Modal decomposition of fiber modes based on direct far-field measurements at two different distances with a multi-variable optimization algorithm.

We present a novel method for modal decomposition of a composite beam guided by a large-mode-area fiber by means of direct far-field pattern measurements with a multi-variable optimization algorithm. For reconstructing far-field patterns, we use finite-number bases of Hermite Gaussian modes that can be converted from all the guided modes in the given fiber and exploit a stochastic parallel gradient descent (SPGD)-based multi-variable optimization algorithm equipped with the D4σ technique in order for completing the modal decomposition with compensating the centroid mismatch between the measured and reconstructed beams. We measure the beam intensity profiles at two different distances, which justifies the uniqueness of the solution obtained by the SPGD algorithm. We verify the feasibility and effectiveness of the proposed method both numerically and experimentally. We have found that the fractional error tolerance in terms of the beam intensity overlap could be maintained below 1 × 10-7 and 3.5 × 10-3 in the numerical and experimental demonstrations, respectively. As the modal decomposition is made uniquely and reliably, such a level of the error tolerance could be maintained even for a beam intensity profile measured at a farther distance.

Serum alanine aminotransferase level and liver-related mortality in patients with chronic hepatitis B: A large national cohort study.

BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear. METHODS: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years. RESULTS: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women. CONCLUSIONS: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal.

A facile single-step synthesis of polyvinylpyrrolidone-silver nanocomposites using a conventional spray dryer.

We have developed a facile single-step synthesis of silver nanocomposite using a conventional spray dryer. We investigated the synthetic conditions by controlling the concentrations of the chemical reactants. Further, we confirmed the effect of the molecular weight of polyvinylpyrrolidones, and revealed that the molecular weight significantly affected the properties of the resultant silver nanocomposites. The long-term stability of the silver nanocomposites was tested, and little change was observed, even after storage for three months. Most of all, the simple commercial implementation, in combination with large-scale synthesis, possesses a variety of advantages, compared to conventional complicated and costly dry-process synthesis methods. Thus, our method presents opportunities for further investigation, for both lab-scale studies and large-scale industrial applications.

Direct interaction of menin leads to ubiquitin-proteasomal degradation of ß-catenin.

Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcription regulator. Menin interacts with various proteins as a scaffold protein and is proposed to play important roles in multiple physiological and pathological processes by controlling gene expression, proliferation, and apoptosis. The mechanisms underlying menin's suppression of tumorigenesis are largely elusive. In this study, we showed that menin was essential for the regulation of canonical Wnt/ß-catenin signaling in cultured cells. The C-terminal domain of menin was able to directly interact with and promote ubiquitin-mediated degradation of ß-catenin. We further revealed that overexpression of menin down-regulated the transcriptional activity of ß-catenin and target gene expression. Moreover, menin efficiently inhibited ß-catenin protein levels, transcriptional activity, and proliferation of human renal carcinoma cells with an activated ß-catenin pathway. Taken together, our results provide novel molecular insights into the tumor suppressor activity of menin, which is partly mediated by proteasomal degradation of ß-catenin and inhibition of Wnt/ß-catenin signaling.

Synthesis of Gold Nanoparticle-Embedded Silver Cubic Mesh Nanostructures Using AgCl Nanocubes for Plasmonic Photocatalysis.

A novel room-temperature aqueous synthesis for gold nanoparticle-embedded silver cubic mesh nanostructures using AgCl templates via a template-assisted coreduction method is developed. The cubic AgCl templates are coreduced in the presence of AuCl4- and Ag+ , resulting in the reduction of AuCl4- into gold nanoparticles on the outer region of AgCl templates, followed by the reduction of AgCl and Ag+ into silver cubic mesh nanostructures. Removal of the template clearly demonstrates the delicately designed silver mesh nanostructures embedded with gold nanoparticles. The synthetic mechanism, structural properties, and surface functionalization are spectroscopically investigated. The plasmonic photocatalysis of the cubic mesh nanostructures for the degradation of organic pollutants and removal of highly toxic metal ions is investigated; the photocatalytic activity of the cubic mesh nanostructures is superior to those of conventional TiO2 catalysts and they are catalytically functional even in natural water, owing to their high surface area and excellent chemical stability. The synthetic development presented in this study can be exploited for the highly elaborate, yet, facile design of nanomaterials with outstanding properties.

