Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Impact of the interpregnancy interval after cesarean delivery on subsequent perinatal risks: a retrospective study.

PURPOSE: To assess the impact of the interpregnancy interval (IPI) after cesarean delivery on the risks of adverse perinatal events during subsequent pregnancies. METHODS: We retrospectively examined perinatal outcomes of subsequent pregnancies of women whose most recent birth experience involved cesarean delivery at our hospital between January 2014 and December 2019. IPI was defined as the time between live birth and subsequent conception. Three IPI groups: < 18 months, 18-60 months, and > 60 months, were assessed. The risks of preterm birth, preeclampsia, placenta previa, placental abruption, fetal growth restriction, and successful vaginal birth were compared among the three IPI groups using uni- and multivariate analyses. RESULTS: We registered 592 births after cesarean delivery: 178, 288, and 126 in the IPI < 18 months, 18-60 months, and > 60 months groups, respectively. The groups did not differ significantly regarding perinatal outcomes. The multivariate analysis revealed no significant differences in the risks of adverse perinatal outcomes among all groups. The odds ratios (ORs) for preterm birth at < 37 weeks of gestation were 1.24 and 1.64 for those in the < 18 months and > 60 months groups, respectively (P = 0.362 and P = 0.055, respectively). The groups did not differ significantly regarding vaginal birth success rate (ORs 1.72 for the < 18 months group, 0.49 for the > 60 months group; P = 0.486 and P = 0.446, respectively). CONCLUSION: After cesarean delivery, IPIs shorter than 18 months and longer than 60 months do not significantly impact the risks of adverse perinatal outcomes or successful vaginal birth compared with IPIs of 18-60 months.

Facilitators and barriers in implementing the nurse practitioner role in Japan: A cross-sectional descriptive study.

AIM: To investigate the distribution of nurse practitioners (NPs) across Japan and their perceived facilitators and barriers to NP implementation in Japan. BACKGROUND: NP certification examinations have been conducted in Japan since 2011, and by 2020, there were 487 NPs in the country. The momentum of NP implementation is slower in Japan compared with other countries. METHODS: A cross-sectional descriptive study, following the STROBE guidelines, was conducted. Web-based survey questionnaires, developed by the authors, were administered to 248 NPs whose email addresses were maintained by the certification management body. RESULTS: Valid responses were obtained from 101 NPs (response rate: 40.7%), of which 34% were male. The respondents had more than 12 years of registered nurse experience on an average before enrolling in the graduate NP program. 53% were employed as NPs from the beginning, while 25% were initially employed as registered nurses and later advanced to NPs, and 11% still worked as RNs. A majority worked in hospitals with beds. Many NPs perceived the lack of NP national licensure and reimbursement benefits as barriers to NP implementation, whereas recognition from superiors and organizations was considered facilitators. CONCLUSIONS: Despite their small numbers in Japan, NPs take on crucial tasks and contribute to the appropriate distribution of medical resources. The NP licensure system and recognition from superiors and organizations may be necessary to promote NP roles in Japan. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Some certified NPs still work as registered nurses. Recognition from nursing and organization administrators is critical to implementing NPs. To this end, a reimbursement system benefiting the organizations and a legislation facilitating NP employment are required.

Bond durability of universal adhesives to intact enamel surface in different etching modes.

This study aimed at determining the enamel bond durability of universal adhesives to intact enamel (IE) and ground enamel (GE) in different etching modes under thermal cycling (TC) and fatigue stresses. Two universal adhesives and a two-step self-etch adhesive were used. Enamel specimens were divided into four groups by treatment: (i) GE in etch-and-rinse, (ii) IE in etch-and-rinse, (iii) GE in self-etch, and (iv) IE in self-etch. Bonded specimens were subjected to TC, and then shear bond strengths (SBS) were conducted. SBS tests were also conducted after storage in 37°C water for 24 h (baseline). For shear fatigue strength (SFS) testing, bonded specimens were subjected to fatigue stress at a frequency of 10 Hz for 50,000 cycles. At baseline, all adhesives showed significantly higher SBS values with GE than IE in self-etch mode in contrast to in etch-and-rinse mode. After TC, the universal adhesives with IE showed lower SBS values than the baseline, regardless of the etching mode. Universal adhesives showed significantly lower SFS values with IE in etch-and-rinse, but not in self-etch mode. Phosphoric acid pre-etching or grinding of the aprismatic enamel may be helpful in establishing reliable initial and long-term bonds to enamel when using universal adhesives in self-etch mode.

