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The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The tumor immune microenvironment in cancer treatment response and resistance is of increasing interest. This retrospective study characterized and investigated programmed death-ligand 1 (PD-L1), PD-L2, and the immune gene expression signature and their association with clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC)., Patients and Methods: PD-L1 and PD-L2 expression on tumor and immune-infiltrating cells (positivity defined as combined positive score or immunohistochemistry proportion score >1) and T-cell-inflamed gene expression profile (Tcell inf GEP) were evaluated in patients with LA HNSCC treated in South Korea from 2000 to 2015. Correlations among the three biomarkers and their associations with overall survival and recurrence-free survival were assessed., Results: Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high Tcell inf GEP (≤-0.162) status were observed in 83.6%, 85.4%, and 73.2% of patients, respectively; 4.1% were posttreatment samples. Correlation between PD-L1 and PD-L2 scores was moderate (r Spearman  = 0.50), and each biomarker was slightly less correlated with Tcell inf GEP (0.41-0.45). PD-L1 expression and high Tcell inf GEP status were associated with human papillomavirus positivity. Higher levels of all biomarkers were observed in oral cavity and oropharyngeal cancers compared with other HNSCC sites. In a multivariable analysis that simultaneously adjusted for all three biomarkers, only high Tcell inf GEP was significantly associated with longer overall survival (adjusted hazard ratio, 0.57; 95% confidence interval 0.33-0.98) and recurrence-free survival (adjusted hazard ratio, 0.41; 95% confidence interval 0.23-0.74)., Conclusion: High Tcell inf GEP status, but not PD-L1 or PD-L2 expression, was independently associated with longer survival in patients with LA HNSCC. Results may have implications for evaluating therapies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) in HNSCC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To examine the associations between food insecurity and health, access to care, affordability of care, financial burden of care, and financial hardships among US adults during the COVID-19 pandemic and examine whether the associations were less pronounced among adults with safety nets., Study Design: We conducted a retrospective longitudinal cohort study using the 2020-2021 Medical Expenditure Panel Survey., Methods: Linear probability models were used to assess the associations between food insecurity in one year and the outcomes of interest in the following year while adjusting for baseline characteristics. We performed the analyses for the entire population and then conducted stratified analyses for adults with and without Supplemental Nutrition Assistance Program (SNAP) benefits or Medicaid coverage., Results: Compared with food-secure adults, food-insecure adults were 9.1 percentage points less likely to report life satisfaction and 9.9, 10.2, and 13.2 percentage points more likely to experience delays in getting medical care, postpone or forgo medical care because of cost, and struggle with paying medical bills. Food-insecure adults were 30.4, 27.2, and 23.5 percentage points more likely to face challenges in affording necessities, paying utility bills, and meeting rent or mortgage payments on time than food-secure adults. Notably, the strengths of these associations were attenuated among adults with SNAP benefits or Medicaid coverage., Conclusions: Food insecurity was associated with poor health, limited access to and affordability of care, and a greater financial burden of care among US adults during the pandemic. Nevertheless, safety net programs can play a critical role in alleviating adverse consequences., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Introduction: Dacomitinib showed superior progression-free survival (PFS) and overall survival compared to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations in the ARCHER1050 study. However, because that study did not include patients with brain metastases, the efficacy of dacomitinib in patients with brain metastases has not been clarified., Patients and Methods: This single-arm phase II study enrolled 30 patients with treatment-naïve advanced NSCLC harboring activating EGFR mutations from January 2021 to June 2021 and started them on dacomitinib (45 mg/day). All patients had non-irradiated brain metastases with a diameter of ≥5 mm. The primary endpoint was confirmed intracranial objective response rate (iORR)., Results: Patients had exon 19 deletions (46.7%) and L858R mutations in exon 21 (55.3%). The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%. Median intracranial PFS (iPFS) was not reached, with 12- and 18-month iPFS rates of 78.6% [95% confidence interval (CI) 64.8% to 95.4%] and 70.4% (95% CI 54.9% to 90.1%), respectively. In the competing risk analysis, the 12-month cumulative incidence of intracranial progression was 16.7%. Regarding the overall efficacy for intracranial and extracranial lesions, the overall ORR was 96.7%, and the median PFS was 17.5 months (95% CI 15.2 months-not reached). Grade 3 or higher treatment-related adverse events were reported in 16.7% of patients, and 83.3% required a reduced dacomitinib dose to manage adverse events. However, none permanently discontinued dacomitinib treatment due to treatment-related adverse events., Conclusions: Dacomitinib has outstanding intracranial efficacy in patients with EGFR-mutant NSCLC with brain metastases., Competing Interests: Disclosures The authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers., Methods: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration., Results: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC., Conclusion: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We evaluated the efficacy of adjuvant durvalumab after neoadjuvant concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC)., Patients and Methods: This randomized, double-blind, phase II study included patients with ESCC who underwent curative surgery after neoadjuvant CCRT. Patients were randomized to receive either durvalumab (20 mg/kg/i.v. every 4 weeks for 12 months) or placebo in a 1:1 ratio and were stratified by age and pathologic tumor stage. The primary endpoint was disease-free survival (DFS)., Results: Between March 2016 and June 2018, 86 patients were randomized to the durvalumab (n = 45) or placebo (n = 41) arm. The median follow-up duration was 38.7 months. There was no difference in DFS [hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.62-2.27, P = 0.61] or overall survival (HR 1.08, 95% CI 0.52-2.24, P = 0.85) between the two arms. Subgroup analysis was performed for patients for whom the post-CCRT programmed death-ligand 1 (PD-L1) expression profile could be assessed (n = 54). In the PD-L1-positive group, based on tumor proportion score ≥1%, durvalumab was associated with longer overall survival compared with the placebo (36-month survival rate: 94% versus 64%; HR 0.42, 95% CI 0.10-1.76), while in the PD-L1-negative group, it was associated with shorter overall survival (42% versus 55%; HR 1.53, 95% CI 0.48-4.83), showing the tendency of interaction between post-CCRT PD-L1 status and adjuvant durvalumab therapy for overall survival (interaction P = 0.18)., Conclusions: We failed to demonstrate that adjuvant durvalumab improved survival after neoadjuvant CCRT in patients with ESCC. However, post-CCRT PD-L1 expression could predict the survival of patients who receive adjuvant durvalumab after neoadjuvant CCRT, which needs to be validated., Competing Interests: Disclosure The authors have declared no competing interests. Data sharing The data that support the findings of this study are available on request from the corresponding author. Ethics approval and consent to participate The trial was conducted in accordance with the Declaration of Helsinki and the International Council for Harmonisation Good Clinical Practice Guidelines. The protocol was approved by the Samsung Medical Center Institutional Review Board and all patients provided written informed consent before enrollment., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear., Patients and Methods: This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H 1  = 30%) for the BM cohort and overall survival (OS) (H 1  = 5 months) for the LM cohort., Results: The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2., Conclusion: Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Backgrounds and Aims: Insulin resistance is a common feature of metabolic syndrome that may be influenced by genetic risk factors. We hypothesized that genetic risk scores (GRS) of SNPs that influence insulin resistance and signaling interact with lifestyles to modulate insulin resistance in Korean adults., Methods and Results: Genome-wide association studies (GWAS) of subjects aged 40-65 years who participated in the Ansung/Ansan cohorts (8842 adults) in Korea revealed 52 genetic variants that influence insulin resistance. The best gene-gene interaction model was explored using the generalized multifactor dimensionality reduction (GMDR) method. GRS from the best model were calculated and the GRS were divided into low, medium and high groups. The best model for representing insulin resistance included SLIT3_rs2974430, PLEKHA5_rs1077044, and PPP2R2C_rs16838853. The odds ratios for insulin resistance were increased by 150% in the High-GRS group compared to the Low-GRS group. However, ORs for insulin secretion capacity, measured by HOMA-B, were not associated with GRS. Coffee and caffeine intake and GRS had an interaction with insulin resistance: In subjects with high coffee (≥10 cups/week) or caffeine intake (≥220 mg caffeine/day), insulin resistance was significantly elevated in the High-GRS group, but not in the Low-GRS. However, alcohol intake, smoking and physical activity did not have an interaction with GRS. Insulin secretion capacity was not significantly influenced by GRS when evaluating the adjusted odds ratios., Conclusions: Subjects with High-GRS may be susceptible to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The effect of carbon and silicon nanotubes (CNTs and SiNTs) and carbon nanofibers (CNFs) to microscopic marine algae Heterosigma akashiwo was studied, using algal growth inhibition for 3 days (acute effect) and 7 days (chronic effect) as toxicity endpoints. The criterion of the toxic effect was the statistically significant reduction of the number of algal cells in the exposed samples compared to the control. Samples did not demonstrate toxic effects at doses 1 mg/l and 10 mg/l. CNTs and SiNTs samples at 100 mg/l exhibited both acute and chronic toxic effects. We assume that the main cause of cell death in these samples was related to the mechanical damage of cell integrity. CNFs at concentrations of 100 mg/l did not inhibit algal growth, but cells with irregular shapes were observed, which were not observed after exposure to CNTs and SiNTs. Nickel impurities present in CNFs samples are presumably the main cause of observed cell deformations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fingermark recovery from metal surfaces is an area of operational interest, both from the association of metals with weapons used in violent crime and from the increasing incidence in metal theft. This paper reports a feasibility study into the effectiveness of a range of fingermark visualisation processes in developing fingermarks on clean metals (brass, bronze and stainless steel), and on the same metals after prolonged exposure to an outdoor environment. Scanning electron microscopy (SEM) was used to investigate how the surface type and condition could influence the development of fingermarks for each of the processes used. It was found that the behaviour observed varied between each of the processes (cyanoacrylate fuming, Lumicyano™, gun blueing and carbon-based powder suspension). In some cases the chemical composition of the surface affected the development of the mark more than the surface condition, and in other cases the reverse was true. The best performing processes differed according to the surface type and condition, with cyanoacrylate fuming processes working best on brass and bronze, and powder suspensions being better on stainless steel. These preliminary results reinforce the need to take into account both surface type and condition before selection of the most effective fingermark visualisation process and demonstrate the value of techniques such as SEM in developing a fundamental understanding of the interactions between fingermarks and surfaces., (Copyright © 2018 The Chartered Society of Forensic Sciences. All rights reserved.)

