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Background/purpose: Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). Materials and methods: To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Results: Various concentrations of lidocaine (0.05, 0.2, and 1 mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Conclusion: Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This in vitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Edible insects have a low environmental impact but are rich in nutrients and have been promoted as alternative protein sources. However, adding insect flour to bread negatively affects the overall quality, especially loaf volume and textural properties. Furthermore, relevant studies on chitin are limited. Therefore, this study examined chitin hydrolysis using lysozymes to enhance the quality characteristics in defatted mealworm (Tenebrio molitor L.) powder (DF-M)-supplemented bread. The chitin hydrolysis degree by lysozymes was evaluated using the 3,5-dinitrosalicylic acid assay and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. The amount of chitin oligomers increased with time, and no significant difference in the hydrolysis efficiency between water and 400 mM acetate buffer was observed. Enzymatic hydrolysis improved the DF-M water- and oil-binding and antioxidant capacities. In addition, chitin hydrolysis increased the volume and softened the texture of white bread. In particular, bread supplemented with DF-M hydrolyzed for 4 h at 10 % had the highest moisture content among the mealworm-added bread groups during storage for 5 days. Moreover, sensory evaluation showed a positive effect of chitin hydrolysis on acceptability. Our findings indicate that chitin hydrolysis can improve the quality of bread containing insect additives. In conclusion, this study provides novel insights into producing high-quality and functional bakery products from edible insects by the enzymatic hydrolysis of edible insect powders and could expand the applications of edible insects as food ingredients.

Abstract Background Remimazolam is a recently approved, ultra-short-acting benzodiazepine. However, few studies have investigated remimazolam in relation to postoperative nausea and vomiting (PONV). This study aimed to compare the effects of remimazolam and propofol on PONV in patients undergoing oral and maxillofacial surgery. Methods Patients (n = 206) aged 19–65 years who were scheduled for oral and maxillofacial surgery were randomized into two groups, the remimazolam (R) and propofol group (P). In the R group (n = 94), remimazolam was used to induce anesthesia at 12 mg/kg/h and to maintain anesthesia at 1–2 mg/kg/h. In the P group (n = 95), anesthesia was induced and maintained with propofol (target effect-site concentration: 3–5 µg/ml). In both groups, remifentanil was administered at a target effect-site concentration of 2.5-4 ng/ml. The primary outcome was the overall incidence of PONV during the first 24 h after surgery. Secondary outcomes included the severity of nausea, use of rescue antiemetics, severity of postoperative pain, use of rescue analgesia, and quality of recovery. Results The incidence of PONV during the first 24 h after surgery was 11.7% and 10.5% in the R group and P group, respectively, and there was no significant difference in the severity of nausea (P > 0.05). Ten patients in the R group and ten patients in the P group required rescue antiemetics during the first 24 h after surgery (P = 0.98). No inter-group differences were observed in terms of postoperative pain score, use of rescue analgesia, and quality of recovery (P > 0.05). Conclusions In this study, remimazolam did not increase the incidence and severity of PONV compared with propofol. Trial registration KCT0006965, Clinical Research Information Service (CRIS), Republic of Korea. Registration date: 26/01/2022.

Background/purpose: Various studies have used stem cells in the field of bone tissue engineering to repair bone defects. Dental pulp stem cells (DPSCs) have multipotent properties and can be acquired in a noninvasive manner; therefore, they are frequently used in experiments in regenerative medicine. The objective of this study was to investigate the odontogenic/osteogenic differentiation of human DPSCs (hDPSCs) using propofol, a widely used intravenous anesthetic agent. Materials and methods: Alkaline phosphatase (ALP) staining was used to investigate the effects of various concentrations of propofol (5, 20, 50 and 100 μM) on the osteogenic differentiation of hDPSCs. Real-time qPCR and Western blot analysis were used to detect the effect of propofol on the expression of odontogenic/osteogenic genes, such as DMP1, RUNX2, OCN, and BMP2. Odontogenic/osteogenic differentiation of hDPSCs was estimated at days 7 and 14. Results: ALP staining of hDPSCs was significantly decreased by propofol treatment. The mRNA expression of DMP1, RUNX2, OCN, and BMP2 decreased after propofol treatment for 14 days. The protein expression of DMP1 and BMP2 was decreased by propofol at days 7 and 14, and that of RUNX2 was decreased by propofol at day 14 only. Conclusion: Propofol attenuated odontogenic/osteogenic differentiation of hDPSCs in vitro. This result suggests that propofol, which is widely used for dental sedation, may inhibit the odontogenic/osteogenic differentiation of hDPSCs.

Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.

Abstract Background Patients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus erythematosus (SLE). We sought to examine the clinical characteristics of patients with primary ITP who later developed SLE and identified the risk factors for the development of SLE. Methods We retrospectively examined patients who were diagnosed with primary ITP at a tertiary hospital between August 2001 and November 2019. We compared the clinical characteristics according to the development of SLE. Logistic regression analysis was performed to identify the factors associated with the development of SLE. Results Of 130 patients with primary ITP, 10 (7.7%) were later diagnosed with SLE during follow-up (median, 30 months [IQR, 15.5–105]). The presence of skin bleeding, organ bleeding, lymphocytopenia, anemia, and antinuclear antibody (ANA) positivity (≥ 1:160) were more common among patients who later developed SLE than did those who did not develop SLE. Multivariate analysis showed that young age (

With the increasing number of people affected by gluten consumption-related diseases, adhering to a gluten-free (GF) diet is the most effective preventive measure. Herein, we aimed to isolate and characterize the functional properties of autochthonous lactic acid bacteria (LAB) and yeast from various GF sourdoughs to determine their suitability in starter cultures for sourdough preparation. Three LAB, Weissella confusa BAQ2, Lactobacillus brevis AQ2, Leuconostoc citreum YC2, and Saccharomyces cerevisiae BW1, were identified. The isolated LAB exhibited greater TTA, faster acidification rates, and higher acid tolerance than commercial LAB. W. confusa BAQ2 exhibited the highest EPS production, W. confusa BAQ2 and L. brevis AQ2 showed high maltose utilization, and S. cerevisiae BW1 exhibited the highest CO2 production rate. Accordingly, all four microbial strains were mixed for the starter culture. The sourdough prepared with starter cultures exhibited differences in gas production depending on fermentation time, which influenced the volume of GF bread dough. GF bread prepared with fermented sourdough exhibited a 16% higher specific volume and enhanced crumb firmness and elasticity than that prepared using non-fermented sourdough. Thus, autochthonous LAB strains isolated from various GF sourdoughs can be used together to improve the quality of sourdough bread, demonstrating their potential for use in starter cultures for GF sourdough production.

Background/Aims Recent advances in the understanding of the pathophysiology of myeloproliferative neoplasms (MPN) were not paralleled with advances in treatment options; thus many questions regarding optimal MPN management remain unanswered. Here, we report the results of descriptive survey study of Korean MPN patients and their attending physicians. Methods A total of 105 Korean patients (myelofibrosis [MF], 39; polycythemia vera [PV], 25; essential thrombocythemia [ET], 41) and 30 physicians completed the Landmark Health Survey, then data from the survey were analyzed. Results Among the MPN-Symptom Assessment Form symptoms, the most severe symptom reported was ‘fatigue or tiredness’ in MF and ET patients and ‘itching’ in PV patients. The majority of the patients agreed that MPN reduced their quality of life (QoL). Interestingly, physicians gave higher scores regarding the impact of MPN on patient’s daily and social life compared to patients themselves. For patients, the most important treatment goal was symptom improvement regardless of MPN subtype, while for physicians the highest priority for treatment was better QoL regardless of MPN subtype. Generally, both patients and physicians were satisfied with the overall treatment/management of MPN and communications. However, many patients felt there was not enough time during the appointment for discussion, while many physicians felt they lacked effective drugs to offer to their patients. Conclusions Our study suggests there are room for better-standardized monitoring of symptoms and treatment options and those continuous efforts to bridge the gap between patients and physicians are necessary for better care of MPN patients.