Random mutagenesis of a hyperthermophilic archaeon identified tRNA modifications associated with cellular hyperthermotolerance.

Random mutagenesis for the hyperthermophilic archaeon Thermococcus kodakarensis was established by the insertion of an artificial transposon designed to allow easy identification of the transposon-inserted locus. The phenotypic screening was applied for the isolation of thermosensitive mutants of T. kodakarensis, which resulted in the isolation of 16 mutants showing defective growth at the supraoptimal temperature 93°C. The high occurrence of the mutants suggested that the high thermotolerance of hyperthermophiles was achieved by a combination of diverse gene functions. The transposon insertion sites in two-thirds of the mutants were identified in a group of genes responsible for tRNA modifications including 7-formamidino-7-deaza-guanosine (archaeosine), N1-methyladenosine/N1-methylinosine, N4-acetylcytidine, and N2-dimethylguanosine/N2,N2-dimethylguanosine. LC-MS/MS analyses of tRNA nucleosides and fragments exhibited disappearance of the corresponding modifications in the mutants. The melting temperature of total tRNA fraction isolated from the mutants lacking archaeosine or N1-methyladenosine/N1-methylinosine decreased significantly, suggesting that the thermosensitive phenotype of these mutants was attributed to low stability of the hypomodified tRNAs. Genes for metabolism, transporters, and hypothetical proteins were also identified in the thermosensitive mutants. The present results demonstrated the usefulness of random mutagenesis for the studies on the hyperthermophile, as well as crucial roles of tRNA modifications in cellular thermotolerance.

Coronary Flow Disturbance Phenomenon After Percutaneous Coronary Intervention Is Associated with New-Onset Atrial Fibrillation in Patients with Acute Myocardial Infarction.

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI). Although previous studies have investigated mortality rates and the incidences of adverse events associated with new-onset AF (NOAF) in patients with AMI, the effects of emergency percutaneous coronary intervention (PCI) on the incidence of NOAF in patients with AMI remain unclear. The purpose of this study was to investigate the relationship of clinical characteristics, medical history, and the coronary flow disturbance phenomenon (TIMI < 3) following emergency PCI with NOAF in patients with AMI. Between 2012 and 2016, 731 patients with AMI underwent PCI at our facility. Among these, 52 had a history of chronic/paroxysmal AF before admission and were excluded. The remaining 679 patients (mean age 66.4 years, 532 males) were analyzed in this retrospective observational study.New-onset AF was observed in 45 patients (6.6%). In univariate analysis, the hazard ratios (HRs) for patient age (HR 1.04, 95%CI 1.02-1.07), Killip II-IV (HR 2.34, 95%CI 1.29-4.23), elevated D-dimer level (> 1.0 µg/mL; HR 3.32; 95%CI 1.77-6.23), and coronary flow disturbance phenomenon (HR 5.61; 95%CI 2.88-10.9) were significantly higher in the NOAF group. In multivariate analysis, an elevated D-dimer level (> 1.0 µg/mL; HR 2.44; 95%CI 1.17-5.11) and coronary flow disturbance phenomenon (HR 4.61; 95%CI 2.29-9.27) were found to be independent risk factors for NOAF. An elevated D-dimer level at admission and the presence of coronary flow disturbance phenomenon after PCI were risk factors for NOAF following emergency PCI in patients with AMI.

Evaluation of Caspase-3 Activity During Apoptosis with Fluorescence Lifetime-Based Cytometry Measurements and Phasor Analyses.

Caspase-3 is a well-described protease with many roles that impact the fate of a cell. During apoptosis, caspase-3 acts as an executioner caspase with important proteolytic functions that lead to the final stages of programmed cell death. Owing to this key role, caspase-3 is exploited intracellularly as a target of control of apoptosis for therapeutic outcomes. Yet the activation of caspase-3 during apoptosis is challenged by other roles and functions (e.g., paracrine signaling). This brief report presents a way to track caspase-3 levels using a flow cytometer that measures excited state fluorescence lifetimes and a signal processing approach that leads to a graphical phasor-based interpretation. An established Förster resonance energy transfer (FRET) bioprobe was used for this test; the connected donor and acceptor fluorophore is cleavable by caspase-3 during apoptosis induction. With the cell-by-cell decay kinetic data and phasor analyses we generate a caspase activation trajectory, which is used to interpret activation throughout apoptosis. When lifetime-based cytometry is combined with a FRET bioprobe and phasor analyses, enzyme activation can be simplified and quantified with phase and modulation data. We envision extrapolating this approach to high content screening, and reinforce the power of phasor approaches with cytometric data. Analyses such as these can be used to cluster cells by their phase and modulation "lifetime fingerprint" when the intracellular fluorescent probe is utilized as a sensor of enzyme activity. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.

