Search

Summary Background and aims Since there is a shortage of liver donors, we investigated recurrence patterns and outcomes after liver resection (LR) to determine the feasibility of salvage liver transplantation (SLT). Methods We analyzed 468 patients with hepatocellular carcinoma (HCC) within the Milan criteria (MC) who were mainly associated with Hepatitis B virus infection (76.3%) and had undergone curative LR as an initial treatment. Results The overall survival (OS) rates were 86.6% and 67.4% at 5 and 10 years after LR, respectively. During a median follow-up of 59 months, 211 patients experienced recurrences including 175 (37.4%) within MC and 36 (7.7%) beyond MC. Survival was lowest in patients with beyond MC-recurrence followed by within MC- and no-recurrence groups (26.5%, 86.6%, and 94.7% at 5 years, respectively, P Conclusion Curative LR achieved a 5-year survival of > 85% in patients with transplantable HCC, but early SLT after recurrence within MC is advocated because of poor survival and high risk of progression thereafter. Further, prophylactic LT could be considered for those with high risk of recurrence.

In this study, we developed organelle-specific blue-emitting two-photon (TP) probes for Ca

Research question Are single nucleotide polymorphisms of microRNAs (miRNAs) and risk of idiopathic recurrent pregnancy loss (RPL) associated? Design A total 375 patients with idiopathic RPL (age, mean ± standard deviation [SD] 33.02 ± 4.24 years; body mass index [BMI], mean ± SD, 21.57 ± 3.70 kg/m2) and 276 control participants (age, mean ± SD, 33.01 ± 5.27 years; BMI, mean ± SD, 21.58 ± 3.20) were recruited. Pregnancy loss was diagnosed using human chorionic gonadotrophin concentrations, ultrasonography and/or physical examination prior to 20 weeks of gestation. The genotype of the participants was determined by polymerase chain reaction restriction fragment length polymorphism analysis. Statistical analysis was performed to investigate the differences in frequencies between the control and RPL genotypes Results The miR-150G>A heterozygous genotype was significantly associated with increased risk of RPL (adjusted odds ratio 2.502, 95% confidence interval 1.555–4.025; P = 0.0002). The miR-1179A>T heterozygous genotype was significantly associated with decreased risk of RPL (adjusted odds ratio 0.633, 95% confidence interval 0.454–0.884; P = 0.007). Some allele combinations that included miR-150A or miRNA-1179T resulted in an increase or decrease in risk of RPL, respectively. Conclusions The miR-150G>A and miR-1179A>T polymorphisms were more frequently associated with RPL compared with controls.

Background Subepithelial tumors (SETs) originating from the muscularis propria layer are unlikely to be resected completely and safely. We developed the Forcep Strip Method (FSM) for the resection of SETs in the stomach. Aims This study aimed to evaluate the feasibility and safety of the FSM. Methods Endoscopic SET resection using electrical forceps was performed in 11 consecutive patients with clinical indications for lesion removal. Following injection around the tumor, the adjacent mucosa or submucosa was grasped with the hot forceps and pulled away to form a “tent”. The tumor was dissected from the muscularis propria layer and carefully removed using coagulating forceps. Results The FSM was successful in 10 of the 11 patients in the series; one patient required surgery due to respiratory depression during the procedure. The complete resection rate was 100% and no major complications including bleeding and perforation occurred. Mean procedure time was 39.3 ± 14.7 min, mean hospitalization time was 5.0 ± 1.2 days, and mean tumor size was 17.1 ± 4.7 mm. Conclusion FSM was found to be an easy, safe, and effective procedure for the treatment of gastric SETs originating from the muscularis propria layer.

Objectives To investigate the concordance of results of blood and tissue cultures in patients with pyogenic spondylitis. Methods We searched for patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures by retrospective review of medical records in three tertiary university-affiliated hospitals between January 2005 and December 2015. The species and antimicrobial susceptibility patterns of isolates from blood and tissue cultures were compared. Results Among 141 patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures, the species of blood and tissue isolates were identical in 135 patients (95.7%, 135/141). Excluding the four anaerobic isolates, we investigated antimicrobial susceptibility patterns of 131 isolates of the same species from blood and tissue cultures. Antibiotic susceptibility patterns were identical in 128 patients (97.7%, 128/131). The most common isolates were Staphylococcus aureus (86 patients; 85 concordant and one discordant), followed by streptococcus (24 patients; 22 concordant and two discordant), and Escherichia coli (eight patients; all concordant). Conclusions We suggest that a positive blood culture from patients with pyogenic spondylitis could preclude the need for additional tissue cultures, especially when S. aureus and streptococcus grew in blood cultures.

