbreak, surgical tracheostomy was performed in one of seven patients with COVID-19. We reviewed related documents and collected information through interviews with healthcare workers who had participated in designing a tracheostomy protocol., Results: Compared with previous guidelines, our protocol consisted of enhanced PPE, simplified procedures (no limitation in the use of electrocautery and wound suction, no stay suture, and delayed cannula change) and a validated screening strategy for healthcare workers. Our protocol allowed for all associated healthcare workers to continue their routine clinical work and daily life. It guaranteed safe return to general patient care without any related complications or nosocomial transmission during the MERS and COVID-19 outbreaks., Conclusion: Our protocol and experience with tracheostomies for MERS and COVID-19 may be helpful to other healthcare workers in building an institutional protocol optimized for their own COVID-19 situation., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia., Methods: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset., Results: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure., Conclusions: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The in-situ mitigation of methane (CH 4 ) in landfill gas using landfill cover soil (LCS) is a cost-effective approach, but its efficiency needs to be enhanced. In this study, we incorporated an enriched methane-oxidizing bacteria (MOB) consortium into LCS and established four biochar-amended LCS groups with biochar produced at 300 °C (BC300), 400 °C (BC400), 500 °C (BC500), and 600 °C (BC600). The purpose was to evaluate the CH 4 oxidation capacity of biochar-amended LCS after inoculation with MOB and to investigate how the physicochemical properties of biochar that are influenced by the pyrolysis temperature affect the performance and microbial activity of biochar-amended LCS. It was found that a 15% volume ratio (representing a mass ratio of 2.49%-2.78%) for biochar amendment in LCS enhanced CH 4 removal efficiency, with the highest removal observed to be 46% for BC400-amended LCS compared to 30% for the original LCS. In addition, CH 4 adsorption by the biochar was not observed, and a 15% mass ratio for biochar in the LCS had no or a negative impact. Besides improving the water-holding capacity and gas permeability of LCS, other possible advantages of biochar amendment in terms of CH 4 oxidization include greater retention of nutrients, electron acceptors, and exchangeable cations, as well as introducing iron ions. It was also found that CH 4 oxidation capacity and the methanotroph activity of biochar-amended LCS did not continue to increase with higher pyrolysis temperatures, even though higher micropore volumes and surface areas were obtained at higher pyrolysis temperatures. From this study, BC400 was identified as the optimal choice for the best performance in terms of enhancing both the CH 4 oxidation capacity of the amended LCS and the growth of type II methanotroph Methylocystaceae, which can possibly be attributed to having the highest cation exchange capacity of the four biochars., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Co-disposal of bottom ash (BA) with municipal solid waste (MSW) in landfills is a common way for BA management. However, BA co-disposal in MSW landfills may accelerate geotextile clogging and reduce the performance of leachate collection system. This study compared geotextile clogging in a simulated MSW landfill leachate (MSWL) and a BA co-disposed landfill leachate (BAL) at different landfill stages. Geotextile clogging test was conducted using the MSWL and BAL taken from the simulated landfills on the 10th, 80th, 140th and 200th day, respectively. The results demonstrated that geotextile clogging varied with landfill age, due to the change of leachate characteristics. The mass of clogging material in geotextiles with BAL increased from 0.45 g to 2.74 g, which was 43.87%-63.73% greater than those with MSWL. The formation of biofilm was the main contributor for the geotextile clogging. At the same stage, the amount of biofilm formed on geotextile in different leachate was comparable. However, the amounts of CaCO 3 precipitation on geotextile in BAL were 3.85-10.44 times of those in MSW leachate. The pH of leachate played a critical role in CaCO 3 precipitation. The microbial analysis revealed that the co-disposal of the BA greatly influenced the microbial community diversity and structure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An epidemiologic surveillance of non-albicans candidemia for a 6-year period was conducted in Korea. Compared to the published epidemiologic data for the previous 6 years, an increase of C. glabrata (from 21.3% to 28.5%) and a decrease of C. parapsilosis (from 36.5% to 24.7%) were noticed. During the study period, C. tropicalis (36.4%) was most frequently isolated non-albicans Candida, followed by C. glabrata (28.5%), C. parapsilosis (24.7%), and C. krusei (2.6%). Replacement