Therapeutic efficacy and limitations of potassium iodide for patients newly diagnosed with Graves' disease.

The efficacy of potassium iodide (KI) for Graves' disease (GD) has been reported, although few clinical reports have examined the long-term efficacy of treatment. The objective of this study was to investigate the efficacy and limitations of KI treatment for GD. This study enrolled patients newly diagnosed with mild GD, defined as free thyroxine (FT4) <5.0 ng/dL, between July 2014 and June 2016. KI was started at a dose of 50 mg/day, and if FT4 values did not decrease after initiation of treatment, doses were increased to 100 mg/day. Patients for whom thyroid hormone levels could not be controlled with KI at 100 mg/day were regarded as non-responders. Of the 122 patients (13 males, 109 females) included in this study, 71 (58.2%) responded to KI therapy. The remaining 51 patients (41.8%) were non-responders. The median duration required to judge non-responsiveness was 5.9 months. Multiple logistic regression analysis performed on parameters measured at the initial visit indicated FT4 (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28-3.75; p = 0.0007) and male sex (OR 3.58, 95%CI 1.04-12.3; p = 0.04) were significantly associated with KI responsiveness. Receiver operating characteristic (ROC) curve analysis of the relationship between FT4 and KI responsiveness indicated an FT4 cut-off of 2.76 ng/dL was optimal for differentiating between responders and non-responders. KI therapy was effective and safe for about 60% of patients with mild GD.

Anti-cyclic citrullinated peptide antibody titers decrease in rheumatoid arthritis patients treated with tocilizumab: A pilot study.

Objectives: To analyze the effects of tocilizumab on peripheral B-cell subpopulation and its ability to produce anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA).Methods: Thirteen consecutive RA patients initiated with tocilizumab were enrolled in our prospective study. Anti-CCP antibody titers and clinical parameters were evaluated during treatment. Peripheral blood B-cell subsets were analyzed using flow cytometry according to the Human Immunology Project.Results: Disease activity was significantly improved and anti-CCP antibody titers significantly decreased at week 24 compared to baseline. The percentages of post-switch memory B cells in CD19+ cells transiently increased at week 12, but there was no significant difference in any of the investigated B-cell subpopulations at week 24 compared to baseline. The ratios of post-switch memory to naïve B cells (post-switch/naïve) correlated negatively with anti-CCP antibody titers regardless of the time-points.Conclusion: Our study indicated that tocilizumab has a potential to reduce anti-CCP antibody production presumably by affecting post-switch/naïve ratio, and that anti-CCP antibody titers reflect B-cell distribution/subpopulation. As anti-CCP antibodies are produced in lymph nodes or ectopic lymphoid structures in synovial tissues, not in circulation, transient increment of post-switch memory B cells after tocilizumab treatment may reflect the altered balance of B-cell distribution between circulation and arthritic joints, resulting in suppressed production of anti-CCP antibody in situ.

Medication Adherence Among Patients With Chronic Hepatitis Receiving Antiviral Treatment.

This study aimed to evaluate medication adherence and associated factors among patients with chronic viral hepatitis. A cross-sectional questionnaire survey was conducted in 171 outpatients receiving antiviral treatment of chronic viral hepatitis at 6 national/regional liver disease treatment centers in Japan. Medication adherence was calculated as the subject-reported number of antiviral tablets taken in the past 2 weeks compared with the prescribed number of tablets. Subjects were divided according to 100% adherence or nonadherence. The impact of items pertaining to everyday experiences and perceptions regarding medication adherence were examined. Factors associated with medication adherence were identified via multiple logistic regression. The mean medication adherence rate was 95.8% ± 9.5% (range = 0%-100%), although a smaller proportion (95 subjects; 55.6%) was 100% adherent. Multiple logistic regression indicated a greater "lack of understanding of need for medication" (1 point: odds ratio (OR) = 1.51, 95% confidence interval (CI) [1.30, 1.76], p ≤ .01) and greater "restriction in life due to medication" (1 point: OR = 1.26, 95% CI [1.03, 1.54], p = 0.03) as associated with nonadherence. In conclusion, to improve medication adherence, healthcare professionals should improve patients' understanding of the need for medication and minimization of life restrictions.