Background: Current standard treatment, including non-anthracycline-based chemotherapy and optimal combining of radiotherapy, has dramatically improved outcomes of patients with extranodal natural killer/T-cell lymphoma (ENKTL) during the last decade. This study was conducted to investigate the clinical outcome of ENKTL patients with relapsed or progressive disease after initial current standard therapy., Patients and Methods: We retrospectively reviewed patients diagnosed with ENKTL at six centers in four countries (China, France, Singapore, and South Korea) from 1997 to 2015 and analyzed 179 patients who had relapsed or progressed after initial current standard therapy., Results: After a median follow-up of 58.6 months (range 27.9-89.2), the median second progression-free survival (PFS) was 4.1 months [95% confidence interval (CI) 3.04-5.16] and overall survival (OS) was 6.4 months (95% CI 4.36-8.51). Multivariate Cox-regression analysis revealed that elevated lactate dehydrogenase, multiple extranodal sites (≥2), and presence of B symptoms were associated with inferior OS (P < 0.05). OS and PFS were significantly different according to both prognostic index of natural killer lymphoma (PINK) and PINK-E (Epstein-Barr virus) models. Salvage chemotherapy with l-asparaginase (l-Asp)-based regimens showed a significantly better clinical benefit to response rate and PFS, although it did not lead to OS improvement. First use of l-Asp in the salvage setting and l-Asp rechallenge at least 6 months after initial treatment were the best candidates for salvage l-Asp containing chemotherapy., Conclusions: Most patients with relapsed or refractory ENKTL had poor prognosis with short survival. Further studies are warranted to determine the optimal treatment of patients with relapsed or refractory ENKTL., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored., Patients and Methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes., Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells., Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Aims: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy rather than from conventional laparoscopic gastrectomy., Methods: A prospective multicenter comparative study comparing laparoscopic and robotic gastrectomy was previously conducted. We divided the patients into subgroups according to obesity, type of gastrectomy performed, and extent of lymph node dissection. Surgical outcomes were compared between the robotic and laparoscopic groups in each subgroup., Results: A total of 434 patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211) surgery groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes, complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than did the laparoscopic group after D2 dissection (P = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (P = 0.365)., Conclusion: Patients with gastric cancer undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE., (Copyright © 2016. Published by Elsevier Ltd.)

