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Background and Purpose: To train and validate a deep learning (DL)-based segmentation model for cerebral microbleeds (CMB) on susceptibility-weighted MRI; and to find associations between CMB, cognitive impairment, and vascular risk factors., Materials and Methods: Participants in this single-institution retrospective study underwent brain MRI to evaluate cognitive impairment between January-September 2023. For training the DL model, the nnU-Net framework was used without modifications. The DL model's performance was evaluated on independent internal and external validation datasets. Linear regression analysis was used to find associations between log-transformed CMB numbers, cognitive function (mini-mental status examination [MMSE]), white matter hyperintensity (WMH) burden, and clinical vascular risk factors (age, sex, hypertension, diabetes, lipid profiles, and body mass index)., Results: Training of the DL model (n = 287) resulted in a robust segmentation performance with an average dice score of 0.73 (95% CI, 0.67-0.79) in an internal validation set, (n = 67) and modest performance in an external validation set (dice score = 0.46, 95% CI, 0.33-0.59, n = 68). In a temporally independent clinical dataset (n = 448), older age, hypertension, and WMH burden were significantly associated with CMB numbers in all distributions (total, lobar, deep, and cerebellar; all P <.01). MMSE was significantly associated with hyperlipidemia (β = 1.88, 95% CI, 0.96-2.81, P <.001), WMH burden (β = -0.17 per 1% WMH burden, 95% CI, -0.27-0.08, P <.001), and total CMB number (β = -0.01 per 1 CMB, 95% CI, -0.02-0.001, P = .04) after adjusting for age and sex., Conclusions: The DL model showed a robust segmentation performance for CMB. In all distributions, CMB had significant positive associations with WMH burden. Increased WMH burden and CMB numbers were associated with decreased cognitive function., Abbreviations: CMB = cerebral microbleed; DL = deep learning, DSC = dice similarity coefficient; MMSE = mini-mental status examination; SVD = small vessel disease; SWI = susceptibility-weighted image; WMH = white matter hyperintensity., Competing Interests: The authors declare no conflicts of interest related to the content of this article, (© 2024 by American Journal of Neuroradiology.)

Background/aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes., Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated., Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs., Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Background/aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors., Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis., Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050)., Conclusions: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.

Background: Xenotransplantation, particularly when involving pig donors, presents challenges related to the transmission of porcine cytomegalovirus (pCMV) and its potential impact on recipient outcomes. This study aimed to investigate the relationship between pCMV positivity in both donors and recipients and the survival time of cynomolgus monkey recipients after xenogeneic kidney transplantation., Methods: We conducted 20 cynomolgus xenotransplants using 18 transgenic pigs. On the surgery day, donor pig blood was sampled, and DNA was extracted from serum and peripheral blood mononuclear cells. Recipient DNA extraction followed the same protocol from pre-transplantation to post-transplantation. Porcine cytomegalovirus detection used real-time polymerase chain reaction (real-time PCR) with the ViroReal kit, achieving a sensitivity of 50 copies/reaction. A Ct value of 37.0 was the pCMV positivity threshold., Results: Of 20 cynomolgus recipients, when donors tested negative for pCMV, recipients also showed negative results in 9 cases. In 4 cases where donors were negative, recipients tested positive. All 5 cases with pCMV-positive donors resulted in positive assessments for recipients. Detection of donor pCMV correlated with shorter recipient survival. Continuous recipient positivity during observation correlated with shorter survival, whereas transient detection showed no significant change in survival rates. However, donor pig phenotypes and transplantation protocols did not significantly impact survival., Conclusion: The detection of pCMV in both donors and recipients plays a crucial role in xenotransplantation outcomes. These findings suggest the importance of monitoring and managing pCMV in xenotransplantation to enhance long-term outcomes., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although non-human primates are the closest animals to humans to simulate physiological and metabolic responses, there is a paucity of primate hemorrhagic shock models that are standardized and reproducible. Herein, we describe a model that is a clinical replica of extreme class IV hemorrhagic shock with a step-by-step description of the procedure in cynomolgus macaque monkeys., Methods: The physiological changes that occurred during the process were evaluated using hemodynamic parameters, echocardiogram, and laboratory values. Five female monkeys were subjected to trauma laparotomy, followed by cannulation of the abdominal aorta to achieve graded hemorrhage. A central line was placed in the right internal jugular vein, which was subsequently used for laboratory sampling and volume resuscitation. The withdrawal of blood was ceased when a predefined cardiac endpoint with cardiac arrhythmia or bradycardia was reached. The animals were then immediately resuscitated with transfusion. The primary cardiac endpoint was consistently reached in all 5 animals during the fourth hemorrhage when more than 70% of the estimated total blood volume was lost., Results: No mortality occurred during the process. The blood pressure, cardiac output measured from an echocardiogram, and hemoglobin correlated well with increasing loss of circulating volume, whereas the pulse pressure variation did not. The echocardiogram was also a useful predictor for urgent volume replacement., Conclusion: This model offers a safe and reproducible surgical hemorrhagic model in non-human primates and simulates clinical practice. This could provide a useful platform on which further studies can be carried out to address unanswered questions in trauma management., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Immunosenescence gradually deteriorates the function of the immune system, making elderly patients susceptible to infection, while reducing rejection of organ transplants. Therefore, age-adaptive immunosuppression is necessary in the elderly. We evaluated clinical outcomes such as rejection and infection rate when using basiliximab and rabbit anti-thymocyte globulin (r-ATG) as induction agents in elderly and young organ transplant recipients., Methods: We retrospectively reviewed patients who underwent kidney transplantation (KT) between June 2011 and April 2019. We enrolled 704 adult KT patients and classified the patients into groups according to patient age. We compared the outcomes of infection and biopsy-proven acute rejection (BPAR) according to the type of induction agent (basiliximab and r-ATG [4.5 mg/kg])., Results: The patient group included 520 recipients (74.6%) in the younger recipient group and 179 recipients (25.4%) in the older recipient group. When r-ATG was used as an induction agent, BPAR within 6 months occurred less (p = 0.03); however, infections within 6 months were higher in older recipients. Deaths due to infection were more common in older recipients (p = 0.003)., Conclusion: It may be necessary to use less intensive induction therapy for older recipients, of which dose reduction of r-ATG is one option.

