The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.

BACKGROUND: Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001. METHODS: This was a multicenter, open-label, dose-escalation, phase I study of DS-1001 for recurrent/progressive IDH1-mutant (R132) glioma (N = 47) (NCT03030066). DS-1001 was administered orally at 125-1400 mg twice daily. Dose-escalation used a modified continual reassessment method. RESULTS: The maximum tolerated dose was not reached. Eight patients were continuing treatment at the data cutoff. Most adverse events (AEs) were grade 1-2. Twenty patients (42.6%) experienced at least 1 grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples. CONCLUSIONS: DS-1001 was well tolerated with a favorable brain distribution. Recurrent/progressive IDH1-mutant glioma patients responded to treatment. A study of DS-1001 in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 glioma is ongoing (NCT04458272).

Association between intraoperative hypotension and postoperative nausea and vomiting: a retrospective analysis of 247 thyroidectomy cases.

BACKGROUND: Postoperative nausea and vomiting (PONV) are major complications after general anesthesia. Although various pathways are involved in triggering PONV, hypotension plays an important role. We hypothesized that intraoperative hypotension during general anesthesia might be responsible for the incidence of PONV. METHODS: We retrospectively investigated patients who underwent thyroidectomy. The initial blood pressure measured before induction of anesthesia was used as the baseline value. The systolic blood pressure measured during the operation from the start to the end of anesthesia was extracted from anesthetic records. The time integral value when the measured systolic blood pressure fell below the baseline value was calculated as area under the curve (AUC) of s100%. RESULTS: There were 247 eligible cases. Eighty-eight patients (35.6%) had PONV. There was no difference in patient background between the patients with or without PONV. Univariate analysis showed that the total intravenous anesthesia (TIVA) (p=0.02), smoking history (p=0.02), and AUC-s100% (p=0.006) were significantly associated with PONV. Multiple logistic regression analysis revealed that TIVA (OR: 0.54, 95% CI: 0.29...0.99), smoking history (OR: 0.60, 95% CI: 0.37...0.96), and AUC-s100% (OR: 1.006, 95% CI: 1.0...1.01) were significantly associated with PONV. CONCLUSION: Intraoperative hypotension evaluated by AUC-s100% was related to PONV in thyroidectomy.

Association between intraoperative hypotension and postoperative nausea and vomiting: a retrospective analysis of 247 thyroidectomy cases

Abstract Background: Postoperative nausea and vomiting (PONV) are major complications after general anesthesia. Although various pathways are involved in triggering PONV, hypotension plays an important role. We hypothesized that intraoperative hypotension during general anesthesia might be responsible for the incidence of PONV. Methods: We retrospectively investigated patients who underwent thyroidectomy. The initial blood pressure measured before induction of anesthesia was used as the baseline value. The systolic blood pressure measured during the operation from the start to the end of anesthesia was extracted from anesthetic records. The time integral value when the measured systolic blood pressure fell below the baseline value was calculated as area under the curve (AUC) of s100%. Results: There were 247 eligible cases. Eighty-eight patients (35.6%) had PONV. There was no difference in patient background between the patients with or without PONV. Univariate analysis showed that the total intravenous anesthesia (TIVA) (p = 0.02), smoking history (p = 0.02), and AUC-s100% (p = 0.006) were significantly associated with PONV. Multiple logistic regression analysis revealed that TIVA (OR: 0.54, 95% CI: 0.29-0.99), smoking history (OR: 0.60, 95% CI: 0.37-0.96), and AUC-s100% (OR: 1.006, 95% CI: 1.0-1.01) were significantly associated with PONV. Conclusion: Intraoperative hypotension evaluated by AUC-s100% was related to PONV in thyroidectomy.

Construction of tomato plants with suppressed endo-ß-N-acetylglucosaminidase activity using CRISPR-Cas9 mediated genome editing.