Objectives: Using longitudinal datasets, we investigated whether gaining employment was associated with improvements in perceived mental health and overall health among previously unemployed U.S. residents. We additionally examined whether the association varied across types of employment and socio-demographic characteristics., Methods: We used multiple two-year panel datasets of the Medical Expenditure Panel Survey during 2004-2012. We studied two health outcomes: perceived mental health and overall health. Our independent variables were employment status: full-time, part-time, self-employment, and unemployment. To examine the association between gaining employment and perceived health, we employed population-averaged models with generalized estimating equations. We secondarily examined the association across subpopulations (gender, race/ethnicity, and education)., Results: Those who gained full-time, part-time, and self-employment were more likely to report good mental health than those who stayed unemployed (AOR [Adjusted Odds Ratio] = 2.90, 95% CI 2.23 to 3.78, AOR = 1.63, 95% CI 1.28 to 2.06, and AOR = 3.24, 95% CI 1.08 to 9.70, respectively). Those who became full-time and part-time employed were more likely to report good overall health relative to those who stayed unemployed (AOR = 2.28, 95% CI 1.82 to 2.86 and AOR = 1.91, 95% CI 1.52 to 2.40, respectively). For both measures of perceived health, the magnitudes of the association were larger for those who gained full-time employment than part-time employment. AORs were relatively higher for males, black persons, and people with less than a college education relative to other groups in each subpopulation., Conclusion: Improving employment outcomes may improve perceived health. Transiting toward full-time employment, in particular, may maximize the benefits of employment., (Copyright © 2015 The Royal Institute of Public Health. All rights reserved.)