Purpose: The skeletal muscle index (SMI) at the L3 level is widely used to diagnose sarcopenia. The upper thigh (UT) also reflects changes in whole-body muscle mass, but no study has examined this using the UT to diagnose sarcopenia in liver transplantation (LT). This study aimed to determine an optimal cut-off value for UT-SMI and investigate how sarcopenia diagnosed by UT-SMI correlates with outcomes in LT recipients., Methods: In this retrospective study of 332 LT patients from 2018 to 2020, we investigated the association between sarcopenia diagnosed by UT-SMI and patient outcomes after LT., Results: The cut-off values for UT-SMI were 38.3 cm 2 /m 2 for females (area under the curve [AUC], 0.927; P < 0.001) and 46.7 cm 2 /m 2 for males (AUC, 0.898; P < 0.001). The prevalence of sarcopenia diagnosed by UT-SMI was 33.4% in our cohort. Patient and graft survival rates in the UT-SMI sarcopenia group were significantly poorer than those in the UT-SMI non-sarcopenia group (P < 0.001 and P < 0.001). UT-SMI was an independent prognostic factor for patient survival (hazard ratio [HR], 2.182; 95% confidence interval [CI], 1.183-4.025; P = 0.012) and graft survival (HR, 2.227; 95% CI, 1.054-4704; P = 0.036) in our multivariable Cox analysis., Conclusion: We confirmed that sarcopenia diagnosed by UT-SMI is associated with outcomes in LT recipients. In addition, UT-SMI was identified as an independent prognostic factor for patient survival and graft survival. Therefore, UT-SMI could be a good option for CT-based evaluations of sarcopenia in LT recipients., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2023, the Korean Surgical Society.)

Amyloid beta (Aβ) aggregation and tau hyper phosphorylation (p-tau) are key molecular factors in Alzheimer's disease (AD). The abnormal formation and accumulation of Aβ and p-tau lead to the formation of amyloid plaques and neurofibrillary tangles (NFTs) which ultimately leads to neuroinflammation and neurodegeneration. β- and γ-secretases produce Aβ peptides via the amyloidogenic pathway, and several kinases are involved in tau phosphorylation. Exosomes, a recently developed method of intercellular communication, derived from neuronal stem cells (NSC-exos), are intriguing therapeutic options for AD. Exosomes have ability to cross the BBB hence highly recommended for brain related diseases and disorders. In the current study, we examined how NSC-exos could protect human neuroblastoma cells SH-SY5Y (ATCC CRL-2266). NSC-exos were derived from Human neural stem cells (ATCC-BYS012) by ultracentrifugation and the therapeutic effects of the NSC-exos were then investigated in vitro. NSC-exos controlled the associated molecular processes to drastically lower Aβ and p-tau. A dose dependent reduction in β- and γ-secretase, acetylcholinesterase, GSK3β, CDK5, and activated α-secretase activities was also seen. We further showed that BACE1, PSEN1, CDK5, and GSK-3β mRNA expression was suppressed and downregulated, while ADAM10 mRNA was increased. NSC- Exos downregulate NF-B/ERK/JNK-related signaling pathways in activated glial cells HMC3 (ATCC-CRL-3304) and reduce inflammatory mediators such iNOS, IL-1β, TNF-α, and IL-6, which are associated with neuronal inflammation. The NSC-exos therapy ameliorated the neurodegeneration of human neuroblastoma cells SH-SY5Y by enhancing viability. Overall, these findings support that exosomes produced from stem cells can be a neuro-protective therapy to alleviate AD pathology., (© 2023. Springer Nature Limited.)

Bifunctional catalysts can facilitate two different electrochemical reactions with conflicting characteristics. Here, a highly reversible bifunctional electrocatalyst for rechargeable zinc-air batteries (ZABs) is reported featuring a "core-shell structure" in which N-doped graphene sheets wrap around vanadium molybdenum oxynitride nanoparticles. Single Mo atoms are released from the particle core during synthesis and anchored to electronegative N-dopant species in the graphitic shell. The resultant Mo single-atom catalysts excel as active oxygen evolution reaction (OER) sites in pyrrolic-N and as active oxygen reduction reaction (ORR) sites in pyridinic-N environments. ZABs with such bifunctional and multicomponent single-atom catalysts deliver high power density (≈376.4 mW cm -2 ) and long cycle life of over 630 h, outperforming noble-metal-based benchmarks. Flexible ZABs that can tolerate a wide range of temperatures (-20 to 80 °C) under severe mechanical deformation are also demonstrated., (© 2023 Wiley-VCH GmbH.)

With the increase in international travel and trade, in conjunction with the development of insecticide resistance, infestations of Cimex lectularius (L.) and Cimex hemipterus (F.) (Hemiptera: Cimicidae) have resurged globally in the last 2 decades. Recently, it was reported that C. hemipterus was also found in temperate regions, indicating the possibility of its expansion outside tropical regions. Cimex hemipterus has not been officially recorded in Korea since its initial description in 1934. Here, we report the first recent case of C. hemipterus in Korea based on morphological and molecular identification. Partial sequencing of the voltage-sensitive sodium channel gene revealed super-kdr mutations (M918I and L1014F) that are associated with pyrethroid resistance. This case report serves as a warning to intensify the bed bug surveillance system in Korea regarding the presence of C. hemipterus and to prepare effective alternative insecticides for pyrethroids., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Molecular hydrogen (H 2 ) is a versatile therapeutic agent. H 2 gas inhalation is reportedly safe and has a positive impact on a range of illnesses, including Alzheimer's disease (AD). Herein, we investigated the effects of 4 weeks of H 2 gas inhalation on community-dwelling adults of various ages. Fifty-four participants, including those who dropped out (5%), were screened and enrolled. The selected participants were treated as a single group without randomization. We evaluated the association between total and differential white blood cell (WBC) counts and AD risk at individual levels after 4 weeks of H 2 gas inhalation treatment. The total and differential WBC counts were not adversely affected after H 2 gas inhalation, indicating that it was safe and well tolerated. Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment. Furthermore, evaluation of dementia-related biomarkers, such as beta-site APP cleaving enzyme 1 (BACE-1), amyloid beta (Aβ), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases. Collectively, our results indicate that H 2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction in community-dwelling adults of different ages.

Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, multifactorial and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Excessive levels of both pro- and anti-oxidant species qualify as oxidative stress (OS) and result in damage to molecules and cells. OS plays a crucial role in the development of age-related diseases. In fact, damage due to oxidation depends strongly on the inherited or acquired defects of the redox-mediated enzymes. Molecular hydrogen (H 2 ) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer's, Parkinson's, cancer and osteoporosis. Additionally, H 2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review focuses on the therapeutic role of H 2 in the treatment of neurological diseases. This review manuscript would be useful in knowing the role of H 2 in the redox mechanisms for promoting healthful longevity.