of primary amphotericin B treatment with echinocandins (P < 0.001) eliminated amphotericin B resistance (from 7.8% in 2011 to 0% in 2014)., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections., Objectives: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections., Data Sources: PubMed and EMBASE., Study Eligibility Criteria: Clinical studies reporting mortality outcomes of S. maltophilia infections., Participants: Patients with clinical infections caused by S. maltophilia., Interventions: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy., Methods: Systematic review with meta-analysis technique., Results: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I 2  = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole., Conclusions: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is an estrogenic endocrine disruptor which disturbs a normal animal development. We generated an indicator plant that senses and provides a clear visual indicator of an estrogen-like compound BPA in the environment. We developed transgenic Arabidopsis lines expressing a construct designed to synthesize anthocyanin (thus showing a red color) in response to BPA. We transformed Arabidopsis with a recombinant vector containing the chimeric estrogen receptor (XVE region), LAP and coding region of PtrMYB119 (transcription factor involved in anthocyanin biosynthesis in poplar and Arabidopsis). Upon binding of the estrogen compound to the ligand-binding domain of E (estrogen receptor) in XVE, the XV domain binds to LAP promoter and triggering the transcription of PtrMYB119 with a subsequent enhancement of anthocyanin biosynthetic gene expression, resulting in anthocyanin synthesis. The leaves of the transgenic Arabidopsis line XVE-PtrMYB119 turned red in the presence of 10 ppm BPA. The transcript level of PtrMYB119 peaked at day 3 of BPA exposure, then decreased to its minimal level at day 5. Similar expression patterns to that of PtrMYB119 were detected for genes encoding the anthocyanin biosynthetic enzymes chalcone synthase, chalcone flavanone isomerase, flavanone 3-hydroxylase, dihydroflavonol 4-reductase, anthocyanidin synthase, and UFGT (UGT78D2). The leaves of transgenic plants did not turn red in response to BPA at concentrations below 10 ppm, but PtrMYB119 expression was induced by BPA at concentrations as low as 1 ppt BPA. Since this transgenic plant turns red in the presence of BPA without any experimental procedures, this line can be easily used by non-scientists., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Seven new chalcones, lanceolein A-G (compounds 5 and 7-12), as well as five known chalcones (1-4 and 6), were isolated from the methanolic extract of Coreopsis lanceolata flowers. The chemical structures of 5 and 7-12 were determined on the basis of spectroscopic data interpretation. All compounds inhibited the production of nitrite oxide (NO) induced by LPS in RAW264.7 macrophage cells. Also, compounds 1-6 showed moderated cytotoxicity against human colon cancer cell lines, while compounds 7-12 hardly showed the cytotoxicity. Especially, compounds 2, 5, and 6 exhibited a little higher cytotoxicity on HCT15 cells, with IC 50 values of 43.7 ± 2.17 μM, 35.6 ± 0.24 μM, and 47.9 ± 1.18 μM, respectively. In the Tali assay, compounds 2 and 5 increased the numeral of apoptotic cells. These compounds also significantly promoted the expression of apoptotic proteins including PARP and caspase-3., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate the effects of relaxin (RLN) expression on fibrosis inhibition in synovial fibroblasts., Materials and Methods: Tissue cells from patients with knee osteoarthritis and >30° flexion contractures were utilised. Synovial fibroblasts were activated by TGF-β1 (two nanograms per millilitre) and then exposed to Ad-RLN as a therapeutic gene, adenovirus-lacZ construct as a marker gene, and SB505124 as an inhibitor for TGF-β1 signal for 48 h. The mRNA expression levels of collagens and MMPs were analysed by reverse transcription-polymerase chain reaction. Also, fibronectin, phosphorylation of Smad2 and ERK1/2, alpha smooth muscle actin, TIMP-1, TIMP-2, MMP-1 and MMP-13 levels were estimated using western blotting, and the total collagen synthesis was assayed., Results: Ad-RLN-transduced synovial fibroblasts demonstrated 17%, 13%, and 48% reduction in collagen I, III and IV mRNA expression levels, respectively, and a 40% decrease in MMP-3, MMP-8, 20% decrease in MMP-9, MMP-13 mRNA expression, compared to non-Ad-RLN-transduced cells. In protein expression, Ad-RLN-transduced synovial fibroblasts demonstrated 46% increase in MMP-1, 5% decrease in MMP-2, 51% increase in MMP-9, and 22% increase in MMP-13, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts showed a 25% decrease in TIMP-1 and 65% decrease in TIMP-2 protein expression at 48h, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts demonstrated a 45% inhibition of fibronectin in protein expression level and 38% decrease in total collagen synthesis at 48h, compared to