Objective Lidocaine is an amide local anaesthetic commonly used for pain control, however, few studies have investigated the effect of lidocaine on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). The present study aimed to determine the effect of lidocaine on HDPSC viability and osteogenic differentiation. Methods HDPSCs were incubated with 0, 0.05, 0.2, 0.5, and 1 mM lidocaine for 24, 48 and 72 h, after which, MTT assays were performed. HDPSCs cultured with the above lidocaine concentrations and osteogenic differentiation medium for 7 and 14 days were stained for alkaline phosphatase (ALP). Protein and mRNA levels of relevant osteogenic factors (bone morphogenetic protein-2 [BMP-2] and runt-related transcription factor 2 [RUNX2]) were examined using western blotting and real-time reverse-transcription polymerase chain reaction, respectively. Results Lidocaine did not affect the viability of HDPSCs, however, lidocaine reduced ALP activity in HDPSCs. Levels of ALP, BMP-2, and RUNX2 mRNA were reduced with lidocaine, and levels of BMP-2 and RUNX2 proteins were decreased, versus controls. Conclusions Lidocaine inhibits osteogenic differentiation markers in HDPSCs in vitro , even at low concentrations, without cytotoxicity. This study suggests that lidocaine may inhibit osteogenic differentiation in HDPSC-mediated regenerative medicine, including pulp regeneration and repair.

Objectives Postoperative opioid use and pain are related to postoperative delirium. This study aims to compare the incidence of delirium in patients with and without patient-controlled intravenous analgesia (PCIA) among liver transplant recipients. Methods The medical records of 253 patients who received liver transplantation (LT) from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided into two groups: the patients who had used PCIA (P group, n = 71) and those who did not use PCIA (C group, n = 182) after LT in intensive care unit (ICU). The patient data were collected, which included demographic data, and details about perioperative management and postoperative complications. Results There was no difference in the model for end-stage liver disease (MELD) score between the two groups. Postoperative delirium occurred in 10 / 71 (14.08 %) in the P group and 26 / 182 (14.29 %) in the C group after LT, respectively (P = 0.97). After propensity score matching, no differences were observed in the incidence of delirium (P = 0.359) and the time from surgery to discharge (P = 0.26) between the two groups. Conclusions Patients with PCIA after LT exhibited no relationship with postoperative delirium. Therefore, it is necessary to actively control postoperative pain using PCIA.

Acute myeloid leukemia (AML) is an aggressive blood cancer with a high rate of relapse associated with adverse survival outcomes, especially in elderly patients. An aberrant expression of cyclin dependent kinase 7 (CDK7) is associated with poor outcomes and CDK7 inhibition has showed antitumor activities in various cancers. We investigated the efficacy of YPN-005, a CDK7 inhibitor in AML cell lines, xenograft mouse model, and primary AML cells. YPN-005 effectively inhibited the proliferation of AML cells by inducing apoptosis and reducing phosphorylation of RNA polymerase II. The c-MYC expression decreased with treatment of YPN-005, and the effect of YPN-005 was negatively correlated with c-MYC expression. YPN-005 also showed antileukemic activities in primary AML cells, especially those harboring FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutation and in in vivo mouse model. Phosphorylated FLT3/Signal transducer and activator of transcription 5 (STAT5) was decreased and FLT3/STAT5 was downregulated with YPN-005 treatment. Our data suggest that YPN-005 has a role in treating AML by suppressing c-MYC and FLT3.