Background/aims: Acute upper gastrointestinal (UGI) bleeding is a significant emergency situation with a mortality rate of 2% to 10%. Therefore, initial risk stratification is important for proper management. We aimed to evaluate the role of contrast-enhanced multidetector computed tomography (MDCT) for risk stratification in patients with acute UGI bleeding in the emergency room (ER)., Methods: This retrospective study included patients with UGI bleeding in the ER. Glasgow-Blatchford risk score-computed tomography (GBS-CT) was assessed using a combination of GBS and the MDCT scan scoring system., Results: Of the 297 patients with UGI bleeding, 124 (41.8%) underwent abdominal MDCT. Among them, 90.3% were classified as high-risk by GBS, and five patients died (4.0%). Rebleeding occurred in nine patients (7.3%). The high-risk GBS-CT group had significantly higher in-hospital mortality (10.5% in high-risk vs. 1.4% in moderate risk vs. 0% in low-risk, p = 0.049), transfusion amount (p &lt; 0.001), and endoscopic hemostasis (p &lt; 0.001) compared to the moderate- and low-risk groups., Conclusion: Adding MDCT scans to the existing validated prognosis model when predicting the risk of UGI bleeding in patients in the ER plays a significant role in determining in-hospital mortality, transfusions, and the need for endoscopic hemostasis.

The heterogeneous catalysts of Pt/transition-metal oxides are typically synthesized through calcination at 500 °C, and Pt nanoparticles are uniformly and highly dispersed when hydrogen peroxide (H 2 O 2 ) is applied before calcination. The influence of H 2 O 2 on the dispersion and the stability of Pt nanoparticles on titania-incorporated fumed silica (Pt/Ti-FS) supports was examined using X-ray absorption fine structure (XAFS) measurements at the Pt L 3 and Ti K edges as well as density functional theory (DFT) calculations. The local structural and chemical properties around Pt and Ti atoms of Pt/Ti-FS with and without H 2 O 2 treatment were monitored using in-situ XAFS during heating from room temperature to 500 °C. XAFS revealed that the Pt nanoparticles of H 2 O 2 -Pt/Ti-FS are highly stable and that the Ti atoms of H 2 O 2 -Pt/Ti-FS support form into a distorted-anatase TiO 2 . DFT calculations showed that Pt atoms bond more stably to oxidized-TiO 2 surfaces than they do to bare- and reduced-TiO 2 surfaces. XAFS measurements and DFT calculations clarified that the presence of extra oxygen atoms due to the H 2 O 2 treatment plays a critical role in the strong bonding of Pt atoms to TiO 2 surfaces., (© 2022. The Author(s).)

We successfully report a liquid-liquid chemical reduction and hydrothermal synthesis of a highly stable columbite-tantalite electrocatalyst with remarkable hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance in acidic media. The reduced Fe 0.79 Mn 0.21 Nb 0.16 Ta 0.84 O 6 (CTr) electrocatalyst shows a low overpotential of 84.23 mV at 10 mA cm -2 and 103.7 achieved at 20 mA cm -2 current density in situ for the HER and OER, respectively. The electrocatalyst also exhibited low Tafel slopes of 104.97 mV/dec for the HER and 57.67 mV/dec for the OER, verifying their rapid catalytic kinetics. The electrolyzer maintained a cell voltage of 1.5 V and potential-time stability close to that of Pt/C and RuO 2 . Complementary first-principles density functional theory calculations identify the Mn sites as most active sites on the Fe 0.75 Mn 0.25 Ta 1.875 Nb 0.125 O 6 (100) surface, predicting a moderate Gibbs free energy of hydrogen adsorption (Δ G H* ≈ 0.08 eV) and a low overpotential of η = 0.47 V. The |Δ G Mn H *| = 0.08 eV on the Fe 0.75 Mn 0.25 Ta 1.875 Nb 0.125 O 6 (100) surface is similar to that of the well-known and highly efficient Pt catalyst (|Δ G Pt H *| ≈ 0.09 eV).

Repeat liver resection (RLR) is a good treatment option for recurrent hepatocellular carcinoma (HCC). However, laparoscopic repeat liver resection (LRLR) is more technically demanding than open repeat liver resection (ORLR). The purpose of our study is to compare the surgical outcomes of ORLR and LRLR and to carefully present LRLR guidelines for HCC. We performed RLR at a single institution from January 2017 to November 2019. We divided the patients into an ORLR group and an LRLR group. Inverse probability of treatment weighting (IPTW) was applied in this study to compare the ORLR group and the LRLR group. There was no difference between the two groups in patient characteristics, preoperative blood tests and pathological characteristics. After stabilized IPTW, the LRLR group had a shorter hospital stay (5.52 vs. 9.27 days, p = 0.001) and superior disease-free survival (p = 0.020). LRLR yielded better short-term outcomes than ORLR. And if a regular radiologic examination is performed, most of the recurrent tumors could be detected less than 3 cm. In conclusion, LRLR might be feasible and useful for recurrent HCC located contralateral to the previous tumor at a size of less than 3 cm., (© 2022. Italian Society of Surgery (SIC).)

Background: Pulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit., Case Presentation: A 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50-200 μm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages., Conclusions: To the author's best knowledge, this is the first report of a PVA in a rabbit., (© 2022. The Author(s).)

Background: Protocol biopsy in renal allograft helps to early detect subclinical rejection (SCR) in patients who have no abnormal clinical and laboratory findings. Still, there are rare reports about the techniques and outcomes of two-week protocol biopsy. The aim of this study was to assess two-week protocol biopsy regarding the technical feasibility, procedure safety, and clinical outcomes., Methods: A total of 894 protocol biopsies were performed in adult recipients between 2012 and 2019. Two-week and one-year protocol biopsies were guided with ultrasound in 842 and 399 patients by one of four radiologists with wide range of biopsy experience, respectively. These protocol biopsies were compared in terms of feasibility and safety. Standard references were clinico-laboratory findings and biopsy examinations., Results: The median period of two-week and one-year protocol biopsies were 12 days (10-20 days) and 383 days (302-420 days), respectively. All protocol biopsies were technically successful and there was no difference between radiologists regarding technical success and complications ( p = 0.453). Major complication (Clavien-Dindo grading II-IV) rates of two-week and one-year protocol biopsies were 0.3% (3/842) and 0.2% (1/399), respectively ( p = 1.000). However, univariate analysis demonstrated that platelet count < 100 K/mL and blood urea nitrogen ≥ 40 mg/dL were associated with major complications in two-week protocol biopsy. The SCRs of these protocol biopsies were 15.4% (130/842) and 33.6% (134/399), respectively ( p < 0.001)., Conclusion: Two-week protocol biopsy is technically feasible and safe. It contributes to early detecting a substantial number of SCRs. Prior to the biopsy, platelet count and blood urea nitrogen should be carefully checked to predict major complications.