non-Ad-RLN-transduced cells., Conclusion: Relaxin expression exerted anti-fibrogenic effects on synovial fibroblasts from patients with knee osteoarthritis and flexion contractures. Therefore, relaxin could be an alternative therapeutic agent during the initial stage of osteoarthritis with flexion contracture by exerting its anti-fibrogenic effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Conventional suture repairs, when stressed, fail by suture rupture, knot slippage, or suture pull-through, when the suture cuts through the intervening tissue. The purpose of this study was to compare the biomechanical properties of flexor tendon repairs using a novel mesh suture with traditional suture repairs., Methods: Sixty human cadaveric flexor digitorum profundus tendons were harvested and assigned to 1 of 3 suture repair groups: 3-0 and 4-0 braided poly-blend suture or 1-mm diameter mesh suture. All tendons were repaired using a 4-strand core cruciate suture configuration. Each tendon repair underwent linear loading or cyclic loading until failure. Outcome measures included yield strength, ultimate strength, the number of cycles and load required to achieve 1-mm and 2-mm gap formation, and failure., Results: Mesh suture repairs had significantly higher yield and ultimate force values when compared with 3-0 and 4-0 braided poly-blend suture repairs under linear testing. The average force required to produce repair gaps was significantly higher in mesh suture repairs than in conventional suture. Mesh suture repairs endured a significantly greater number of cycles and force applied before failure compared with both 3-0 and 4-0 conventional suture., Conclusions: This ex vivo biomechanical study of flexor tendon repairs using a novel mesh suture reveals significant increases in average yield strength, ultimate strength, and average force required for gap formation and repair failure with mesh suture repairs compared with conventional sutures., Clinical Relevance: Mesh suture-based flexor tendon repairs could lead to improved healing at earlier time points. The findings could allow for earlier mobilization, decreased adhesion formation, and lower rupture rates after flexor tendon repairs., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

A new glycosyl glyceride (5) along with twelve known ones (1-4 and 6-13) including two sulfoquinovosyl glycerides (1 and 2) were isolated from the aerial parts of Malva verticillata. Based on several spectroscopic methods, compound 5 was identified to be (2S)-1-O-β-d-galactopyranosyl-3-O-isostearoyl glyceride, and named malvaglycolipid A. Compounds 1 and 2 contained a unique sugar, (6-deoxy-6-sulfo)-α-d-glucopyranose, which very rarely occurs in natural sources. This is the first report for the isolation of compounds 1 and 2 from natural sources and the structure determination using NMR experiment. It was also of note that no glycosyl glyceride has previously been isolated from the family of Malvaeae. Most glycosyl glycerides showed cytotoxicity to HepG2, AGS, HCT-15, and A549 human cancer cells. Especially, compounds 1, 2, and 11 exhibited significant cytotoxicity to AGS cells, with IC 50 values of 33.7 ± 0.64 μM, 11.1 ± 0.07 μM, and 10.6 ± 0.10 μM, respectively. The n-BuOH fraction and compounds 1, 2, and 11 increased the number of apoptotic cells in the Tali assay and had a significant effect on the levels of proteins related to apoptosis including PARP, caspase-3, Bcl-2, Bax, and β-actin., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Our previous study showed that the level of glutamate carboxypeptidase II (GCPII) protein is regulated by valproic acid, a histone deacetylase (HDAC) inhibitor, through acetylation of lysine residue in the GCPII protein in human astrocytes, U-87MG. The present study further investigated which HDAC subtype is involved in the acetylation of GCPII. The results revealed that GCPII interacted with HDAC1 but not with HDAC2, HDAC3, HDAC4, HDAC5, and HDAC6. Overexpression of catalytic domain (1-56 aa)-deleted HDAC1, which poorly binds to GCPII, enhanced lysine acetylation in GCPII and increased the level of GCPII protein when compared with that of the wild-type HDAC1. Further experiments showed that HDAC1 regulated the stability of GCPII protein. These data suggest that acetylation of GCPII is facilitated by HDAC1, and the acetylated GCPII is more stable than the non-acetylated GCPII. Additional experiments using siRNA HDAC1 and by HDAC1 overexpression confirmed the role of HDAC1 in regulating the stability of GCPII protein. Further, database search of acetylation and ubiquitination sites showed four candidate lysine sites in human GCPII protein that can be both acetylated and ubiquitinylated (K207, K479, K491, and K699). Mutation (lysine residues to arginine (R)) analysis showed that in the presence of cycloheximide K479R- and K491R-hGCPII mutants were less ubiquitinylated and degraded, and decrease in the level of GCPII protein by HDAC1 was significantly blocked by K479R mutants. These data suggest that K479 is a possible