A novel variable optical delay line based on a hollow-core photonic bandgap fiber is proposed. The device incorporates microfluid, the end surface of which serves as an optical reflector, in the hollow-core of the fiber. The position of the fluid end is controlled by a syringe pump to change the optical delay of the reflected beam. We demonstrate wide tunability of the optical delay up to 1 m with a scan speed of several mm/s. The return loss and beat pattern in the reflected signal is studied and the potential of the device as an ultra-long delay line is discussed.

Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500-750 mg of cycloserine QD, 4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment.

Electron-deficient and porous WO 3 particles were prepared by the simple thermal oxidation of commercial bulk WC. The crystal structure of as-prepared WO 3 particles was monoclinic phases and its crystallinity and morphology were controlled by varying the calcination temperature. Small and interconnected WO 3 particles were divided and formed from bulk WC particles with increasing calcination temperature. The electronic structure of thermally oxidized particles was studied by W L III -edge XANES. Interestingly, as-prepared WO 3 samples were in an electron-deficient state (W +6−δ ). The photocatalytic performance of as-prepared samples was investigated in terms of oxygen production in AgNO 3 aqueous solution and decomposition of the organic dye, Rhodamine B. The photoelectrochemical and photocatalytic activity were correlated and the results were most favorable for WO 3 particles thermally oxidized at 700 °C for oxygen production and 600 °C for photocurrent production.

Background Oropharyngeal squamous cell carcinoma (OPSC) continues to increase in incidence with human papillomavirus (HPV) infection. Despite the good overall prognosis, it needs to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure to guide de-intensification regimens. This study aimed to investigate the expression of estrogen receptor (ER) and programmed cell death-ligand 1 (PD-L1) proteins according to the status of HPV infection and their prognostic implication in OPSCC patients. Methods Consecutive 80 patients diagnosed with OPSCC with surgical treatment from 2004 to 2017 were included. Immunohistochemistry for ER and PD-L1 was performed formalin-fixed, paraffin embedded tissues. HPV status assessed with p16 immunohistochemistry and HPV DNA testing. Results ER and PD-L1 expression were observed in 37.5% (30/80) and 60% (48/80), respectively. Both ER and PD-L1 protein expression were higher in HPV-positive OPSCC than in HPV-negative subgroup (47.5% vs. 9.5% for ER, 66.1% vs. 42.9% for PD-L1). There was no significant association between ER and PD-L1 expression (correlation coefficient: 0.105, p > 0.05). Using Kaplan-Meier curves, PD-L1 expression was associated with longer recurrence-free duration (p = 0.013), whereas ER expression was associated with prolonged overall survival (p = 0.043). In subgroup analysis, PD-L1 expression was found to be an independent excellent prognostic factor for recurrence-free duration in HPV-positive OPSCC (p = 0.002, HR = 0.085 [0.018-0.399]). ER expression also tended to be associated with longer overall survival in the HPV-positive OPSCC subgroup, but no statistical significance was observed. In HPV-negative subgroup, both ER and PD-L1 expression were not associated with any clinicopathologic factor nor survival. Conclusions ER and PD-L1 expression can be complementary prognostic factors in HPV-positive OPSCC. It may allow us to investigate the independent role of anti-hormone receptors and the tumor microenvironment in the treatment of OPSCC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow (SA), fourteen intermediate (IA) and six rapid acetylators (RA). As expected, isoniazid exposure was higher (mean AUC, 28.4 versus 7.6 mg*h/L) and systemic clearance lower (mean apparent clearance, 14.8 versus 50.6 L/h) in SAs than RAs. The formulas to estimate isoniazid exposure were constructed using one or more concentration-time points that correlate with the area under the concentration-time curve (AUC). The LSS using a formula of single concentration-time point at 4 h post dose (C4) is applicable for all acetylators to the therapeutic drug monitoring (TDM) of isoniazid in patients with tuberculosis when evaluated using the Deming regression and Bland-Altman plot (AUC = 1.53 + 10.03*C4, adjusted r2 = 0.95, p