Introduction: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation., Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route., Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice., Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Diverse extracellular matrix (ECM) proteins physically interact with stem cells and regulate stem cell function. However, the large molecular weight of the natural ECM renders large-scale fabrication of a similar functional structure challenging., Objective: The objective of this study was to construct a low molecular weight and multifunctional chimeric form of recombinant ECM to stimulate mesenchymal stem cell (MSC) for tissue repair. We engineered Fibrillin-1PF14 fused to an elastin-like polypeptide to develop a new biomimetic ECM for stem cell differentiation and investigated whether this recombinant chimeric Fibrillin-Elastin fragment (rcFE) was effective on human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs)., Methods: hTMSCs were grown in the medium supplemented with rcFE, then the effect of the protein was confirmed through cell adhesion assay, proliferation assay, and real-time PCR., Results: rcFE enhanced the adhesion activity of hTMSCs by 2.7-fold at the optimal concentration, and the proliferation activity was 2.6-fold higher than that of the control group (non-treatment rcFE). In addition, when smooth muscle cell differentiation markers were identified by real-time PCR, Calponin increased about 6-fold, α-actin about 9-fold, and MYH11 about 10-fold compared to the control group., Conclusion: Chimeric rcFE enhanced cellular functions such as cell adhesion, proliferation, and smooth muscle differentiation of hTMSCs, suggesting that the rcFE can facilitate the induction of tissue regeneration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Titanium is a biomaterial that meets a number of important requirements, including excellent mechanical and chemical properties, but has low bioactivity. To improve cellular response onto titanium surfaces and hence its osseointegration, the titanium surface was bio-functionalized to mimic an extracellular matrix (ECM)-like microenvironment that positively influences the behavior of stem cells. In this respect, fibronectin and elastin are important components of the ECM that regulate stem cell differentiation by supporting the biological microenvironment. However, each native ECM is unsuitable due to its high production cost and immunogenicity. To overcome these problems, a recombinant chimeric fibronectin type III9-10 and elastin-like peptide fragments (FN9-10ELP) was developed herein and applied to the bio-functionalized of the titanium surface. An evaluation of the biological activity and cellular responses with respect to bone regeneration indicated a 4-week sustainability on the FN9-10ELP functionalized titanium surface without an initial burst effect. In particular, the adhesion and proliferation of human mesenchymal stem cells (hMSCs) was significantly increased on the FN9-10ELP coated titanium compared to that observed on the non-coated titanium. The FN9-10ELP coated titanium induced osteogenic differentiation such as the alkaline phosphatase (ALP) activity and mineralization activity. In addition, expressions of osteogenesis-related genes such as a collagen type I (Col I), Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), bone sialo protein (BSP), and PDZ-binding motif (TAZ) were further increased. Thus, in vitro the FN9-10ELP functionalization titanium not only sustained bioactivity but also induced osteogenic differentiation of hMSCs to improve bone regeneration., Competing Interests: The authors have declared that no competing interests exist.

Oxidative stress (OS) is one of the causative factors in the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease (AD) and cognitive dysfunction. In the present study, we investigated the effects of hydrogen (H 2 ) gas inhalation in trimethyltin (TMT)-induced neurotoxicity and cognitive dysfunction in the C57BL/6 mice. First, mice were divided into the following groups: mice without TMT injection (NC), TMT-only injection group (TMT only), TMT injection + lithium chloride-treated group as a positive control (PC), and TMT injection + 2% H 2 inhalation-treated group (H 2 ). The TMT injection groups were administered a single dosage of intraperitoneal TMT injection (2.6 mg/kg body weight) and the H 2 group was treated with 2% H 2 for 30 min once a day for four weeks. Additionally, a behavioral test was performed with Y-maze to test the cognitive abilities of the mice. Furthermore, multiple OS- and AD-related biomarkers such as reactive oxygen species (ROS), nitric oxide (NO), calcium (Ca 2+ ), malondialdehyde (MDA), glutathione peroxidase (GPx), catalase, inflammatory cytokines, apolipoprotein E (Apo-E), amyloid β (Aβ)-40, phospho-tau (p-tau), Bcl-2, and Bcl-2- associated X (Bax) were investigated in the blood and brain. Our results demonstrated that TMT exposure alters seizure and spatial recognition memory. However, after H 2 treatment, memory deficits were ameliorated. H 2 treatment also decreased AD-related biomarkers, such as Apo-E, Aβ-40, p-tau, and Bax and OS markers such as ROS, NO, Ca 2+ , and MDA in both serum and brain. In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H 2 gas treatment in serum and brain. In addition, inflammatory cytokines such as granulocyte colony-stimulating factors (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H 2 treatment in both serum and brain lysates. In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H 2 treatment. Taken together, our results demonstrated that 2% H 2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers. Therefore, H 2 might be a candidate for repairing neurodegenerative diseases with cognitive dysfunction. However, further mechanistic studies are needed to fully clarify the effects of H 2 inhalation on TMT-induced neurotoxicity and cognitive dysfunction.

The use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5- u RCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5- u RCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5- u RCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5- u RCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5- u RCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5- u RCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.

The crystallization mechanism of transition-metal oxides (TMOs) in a solution was examined based on ZnO crystallization using in-situ x-ray absorption fine structure (XAFS) measurements at the Zn K edge and semi-empirical quantum chemistry (SEQC) simulations. The XAFS results quantitatively determine the local structural and chemical properties around a zinc atom at successive stages from Zn(NO 3 ) 2 to ZnO in an aqueous solution. The results also show that a zinc atom in Zn(NO 3 ) 2 ions dissolves in a solution and bonds with approximately three oxygen atoms at room temperature (RT). When hexamethylenetetramine (C 6 H 12 N 4 ) is added to the solution at RT, a stable Zn-O complex consisting of six Zn(OH) 2 s is formed, which is a seed of ZnO crystals. The Zn-O complexes partially and fully form into a wurtzite ZnO at 60 and 80 °C, respectively. Based on the structural properties of Zn-O complexes determined by extended-XAFS (EXAFS), SEQC simulations clarify that Zn-O complexes consecutively develop from a linear structure to a polyhedral complex structure under the assistance of hydroxyls (OH - s) in an aqueous solution. In a solution with a sufficient concentration of OH - s, ZnO spontaneously grows through the merging of ZnO seeds (6Zn(OH) 2 s), reducing the total energy by the reactions of OH - s. ZnO crystallization suggests that the crystal growth of TMO can only be ascribed to Ostwald ripening when it exactly corresponds to the size growth of TMO particles.