High mannose-type free N-glycans with a single N-acetyl-D-glucosamine (GlcNAc) residue at the reducing end (GN1-HMT-FNGs) are produced by cytosolic endo-ß-N-acetylglucosaminidase (EC:3.2.1.96) (ENGase) and are ubiquitous in differentiating and growing plant cells. To elucidate the physiological functions of HMT-FNGs in plants, we identified the ENGase gene in tomato (Solyc06g050930) and detected ENGase activity and increased production of GN1-HMT-FNGs during tomato fruit maturation. However, the precise role of GN1-HMT-FNGs in fruit maturation remains unclear. In this study, we established tomato ENGase mutants with suppressed ENGase activity via CRISPR/Cas9 genome editing technology. DNA sequencing of the Δeng mutants (T0 and T1 generations) revealed that they had the same mutations in the genomic DNA around the target sequences. Three null CRISPR/Cas9 segregant plants of the T1 generation (Δeng1-2, -22, and -26) were used to measure ENGase activity and analyze the structural features of HMT-FNGs in the leaves. The Δeng mutants did not exhibit ENGase activity and produced GN2-HMT-FNGs bearing tow GlcNAc residues at the reducing end side instead of GN1-HMT-FNGs. The Δeng mutants lack the N-terminal region of ENGase, indicating that the N-terminal region is important for full ENGase activity. The fruits of Δeng mutants (T2 generation) also showed loss of ENGase activity and similar structural features of HMT-FNGs of the T1 generation. However, there was no significant difference in fruit maturation between the T2 generation of the Δeng mutants and the wild type. The Δeng mutants rich in GN2-HMT-FNGs could be offered as a new tomato that is different from wild type containing GN1-HMT-FNGs.

Efficacy of modified thoracoabdominal nerves block through perichondrial approach in open gynecological surgery: a prospective observational pilot study and a cadaveric evaluation.

BACKGROUND: Modified thoracoabdominal nerves block through perichondrial approach (M-TAPA) was first described as a peripheral nerve block by Tulgar in 2019. This technique provides an analgesic effective range from Th7-11 with a single puncture per side. Although the efficacy and effective duration of M-TAPA have been reported, further examination is required. Therefore, this study aimed to evaluate the analgesic range and effective duration of M-TAPA in open gynecologic surgery. METHODS: Following approval, 10 adult female patients scheduled for open radical hysterectomy via a vertical incision or laparotomy using a midline incision from under the xiphoid process to the symphysis pubis were enrolled. The primary outcome was the number of anesthetized dermatomes at 2 and 24 h postoperatively. Secondary outcomes included numerical rating scale scores and the total amount of fentanyl used. Cadaveric evaluation was performed to assess the spread of the dye. RESULTS: The median numbers (interquartile range) of anesthetized dermatomes at 2 and 24 h postoperatively were 6 (5-7) and 6.5 (5-7) in the anterior cutaneous branch area and 5 (4-7) and 7 (5-7) in the lateral cutaneous branch area, respectively. There was an 85% chance of simultaneously acquiring analgesia in areas innervated by Th8-11, including complete block in areas innervated by the anterior cutaneous branches of Th9-10. Cadaveric evaluation showed the spread of the dye in Th8-11. CONCLUSIONS: M-TAPA may have analgesic effects in the areas supplied by the anterior cutaneous branches of Th8-11. TRAIL REGISTRATION: IRB approval (No.2700; registered on July 10, 2020) and registration (UMIN Clinical Trials Registry: UMIN000041137 ; registered on July 17, 2020).

Purification, Characterization, and Gene Expression of Rice Endo-ß-N-Acetylglucosaminidase, Endo-Os.

In the endoplasmic reticulum-associated degradation system of plant and animal cells, high-mannose type free N-glycans (HMT-FNGs) are produced from misfolded glycoproteins prior to proteasomal degradation, and two enzymes, cytosolic peptide:N-glycanase (cPNGase) and endo-ß-N-acetylglucosaminidase (endo-ß-GlcNAc-ase), are involved in the deglycosylation. Although the physiological functions of these FNGs in plant growth and development remain to be elucidated, detailed characterization of cPNGase and endo-ß-GlcNAc-ase is required. In our previous work, we described the purification, characterization, and subcellular distribution of some plant endo-ß-GlcNAc-ases and preliminarily reported the gene information of rice endo-ß-GlcNAc-ase (Endo-Os). Furthermore, we analyzed the changes in gene expression of endo-ß-GlcNAc-ase during tomato fruit maturation and constructed a mutant line of Arabidopsis thaliana, in which the two endo-ß-GlcNAc-ase genes were knocked-out based on the Endo-Os gene. In this report, we describe the purification, characterization, amino acid sequence, and gene cloning of Endo-Os in detail. Purified Endo-Os, with an optimal pH of 6.5, showed high activity for high-mannose type N-glycans bearing the Manα1-2Manα1-3Manß1 unit; this substrate specificity was almost the same as that of other plant endo-ß-GlcNAc-ases, suggesting that Endo-Os plays a critical role in the production of HTM-FNGs in the cytosol. Electrospray ionization-mass spectrometry analysis of the tryptic peptides revealed 17 internal amino acid sequences, including the C terminus; the N-terminal sequence could not be identified due to chemical modification. These internal amino acid sequences were consistent with the amino acid sequence (UniProt ID: Q5W6R1) deduced from the Oryza sativa cDNA clone AK112067 (gene ID: Os05g0346500). Recombinant Endo-Os expressed in Escherichia coli using cDNA showed the same enzymatic properties as those of native Endo-Os.