Background Pierre Robin sequence (PRS) patients have an increased risk of difficult intubation due to anatomical airway abnormalities, and intubation simulation with a three-dimensional (3D) printed airway model before anesthesia may facilitate safe airway management. Case We describe the case of a 6.5-year-old boy with a history of PRS (a triad of micrognathia, glossoptosis, and airway obstruction), tracheostomy, and subglottic fibrosis who required general anesthesia. Preparation for this potentially difficult intubation included estimation of endotracheal tube size using a 3D printed airway model derived from 3D computed tomography of the airway, which enabled successful endotracheal intubation via video laryngoscopy. Conclusions If general anesthesia is necessary in patients with dysmorphic features such as PRS and there is a history of tracheal pathology, the possibility of difficult intubation should always be considered and simulation of endotracheal intubation using a 3D printed model of the airway can be helpful clinically in such situations.

Introduction: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer’s disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer’s disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. Methods: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into “with” and “without ADP” groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. Results: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated “low” to “moderate” in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. Conclusion: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

Background: The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD. Methods: Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment. Results: The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067). Conclusion: A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD. Trial registration: The protocol was registered at Korean Clinical Trial Registry (CRIS-KCT0001810)

Background and objectives: Herpes zoster (HZ) is caused by the reactivation of a pre-existing latent varicella zoster virus, which is one of the viruses that causes hearing loss, and hearing loss may occur due to a systemic immune response even if it does not invade the auditory nerve. This study aimed to determine the correlation between sudden sensorineural hearing loss (SSNHL) in older adult patients who received HZ treatment. Materials and Methods: We used the cohort data of patients aged 60 years and above (n = 624,646) between 2002 and 2015 provided by the National Health Insurance Service. The patients were divided into two groups: those who were diagnosed with HZ between 2003 and 2008 (group H, n = 36,121) and those who had not been diagnosed with HZ between 2002 and 2015 (group C, n = 584,329). Results: In the main model (adjusted HR = 0.890, 95% CI = 0.839–0.944, p < 0.001) adjusted for sex, age, and income, and the full model (adjusted HR = 0.894, 95% CI = 0.843–0.949, p < 0.001) adjusted for all comorbidities, group H had a lower risk of SSNHL than group C. Conclusions: This study showed that patients who received HZ treatment had a lower incidence of SSNHL within five years after diagnosis.

Background Despite significant technological advances in the implantable pulse generator (IPG), complications can still occur. We report a case that unexpected extrusion of the IPG of spinal cord stimulation (SCS) was promptly identified and successfully removed without any complications. Case After a car accident 4 years ago, a 55-year-old male who was diagnosed with complex local pain syndrome in his right leg. The SCS was inserted with 2 leads, with the IPG being implanted in the right lower abdomen region. Four years later, he developed extrusion of the IPG from his abdominal region. This unexpected extrusion may have been related to pressure necrosis caused by continued compression of pocket site where a belt was frequently tied. The IPG and the leads were successfully removed without infection occurring. Conclusions To prevent unexpected extrusion of IPG, it is necessary to consider in advance whether the pocket site is pressed against the belt.

BackgroundScoring systems developed for predicting survival after allogeneic hematopoietic cell transplantation (HCT) show suboptimal prediction power, and various factors affect posttransplantation outcomes. ObjectiveA prediction model using a machine learning–based algorithm can be an alternative for concurrently applying multiple variables and can reduce potential biases. In this regard, the aim of this study is to establish and validate a machine learning–based predictive model for survival after allogeneic HCT in patients with hematologic malignancies. MethodsData from 1470 patients with hematologic malignancies who underwent allogeneic HCT between December 1993 and June 2020 at Asan Medical Center, Seoul, South Korea, were retrospectively analyzed. Using the gradient boosting machine algorithm, we evaluated a model predicting the 5-year posttransplantation survival through 10-fold cross-validation. ResultsThe prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.788 (SD 0.03). Furthermore, we developed a risk score predicting probabilities of posttransplantation survival in 294 randomly selected patients, and an agreement between the estimated predicted and observed risks of overall death, nonrelapse mortality, and relapse incidence was observed according to the risk score. Additionally, the calculated score demonstrated the possibility of predicting survival according to the different transplantation-related factors, with the visualization of the importance of each variable. ConclusionsWe developed a machine learning–based model for predicting long-term survival after allogeneic HCT in patients with hematologic malignancies. Our model provides a method for making decisions regarding patient and donor candidates or selecting transplantation-related resources, such as conditioning regimens.