Objectives: The impact of characteristics of neighbourhood environment on physical activity and obesity-related diseases is still the subject of debate. This study aimed to explore the impact of urban neighbourhood environment on physical activity and obesity-related diseases., Study Design: Cross-sectional study., Methods: Individuals who participated in the 2009 national health-screening programme, submitted all necessary information, and had lived in Community 1 (Haengdang) or Community 2 (Ilsan) for at least 2 years (n = 16,178) were selected for inclusion in this study. Anthropometric measures were taken and physical activity was assessed using a short questionnaire., Results: No significant difference in the trigger factors for walking, including the amount of neighbourhood park space, number of shopping malls, and distance between the community and shopping malls, was found between the two communities. However, Community 2 had a better street environment than Community 1. Participants who lived in Community 2 were more physically active [adjusted odds ratio (OR) 1.31, 95% confidence interval (CI) 1.16-1.48] and walked more regularly (adjusted OR 1.09, 95% CI 1.02-1.17) than participants who lived in Community 1, and were less likely to have abdominal obesity (adjusted OR 0.83, 95% CI 0.77-0.91), hypertension (adjusted OR 0.88, 95% CI 0.80-0.97) and diabetes (adjusted OR 0.86, 95% CI 0.75-0.99). However, the risk of dyslipidaemia, especially in terms of low-density lipoprotein cholesterol, was higher in Community 2., Conclusions: These results suggest that a walkable environment has a positive influence on hypertension and diabetes, and physical activity is the possible mechanism for this association. A walkable environment may function as an important tool for health promotion in urban areas., (Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic inflammation is known to be one of the main steps in carcinogenesis. Identification of those with chronic inflammation may help identify subjects at risk of cancer. Previous studies have reported low albumin-to-globulin ratio (AGR) to be associated with increased cancer mortality in cancer patients, but there has been no study based on healthy populations., Patients and Methods: Our retrospective cohort study involved 26 974 generally healthy adults aged 30 or older who visited Seoul National University Hospital Health Promotion Center for self-referred health checkup. National medical service claims data were used to determine cancer incidence, and Korean death registry data was used to determine mortality. Median follow-up time for survival was 5.9 years (interquartile range 4.1 years)., Results: Compared with subjects with AGR ≥ 1.5, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR showed adjusted hazard ratio (aHR) 2.69 (95% confidence interval, CI, 1.54-4.72) and aHR 6.71 (95% CI 3.56-12.66) for all-cause mortality, aHR 2.95 (95% CI 1.42-6.11) and aHR 4.38 (95% CI 1.57-12.25) for cancer mortality, and aHR 2.07 (95% CI 1.28-3.36) and aHR 3.99 (95% CI 2.10-7.58) for cancer incidence, respectively. When cancer incidence events after 2 years from baseline were separately analyzed, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR were associated with aHR 1.88 (95% CI 1.01-3.48) and aHR 2.55 (95% CI 1.03-7.11) for cancer incidence, respectively. Cancer events were increased in all types of cancer, but especially in liver and hematologic malignancies., Conclusions: Low AGR is a risk factor for cancer incidence and mortality, both short- and long terms, in a generally healthy screened population. The results of this study need to be replicated in larger studies, along with the determination of the sensitivity and other diagnostic values of low AGR., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Autophagy regulates cellular homeostasis through degradation of aged or damaged subcellular organelles and components. Interestingly, autophagy-deficient beta cells, for example Atg7-mutant mice, exhibited hypoinsulinemia and hyperglycemia. Also, autophagy response is diminished in heart of diabetic mice. These results implied that autophagy and diabetes are closely connected and affect each other. Although protein O-GlcNAcylation is up-regulated in hyperglycemia and diabetes, and O-GlcNAcylated proteins play an important role in metabolism and nutrient sensing, little is known whether autophagy affects O-GlcNAc modification and vice versa. In this study, we suppressed the action of mTOR by treatment of mTOR catalytic inhibitors (PP242 and Torin1) to induce autophagic flux. Results showed a decrease in global O-GlcNAcylation, which is due to decreased OGT protein and increased OGA protein. Interestingly, knockdown of ATG genes or blocking of lysosomal degradation enhanced protein stability of OGT. In addition, when proteasomal inhibitor was treated together with mTOR inhibitor, protein level of OGT almost recovered to control level. These data suggest that mTOR inhibition is a more efficient way to reduce protein level of OGT rather than that of CHX treatment. We also showed that not only proteasomal degradation regulated OGT stability but autophagic degradation also affected OGT stability in part. We concluded that mTOR signaling regulates protein O-GlcNAc modification through adjustment of OGT stability., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the effectiveness of laparoscopic varicocelectomy (LV) in adolescents with varicocele and analyze the impact of internal spermatic artery (ISA) preservation on surgical outcomes., Materials and Methods: Data on 92 adolescents with left varicocele who underwent LV between December 1998 and January 2011 were retrospectively analyzed. The mean age of the patients was 13.2 ± 2.1 years. Age, grade of disease, number of ligation veins, recurrence rates, and catch-up growth were analyzed in patients who underwent ISA preservation and ligation. The median duration of the follow-up was 21 months., Results: ISA preservation was performed on 50 patients (54%). There were no significant inter-group differences in terms of age, varicocele grade, number of ligation veins, and catch-up growth (93% vs. 90%). The patients who received artery preservation demonstrated a higher recurrence rate (22%) than those who received artery ligation (5%; p = 0.032). Among 13 patients who had persistent or recurrent varicocele, nine were treated with embolization and one was treated with magnification-assisted subinguinal varicocelectomy. None of these 10 patients demonstrated recurrence or testicular atrophy., Conclusions: LV with ISA ligation can reduce the recurrence rate and results in the same catch-up growth rate in comparison with LV with ISA preservation., (Copyright © 2013 Journal of Pediatric Urology Company. All rights reserved.)