To improve both the mechanical and chemical durability of Nafion membranes for polymer electrolyte membrane fuel-cells (PEMFCs), Nafion composite membranes containing sulfonated graphene oxide (SGO) and cerium oxide (CeO 2 ; ceria) were prepared by solution casting. The structure and chemical composition of SGO were investigated by FT-IR and XPS. The effect of the sulfonation, addition of SGO and ceria on the mechanical properties, proton conductivity, and chemical stability were evaluated. The addition of SGO gave rise to an increase in the number of sulfonic acid groups in Nafion, resulting in a higher tensile strength and proton conductivity compared to that of graphene oxide (GO). Although the addition of ceria was found to decrease the tensile strength and proton conductivity, Nafion/SGO/ceria composite membranes exhibited a higher tensile strength and proton conductivity than recast Nafion. Measurement of the weight loss and SEM observations of the composite membranes after immersing in Fenton's reagent indicate an excellent radical scavenging ability of ceria under radical degradation conditions.

Purpose: We aimed to compare the operative outcomes of laparoscopic right posterior sectionectomy (RPS) and open RPS and evaluate the feasibility of laparoscopic RPS., Methods: From January 2009 to December 2017, laparoscopic liver resections were performed in 235 patients at Chonnam National University Hwasun Hospital, South Korea. We retrospectively analyzed the clinical data of 16 patients who underwent laparoscopic RPS and compared the outcomes with those who underwent open RPS (n=17)., Results: The laparoscopic group had a mean tumor size of 3.82±1.73 cm (open group [OG]; 4.18±2.07 cm, p =0.596), mean tumor-free margin of 10.44±9.69 mm (OG; 10.06±10.62 mm, p =0.657), mean operation time of 412.2±102.2 min (OG; 275.0±60.5, p <0.001), mean estimated blood loss of 339.4±248.3 ml (OG; 236.4±102.7 ml, p =0.631), mean postoperative hospital stay of 11.63±2.58 days (OG; 14.71±4.69 days, p =0.027), and mean postoperative peaks of aspartate aminotransferase, alanine aminotransferase, total bilirubin, and prothrombin time of 545 mg/dl, 538 mg/dl, 1.39 mg/dl, 1.41 international normalized ratio (OG; 237 ( p <0.001), 216 ( p <0.001), 1.52 ( p =0.817), and 1.45 ( p =0.468)), respectively. There were no deaths or major complications in ether group. There were no cases of open conversion. Laparoscopic RPS was associated with a shorter hospital stay, prolonged operation time and lower complication rate. With long-term prognosis, no difference was found in overall survival rate and disease-free survival rate between the two groups., Conclusion: Laparoscopic RPS can be performed, but the problems of long operative time and decrease in liver function should be resolved., Competing Interests: CONFLICT OF INTEREST None., (Copyright © 2020 The Journal of Minimally Invasive Surgery. All rights reserved.)

Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5- u RCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5- u RCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5- u RCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5- u RCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5- u RCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5- u RCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5- u RCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5- u RCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5- u RCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol., Competing Interests: The authors declare no conflict of interest.

Background: Graft survival rate of kidney transplantation recipients improves after induction therapy. However, there is no conclusive evidence on which regimen is superior for deceased donor kidney transplantation (DDKT). This study aims at discussing effective induction therapy in DDKT., Methods: Between 2003 and 2016, 395 DDKT recipients were divided into three groups following induction therapy. Recipients of the basiliximab group (n=184) received basiliximab (20 mg/kg) on days 0 and 4. Recipients of the low-dose rabbit anti-thymocyte globulin (rATG) group (n=113) received rATG (1.5 mg/kg) on days 0, 1, and 2, while those of the high-dose rATG group (n=98) received it for more than 4 days. We retrospectively reviewed and analyzed the clinical outcomes and adverse effects of induction therapy., Results: Compared to other groups, the low-dose rATG group donors were older (P<0.001); rATG group donors had higher serum creatinine levels (P<0.001), and the basiliximab group showed a lower delayed graft function rate (P=0.004). In graft failure, the low-dose rATG group did not differ significantly from the basiliximab group (P=0.080), but was significantly different from the high-dose rATG group (P=0.004)., Conclusions: The low-dose rATG group had the best graft survival rate, although it had older donors and higher serum creatinine levels. Therefore, low-dose rATG may be considered an effective induction therapy in DDKT., (Copyright: © 2019 The Korean Society for Transplantation.)

Introduction: Simulation has emerged as a useful educational tool for the continued training of paramedics. Practicing paramedics are thought to learn through reflecting on their own actions in practice, and it is hoped that simulation could spur similar reflection, which could then lead to practice change. Despite this, there is limited data on how these practitioners use simulated experiences to set learning objectives. This study aimed to explore how simulation training affects self-identification of learning objectives in emergency medical services (EMS) providers (a.k.a. paramedics)., Methods: Paramedics (primary care and advanced care) participated in a 30-minute simulated learning session. All participants filled out pre-post surveys identifying their own learning objectives immediately before and after the simulation. An inductive qualitative analysis of these responses were conducted by two authors (EJ, TC) using an interpretive description approach, yielding a list of key themes commonly found in the learning objectives. Pre-post learning objectives were individually compared by the level of specificity as determined by the authorship team. Simple descriptive statistics were generated to describe the number of times that the paramedics' learning objectives became more or less specific, different, or same., Results: Thirty-five paramedics who completed the simulation and survey were included. Four major themes emerged in the learning objectives: 1) assessment and diagnostic; 2) communication and collaboration; 3) integration of knowledge; and 4) treatment and management. After simulation, the learning objectives became more specific in 6 (17.1%), less specific in 3 (8.6%), different in 22 (62.9%), and remained same in 4 (11.4%)., Conclusion: Simulation training shows promise in refining perceived learning needs. The results from this study offer insight into paramedics' self-identification of learning objectives and gaps pre-post simulation experiences. Understanding the underlying psychology of paramedics participating in simulation may help educators better understand how to guide reflection and continuous improvement., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2019, Hernandez et al.)

Aim: Hypertension is a common condition contributing to many diseases. Factors influencing blood pressure (BP) classification for adults have changed over time. This study aimed to identify factors influencing BP classification according to gender., Methods: Data from the Sixth Korean National Health and Nutrition Examination Survey (2014) were used in this descriptive, cross-sectional study. Participants were 1555 adults (589 men, 966 women). Measures included demographic, health-related, and lifestyle factors., Results: Compared with the male normal BP group, in the male prehypertension group, body mass index, problem drinking, and reduced sleep duration were higher; and in the male hypertension group, age, poor subjective health status, body mass index, diabetes, problem drinking, smoking, and sodium intake were higher. Compared with the female normal BP group, age, and body mass index were higher in the female prehypertension group; and age, poor subjective health status, body mass index, menopause, and diabetes were higher in the female hypertension group., Conclusion: Hypertension and prehypertension prevention interventions for adults should be distinguished according to gender., (© 2018 John Wiley & Sons Australia, Ltd.)