Background There are various reports on the effects of the anesthetic method on neurologic complications. A population-based study was conducted to estimate the effect of anesthetic method on the incidence of postoperative delirium in patients that underwent total hip replacement arthroplasty in South Korea. Methods The Korean National Health Insurance claims database was used to retrospectively identify and analyze 24,379 cases of total hip replacement arthroplasty, defined as patients having a claim record with the operation code ‘N0711,’ from January 2008 to December 2017. Patients were divided into two groups, a general anesthesia group (n = 9,921) and a regional anesthesia group (n = 14,458). The incidence of delirium was assessed in cases when patients used medications for delirium, such as haloperidol, chlorpromazine, olanzapine, and risperidone. Results Of the 9,921 patients receiving general anesthesia and 14,458 receiving regional anesthesia, 142 (1.43%) and 209 (0.86%) experienced postoperative delirium after total hip replacement arthroplasty, respectively. There was no significant difference between the groups (P = 0.92). In logistic regression analysis, sex (P = 0.038) and patients with acquired immune deficiency syndrome (P = 0.008) were predictors of postoperative delirium. Conclusions Our results revealed that the anesthetic method was not associated with the incidence of postoperative delirium. In addition, the results suggest that male patients and patients with acquired immune deficiency syndrome undergoing total hip replacement arthroplasty carefully managed for postoperative delirium after surgery.

Background Intravenous dexmedetomidine has been reported to potentiate the anesthetic effect of local anesthetics and improve the quality of postoperative analgesia when used as an adjuvant in neuraxial block. We compared the effects of intravenous dexmedetomidine and midazolam for sedation on combined spinal-epidural (CSE) anesthesia. Methods This study included 50 patients undergoing total knee arthroplasty. CSE anesthesia was given using 10 mg bupivacaine for all patients. After checking the maximum sensory and motor levels, the patients were randomly allocated into two groups of 25 each to receive intravenous continuous infusion of dexmedetomidine (Group D) or midazolam (Group M) for sedation during surgery. Regression block level, hemodynamic changes, and sedation score were compared between the groups when the patients entered the postanesthetic care unit (PACU). For patient-controlled epidural analgesia, 0.2% levobupivacaine with 650 µg of fentanyl (150 ml in total) was infused at a rate of 1 ml/h, in addition to a 3-ml bolus dose with a 30-min lockout time. The visual analogue scale scores, additional analgesic demand, patient satisfaction, and adverse events between the two groups were also compared postoperatively. Results A significant difference was observed in relation to the sensory block level in the PACU (Group D: 6.3 ± 2.1; Group M: 3.2 ± 1.9) (P = 0.002). The motor block level and other outcomes showed no significant intergroup differences. Conclusions Intravenous injection of dexmedetomidine, rather than midazolam, for procedural sedation is associated with prolonged sensory block, with comparable incidences of adverse events during CSE anesthesia.

Background: The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD. Methods: Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment. Results: The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067). Conclusion: A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD.