Background: To assess the safety of transorally-inserted anvil (TOA) for use during esophagojejunostomy (EJ) reconstruction during laparoscopic total gastrectomy (LTG)., Methods: Between March 2009 and December 2011, 39 consecutive open total gastrectomies (OTGs) and 36 LTGs using TOA for gastric cancer were comparatively evaluated. We investigated postoperative complications, using the Clavien-Dindo classification. To evaluate the effect of a learning period in using TOA for LTG, we also investigated shifts in the patterns of complications and changes in total operation time over the course of the study., Results: The patient characteristics at baseline were not different between both groups, except for the extent of lymphadenectomy (P < 0.001) and depth of tumor invasion (P = 0.003). Multivariate analysis revealed that TOA usage elevated the occurrence of infectious complications significantly (OR = 3.32, P = 0.042), but was not associated with EJ-related complications. TOA usage did not need a learning period for the length of time required to complete the operation, or the likelihood of developing an EJ-related or infectious complication., Conclusions: TOA use for EJ during LTG is relatively simple and easy enough not to require a learning period for surgeons. This procedure did not elevated the occurrence of EJ-related complications compared to circular stapling in open surgery, but it does require special prevention efforts to avoid infectious complications., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Helical tomotherapy is a recent modality of intensity-modulated, rotational irradiation being developed for treatment of an increasing number of malignancies. It allows delivering an accurate treatment while sparing critical organs thus optimizing the therapeutic ratio. In particular, it allows treating some tumour locations that could not be efficiently irradiated through more conventional irradiation devices. We report the usefulness of this approach for the treatment of complex lesions such as circumferential cutaneous lymphoma of the trunk., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Most investigations into the negative effects of viewing stereoscopic 3D content on human health have addressed 3D visual fatigue and visually induced motion sickness (VIMS). Very few, however, have looked into changes in autonomic balance and heart rhythm, which are homeostatic factors that ought to be taken into consideration when assessing the overall impact of 3D video viewing on human health. In this study, 30 participants were randomly assigned to two groups: one group watching a 2D video, (2D-group) and the other watching a 3D video (3D-group). The subjects in the 3D-group showed significantly increased heart rates (HR), indicating arousal, and an increased VLF/HF (Very Low Frequency/High Frequency) ratio (a measure of autonomic balance), compared to those in the 2D-group, indicating that autonomic balance was not stable in the 3D-group. Additionally, a more disordered heart rhythm pattern and increasing heart rate (as determined by the R-peak to R-peak (RR) interval) was observed among subjects in the 3D-group compared to subjects in the 2D-group, further indicating that 3D viewing induces lasting activation of the sympathetic nervous system and interrupts autonomic balance., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors., Patients and Methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT., Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months., Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.

Background: Current tracheal tubes (TTs) cannot guarantee a perfect seal against pulmonary aspiration of upper airway secretions. The purpose of this study was to investigate whether a gel layer between the tracheal tube with double cuffs (Double cuffs) prevents fluid leakage past TT cuffs., Methods: In vitro fluid leakage tests were performed using the Double cuff with or without a gel layer between the two cuffs and four commercially available TTs (Euromedical Standard TT, Mallinckrodt Hi-Lo™, Microcuff, and Mallinckrodt TaperGuard™) when placed in artificial tracheas with three-different internal diameters (ID; 16, 20, and 22 mm). Blue-dyed water (5 ml) was placed above the cuff, and the extent of fluid leakage was observed for 48 h. Each test was repeated five times with new tubes at six different intracuff pressures (15, 20, 25, 30, 40, and 50 cm H2O)., Results: In all of the conventional TTs and the Double cuff without a gel layer, fluid leakage was observed even at clinically acceptable intracuff pressures (25-30 cm H2O). However, in the Double cuff with a gel layer, no fluid leakage was observed for 48 h at all intracuff pressures in three-different sized artificial tracheas. At an intracuff pressure of 20 cm H2O in a 20 mm ID trachea, the average volume of injected gel was 2.0 ml. After removal of the TT, the mean volume of the remaining gel in the trachea was 0.10 ml., Conclusions: A prototype TT with gel-layered Double cuffs completely blocked fluid leakage past the cuffs for 48 h in a bench-top model. Clinical studies are required to determine whether this TT reduces the risk of ventilator-associated pneumonia.

Background: In the United States, fatal drug overdoses have tripled since 1991. This escalation in deaths is believed to be driven primarily by prescription opioid medications. This investigation compared trends and patterns in sales of opioids, opioid drug overdoses treated in emergency departments (EDs), and unintentional overdose deaths in North Carolina (NC)., Methods: Our ecological study compared rates of opioid sales, opioid related ED overdoses, and unintentional drug overdose deaths in NC. Annual sales data, provided by the Drug Enforcement Administration, for select opioids were converted into morphine equivalents and aggregated by zip code. These opioid drug sales rates were trended from 1997 to 2010. In addition, opioid sales were correlated and compared to opioid related ED visits, which came from a Centers for Disease Control and Prevention syndromic surveillance system, and unintentional overdose deaths, which came from NC Vital Statistics, from 2008 to 2010. Finally, spatial cluster analysis was performed and rates were mapped by zip code in 2010., Results: Opioid sales increased substantially from 1997 to 2010. From 2008 to 2010, the quarterly rates of opioid drug overdoses treated in EDs and opioid sales correlated (r=0.68, p=0.02). Specific regions of the state, particularly in the southern and western corners, had both high rates of prescription opioid sales and overdoses., Conclusions: Temporal trends in sales of prescription opioids correlate with trends in opioid related ED visits. The spatial correlation of opioid sales with ED visit rates shows that opioid sales data may be a timely way to identify high-risk communities in the absence of timely ED data., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Given the more comorbidities with a decline in physiologic reserve, it can be challenging to make appropriate treatment decisions in the elderly., Patients and Methods: Here, we prospectively evaluated and compared the health-related quality of life (HRQOL) of patients aged ≥ 65 with aged <65 who were treated with a postoperative chemotherapy for completely resected stage Ib, II or IIIa non-small-cell lung cancer (NSCLC). Either four cycles of paclitaxel (Taxol)-carboplatin (PC) or vinorelbine-cisplatin (NP) was used. The HRQOL was assessed with EORTC QLQ-C30 and EORTC QLQ-LC13., Results: Between October 2008 and October 2011, a total of 139 patients (aged <65, n = 73; ≥ 65, n = 66) were enrolled, and 127 (91.4%) completed the questionnaire. Overall, the quality of life (QOL) in elderly patients did not significantly deteriorate with adjuvant chemotherapy and the time trend of QOL in elderly patients was similar to that of younger patients. Although the elderly suffered from increased treatment-related adverse events involving sore mouth, peripheral neuropathy and alopecia compared with the baseline, the same time trends were also observed in younger group. The mean dose intensities (MDIs) for PC and NP regimen were not significantly different between the two age groups., Conclusions: Postoperative chemotherapy did not substantially reduce HRQOL in elderly NSCLC patients, and HRQOL during and after adjuvant chemotherapy did not significantly differ by age.