Introduction How long persistent and stable ground-glass nodules (GGNs) should be followed is uncertain, although a minimum of 3 years is suggested. Here, we evaluated a group of GGNs that had remained stable for an initial period of 3 years with the aim of determining the proportion of GGNs showing subsequent growth after the initial 3 years and identifying the clinical and radiologic factors associated with subsequent growth. Methods We retrospectively analyzed patients who underwent further computed tomography (CT) after the initial 3-year follow-up period showing a persistent and stable GGN (at least 5 years of follow-up from the initial CT). Results Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of the 218 patients, 14 had 15 GGNs showing subsequent growth after the initial 3 years during the median follow-up period of 6.4 years. For the person-based analysis, the frequency of subsequent growth of GGNs that had been stable during the initial 3 years was 6.7% (14 of 218). For the nodule-based analysis, the frequency was 3.3% (15 of 453). In a multivariate analysis, age 65 years or older (OR = 5.51, p = 0.012), history of lung cancer (OR = 6.44, p = 0.006), initial size 8 mm or larger (OR = 5.74, p = 0.008), presence of a solid component (OR = 16.58, p = 0.009), and air bronchogram (OR = 5.83, p = 0.015) were independent risk factors for subsequent GGN growth. Conclusions For the individuals with GGNs having the aforementioned risk factors, the longer follow-up period is required to confirm subsequent GGN growth.

When defective or absent, Werner syndrome protein (WRN) causes a genetic premature aging disorder called Werner syndrome. Several studies have reported that defects in WRN function are responsible for not only progeria syndrome but also genomic instability via the deregulation of DNA repair, replication, recombination, and telomere stability. Given the importance of WRN in the repair process, we herein investigated the potential role of WRN in drug response by evaluating the DNA repair following exposure to cisplatin in human cancer cell lines. We found that the down-regulation of SIRT1 and inhibition of SIRT1 deacetylase activity blocked the translocation of WRN from the nucleolus to the nucleoplasm in response to genotoxic stresses. In addition, cells expressing low levels of WRN responded favorably to cisplatin, whereas cells expressing high levels responded poorly to cisplatin. The forced expression of WRN protein in chemosensitive cells resulted in an approximately two-fold increase in cell viability in response to cisplatin compared with vector controls and promoted DNA repair, while WRN-deficient cells accumulate unrepaired double-strand breaks following cisplatin exposure. These results suggest that WRN is regulated by SIRT1 and increased expression of WRN might be one of the determinants for the development of chemotherapeutic drug resistance.

Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD.

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays key roles in glucose and lipid metabolism. Its transcriptional control of target genes is mediated by ligand-dependent recruitment of coactivators. In this study, we demonstrate that a novel transcriptional modulator of PPARγ, Flightless-I (FLII) binds directly to and suppresses the transcriptional activity of PPARγ. The LXXLL motif within the leucine-rich repeat (LRR) domain of FLII interacts directly with the DNA-binding domain of PPARγ. Interestingly, in the presence of PPARγ ligands, such as rosiglitazone and SR1664, this interaction was abolished in vitro. When FLII was overexpressed, both the transcriptional activity of PPARγ and adipogenesis were suppressed significantly, whereas specific knockdown of FLII reversed these effects. Furthermore, DNA occupancy of PPARγ on its target gene promoters was enhanced by FLII knockdown, and the interaction between PPARγ and retinoid X receptor α (RXRα) was blocked by FLII. Together, these findings strongly suggest that FLII functions in PPARγ activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPARγ/RXRα complex, and FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes.

No study has determined whether the risk of mortality predicted by the GAP (gender, age, and physiologic variables) model matches the observed mortality from idiopathic pulmonary fibrosis (IPF) in non-Western populations. We evaluated the clinical course of IPF and validated the GAP model in Korean patients with IPF.We included 268 patients who received a diagnosis of IPF at Seoul National University Hospital between 2005 and 2009. For each patient, demographics and clinical data, such as lung physiologic parameters at IPF diagnosis, were evaluated. We validated the GAP model using discrimination and calibration to predict the risk of death in Korean patients with IPF.The study population comprised 181 men and 87 women (mean age, 65.9 years). The mean baseline % predicted FVC was 77, and % predicted diffusing capacity of lung for carbon monoxide was 65.9. A total of 157 deaths (58.6%) occurred during follow-up, and the median time to death was 4.64 years. The observed cumulative mortality at 1, 2, and 3 years was 10.4%, 20.9%, and 31.0%, respectively. The GAP model produced estimates of 1-year mortality risk consistent with the observed data (C statistic: GAP calculator, 0.74; GAP index and staging system, 0.72; P.29). However, calibration of the GAP model at 3 years was not satisfactory.The GAP model showed similar discrimination power compared with the original cohort but did not predict the 3-year risk of death accurately. Further multinational validation studies are needed.