Background: The purpose of this study was to determine whether components of the ProVent model can predict the high medical costs in Korean patients requiring at least 21 days of mechanical ventilation (prolonged mechanical ventilation [PMV])., Methods: Retrospective data from 302 patients (61.6% male; median age, 63.0 years) who had received PMV in the past 5 years were analyzed. To determine the relationship between medical cost per patient and components of the ProVent model, we collected the following data on day 21 of mechanical ventilation (MV): age, blood platelet count, requirement for hemodialysis, and requirement for vasopressors., Results: The mortality rate in the intensive care unit (ICU) was 31.5%. The average medical costs per patient during ICU and total hospital (ICU and general ward) stay were 35,105 and 41,110 US dollars (USD), respectively. The following components of the ProVent model were associated with higher medical costs during ICU stay: age <50 years (average 42,731 USD vs. 33,710 USD, p=0.001), thrombocytopenia on day 21 of MV (36,237 USD vs. 34,783 USD, p=0.009), and requirement for hemodialysis on day 21 of MV (57,864 USD vs. 33,509 USD, p<0.001). As the number of these three components increased, a positive correlation was found betweeen medical costs and ICU stay based on the Pearson's correlation coefficient (γ) (γ=0.367, p<0.001)., Conclusion: The ProVent model can be used to predict high medical costs in PMV patients during ICU stay. The highest medical costs were for patients who required hemodialysis on day 21 of MV., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Background: Recently, the use of common marmoset ( Callithrix jacchus ) has increased in biomedical research as an animal model. This study aimed to test fecal samples to monitor bacterial and parasite infections in common marmoset at the Laboratory Animal Center of Osong Medical Innovation Foundation in Korea., Methods: To monitor bacteria and parasites in common marmoset, we tested 43 fecal samples of 43 common marmosets by culture and parasitological test in 2014. Infection by Chilomastix mesnili was determined by PCR method., Results: We identified nonpathogenic bacteria such as Proteus mirabilis and Escherichia coli in feces of normal common marmosets. Interestingly, C. mesnili was isolated from a healthy common marmoset by fecal centrifugation concentration and PCR. The monkey infected with C. mesnili was treated with metronidazole. After the treatment, C. mesnili were not found in feces using fecal centrifugation concentration and PCR., Conclusion: This is the first case report of C. mesnili infection in common marmoset. Treatment with metronidazole is found to be highly effective in eradicating C. mesnili infection in common marmoset., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest.

Background: The purpose of this study was to evaluate the clinical application of modified Burns Wean Assessment Program (m-BWAP) scoring at first spontaneous breathing trial (SBT) as a predictor of successful liberation from mechanical ventilation (MV) in patients with endotracheal intubation., Methods: Patients requiring MV for more than 72 hours and undergoing more than one SBT in a medical intensive care unit (ICU) were prospectively enrolled over a 3-year period. The m-BWAP score at first SBT was obtained by a critical care nursing practitioner., Results: A total of 103 subjects were included in this study. Their median age was 69 years (range, 22 to 87 years) and 72 subjects (69.9%) were male. The median duration from admission to first SBT was 5 days (range, 3 to 26 days), and the rate of final successful liberation from MV was 84.5% (n=87). In the total group of patients, the successful liberation from MV group at first SBT (n=65) had significantly higher m-BWAP scores than did the unsuccessful group (median, 60; range, 43 to 80 vs. median, 53; range, 33 to 70; P<0.001). Also, the area under the m-BWAP curve for predicting successful liberation of MV was 0.748 (95% confidence interval, 0.650 to 0.847), while the cutoff value based on Youden's index was 53 (sensitivity, 76%; specificity, 64%)., Conclusions: The present data show that the m-BWAP score represents a good predictor of weaning success in patients with an endotracheal tube in place at first SBT., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018 The Korean Society of Critical Care Medicine.)

Dual energy X-ray absorptiometry (DXA) has become the most common method for measuring bone mineral density (BMD) of small animals in metabolic bone disease research, and errors should be minimized in all procedures involved in research studies in order to increase the accuracy of the study results. DXA is simpler and rapid compared to micro-computed tomography for quantitative analysis of change in trabecular bone of test subject. In human research, measuring BMD is widely used; postoperative evaluation on orthopedic surgery, evaluation of osteoporosis medication in menopause and many other areas of study. For the study, the inspector should be trained by the equipment manufacturer regarding the utilization and analysis of the equipment and regular phantom testing should be conducted to ensure the stability of the equipment, and precision tests should be conducted to analyze the positioning and data analysis. They should also be familiar with the clinical trials and conduct studies based on the approval of the Institutional Review Board. In the absolute BMD measurement of the human body, it is necessary to apply and compare the position and condition, rotation degree, region of interest, and area of the scan in the follow-up test. In the case of small animals, animal selection, measurement and equipment should be modeled to match the research. Therefore, we would like to provide information for researchers to minimize the errors, effective data management and accurate data presentation. This article reviews the process of DXA measurement for research purpose including plan for DXA examination, BMD measurement in a human body study and small animal studies.

Purpose: The aim of this pre- and postintervention cohort study was evaluating how effectively rapid pathogen identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detected the causative organisms in sepsis., Methods: All consecutive adult patients who had bacteremia within 72 h of intensive care unit admission and met ≥2 quick Sequential Organ Failure Assessment criteria at intensive care unit admission were analyzed. The patients whose microorganisms were identified via MALDI-TOF MS between March 2014 and February 2016 formed the postintervention group. The patients whose microorganisms were identified by using conventional methods between March 2011 and February 2013 formed the preintervention group., Results: The postintervention group ( n =58) had a shorter mean time from blood draw to receiving the antimicrobial susceptibility results than the preintervention group ( n =40) (90.2 ± 32.1 vs. 108.7 ± 43.1 h; p =0.02). The postintervention group was also more likely to have received active antimicrobial therapy by the time the susceptibility report became available (77% vs. 47%; p =0.005). Its 28-day mortality was also lower (40% vs. 70%; p =0.003). Univariate analysis showed that identification via MALDI-TOF MS (odds ratio, 0.28; 95% confidence interval, 0.12-0.66; p =0.004) and active therapy (odds ratio, 0.38; 95% confidence interval, 0.16-0.95; p =0.04) were associated with lower 28-day mortality., Conclusion: Rapid microorganism identification via MALDI-TOF MS followed by appropriate antimicrobial therapy may improve the clinical outcomes of patients with sepsis.