Translation and validation of the Japanese Version of the Quality of Recovery-15 Questionnaire.

PURPOSE: Patient-reported outcomes after surgery and anaesthesia have recently attracted attention. A recent systematic review and a consensus guideline recommend that patients' recovery can be adequately measured using the quality of recovery-15 (QoR-15) during the perioperative period; however, the Japanese version of the QoR-15 (QoR-15J) is not available. We aimed to translate the QoR-15 into Japanese and assess its validity. METHODS: After translating into Japanese, 205 patients who underwent various types of surgery under general anaesthesia were enrolled in the study. QoR-15J was evaluated before surgery and 24 h and 48 h after surgery. Additionally, 30 patients answered the QoR-15J at 25 h after surgery. We assessed the feasibility, reliability, validity, and responsiveness of the QoR-15J. RESULTS: One patient who did not undergo surgery and two patients who were discharged within 24 h were excluded. One hundred and eighty-seven patients answered the QoR-15J at 24 h after surgery (completion rate, 92.6%) and 183 patients with complete data were included in the final analysis. The Cronbach's alpha coefficient for internal reliability and Spearman rank correlation coefficient for test-retest reliability were 0.84 and 0.91, respectively. The Cohen effect size for all items was 1.42. CONCLUSIONS: QoR-15 was translated into Japanese and the Japanese version's validity was assessed in patients undergoing various types of surgery under general anaesthesia. Our results suggest that QoR-15J is feasible, reliable, valid, and responsive.

The Association between Family Caregiver Burden and Subjective Well-Being and the Moderating Effect of Social Participation among Japanese Adults: A Cross-Sectional Study.

We examined the association between family caregiver burden and subjective well-being with social participation's moderating effect among Japanese adults. Data were obtained from a cross-sectional survey by the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Study participants included 5321 adults who visited the Public Health Center for annual health check-ups and answered a questionnaire regarding health status and lifestyle. Subjective well-being was assessed by a single item, out of 10 points, and analyzed with multivariable linear regression analysis models by subjective family caregiver burden ("none", "mild", "severe"), stratified by gender. Ultimately, 2857 men and 2223 women were included. Mean participant age (standard deviation) in years was 64.7 (10.4) for men and 61.3 (10.0) for women. Multivariable analysis revealed that, among women, higher caregiver burden was inversely associated with subjective well-being (p for trend < 0.001), and the interaction of severe caregiver burden and social participation on subjective well-being was positive and significant (p for interaction < 0.05). High family caregiver burden was inversely associated with subjective well-being among Japanese women, but moderated by the caregiver's social participation, suggesting the importance of community development that enables family caregivers' social participation to protect their subjective well-being.

Successful Treatment of Pediatric Refractory/Relapsed AML with KIR-Ligand-Mismatched Cord Blood Transplant after FLAG-IDA Reinduction Therapy with or without the GO Regimen.

Prognosis in pediatric patients with refractory/relapsed acute myeloid leukemia (AML) is grim, and there is no standard treatment for such patients. Combined treatment with intensive chemotherapy and gemtuzumab ozogamicin (GO), a monoclonal anti-CD33 antibody conjugated with calicheamicin, is useful as reinduction therapy in refractory/relapsed AML. Here, we describe three cases of pediatric refractory/relapsed AML that were successfully managed with FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), with or without GO, as reinduction therapy before a KIR-ligand-mismatched cord blood transplant. This strategy relies on the fact that killer cell immunoglobulin-like receptors (KIR) on cord blood natural killer (NK) cells recognize human leukocyte antigen (HLA) class I alleles, and that donor KIR-ligand incompatibility may be associated with lower incidence of relapse and improved survival in AML, as cells that lack these inhibitory HLA ligands can activate NK cells. All three patients are currently alive and have been disease-free for 24-65 months, although one patient developed severe sinusoidal obstructive syndrome (SOS). Thus, our strategy can result in excellent outcomes in pediatric patients with refractory/relapsed AML.