Hypertrophic pyloric stenosis (HPS) is one of the most common gastrointestinal disorders that require surgical intervention in early infancy. Clinical presentation, diagnosis, and treatment have been well established in typical cases. We herein describe an unusual case of early presenting HPS with transient postoperative feeding intolerance after complete myotomy in a preterm newborn. An ex-31-week preterm newborn (birth weight, 1760 g) with persistent feeding intolerance since the first feeding was referred for surgery on the 7th day of life. Abdominal ultrasonography (USG) revealed an elongated pyloric channel (11 mm) with thickened pyloric muscle (2.1 mm). Laparotomy was performed and confirmed suspected HPS. Pylomyotomy was successful, but feeding intolerance persisted until postoperative day 12. USG on postoperative day 12 noted antroduodenal dysmotility, and transpyloric tube feeding was started. Full feeds were reached 8 days after tube feeding, which was then converted to full oral feeding. HPS should be considered in patients who show feeding intolerance shortly after birth. USG criteria for HPS in preterm infants has not yet been established. Transient antroduodenal dysmotility could be a reason for persistent feeding intolerance after complete myotomy in preterm infants, and transpyloric tube feeding could be a treatment in such cases.

Aims Polaprezinc (PZ), which consists of l -carnosine and zinc, is widely used to treat gastric ulcers. We compared the effects of PZ with those of rebamipide (RM) on the expression of inflammatory cytokines, antioxidants, growth factors, and heat shock proteins (HSP) in a rat model. Main methods Seventy Sprague–Dawley rats were randomly assigned to test groups according to the dose of PZ at 5, 10, or 30 mg/kg or RM at 10, 30, or 100 mg/kg. Next, we obtained ulcer indices from rats with ethanol-induced gastric mucosal damage. Western blot analysis was used to evaluate the expression of various target proteins. Key findings Pathological ulcer indices in the PZ and RM groups were significantly lower than those in the control group. The levels of inflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-8, and tumor necrosis factor α) decreased, whereas the levels of platelet-derived growth factor-B, vascular endothelial growth factor, and nerve growth factor significantly increased after PZ administration. Furthermore, the expression of antioxidants (superoxide dismutase 1 [SOD-1], SOD-2, heme oxygenase-1, glutathione S-transferase, peroxidredoxin-1, and peroxidredoxin-5) was significantly higher in the PZ group, and the levels of HSP 90, 70, 60, 47, 27, and 10 significantly increased with an increase in PZ dose. Significance In a rat model of ethanol-induced gastric mucosal damage, PZ administration ameliorated ethanol-induced mucosal injury and showed protective effects on the mucosa by reducing the levels of inflammatory cytokines and increasing the expression of antioxidant enzymes and growth factors. Furthermore, PZ showed cytoprotective effects by increasing the HSP levels.

Mesoporous cobalt-doped ZnS and ZnO nanoplates were fabricated by calcination of a Zn 0.95 Co 0.05 S(en) 0.5 complex (en = ethylenediamine), which was hydrothermally synthesized using ethylenediamine as a single solvent and chelating agent. When the as-prepared Zn 0.95 Co 0.05 S(en) 0.5 complex was calcined, mesoporous nanoplates of wurtzite Zn 0.95 Co 0.05 S were formed, which then transformed to Zn 0.95 Co 0.05 O platelets upon further oxidation. Photocatalytic performance of the as-prepared materials was investigated for decomposition of the azo dye (acid red 14) and photoelectrochemical current generation in aqueous Na 2 S/Na 2 SO 3 solution as probe reactions. The Zn 0.95 Co 0.05 S calcined at 500 °C exhibited the highest photocatalytic activity under UV irradiation and also showed the photocatalytic performance under visible light irradiation.

Disintegration of carbon nanotubes (CNTs) into C atoms and dissolution into Al nanoparticles is achieved by mechanically grinding two materials together. This low-temperature solid-state dissolution process involves several steps: (i) mixing CNTs with Al particles; (ii) Al nanoparticle formation; (iii) disintegration of CNTs into C atoms; and (iv) embedding of C atoms into Al nanoparticles. C atom are embedded into Al nanoparticles up to a level of ∼50 wt.% via the formation of an amorphous phase. This enhances hardness by more than 50%.

An efficient synthesis of dihydroindenofurans was carried out starting from the Baylis–Hillman adducts via a Pd-catalyzed 5-endo-trig-carbopalladation and enolate O-alkylation cascade as a key step. This is the first example of enolate O-alkylation with a C(sp3)-bound palladium intermediate.