TFL1-Like Proteins in Rice Antagonize Rice FT-Like Protein in Inflorescence Development by Competition for Complex Formation with 14-3-3 and FD.

Hd3a, a rice homolog of FLOWERING LOCUS T (FT), is a florigen that induces flowering. Hd3a forms a ternary 'florigen activation complex' (FAC) with 14-3-3 protein and OsFD1 transcription factor, a rice homolog of FD that induces transcription of OsMADS15, a rice homolog of APETALA1 (AP1), which leads to flowering. TERMINAL FLOWER 1 (TFL1) represses flowering and controls inflorescence architecture. However, the molecular basis for floral repression by TFL1 remains poorly understood. Here we show that RICE CENTRORADIALIS (RCN), rice TFL1-like proteins, compete with Hd3a for 14-3-3 binding. All four RCN genes are predominantly expressed in the vasculature, and RCN proteins are transported to the shoot apex to antagonize florigen activity and regulate inflorescence development. The antagonistic function of RCN to Hd3a is dependent on its 14-3-3 binding activity. Our results suggest a molecular basis for regulation of the balance between florigen FT and anti-florigen TFL1.

A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer.

PURPOSE: This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). METHODS: Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion. All patients received opioid-based pain control and oral care programs that we previously reported. The primary endpoint was the incidence of grade ≥ 3 OM (functional/symptomatic) according to the Common Terminology Criteria of Adverse Events version 3.0. Quality of life (EORTC QLQ-C30/PROMS) at baseline and upon radiotherapy at a dosage of 50 Gy were assessed. RESULTS: Thirty-five patients with HNC were enrolled. Sixteen of them (45.7%) developed grade ≥ 3 OM (i.e., functional/symptomatic). The incidence of grade ≤ 1 OM (functional/symptomatic) was 51.5% at 2 weeks and 82.9% at 4 weeks after radiotherapy completion. Clinical examination revealed that 10 patients (28.6%) developed grade ≥ 3 OM. The incidence of grade ≤ 1 OM (clinical exam) was 80.0% at 2 weeks and 100% at 4 weeks after radiotherapy completion. Adverse events related to HMB/Arg/Gln were an increase in blood urea nitrogen and diarrhea, but were easily managed. CONCLUSIONS: The addition of HMB/Arg/Gln to opioid-based pain control and oral care programs was feasible but still insufficient at reducing the incidence of CRT-induced severe OM. However, the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM. TRIAL REGISTRATION: UMIN000016453.

Mechanical force effect on the two-state equilibrium of the hyaluronan-binding domain of CD44 in cell rolling.

CD44 is the receptor for hyaluronan (HA) and mediates cell rolling under fluid shear stress. The HA-binding domain (HABD) of CD44 interconverts between a low-affinity, ordered (O) state and a high-affinity, partially disordered (PD) state, by the conformational change of the C-terminal region, which is connected to the plasma membrane. To examine the role of tensile force on CD44-mediated rolling, we used a cell-free rolling system, in which recombinant HABDs were attached to beads through a C-terminal or N-terminal tag. We found that the rolling behavior was stabilized only at high shear stress, when the HABD was attached through the C-terminal tag. In contrast, no difference was observed for the beads coated with HABD mutants that constitutively adopt either the O state or the PD state. Steered molecular dynamics simulations suggested that the force from the C terminus disrupts the interaction between the C-terminal region and the core of the domain, thus providing structural insights into how the mechanical force triggers the allosteric O-to-PD transition. Based on these results, we propose that the force applied from the C terminus enhances the HABD-HA interactions by inducing the conformational change to the high-affinity PD transition more rapidly, thereby enabling CD44 to mediate lymphocyte trafficking and hematopoietic progenitor cell homing under high-shear conditions.

Obesity does not diminish the efficacy of IL-6 signalling blockade in mice with collagen-induced arthritis.

