Perspectives on follow-up care and research for childhood cancer survivors: results from an international SIOP meet-the-expert questionnaire in Kyoto, 2018.

INTRODUCTION: Survival of childhood cancer has increased over the past decades. This has led to the development of strategies aiming to enhance follow-up care and research, for which priorities may vary globally. We explored perspectives of an international healthcare workers panel. METHODS: Attendants of a meet-the-expert session on childhood cancer survivorship at the 2018 SIOP conference completed a survey about their view on important follow-up care and research aspects for survivors below and over 18 years. We analysed overarching categories and subtopics, and compared Asian versus European and North American healthcare workers. RESULTS: A total of 58 participants from different medical specialties (67.2% paediatric oncologists) and continents (48.3% Asia, 39.7% Europe/North America) responded. Follow-up care priorities for survivors below and over 18 years included physical care (39.3% ≤18 years, 35.9% >18 years) and healthcare structure (29.4%, 26.0%). Physical care was also the most important research aspect for both age groups (52.5%, 50.7%). Psychological support was the most frequently reported subtopic. Asian clinicians (n = 22) primarily prioritized physical care aspects of follow-up care, whereas European/North American (n = 19) clinicians underscored the importance of healthcare structure. CONCLUSION: Physical care is the most important aspect of survivorship care and research according to clinicians from several continents. Asian and European/North American respondents shared most priorities, however, healthcare structure was a more important category for European/North American clinicians. The most common subtopic was psychological support, underlining also the need to involve psychologists in follow-up.

Lack of ethnic differences of moxifloxacin and metabolite pharmacokinetics in East Asian men.

This study was designed to investigate ethnic differences in the pharmacokinetics (PKs) of moxifloxacin and its metabolites, M1 (sulfo conjugate) and M2 (acyl-glucuronate), among Japanese, Chinese, and Korean populations, following oral administration. We used a population PK modeling approach using data from a clinical study involving 79 healthy male volunteers. A comprehensive population PK model considering the PK mechanism of moxifloxacin and its metabolites was newly built. The structures of the final model were two-compartment for moxifloxacin and one-compartment for M1 and M2, with first-order absorption with lag time for all three compounds. The formation of M1 and M2 from moxifloxacin via a first-pass effect and subsequent metabolic clearance in the system were also modeled. Lean body mass on the central volume of distribution (V c ) and estimated glomerular filtration rate on renal clearance (CL r ) were identified as covariates of PKs of moxifloxacin. Additionally, bioavailability was slightly higher in Koreans, whereas CL r , non-renal clearance (CL nr ), and V c were slightly lower. Regarding M1 and M2, body surface area on CL r of M2 and UGT1A1*6 on F of M2 were modeled. Korean ethnicity was observed to influence CL nr of M2, F of M2, and the metabolic clearance of moxifloxacin to M2. However, the exposure levels of moxifloxacin, M1, and M2 in Koreans were comparable to those in Japanese and Chinese because the effects of Korean ethnicity on some PK parameters were counterbalanced. These results suggest that PKs for moxifloxacin and its metabolites among East Asian populations are essentially similar.

SurePath® LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma.

INTRODUCTION: The current study aimed to compare cytology using SurePath® (SP)-LBC and biliary tissue histology (BTH) for the diagnosis of biliary disease. METHODS: Between January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP-LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow-up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H-CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP-LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP-LBC and BTH. RESULTS: Although 23% (13/57) of BTH samples were classified as inadequate, all SP-LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP-LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP-LBC and BTH. Furthermore, limited to intra/H-CC, accuracy was significantly higher using SP-LBC than using BTH (P < .001). CONCLUSIONS: SP-LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H-CC.

Perceptions of dental students in Japanese national universities about studying abroad.

PURPOSE: Dental faculties in Japan have organised many short-term international exchange programs to enable their undergraduates to study abroad. However, not many students apply for those programs. In this present study, we attempted to clarify the factors that discourage undergraduate dental students from studying abroad. METHODS: We administered a questionnaire survey to 512 undergraduate dental students in three national universities located in different areas in Japan. RESULTS: Although 61.7% of the participants expressed interest in studying abroad, only 19.1% of them had prior experiences of study abroad or plans to do so. Their main worries were about lack of sufficient language ability in academic fields. Comparing those who were interested in studying abroad with those who were not revealed significant differences regarding their concern about lack of language ability and lack of specialised knowledge in dentistry. Participants who did not want to study abroad indicated that they did not perceive a purpose in doing so and cited not having foreign friends as a problem. Household income was significantly correlated with concerns about overall expenses. CONCLUSION: Overall, language ability and academic knowledge appeared to be the two strongest factors affecting dental students' consideration of studying abroad. Dental schools in Japan can use the findings of this study to improve their undergraduate exchange programs in such a way as to stimulate greater interest amongst their students.

Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress.

Argpyrimidine (ARP) is an advanced glycation end product thought to be generated from a reaction between methylglyoxal and arginine residues in proteins. In this study, we observed marked accumulation of an approximately 56 kD protein, reactive to anti-ARP antibodies, in the red blood cells (RBCs) of some patients with refractory schizophrenia. This ARP-modified protein was purified from the blood of schizophrenic patients and identified as selenium binding protein 1 (SBP1) by LC-MS/MS. This is the first report of ARP-modified proteins accumulating in RBCs of patients with diseases involving carbonyl stress. We also observed high accumulation of ARP-modified SBP1 in the RBCs of patients with chronic kidney disease. Therefore, this modified protein may be a novel marker of carbonyl stress.

Topologically Entangled Rashba-Split Shockley States on the Surface of Grey Arsenic.

We discover a pair of spin-polarized surface bands on the (111) face of grey arsenic by using angle-resolved photoemission spectroscopy (ARPES). In the occupied side, the pair resembles typical nearly-free-electron Shockley states observed on noble-metal surfaces. However, pump-probe ARPES reveals that the spin-polarized pair traverses the bulk band gap and that the crossing of the pair at Γ[over ¯] is topologically unavoidable. First-principles calculations well reproduce the bands and their nontrivial topology; the calculations also support that the surface states are of Shockley type because they arise from a band inversion caused by crystal field. The results provide compelling evidence that topological Shockley states are realized on As(111).

TNF-α-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell line established by hTERT.

OBJECTIVE: Ameloblastoma (AM) shows locally invasive behaviour. However, biological investigations regarding regulation of gene expression associated with AM pathological features are difficult to perform, because AM cells can be passaged for a few generations due to senescence. We report a newly established immortalized AM cell line, AMB cells, by transfection with human telomerase reverse transcriptase (hTERT). Furthermore, we examined whether TNF-α modulates bone resorption-related genes, IL-6 and MMP-9 in cooperation with TGF-ß or IFN-γ. MATERIALS AND METHODS: Following transfection of an hTERT expression vector into AM cells using a non-viral method, the effects of cytokines on the expressions of IL-6 and MMP-9 mRNA were examined using real-time PCR. TNF-α-induced NF-κB activity was examined by western blotting and transcription factor assays. RESULTS: AMB cells continued to grow for more than 100 population doublings. Stimulation with TNF-α increased IL-6 and MMP-9 mRNA expressions, as well as NF-κB activation. Furthermore, TGF-ß and IFN-γ dramatically increased TNF-α-mediated expressions of MMP-9 and IL-6 mRNA, respectively, while those responses were suppressed by NF-κB inhibitor. CONCLUSION: We established an immortalized AM cell line by hTERT transfection. TNF-α-mediated regulation of MMP-9 and IL-6 via NF-κB may play an important role in the pathological behaviour of AMs, such as bone resorption.

The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects.

Exercise has a variety of beneficial effects on brain structure and function, such as hippocampal neurogenesis, mood and memory. Previous studies have shown that exercise enhances hippocampal neurogenesis, induces antidepressant effects and improves learning behavior. Brain serotonin (5-hydroxytryptamine, 5-HT) levels increase following exercise, and the 5-HT system has been suggested to have an important role in these exercise-induced neuronal effects. However, the precise mechanism remains unclear. In this study, analysis of the 5-HT type 3A receptor subunit-deficient (htr3a(-/-)) mice revealed that lack of the 5-HT type 3 (5-HT3) receptor resulted in loss of exercise-induced hippocampal neurogenesis and antidepressant effects, but not of learning enhancement. Furthermore, stimulation of the 5-HT3 receptor promoted neurogenesis. These findings demonstrate that the 5-HT3 receptor is the critical target of 5-HT action in the brain following exercise, and is indispensable for hippocampal neurogenesis and antidepressant effects induced by exercise. This is the first report of a pivotal 5-HT receptor subtype that has a fundamental role in exercise-induced morphological changes and psychological effects.

An innovative masticatory efficiency test using odour intensity in the mouth as a target marker: a feasibility study.