Herein, gas-phase polycyclic aromatic hydrocarbons (PAHs) as nonpolar compounds were ionized to protonated molecular ions [M + H] + without radical cations and simultaneously analyzed using gas chromatography (GC)/electrospray ionization (ESI)-tandem mass spectrometry (MS/MS). The ionization profile, dissociation, and sensitivity were first investigated to understand the significant behavior of gas-phase PAHs under ESI. The formation of protonated molecular ions of PAHs was distinguished according to the analyte phase and ESI spray solvents. The protonated PAHs exhibited characteristic dissociations, such as H-loss, H 2 -loss, and acetylene-loss, via competition of internal energy. In addition, GC/ESI-MS/MS resulted in relatively lower concentration levels (better sensitivity) for the limits-of-detection (LODs) of PAHs than liquid chromatography (LC)/ESI-MS/MS, and it seems to result from the characteristic ionization mechanism of the gas-phase analyte under ESI. Furthermore, the LODs of gas-phase PAHs depended on molecular weight and proton affinity (PA). Consequently, we demonstrated the relationship among the analyte phases, sensitivities, and structural characteristics (molecular weight and PA) under ESI. The gas-phase PAHs provided enhanced protonation efficiency and sensitivity using GC/ESI-MS/MS, as their molecular weight and PA increased. Based on these results, we offered important information regarding the behavior of gas-phase analytes under ESI. Therefore, the present GC/ESI-MS/MS method has potential as an alternative method for simultaneous analysis of PAHs.

Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively utilized in treatment of life-threatening ventricular and supraventricular arrhythmias. However, amiodarone also produces adverse side effects including liver injury due to its metabolites rather than parent drug. The purpose of the present study was to identify metabolites of amiodarone in the plasma and urine of rats administered the drug by using an untargeted metabolomics approach. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and results subjected to multivariate data analysis. A total of 49 amiodarone metabolites were identified and their structures were characterized by tandem mass spectrometry. Amiodarone metabolites are presumed to be generated via five major types of metabolic reactions including N-desethylation, hydroxylation, carboxylation (oxo/hydroxylation), de-iodination, and glucuronidation. Data demonstrated that an untargeted metabolomics approach appeared to be a reliable tool for identifying unknown metabolites in a complex biological matrix.

In this study, a hydrogen/deuterium (H/D) exchange method using gas chromatography-electrospray ionization/mass spectrometry (GC-ESI/MS) was first investigated as a novel tool for online H/D exchange of multitarget analytes. The GC and ESI source were combined with a homemade heated column transfer line. GC-ESI/MS-based H/D exchange occurs in an atmospheric pressure ion source as a result of reacting the gas-phase analyte eluted from GC with charged droplets of deuterium oxide infused as the ESI spray solvent. The consumption of the deuterated solvent at a flow rate of 2 μL min -1 was more economical than that in online H/D exchange methods reported to date. In-ESI-source H/D exchange by GC-ESI/MS was applied to 11 stimulants with secondary amino or hydroxyl groups. After H/D exchange, the spectra of the stimulants showed unexchanged, partially exchanged, and fully exchanged ions showing various degrees of exchange. The relative abundances corrected for naturally occurring isotopes of the fully exchanged ions of stimulants, except for etamivan, were in the range 24.3-85.5%. Methylephedrine and cyclazodone showed low H/D exchange efficiency under acidic, neutral, and basic spray solvent conditions and nonexchange for etamivan with an acidic phenolic OH group. The in-ESI-source H/D exchange efficiency by GC-ESI/MS was sufficient to determine the number of hydrogen by elucidation of fragmentation from the spectrum. Therefore, this online H/D exchange technique using GC-ESI/MS has potential as an alternative method for simultaneous H/D exchange of multitarget analytes.

Robusta beans cultivated with Monascus ruber (RMR) were successively fermented with Leuconostoc mesenteroides (LM) and the antiobesity effects were examined. To produce an obese mouse model to investigate the hypolipidemic effects, ICR mice were fed the same high-fat diet for 6 weeks. Treatment groups were given 10 or 20% RMR-LM. Body weight changes in the 20% RMR-LM group were lower compared with those in the control group. Visceral adipose tissue weight and adipose size were significantly lower in the 20% RMR-LM group compared with those in the control group. Significant improvement in glucose tolerance was observed in the 10 and 20% RMR-LM groups compared with the control group. The 20% RMR-LM group exhibited a significant reduction in serum glucose concentration. Hepatic mRNA levels of sterol regulatory element-binding protein 1, fas cell surface death receptor, and peroxisome proliferator-activated receptor γ, which are associated with lipid, and fatty acid metabolism, in the 20% RMR-LM group were significantly lower compared with those in the control group. The results of the present study demonstrated that 20% RMR-LM may be used to prevent obesity, and ameliorate diabetes and lipid metabolism imbalances.

Klebsiella pneumoniae is an opportunistic and clinically significant emerging pathogen. We investigated the relative roles of Toll-like receptor (TLR) 2 and TLR4 in initiating host defenses against K. pneumoniae . TLR2 knockout (KO), TLR4 KO, TLR2/4 double KO (DKO), and wild-type (WT) mice were inoculated with K. pneumoniae . Mice in each group were sacrificed after either 12 or 24h, and the lungs, liver, and blood were harvested to enumerate bacterial colony-forming units (CFU). Cytokine and chemokine levels were analyzed using enzyme-linked immunosorbent assay and real-time PCR, and pneumonia severity was determined by histopathological analysis. Survival was significantly shortened in TLR4 KO and TLR2/4 DKO mice compared with that of WT mice after infection with 5 × 10 3 CFU. TLR2 KO mice were more susceptible to infection than WT mice after exposure to a higher infectious dose. Bacterial burdens in the lungs and liver were significantly higher in TLR2/4 DKO mice than in WT mice. Serum TNF-α, MCP-1, MIP-2, and nitric oxide levels were significantly decreased in TLR2/4 DKO mice relative to those in WT mice, and TLR2/4 DKO mice showed significantly decreased levels of TNF-α, IL-6, MCP-1, and inducible nitric oxide synthase mRNA in the lung compared with those in WT mice. Collectively, these data indicate that TLR2/4 DKO mice were more susceptible to K. pneumoniae infection than single TLR2 KO and TLR4 KO mice. These results suggest that TLR2 and TLR4 play cooperative roles in lung innate immune responses and bacterial dissemination, resulting in systemic inflammation during K. pneumoniae infection.

Background: We evaluated the clinical usefulness of the quick Sepsis-Related Organ Failure Assessment (qSOFA) score (based on the 2016 definition of sepsis) at intensive care unit admission in Korean patients with bacteremia., Methods: We retrospectively analyzed clinical data from 236 patients between March 2011 and February 2016. In addition to the qSOFA, the Modified Early Warning score (MEWS) and systemic inflammatory response syndrome (SIRS) criteria were calculated., Results: The patients' median age was 69 years, and 61.0% were male. Of the patients, 127 (53.8%) had a qSOFA score ≥2 points. They had significantly higher rates of septic shock, thrombocytopenia, and hyperlactatemia, and increased requirements for ventilator care, neuromuscular blocking agents, vasopressors, and hemodialysis within 72 hours after intensive care unit admission. They also had a significantly higher 28-day mortality rate. When analyzed using common thresholds (MEWS ≥5 and ≥2 SIRS criteria), patients with a MEWS ≥5 had the same results as those with a qSOFA score ≥2 (P < 0.05). However, patients with ≥2 SIRS criteria showed no significant differences., Conclusions: Our results show that a qSOFA score ≥2 at admission is a useful screening tool for predicting disease severity and medical resource usage within 72 hours after admission, and for predicting 28-day mortality rates in patients with bacteremia. In addition, qSOFA scores may be more useful than SIRS criteria in terms of prognostic utility., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017 The Korean Society of Critical Care Medicine.)