OBJECTIVES: Obese rheumatoid arthritis patients often have higher disease activity and a poorer response to treatment than do non-obese patients. The present study aims to clarify the influence of obesity on the action of IL-6 and to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity. METHODS: Mice were fed a high-fat diet for 5 weeks, and the influence of this diet on macrophages and type II collagen-induced arthritis was investigated. RESULTS: The mice fed the high-fat diet showed greater expression of macrophage marker F4/80, not only in subcutaneous fat but also in knee synovium and the calcaneal region, than did the mice fed a normal diet. Furthermore, macrophages isolated from mice on the high-fat diet tended to show higher expression of cyclooxygenase-2 following IL-6 stimulation than did macrophages from mice fed the normal diet. Moreover, mice fed the normal or high-fat diet were immunised with type II collagen, and were treated with anti-mouse IL-6 receptor antibody (MR16-1). The anti-arthritis effect of MR16-1 was not reduced in mice fed the high-fat diet compared to mice fed the normal diet (inhibition ratio: 87% vs. 62%). Furthermore, at the peak of arthritis, cyclooxygenase-2 expression in the calcaneal region of mice fed the high-fat diet was higher than that in the mice fed the normal diet. CONCLUSIONS: These results suggested that a high-fat diet induces inflammatory changes in the synovium. We demonstrated that IL-6 signalling blockade by an anti-IL-6 receptor antibody can be effective in treating arthritis, even with obesity.

The Ciona intestinalis cleavage clock is independent of DNA methylation.

The initiation of embryonic gene expression in ascidian embryos appears to be tightly regulated by the number of DNA replication cycles. DNA methylation is thought to contribute to the clock mechanism that counts the rounds of DNA replication. We used mass spectrometry and whole genome bisulfite sequencing to characterize DNA methylation changes that occur in early developmental stages of the ascidian, Ciona intestinalis. We found that global DNA methylation in early Ciona development was static, and a base-wise comparison between the genomes of consecutive developmental stages found no DNA demethylation that was related to zygotic gene activation. Additionally, 5hmC was hardly detected by mass spectrometry in the developmental samples, suggesting a lack of demethylation mediated by ten eleven translocation (TET) methylcytosine dioxygenase in C. intestinalis. We conclude that DNA methylation is not involved in regulating DNA replication-dependent transcriptional activation.

A Microfluidic pH Measurement Device with a Flowing Liquid Junction.

The pH values of aqueous solutions are conventionally measured with pH-sensitive electrodes such as glass electrodes or ion-sensitive field-effect transistors (ISFETs) used in conjunction with Ag/AgCl reference electrodes and KCl solutions. The speed of pH measurement with these systems can be deficient, however, as the glass electrode responds slowly during measurements of sample solutions with low buffering capacities. Our group has constructed a new pH measurement system using a microfluidic device and ISFET sensors. The device has a channel with two inlets and one outlet, with a junction connected to a Y-shaped channel on the same plane. Two ISFET sensors and an Ag/AgCl pseudo reference electrode are fitted into the channel to construct a differential measurement device. A sample solution and baseline solution supplied into the inlets by gravity-driven pumps form a flowing liquid junction during measurement. The small size and fast response of the ISFET sensors enable measurement of about 2.0 mL of sample solution over a measurement period of 120 s. The 90% response time is within 2 s. The calibrated sensor signal exhibits a wide range (pH 1.68-10.0) of linearity with a correlation factor of 0.9997. The measurement error for all solutions tested, including diluted solutions, was 0.0343 ± 0.0974 pH (average error ± standard deviation (S.D.), n = 42). The new device developed in this research will serve as an innovative technology in the field of potentiometry.

[A case of hemangioma at the left renal papilla of the calix with anemia and gross hematuria].

An 18-year-old man was admitted to our hospital due to gross hematuria and proteinuria after a marathon race. Contrast-enhanced CT showed no remarkable findings. His gross hematuria and proteinuria disappeared with- out treatment. One year later, he was admitted to our hospital due to reburrent gross hematuria and anemia (serum hemoglobin level of 8.0 g/dL). Both contrast-enhanced CT and renal arteriography revealed no remarkable find- ings; however, cystoscopy showed that his hematuria came from the left ureteral orifice. Ureteroscopy revealed hemorrhage from a large hemangioma at the left renal papilla of the calix. He presented with intermittent gross hematuria, proteinuria, and hypocomplimentemia, suggesting the possibility of glomerulonephritis. His gross hematuria and proteinuria improved after laser coagulation was performed.

The prognostic factors and trajectory of HRQOL in patients with pancreatic cancer who received psychiatric intervention.