Combination of Helicobacter pylori infection and the interleukin 8 -251 T > A polymorphism, but not the mannose-binding lectin 2 codon 54 G > A polymorphism, might be a risk factor of gastric cancer.

BACKGROUND: Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population. METHODS: We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay. RESULTS: MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC. CONCLUSIONS: We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population.

Liver cirrhosis stages and the incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy.

OBJECTIVES: Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy. METHODS: The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3). RESULTS: The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93-75.01, p < .001), alcohol consumption (HR 3.84, 95% C.I. 1.99-7.39, p < .001), and older age (HR 1.06, 95% C.I. 1.01-1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314). CONCLUSIONS: LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.

The role of tumor suppressor menin in IL-6 regulation in mouse islet tumor cells.

Menin is a gene product of multiple endocrine neoplasia type1 (Men1), an inherited familial cancer syndrome characterized by tumors of endocrine tissues. To gain insight about how menin performs an endocrine cell-specific tumor suppressor function, we investigated the possibility that menin was integrated in a cancer-associated inflammatory pathway in a cell type-specific manner. Here, we showed that the expression of IL-6, a proinflammatory cytokine, was specifically elevated in mouse islet tumor cells upon depletion of menin and Men(-/-) MEF cells, but not in hepatocellular carcinoma cells. Histone H3 lysine (K) 9 methylation, but not H3 K27 or K4 methylation, was involved in menin-dependent IL-6 regulation. Menin occupied the IL-6 promoter and recruited SUV39H1 to induce H3 K9 methylation. Our findings provide a molecular insight that menin-dependent induction of H3 K9 methylation in the cancer-associated interleukin gene might be linked to preventing endocrine-specific tumorigenesis.

The prevalence of elevated alanine transaminase and its possible causes in the general Korean population.

GOALS: The goal of the study was to investigate the current prevalence and causes of elevated alanine transaminase (ALT) in the general Korean population. BACKGROUND: Incidentally elevated ALT is frequently found because of increasing access to hospitals and blood tests. STUDY: A population-based cross-sectional study was carried out based on the Fourth Korean National Health and Nutrition Examination Survey (K-NHANES). Eligible subjects included 7894 men and 10,197 women. We defined elevated ALT as >43 U/L. Among the subjects with elevated ALT, those who consumed alcohol, had the hepatitis B surface antigen (HBsAg), were obese (body mass index ≥25 kg/m), were insulin resistant (the homeostasis model assessment-insulin resistance), or had metabolic syndrome (MetS) were investigated. RESULTS: The prevalence of elevated ALT was 7.4% in the Korean population. Increased ALT was more common in men (11.6%) than in women (3.1%) (P<0.001). Subjects with hypertension, diabetes, dyslipidemia (cholesterol ≥240 mg/dL or triglycerides ≥150 mg/dL), obesity, significant consumption of alcohol, HBsAg positive, or MetS were associated with elevated ALT (all P<0.001). The most common potential cause of elevated ALT was metabolic disorder (MetS, obesity, and/or insulin resistance), which comprised 74.9% of cases. MetS was found in 42.7% of men and 49.7% of women (P=0.031). Excess alcohol drinking was found in 29.6% of men and 7.5% of women with elevated ALT (P<0.001). HBsAg positivity was found in only 6% of subjects. CONCLUSIONS: Incidentally elevated ALT is common in the Korean population. It is associated with metabolic disorders (obesity, insulin resistance, or MetS) in the majority of patients. This finding suggests that nonalcoholic fatty liver disease might be the most common cause of elevated ALT in the general Korean population.

Oral antiviral therapy improves the diagnostic accuracy of alpha-fetoprotein levels in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. METHODS: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. RESULTS: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. CONCLUSIONS: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB.

Elevation of PRKCDBP, a novel transcriptional target of TNF-α, and its downregulation by infliximab in patients with ulcerative colitis.

BACKGROUND: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α. AIMS: To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy. METHODS: In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies. RESULTS: A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%, and that of TNF-α decreased from 54.5 to 36.2%. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P = 0.001, respectively). CONCLUSIONS: These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.