site of acetylation or ubiquitination. Furthermore, the results also demonstrate that the stability of GCPII protein is regulated by HDAC1 through acetylation at the lysine 479 residue., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447-178.145; P < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402-13.761; P = 0.011) were significantly associated with MERS-CoV infection., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The cells of the innate immune system, in addition to their capacity to elicit immunity, play a substantial role in immune tolerance induction. Our group has recently shown that a distinct subset of MHC II hi B220 hi CD11b mid suppressive macrophages is increased in the lung by intravenous (IV) administration of mesenchymal stem/stromal cells (MSC) and induces immune tolerance. Herein, we demonstrate that circulating CD11b hi Ly6C hi monocytes are precursors to MHC II hi B220 hi CD11b mid macrophages in the lung and required for MSC-induced tolerance in a mouse model of experimental autoimmune uveitis (EAU). Analysis revealed that IV MSC induced an increase in IL-10-expressing MHC II hi B220 hi CD11b mid macrophages in the lung with a concomitant decrease in CD11b hi Ly6C hi monocytes. Selective depletion of circulating CD11b hi Ly6C hi cells abrogated the effects of MSC in the induction of IL-10 hi MHC II hi B220 hi CD11b mid macrophages and immune tolerance in EAU mice. Similarly, an increase in CD4 + CD25 + Foxp3 + Tregs by MSCs was also reversed by CD11b hi Ly6C hi cell depletion. These results suggest that CD11b hi Ly6C hi monocytes are critical for MSC-induced immune tolerance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

During the 2015 Korean MERS outbreak, we experienced atypical presentations of MERS-CoV infections in three immunocompromised hosts that warranted exceptional management. Case 1 showed delayed symptom development after a four-day asymptomatic period, Case 2 experienced a 20-day incubation period, and Case 3 exhibited persistent viral shedding without clinical deterioration. Recognizing these exceptions is extremely important in the management of MERS-CoV-exposed or -infected patients and for control of potential MERS outbreaks., (Copyright © 2017. Published by Elsevier Ltd.)

Background Aims: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs., Methods: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation., Results: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity., Conclusions: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: After major upper extremity traumatic amputation, replantation is attempted based upon the assumption that outcomes for a replanted limb exceed those for revision amputation with prosthetic rehabilitation. While some reports have examined functional differences between these patients, it is increasingly apparent that patient perceptions are also critical determinants of success. Currently, little patient-reported outcomes data exists to support surgical decision-making in the setting of major upper extremity traumatic amputation. Therefore, the purpose of this study is to directly compare patient-reported outcomes after replantation versus prosthetic rehabilitation., Methods: At three tertiary care centers, patients with a history of traumatic unilateral upper extremity amputation at or between the radiocarpal and elbow joints were identified. Patients who underwent either successful replantation or revision amputation with prosthetic rehabilitation were contacted. Patient-reported health status was evaluated with both DASH and MHQ instruments. Intergroup comparisons were performed for aggregate DASH score, aggregate MHQ score on the injured side, and each MHQ domain., Results: Nine patients with successful replantation and 22 amputees who underwent prosthetic rehabilitation were enrolled. Aggregate MHQ score for the affected extremity was significantly higher for the Replantation group compared to the Prosthetic Rehabilitation group (47.2 vs. 35.1, p<0.05). Among the MHQ domains, significant advantages to replantation were demonstrated with respect to overall function (41.1 vs. 19.7, p=0.03), ADLs (28.3 vs. 6.0, p=0.03), and patient satisfaction (46.0 vs. 24.4, p=0.03). Additionally, Replantation patients had a lower mean DASH score (24.6 vs. 39.8, p=0.08)., Conclusions: Patients in this study who experienced major upper extremity traumatic amputation reported more favorable patient-reported outcomes after successful replantation compared to revision amputation with prosthetic rehabilitation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital., Methods: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission., Findings: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2-17, IQR 5-10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4-8] vs 11 days [6-12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure., Interpretation: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases., Funding: None., (Copyright © 2016 Elsevier Ltd. All rights reserved.)