Background: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers., Patients and Methods: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses., Results: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population., Conclusions: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.

AMP-activated protein kinase (AMPK) is activated by upstream kinases and negatively regulated by protein phosphatases. Intracellular calcium mediates protein phosphatase 2A (PP2A), which is in a heterotrimeric complex with the PR72 subunit. The PR72 subunit contains two calcium-binding sites formed by EF hands. Our previous study has shown that chronic calcium exposure decreases AMPK activity. To define the specific molecular mechanism whereby calcium can deactivate AMPK, activities of AMPK and PP2A were analyzed in C2C12 muscle cell cultures and skeletal muscle tissues from mutant pigs possessing the AMPKγ3-mutation or the ryanodine receptor (RyR1) calcium gating mutation, or both. C2C12 myotubes treated with calcium releasing agent (caffeine) for 10h decreased (P<0.05) AICAR-induced AMPK activity to control levels and this negative effect was eliminated by ryanodine receptor stabilizer, dantrolene. Interestingly, muscle from pigs with the RyR1 mutation and C2C12 cells administered with 10h caffeine showed higher (P<0.05) PP2A activity compared to controls. More importantly, the inhibitory effect of caffeine on AMPK activity was attenuated by the PP2A inhibitor, calyculin A or siRNA induced knockdown of PP2A. These data show the inhibitory effect of chronic calcium on AMPK activity is exerted through the activation of PP2A., (Published by Elsevier India Pvt Ltd.)

Background: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients., Methods: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers., Results: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81)., Conclusion: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.

Objectives: Nicotine is the primary factor responsible for tobacco dependence among individuals who smoke. Nicotinic receptors and nicotine-associated metabolism, two significant aspects of nicotine dependence, are influenced by age. To date, however, the relationship between age and nicotine dependence has not been investigated., Study Design: Cross-sectional., Methods: Data were obtained from the national smoking cessation programme for South Korea. Data obtained from current smokers in 2008 (n = 338,566) were used as baseline measures. Nicotine dependence was determined by the Fagerström Test for Nicotine Dependence (FTND). Cigarettes per day (CPD) and FTND were the dependent variables. As CPD is a major component of FTND, scores on the FTND minus scores related to CPD were also used as a dependent variable. The relationships between age and the dependent variables (FTND, CPD, partial FTND) were investigated. Quadratic regression models were used to test the non-linear relationship between age and nicotine dependence after adjusting for other covariates., Results: Analyses relying on nicotine dependence (FTND and partial FTND scores) and CPD produced similar results in relation to age. Specifically, the values of all three dependent variables increased with age until approximately 50 years of age, at which point they decreased. Additionally, nicotine dependence and CPD were associated with age of smoking initiation, smoking duration, alcohol-related problems, body mass index and residential area. After adjusting for other nicotine-dependence-related factors, the linear and quadratic terms of age were statistically significant in the multiple regression models., Conclusions: In the present study, both nicotine dependence and CPD displayed an inverse U-shaped relationship with age, with a significant peak at 50 years of age. The results suggest that tobacco control policies should target issues related to nicotine dependence according to age group., (Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

(-)-Epigallocatechin-3-gallate (EGCG), a main constituent of tea catechins, affects Gram-positive and Gram-negative bacteria differently; however, the underlying mechanisms are not clearly understood. Atomic force microscopy (AFM) was used to compare morphological alterations in Gram-positive and Gram-negative bacteria induced by EGCG and by H(2)O(2) at sub-minimum inhibitory concentrations (MICs). EGCG initially induced aggregates in the cell envelopes of Staphylococcus aureus and eventually caused cell lysis, which was not observed in cells treated with H(2)O(2). It initially induced nanoscale perforations or microscale grooves in the cell envelopes of Escherichia coli O157:H7 which eventually disappeared, similar to E. coli cells treated with H(2)O(2). An E. coli O157:H7 tpx mutant, with a defect in thioredoxin-dependent thiol peroxidase (Tpx), was more severely damaged by EGCG when compared with its wild type. Similar differing effects were observed in other Gram-positive and Gram-negative bacteria when exposed to EGCG; it caused aggregated in Streptococcus mutans, while it caused grooves in Pseudomonas aeruginosa. AFM results suggest that the major morphological changes of Gram-negative bacterial cell walls induced by EGCG depend on H(2)O(2) release. This is not the case for Gram-positive bacteria. Oxidative stress in Gram-negative bacteria induced by EGCG was confirmed by flow cytometry., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers., Patients and Methods: We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR., Results: AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox's models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC., Conclusions: AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.