Postmenopausal obesity is becoming a serious global health concern. Soyasaponin Ab (SA) inhibits adipocyte differentiation; however, the preventive and therapeutic potential of SA in postmenopausal obesity has not been clearly established. Here, we investigated the anti-obesity effects of SA in postmenopausal obesity in vitro and in vivo. SA inhibited adipocytic differentiation of 3T3-L1 cells and reduced lipid accumulation and lipid droplet formation. Moreover, SA significantly decreased weight gain, adipocyte area, serum metabolic profiles in OVX mice. SA also inhibited the lipid metabolism-related factors but increased the thermoregulatory factors in both in vitro and in vivo. SA treatment further increased energy expenditure through beige fat activation. Overall, we found that SA effectively accelerated energy consumption by stimulating beige fat activation, even under estrogen-deficient conditions. Thus, SA treatment may be a promising strategy for the prevention of postmenopausal obesity by promoting weight loss, reducing fat accumulation, and improving obesity-related metabolic disorders.

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.

Elucidating the genetic basis of influenza A viruses (IAVs) is important to understand which mutations will determine the virulence and the host range of mammals. Here, seasonal H3N2 influenza was adapted in mice by serial passage and four mutants, each carrying amino acid substitutions related to mouse adaptation in either the PB2, HA, NP, or NA protein, were generated. To confirm the contribution of each gene to enhanced pathogenicity and mouse adaptation, mice were inoculated with the respective variants, and virulence, replication, histopathology, and infectivity were examined. The virus harboring HA mutations displayed increased infection efficiency and replication competence, resulting in higher mortality in mice relative to those infected with wild-type virus. By contrast, the NP D34N mutation caused rapid and widespread infection in multiple organs without presenting virulent symptoms. Additionally, the PB2 F323L mutation presented delayed but elevated replication competence in the respiratory tract, whereas the S331R mutation in NA showed no considerable effects on mouse adaptation. These results suggested that mouse-adapted changes in HA are major factors in increased pathogenicity and that mutations in NP and PB2 also contribute to cross-species adaptability. Our findings offer a better understanding of the molecular basis for IAV pathogenicity and adaptation in a new host.

Liver transplantation is a current definitive treatment for those with end-stage liver disease. Hepatic encephalopathy is a common complication of hepatic failure, which can be improved and aggravated by various causes. It is important to differentiate hepatic encephalopathy from other diseases causing brain dysfunction such as cerebral hemorrhage, which is also related to high mortality after liver transplant surgery. A 37-year-old patient was presented with acute liver failure and high ammonia levels and seizure-like symptoms. Computed tomography (CT) of his brain showed mild brain atrophy, regarded as a symptom of hepatic encephalopathy, and treated to decrease blood ammonia level. Deceased donor liver transplantation was performed and liver function and ammonia level normalized after surgery, but the patient showed symptoms of involuntary muscle contraction and showed loss of pupil reflex and fixation without recovery of consciousness. Brain CT showed brain edema and bilateral cerebral infarction, and the patient died after a few days. The purpose of this case report is to emphasize the importance of preoperative neurological evaluation, careful transplantation decision, and proper perioperative management of liver transplantation in patients with acute hepatic encephalopathy.

Somatic cell nuclear transfer (SCNT) provides a unique opportunity to reproduce animals with superior genetics. Viable cell lines are usually established from tissues collected by biopsy from living animals in the SCNT program. In the present study, tissues were collected and preserved from a suddenly deceased champion camel. We established cell lines from these decade-old tissues and used them as nuclear donors. After 42 h of in vitro maturation, 68.00 ± 2.40% of oocytes reached the metaphase II (M II) stage while 87.31 ± 2.57% in vivo collected oocytes were matured at collection (p < 0.05). We observed a higher blastocyst formation rate when in vivo matured oocytes (43.45 ± 2.07%) were used compared to in vitro matured oocytes (21.52 ± 1.74%). The live birth rate was 6.45% vs. 16.67% for in vitro and in vivo matured oocytes, respectively. Microsatellite analysis of 13 camel loci revealed that all the SCNT-derived offspring were identical to each other and with their somatic cell donor. The present study succeeded in the resurrection of 11 healthy offspring from the decade-old vitrified tissues of a single somatic cell donor individual using both in vitro and in vivo matured oocytes.