The development of a high-performance oxygen evolution reaction (OER) catalyst is pivotal for the practical realization of a water-splitting system. Although an extensive search for OER catalysts has been performed in the past decades, cost-effective catalysts remain elusive. Herein, an amorphous cobalt phyllosilicate (ACP) with layered crystalline motif prepared by a room-temperature precipitation is introduced as a new OER catalyst; this material exhibits a remarkably low overpotential (η ≈ 367 mV for a current density of 10 mA cm -2 ). A structural investigation using X-ray absorption spectroscopy reveals that the amorphous structure contains layered motifs similar to the structure of CoOOH, which is demonstrated to be responsible for the OER catalysis based on density functional theory calculations. However, the calculations also reveal that the local environment of the active site in the layered crystalline motif in the ACP is significantly modulated by the silicate, leading to a substantial reduction of η of the OER compared with that of CoOOH. This work proposes amorphous phyllosilicates as a new group of efficient OER catalysts and suggests that tuning of the catalytic activity by introducing redox-inert groups may be a new unexplored avenue for the design of novel high-performance catalysts., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice. KLF10-KO mice exhibited lower liver/body weight ratios and 5-bromo-2-deoxy-uridine labeling indices compared with wild-type (WT) mice, and significant differences (P=0.028) were obtained at 72 h after PH. To understand the causes of the gross and histopathological findings, the expression levels of the components of the TGF-β/Smad pathway were examined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The mRNA and protein levels of Smad3, p15, TGF-β1 and TGF-β receptor 1 were significantly increased, while those of cMyc and cyclin D1 (proliferation-associated genes) were significantly lower in the liver tissues of the KLF10-KO mice compared with those of the WT mice at 72 h post-PH. These results indicated that KLF10-KO may exhibit antiproliferative effects on liver regeneration following PH, through strengthening the TGF-β/Smad signaling pathway in a delayed manner.

In this study, gas chromatography (GC) was interfaced with high resolution mass spectrometry (HRMS) with electrospray ionization source (ESI) and the relevant parameters were investigated to enhance the ionization efficiency. In GC-ESI, the distances (x-, y- and z) and angle between the ESI needle, GC capillary column and MS orifice were set to 7 (x-distance), 4 (y-distance), and 1 mm (z-distance). The ESI spray solvent, acid modifier and nebulizer gas flow were methanol, 0.1% formic acid and 5 arbitrary units, respectively. Based on these results, analytical conditions for GC-ESI/HRMS were established. In particular, the results of spray solvent flow indicated a concentration-dependent mechanism (peak dilution effect), and other parameters also greatly influenced the ionization performance. The developed GC-ESI/HRMS was then applied to the analysis of anabolic steroids as trimethylsilyl (TMS) derivatives in human urine to demonstrate its application. The ionization profiles of TMS-derivatized steroids were investigated and compared with those of underivatized steroids obtained from gas chromatography-electrospray ionization/mass spectrometry (GC-ESI/MS) and liquid chromatography-electrospray ionization/mass spectrometry (LC-ESI/MS). The steroids exhibited ionization profiles based on their structural characteristics, regardless of the analyte phase or derivatization. Groups I and II with conjugated or unconjugated keto functional groups at C3 generated the [M+H] + and [M+H-TMS] + ions, respectively. On the other hand, Groups III and IV gave rise to the characteristic fragment ions [M+H-TMS-H 2 O] + and [M+H-2TMS-H 2 O] + , corresponding to loss of a neutral TMS·H 2 O moiety from the protonated molecular ion by in-source dissociation. To the best of our knowledge, this is the first study to successfully ionize and analyze steroids as TMS derivatives using ESI coupled with GC. The present system has enabled the ionization of TMS derivatives under ESI conditions and this method has potential as a novel ionization tool. It is also useful for the simultaneous analysis of steroids as TMS derivatives., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Virus-induced gene silencing (VIGS) has become a powerful tool for post-genomic technology in plant species. This is important, especially in select plants, such as the pepper plant, that are recalcitrant to Agrobacterium -mediated transformation. Although VIGS in plants has been widely employed as a powerful tool for functional genomics, scattering phenotypic effects by uneven gene silencing has been implemented in order to overcome challenges in experiments with fruit tissues., Results: We improved the VIGS system based on the tobacco rattle virus (TRV) containing the An2 MYB transcription factor, which is the genetic determinant of purple colored- or anthocyanin-rich pepper. Silencing of endogenous An2 in the anthocyanin-rich pepper with the modified TRV vector for ligation-independent cloning (LIC) lacked purple pigment in its leaves, flowers, and fruits. Infection with TRV-LIC containing a tandem construct of An2 and phytoene desaturase ( PDS ) resulted in a typical photobleaching event in leaves without the purple pigment, whereas silencing of PDS led to the presence of photobleached and purple-colored leaves. Cosilencing of endogenous An2 and capsaicin synthase in fruits resulted in decreased levels of capsaicin and dihydrocapsaicin as assessed by high performance liquid chromatography analysis coupled with the absence of the purple pigment in fruits., Conclusions: VIGS with tandem constructs harboring An2 as a visible reporter in anthocyanin-rich pepper plants can facilitate the application of functional genomics in the study of metabolic pathways and fruit biology.

Microbially enhanced oil recovery involves the use of microorganisms to extract oil remaining in reservoirs. Here, we report fabrication of microgel particles with immobilized Bacillus subtilis for application to microbially enhanced oil recovery. Using B. subtilis isolated from oil-contaminated soils in Myanmar, we evaluated the ability of this microbe to reduce the interfacial tension at the oil-water interface via production of biosurfactant molecules, eventually yielding excellent emulsification across a broad range of the medium pH and ionic strength. To safely deliver B. subtilis into a permeable porous medium, in this study, these bacteria were physically immobilized in a hydrogel mesh of microgel particles. In a core flooding experiment, in which the microgel particles were injected into a column packed with silica beads, we found that these particles significantly increased oil recovery in a concentration-dependent manner. This result shows that a mesh of microgel particles encapsulating biosurfactant-producing microorganisms holds promise for recovery of oil from porous media.