Masking nanoparticle surfaces for sensitive and selective colorimetric detection of proteins.

We have developed a convenient and efficient colorimetric detection system for protein targets using aptamer-gold nanoparticle conjugates. We take advantage of the correlation between the catalytic properties and the exposed surface area of the nanoparticles, which is inversely proportional to the amount of the aptamer-bound protein targets. As the concentration of the protein target increases, the nanoparticle surface area becomes more masked, thus increasing the reduction time of 4-nitrophenol for the color change. We also reduce the detection time by either redesigning the aptamer sequences or regulating their density. This detection system is highly selective, discriminating the target protein even at a concentration 1000 times higher than the limit of detection (LOD). Importantly, to the best of our knowledge, the LOD with the unaided eye in this work is the lowest for a colorimetric detection system using lysozyme as a model protein (16 nM). Lysozyme in chicken egg whites is directly analyzed using our detection system, whose results are in excellent agreement with the enzyme-linked immunosorbent assay (ELISA) analysis.

Close observation of gastric mucosal pattern by standard endoscopy can predict Helicobacter pylori infection status.

BACKGROUND AND AIM: Common endoscopic findings in stomachs with Helicobacter pylori infections include antral nodularity, thickened gastric folds, and visible submucosal vessels. These findings are suggestive but not diagnostic of H. pylori infection. Magnifying endoscopy can reveal more precisely the abnormal mucosal patterns in an H. pylori-infected stomach; however, it requires more training, expertise, and time. We aimed to establish a new classification for predicting H. pylori-infected stomachs by non-magnifying standard endoscopy alone. METHODS: A total of 617 participants who underwent gastroscopy were prospectively enrolled from August 2011 to January 2012. We performed a careful close-up examination of the corpus at the greater curvature maintaining a distance ≤ 10 mm between the endoscope tip and the mucosal surface. We classified gastric mucosal patterns into four categories: normal regular arrangement of collecting venules (numerous minute red dots), mosaic-like appearance (type A; swollen areae gastricae or snakeskin appearance), diffuse homogenous redness (type B), and untypical pattern (type C; irregular redness with groove) to predict H. pylori infection status. RESULTS: The frequencies of H. pylori infection in patients with a normal regular arrangement of collecting venules pattern and types A, B, and C patterns were 9.4%, 87.7%, 98.1%, and 90.9%, respectively. The sensitivity, specificity, and positive and negative predictive values of all abnormal patterns for prediction of H. pylori infection were 93.3%, 89.1%, 92.3%, and 90.6%, respectively. The overall accuracy was 91.6%. CONCLUSIONS: Careful close-up observation of the gastric mucosal pattern with standard endoscopy can predict H. pylori infection status.

Acid suppression therapy as a risk factor for Candida esophagitis.

BACKGROUND/AIM: As the prevalence of reflux esophagitis increases, so does the use of gastric acid suppressants. This study aimed to document the prevalence of Candida esophagitis (CE) at a single Korean university hospital over the last 5 years and to evaluate its risk factors. METHODS: To investigate the prevalence of CE, we conducted a retrospective analysis of 55,314 individuals who underwent a screening esophagogastroduodenoscopy as part of a health check-up between January 2006 and December 2010 at Kyung Hee University Hospital in Seoul, Korea. A total of 250 patients who were treated for CE between January 2008 and August 2011 and 500 age- and sex-matched non-CE patients were enrolled in this study. The rates of recent gastric acid suppression therapy and other well-known risk factors in the two groups were compared. RESULTS: The prevalence of CE was 0.35 % and increased each year (linear-by-linear association, P = 0.001). Univariate analysis showed that gastric acid suppression therapy, malignancy, DM and steroid therapy were related to CE. Multivariate analysis also showed that gastric acid suppression therapy (OR 5.11, 95 % CI 2.92-8.93 and P < 0.001), malignancy (OR 18.68, 95 % CI 6.37-54.75 and P < 0.001), DM (OR 2.67, 95 % CI 1.70-4.21 and P < 0.001) and steroids therapy (OR 6.74, 95 % CI 1.37-33.05 and P = 0.019) were related to CE. CONCLUSIONS: The prevalence of CE in Korea is increasing. Also, our results indicate that acid suppression therapy is a meaningful risk factor for CE.