The processes regulating the ageing of stem cells are not clearly defined. Here, the authors report that in haematopoietic stem cells (HSC) thioredoxin-interacting protein, known to regulate the cell cycle, binds to p38 mitogen-activated protein kinase and regulates HSC ageing and rejuvenation.

In this study, a series of thermotropic liquid crystalline polyester (TLCP)-based blends containing 1–30 wt% poly(ethylene-co-glycidyl methacrylate) (PEGMA) were fabricated by masterbatch-assisted melt-compounding. The scanning electron microscopy (SEM) images showed a uniformly dispersed microfibrillar structure for the TLCP component in cryogenically-fractured blends, without any phase-separated domains. The FT-IR spectra showed that the carbonyl stretching bands of TLCP/PEGMA blends shifted to higher wavenumbers, suggesting the presence of specific interactions and/or grafting reactions between carboxyl/hydroxyl groups of TLCP and glycidyl methacrylate groups of PEGMA. Accordingly, the melting and crystallization temperatures of the PEGMA component in the blends were greatly lowered compared to the TLCP component. The thermal decomposition peak temperatures of the PEGMA and TLCP components in the blends were characterized as higher than those of neat PEGMA and neat TLCP, respectively. From the rheological data collected at 300 °C, the shear moduli and complex viscosities for the blend with 30 wt% PEGMA were found to be much higher than those of neat PEGMA, which supports the existence of PEGMA-g-TLCP formed during the melt-compounding. The dynamic mechanical thermal analysis (DMA) analyses demonstrated that the storage moduli of the blends decreased slightly with the PEGMA content up to 3 wt%, increased at the PEGMA content of 5 wt%, and decreased again at PEGMA contents above 7 wt%. The maximum storage moduli for the blend with 5 wt% PEGMA are interpreted to be due to the reinforcing effect of PEGMA-g-TLCP copolymers.

Background. Percutaneous radiofrequency ablation (PRFA) is a useful and safe treatment for hepatocellular carcinoma (HCC). Pain management, during and after PRFA, is a critical component of patient care. Objectives. This study reviewed the efficacy of thoracic epidural analgesia, during and after PRFA, for patients with HCC. Study Design. A retrospective, observational chart review. Setting. Tertiary medical center/teaching hospital. Methods. Patients who had undergone PRFA for HCC in the past 5 years were divided into two groups, based on the type of anesthesia administered: thoracic epidural anesthesia group (Group E) and local anesthesia with monitored anesthesia care group (Group C). We retrospectively reviewed changes in the numeric rating scale (NRS) score during and after PRFA, opioid consumption, length of the procedure, length of hospital stay, changes in blood pressure during PRFA, and the incidence of adverse events. Results. The NRS score in Group E was significantly lower than that in Group C (P

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

Although symptomatic carbon dioxide (CO2) embolism is rare, it recognized as a potentially fatal complication of laparoscopic surgery. Sudden hemodynamic instability could be a CO2 embolism especially during insufflation. A 65-year-old man received laparoscopic prostatectomy for 5 hours under CO2 pneumoperitoneum without any problem. After resection of prostate, it was stopped following deflation. Thirty minutes later, peumoperitoneum was re-induced to continue the operation. Shortly after re-insufflation, the patient revealed hemodynamic instability suggested a CO2 embolism; severe hypotension, tachyarrythmia, hypoxemia, increased CVP, and changed end-tidal CO2. Gas insufflation was stopped. He was managed with Durant's position, fluid and cardiotonics for 20 minutes. The residual was completed by open laparotomy. Re-insufflation, inducing gas entry through the injured vessels, might be a risk factor for CO2 embolism in this case. The risk to the patient may be minimized by the surgical team's awareness of CO2 embolism and continuous intra-operative monitoring of end-tidal CO2.