A large number of studies have reported the findings for masticatory efficiency tests; however, some objective masticatory efficiency tests have a drawback, in that subjects are required to spit out the test material. This study examined the possibility of a masticatory efficiency test that evaluates the intensity of odours released when chewing an odour compound-containing material. A total of 20 volunteers were used in this study. The odour intensity in the breath after chewing a gum was measured by portable odour sensor device. The odour intensity after chewing the gum was measured over four chewing durations and at four intervals between spitting out and measurement of the odour intensity. The volume of stimulated saliva was measured by calculating the difference in the weight of the gauze before and after chewing to examine the effect of saliva flow. With an increase in chewing duration, odour intensity reduced. The odour intensity was the highest immediately after chewing. There was a positive correlation between odour intensity and gummy jelly-related masticatory efficiency test value (G-METV), which was significant for 10-s chewing. The regression equation was calculated from three objective variables of odour intensity and G-METV as dependent variable. Pearson's correlation coefficient between G-METV and the odour intensity-related masticatory efficiency value (O-METV) was 0·68. The coefficient of variation of O-METV was significantly lower than that of G-METV. These results suggest that the masticatory performance can be estimated by measuring the odour intensity immediately after chewing food containing odour compounds for 10 s.

Temperature Dependence of Magnetically Active Charge Excitations in Magnetite across the Verwey Transition.

We study the electronic structure of bulk single crystals and epitaxial films of Fe_{3}O_{4}. Fe 2p core level spectra show clear differences between hard x-ray (HAX) and soft x-ray photoemission spectroscopy (PES). The bulk-sensitive spectra exhibit temperature (T) dependence across the Verwey transition, which is missing in the surface-sensitive spectra. By using an extended impurity Anderson full-multiplet model-and in contrast to an earlier peak assignment-we show that the two distinct Fe species (A and B site) and the charge modulation at the B site are responsible for the newly found double peaks in the main peak above T_{V} and its T-dependent evolution. The Fe 2p HAXPES spectra show a clear magnetic circular dichroism (MCD) in the metallic phase of magnetized 100-nm-thick films. The model calculations also reproduce the MCD and identify the contributions from magnetically distinct A and B sites. Valence band HAXPES shows a finite density of states at E_{F} for the polaronic half metal with a remnant order above T_{V} and a clear gap formation below T_{V}. The results indicate that the Verwey transition is driven by changes in the strongly correlated and magnetically active B-site electronic states, consistent with resistivity and optical spectra.

Epidemiological analysis of a large enterohaemorrhagic Escherichia coli O111 outbreak in Japan associated with haemolytic uraemic syndrome and acute encephalopathy.

A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157 occurred in Japan in April 2011. We conducted an unmatched case-control study and trace-back investigation to determine the source of EHEC O111 infection and risk factors for severe complications. Pulsed-field gel electrophoresis was performed to help define cases. A total of 86 individuals met the case definition. Of these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute encephalopathy, and 6% died. Illness was significantly associated with eating the raw beef dish yukhoe (odds ratio 19·64, 95% confidence interval 7·03-54·83), the likely food vehicle. EHEC O111 and its closely related stx-negative variants were found in the beef. HUS occurred most frequently in individuals aged 5-9 years, and this age group was significantly associated with acute encephalopathy. The prevalence of HUS and acute encephalopathy was higher than in previous non-O157-related outbreaks, indicating a high risk of severe complications.

Itraconazole inhibits TNF-α-induced CXCL10 expression in oral fibroblasts.

OBJECTIVE: Itraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF-α, an inflammatory cytokine associated with Th1-mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3-agonistic chemokines including CXCL10. We examined the anti-inflammatory potential of ICZ against TNF-α-induced chemokines in oral fibroblasts. MATERIALS AND METHODS: We investigated the effects of ICZ on mRNA expressions of various TNF-α-induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF-α-induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme-linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF-α-stimulated GT1 was examined by western blotting. RESULTS: ICZ inhibited TNF-α-induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF-α-induced IL-8 mRNA, the mRNAs of TNF-α-induced CXCR3-agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF-α-induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF-α-induced phosphorylation of c-JUN, which is related to CXCL10 production by TNF-α-stimulated GT1. CONCLUSION: ICZ may be useful as therapy for Th1-mediated oral inflammatory disease.

[OPTIMIZATION OF THE METHOD OF SUPRAPANCREATIC LYMPH NODE DISSECTION IN LAPAROSCOPY-ASSISTED GASTRECTOMY (IN THE FINAL ANALYSIS OF INTERNATIONAL CONFERENCES <>)].

The article analyzed the methods of suprapancretic lymph node dissection in laparoscopic gastrectomy which were devel- oped and applied in Japan. The authors described the details of operation technique. There were noted the advantages of medial approach for suprapancreatic lymph node dissection.