Mean platelet volume/platelet count ratio in hepatocellular carcinoma.

Mean platelet volume (MPV) has been actively investigated in liver disease such as steatosis, cirrhosis and hepatitis. Recently, MPV/platelet count (PC) ratio has been proposed as a predictor of long-term mortality after myocardial infarction. As PC is known to be decreased in various liver diseases such as cirrhosis, hepatosplenomegaly and malignancy, we planned to evaluate MPV/PC ratio in patients with hepatocellular carcinoma (HCC) in this study. Mean of MPV levels showed significant difference, which were 8.69 fl (range 6.7-12.2 fl) in patients group and 8.02 fl in control group (range 6.7-11.0 fl). In receiver operating characteristic (ROC) curve analysis, the MPV/PC ratio (fl/(10(9)/l)) presented 74.5% of sensitivity and 96.5% of specificity at the criterion > 0.0491 (area under the curve (AUC) = 0.884), while MPV alone showed 57.4% of sensitivity and 81.4% of specificity at the criterion > 8.4 fl. Further studies should evaluate underlying pathogenic mechanisms of MPV/PC ratio difference and various possibilities of this ratio as an indicator of presence of a tumor in HCC.

Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans.

UNLABELLED: Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival. CONCLUSIONS: These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer.

[Successful resection of locally advanced gastrointestinal stromal tumor of the ampulla of Vater after treatment with imatinib].

Gastrointestinal stromal tumor (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract arising from Cajal's cells, expressing CD 117. The standard treatment for primary GIST is complete surgical resection. Imatinib mesylate, a specific tyrosine kinase inhibitor, is effective against locally advanced and metastatic GIST. There are several reports of the effect of preoperative imatinib in patients with unresectable and locally advanced primary GIST. We report a case of unresectable primary GIST of the ampulla of Vater, which we were able to completely resect after treatment with a dosage of imatinib 400 mg daily for 5 months. Twelve months later, the patient was treated with imatinib and doing well with no evidence of recurrence.

Reduced liver cancer mortality with regular clinic follow-up among patients with chronic hepatitis B: A nationwide cohort study.

BACKGROUND: Regular clinic follow-up is a prerequisite for optimal antiviral therapy and surveillance of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). However, adherence to regular follow-up stays low in practice. This study investigated whether regular follow-up is associated with decreased liver cancer mortality in CHB patients. METHODS: A nationwide population-based historical cohort study was conducted using customized data from the National Health Insurance Service of Korea. The number of hospital visits every 3-month interval was counted for 2 years from the date of CHB diagnosis. Patients were classified into three follow-up groups: regular (four to eight visits), irregular (one to three visits), and no follow-up. The risk of liver cancer mortality was compared among the groups using Cox proportional hazard regression analysis. RESULTS: Of the 414 074 CHB patients, 22.9% had regular follow-up. In multivariable analysis, regular follow-up was independently associated with decreased risk of liver cancer mortality compared to no follow-up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50-0.63, P < .001). Regular follow-up was also associated with the lowest risk of all-cause mortality (HR, 0.60; 95% CI, 0.57-0.63, P < .001). Patients with regular follow-up received more curative treatment (23.1% vs 15.1%, P < .001). Patients were less motivated when they were female, >60 years, of low socioeconomic status, disabled, lived in a rural area, had a higher comorbidity rate, or did not have cirrhosis. CONCLUSIONS: Regular follow-up at least every 3-6 months is significantly associated with reduced liver cancer mortality in patients with CHB.

Long-term Survival of a Patient with a Large Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis and Spontaneous Tumor Rupture.

Optimal treatments for patients with advanced hepatocellular carcinoma (HCC) are still limited and their prognosis remains dismal. Yet, there have been rare cases that have shed light on longer survival in these patients assisted by various treatments. This paper aims to present an extraordinary case of far advanced HCC that had been properly managed in spite of continuous recurrence. A patient visited the hospital with a ruptured large HCC with main portal vein tumor thrombosis but survived longer than 14 years owing to active and prompt interventions.