Calcium is important for muscle contraction and controls many cellular processes. Although there is evidence that calcium-mediated signals regulate AMP-activated protein kinase (AMPK) activity, the molecular mechanisms by which calcium regulates AMPK are poorly understood. To compare the function of sustained vs. intermittent calcium oscillations on AMPK activity and define specific signals in this pathway, we administered mice with aminoimidazole-carboxamide-ribonucleotide (AICAR) and caffeine with or without dantrolene. AMPK activity was increased by 10 d AICAR treatment (P < 0.01). Ten day caffeine treatment decreased AICAR-induced AMPK activity to control level. This repressed AMPK activity was blocked by dantrolene. Different calcium frequencies were simulated in C2C12 myotubes by alternating media containing caffeine and dantrolene. Intermittent calcium oscillation increased AMPK activity compared to control (P < 0.05), whereas sustained calcium oscillation decreases AICAR-induced AMPK activity to control level. This result suggests a biphasic control of AMPK activity by calcium. Knockdown of CaMKII expression by short-hairpin RNA resulted in increased AMPK phosphorylation by AICAR even in the presence of caffeine. These data show different calcium oscillations elicit distinct responses in muscle cells suggesting that the negative effects of chronic calcium treatment on AMPK activity is partly mediated through the CaMKII signals., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: A number of infectious agents have been classified as human carcinogens. The purpose of the current study was to provide an evidence-based assessment of the burden of infection-related cancers in the Korean population., Materials and Methods: The population attributable fraction was calculated using infection prevalence data from 1990 or earlier, relative risk estimates from meta-analyses using mainly Korean studies and national data on cancer incidence and mortality for the year 2007., Results: The fractions of all cancers attributable to infection were 25.1% and 16.8% for cancer incidence in men and women, and 25.8% and 22.7% of cancer mortality in men and women, respectively. Among infection-related cancers, Helicobacter pylori was responsible for 56.5% of cases and 45.1% of deaths, followed by hepatitis B virus (HBV) (23.9% of cases and 37.5% of deaths) and human papillomavirus (HPV) (11.3% of cases and 6% of deaths) and then by hepatitis C virus (HCV) (6% of cases and 9% of deaths). Over 97% of infection-related cancers were attributable to infection with H. pylori, HBV, HCV and HPV., Conclusion: Up to one-quarter of cancer cases and deaths would be preventable through appropriate control of infectious agents in Korea.

Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structures., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Term placenta is a great reservoir of mesenchymal stem cells (MSCs), however, the potential of the earlier placenta is largely unknown. In this report, we established 17 MSC lines from 19 first-trimester human placenta (fPMSC). fPMSC proliferated for 90-150 days in vitro and by enhanced cellular interaction, fPMSC differentiated into nestin-expressing neural progenitor cells (fPMSC-NP), accompanied by inductions of immature neuron-specific genes. Therapeutic effect of the fPMSC-NP was tested in the animal model of hypoxia-ischemia (HI) which was devastating to dopaminergic neurons and to locomotor activity. Improvement of motor activity was evident as early as 2 weeks after transplantation of the fPMSC-NP into bilateral striatum and became indistinguishable from that of the age-matched normal animals by 8 weeks but no spontaneous recovery was observed in the control-grafted animals. Immunohistochemical analyses revealed that the implanted fPMSC-NP matured into ectodermal cells including the tyrosine hydroxylase (TH)-expressing neurons in the recipient striatum. So, the improved motor behavior was likely due to the dopaminergic differentiation of the implanted fPMSC-NP in the dopaminergic-denervated host brain. Based on this result, we propose that progenitors may be more advantageous than the terminally differentiated cells for the purpose of cell replacement therapies since the progenitors are easily obtainable and are expected to be more pliable to the new environment., (Copyright © 2011. Published by Elsevier Ltd.)

Background: To investigate the clinicopathological significance of androgen receptor (AR) expression in primary breast cancers., Patients and Methods: We evaluated AR using immunohistochemistry from 413 whole sections from January 2008 to March 2009 and analyzed the relationship between AR and clinicopathological parameters. Tumors with >/=10% nuclear-stained cells were considered to be positive for AR. The differences among variables were calculated by chi-square test., Results: The expression rate of AR was 72.9% higher than those of estrogen receptors (ER) and progesterone receptors. AR expression was significant in patients with no elevated preoperative serum cancer antigen 15-3 levels, smaller tumor size, lower histologic grade and hormone receptor-positive and non-triple-negative breast cancer. However, AR expression was observed in 35% of triple-negative cancers. Metaplastic, medullary and mucinous types of carcinomas showed less AR expression. In the ER-negative subgroup, AR was significantly correlated with human epidermal growth factor receptor type 2 (HER-2) overexpression., Conclusions: AR is expressed in a significant number of breast cancers and is associated with lower tumor burden and favorable differentiation. There are many issues to be further investigated such as whether AR is an independent prognostic factor, whether it is a therapeutic target for the triple-negative breast cancers and whether it is associated with HER-2 signaling in ER-negative tumors.