BACKGROUND AND AIM: Patients with advanced pancreatic cancer have severe pain, anxiety, and depression, and these symptoms deteriorate quality of life (QOL). Previous study reported that early psychiatric intervention for advanced cancer patients may improve QOL. We evaluated the trajectory of health-related QOL (HRQOL) in patients with pancreatic cancer after an early psychiatric intervention. METHODS: A prospective cohort study was performed in 108 pancreatic cancer patients who received consultation liaison psychiatry from November, 2011 to October, 2014 at Nagoya University Hospital. Longitudinal changes in HRQOL and the association between aspects of HRQOL and survival were evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 before treatment and every month after the start of treatment. RESULTS: Physical functioning significantly decreased after 1, 3, and 6 months of treatment compared with baseline, but global health status (GHS), role functioning, emotional functioning, and social functioning showed a tendency to improve. Severe impairment of GHS, fatigue, and appetite loss were apparent at 3 months prior to death. In multivariate analysis, pain was a significant prognostic factor for survival (hazard ratio [HR], 1.109; 95% confidence interval [CI], 1.021-1.204; P = 0.013), in addition to poor performance status (HR, 5.473; 95%CI, 2.338-12.816; P < .0001) and distant metastases at diagnosis (HR, 3.274; 95%CI, 1.872-5.725; P < .0001). CONCLUSIONS: Early psychiatric intervention in patients with pancreatic cancer may maintain HRQOL. More effective pain management and reduction of psychological distress are important for patients with pancreatic cancer.

Multicenter phase II study of an oral care program for patients with head and neck cancer receiving chemoradiotherapy.

PURPOSE: This multicenter phase II trial assessed the clinical benefit of a multidisciplinary oral care program in reducing the incidence of severe chemoradiotherapy-induced oral mucositis (OM). METHODS: Patients with head and neck cancer (HNC) who were scheduled to receive definitive or postoperative chemoradiotherapy were enrolled. The oral care program included routine oral screening by dentists and a leaflet containing instructions regarding oral care, nutrition, and lifestyle. Oral hygiene and oral care were evaluated continuously during and after the course of chemoradiotherapy. The primary endpoint was the incidence of grade ≥3 OM assessed by certified medical staff according to the Common Terminology Criteria of Adverse Events version 3.0. RESULTS: From April 2012 to December 2013, 120 patients with HNC were enrolled. Sixty-four patients (53.3 %) developed grade ≥3 OM (i.e., functional/symptomatic). The incidence of grade ≤1 OM at 2 and 4 weeks after radiotherapy completion was 34.2 and 67.6 %, respectively. Clinical examination revealed that 51 patients (42.5 %) developed grade ≥3 OM during chemoradiotherapy. The incidence of grade ≤1 OM at 2 and 4 weeks after radiotherapy completion was 54.7 and 89.2 %, respectively. The incidences of grade 3 infection and pneumonitis throughout chemoradiotherapy were <5 %. Only 6.7 % of patients had unplanned breaks in radiotherapy, and 99.2 % completed treatment. CONCLUSIONS: A systematic oral care program alone is insufficient to decrease the incidence of severe OM in patients with HNC being treated with chemoradiotherapy. However, systematic oral care programs may indirectly improve treatment compliance by decreasing infection risk. TRIAL REGISTRATION NUMBER: UMIN000006660.

TSH receptor antibody titers measured with a third-generation assay did not reflect the activity of Graves' ophthalmopathy in untreated Japanese Graves' disease patients.

TSH receptor antibody (TRAb) titer has been reported to be correlated with Graves' ophthalmopathy (GO). However, the correlation between GO activity and TRAb titer assessed with a third-generation assay has not been reported. We enrolled 238 untreated Graves' disease patients who came to the outpatient clinic of Ito Hospital and 28 patients who were euthyroid. All of the patients were assessed for GO by an ophthalmologist within 3 months of their initial visit to Ito Hospital. Clinical activity score (CAS), short inversion time inversion recovery (STIR), and sum of the maximum external orbital muscle areas (SEOMA) on a frontal sectional magnetic resonance imaging (MRI). The TRAb titer was significantly higher in patients with inactive ophthalmopathy (the inactive-GO group) than in patients with active ophthalmopathy (the active-GO group) (17.7 ± 13.5 IU/L vs. 13.0 ± 13.1 IU/L, p=0.0082). The SEOMA values were not correlated with TRAb titer. The prevalence of active-GO was higher in euthyroid patients than in hyperthyroid patients although the difference was not significant. In conclusion, TRAb titer measured with a third-generation assay dose not correlate with GO activity based on MRI findings in untreated Graves' disease patients, and the prevalence of active-GO is higher in euthyroid patients with lower TRAb titers than in hyperthyroid patients.