Background: Many patients with extranodal natural killer/T-cell lymphoma (NTCL) fail to the front-line therapy and need an effective second-line chemotherapy., Patients and Methods: This was single-institutional, phase II study. The primary end point was response rate and secondary end points were toxicity, time to treatment failure (TTF), and overall survival (OS). Patients with relapsed or refractory NTCL were eligible. They received the chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone and it was repeated every 3 weeks., Results: Thirty-two patients were enrolled and 15 patients had achieved partial remission (PR) or complete remission (CR) after the front-line chemotherapy. The International Prognostic Index scores were 0-1 in thirteen, 2 in five, 3 in five, and 4-5 in nine patients. Twelve and two patients achieved CR and PR, respectively. Median OS and TTF of all patients were 8.2 and 3.7 months, respectively. Non-hematologic toxic effects were well tolerated, but grade 3/4 leukopenia occurred in 11.7% of all cycles. Four patients developed febrile neutropenia and one patient died due to pneumonia., Conclusions: This chemotherapy regimen was moderately effective for relapsed/refractory extranodal NTCL, nasal type. Toxic effects were moderate, but caution should be exercised to prevent severe infection.

In this study, we characterized the two-dimensional lattice of bovine serum albumin (BSA) as a chemical and physical barrier against bacterial adhesion, using fluorescence microscopy and atomic force microscopy (AFM). The lattice of BSA on glass surface was fabricated by micro-contact printing (microCP), which is a useful way to pattern a wide range of molecules into microscale features on different types of substrates. The contact-mode AFM measurements showed that the average height of the printed BSA monolayer was 5-6 nm. Escherichia coli adhered rapidly on bare glass slide, while the bacterial adhesion was minimized on the lattices in the range of 1-3 microm(2). Especially, the bacterial adhesion was completely inhibited on a 1 microm(2) lattice. The results suggest that the anti-adhesion effects are due by the steric repulsion forces exerted by BSA.

Objective: To assess the incidence of neovascularization of the inner sclerostomy wound and occurrence of postoperative vitreous cavity hemorrhage (POVCH) after vitrectomy for proliferative diabetic retinopathy (PDR)., Design: Consecutive prospective longitudinal clinical study., Participants: Seventy-three eyes (58 patients) undergoing primary vitrectomy for PDR., Methods: Twenty-megahertz (MHz) high-resolution anterior segment ultrasonography was performed on all sclerostomy sites 2 months postoperatively and repeated at the time of any POVCH. The appearance of the inner sclerostomy wound was divided into 4 classes (normal, spheroidal, tent, and trapezoidal, representing entry site neovascularization). The occurrence, degree, and duration of POVCH and need for revision surgery with vitreous cavity washout (VCW) were recorded. Postoperative vitreous cavity hemorrhage was divided into 3 groups-namely, mild, moderate, and major., Main Outcome Measures: Inner sclerostomy wound appearance on ultrasonography, degree and timing of POVCH, and need for VCW., Results: There were 15 eyes in total with POVCH (20%): one patient had a persistent POVCH that required VCW. Fourteen other eyes (19%) had recurrent POVCH. Four (28%) of these 14 eyes with recurrent POVCH were classified as mild and 3 (21%) moderate: all cleared spontaneously with no further intervention needed. None of these had a trapezoidal image. Seven of the 14 eyes with recurrent POVCH were classified as major. Five of these 7 eyes had a trapezoidal image at 2 months postoperatively, and 4 required VCW (5.5% of total no. of eyes in study). All patients with a trapezoidal image experienced some degree of recurrent vitreous cavity hemorrhage (P = 0.0000024). The odds ratio was approximately 330:1. There was a significant correlation between the severity of POVCH and entry site appearance on ultrasound. In the first year of follow-up, all patients requiring VCW after recurrent POVCH had a trapezoidal image present at 2 months postoperatively (P = 0.009)., Conclusion: The appearance of a trapezoidal image on 20-MHz high-resolution anterior segment ultrasonography at a sclerostomy site after vitrectomy for PDR was highly correlated with the occurrence of nonclearing POVCH and need for VCW. Conversely, the absence of a trapezoidal image in patients with POVCH was associated with spontaneous hemorrhage clearance.

Biofilms are complex microbial communities that are resistant against attacks by bacteriophages and removal by drugs and chemicals. In this study, biofilms of Escherichia coli O157:H7, a bacterial pathogen, were investigated using atomic force microscopy (AFM) in terms of the dynamic transition of morphology and surface properties of bacterial cells over the development of biofilms. The physical and topographical properties of biofilms are different, depending on nutrient availability. Compared to biofilms formed in a high nutrient medium, biofilms form faster and a higher number of bacterial cells were recovered on glass surface in a low nutrient medium. We demonstrate that AFM can obtain high-resolution images and the elastic information about biofilms. As E. coli biofilm becomes mature, the magnitude of the force between a tip and the surface of the biofilm gets stronger, suggesting that extracellular polymeric substances (EPSs), sticky components of biofilms, accumulate over the surface of cells upon the initial attachment of bacterial cells to surfaces.