Association Between Second-hand Smoke Exposure and Depressive Symptoms Among Japanese Adults: A Cross-sectional Study.

BACKGROUND: Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We examined this association in a cross-sectional study among a Japanese general adult population sample. METHODS: Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as "almost never," "sometimes," and "almost every day". Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms. RESULTS: Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation [SD], 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with "almost never" were 1.25 (95% CI, 1.09-1.42) for "sometimes" and 1.41 (95% CI, 1.09-1.84) for "almost every day" (P for trend <0.001); among smokers, PRs compared with "almost never" were 1.30 (95% CI, 0.82-2.06) for "sometimes" and 1.44 (95% CI, 0.90-2.33) for "almost every day" (P for trend = 0.144). CONCLUSIONS: Second-hand smoking and depressive symptoms were associated among non-smokers. Our findings indicate the importance of tobacco smoke control for mental health.

Associated factors with delayed ambulation after abdominal surgery.

PURPOSE: After abdominal surgery, ambulatory status is an important indicator of postoperative recovery. This study investigated the inability to ambulate on postoperative day 1 and identified associated predictive factors in patients undergoing abdominal surgery, focusing on preoperative hematologic markers such as the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index. METHODS: Adult patients undergoing abdominal surgery from May 2018 to October 2018 were investigated consecutively. Only patients with duration of surgery ≥ 3 h were included for observation. Data on patient characteristics were collected from medical charts and laboratory results. Univariate analysis and multivariate logistic regression were used to determine associations with inability to ambulate without human assistance on postoperative day 1 and postoperative length of stay. RESULTS: Of 416 eligible patients, 217 patients were included in the analysis. Sixty-nine patients (31.7%) were not able to ambulate on postoperative day 1. The NLR (odds ratio, 1.11; 95% confidence interval, 1.01-1.23), duration of surgery (odds ratio per 1 h, 1.27; 95% confidence interval, 1.06-1.43), and American Society of Anesthesiologists physical status of 3 (odds ratio, 4.99; 95% confidence interval, 1.15-21.5) were independently associated with the inability to ambulate without assistance on postoperative day 1, which was also associated with longer hospital stays (13 [11, 22] vs 21 [15, 39] days, P < 0.001). CONCLUSIONS: The NLR, surgical duration, and American Society of Anesthesiologists physical status were significantly associated with the inability to ambulate without human assistance on postoperative day 1 and prolonged hospitalization.

The frequency of cooking dinner at home and its association with nutrient intake adequacy among married young-to-middle-aged Japanese women: the POTATO Study.

Home cooking has been suggested as a key to healthy dietary intakes. However, little is known about the association between cooking behaviour and nutrient intake among young-to-middle-aged women. We aimed to investigate the association between home cooking frequency and nutrient intake adequacy among married Japanese women. Self-administered questionnaires were used to assess the weekly frequency of cooking dinner at home and habitual nutrient intake during the preceding month. We evaluated nutrient intake adequacy by comparing the self-reported intake with two indices of the dietary reference intakes for Japanese (2015): the estimated average requirement (EAR) of fourteen nutrients, and the 'tentative dietary goal for preventing lifestyle-related diseases' (DG) of seven nutrients. A total of 143 participants (25-44 years old) completed the questionnaires, with 32·9 % of participants reporting a weekly home cooking frequency of seven times/week. Women with a higher home cooking frequency (seven times/week) were more likely to have children (P = 0·001) than those with a lower home cooking frequency (0-6 times/week). Of the nutrients evaluated, there was no significant difference between the two groups in meeting EAR and DG. Our findings suggest that daily home cooking may not be necessary to achieve adequate nutrient intake, specifically among married, young-to-middle-aged Japanese women.

Handling missing data in an FFQ: multiple imputation and nutrient intake estimates.

OBJECTIVE: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation. DESIGN: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation. SETTING: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2. RESULTS: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation. CONCLUSIONS: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

Gastric antral vascular ectasia in a pediatric patient with neuroblastoma who underwent tandem stem cell transplantation.

Gastric antral vascular ectasia (GAVE) is an angiodysplastic disorder, which causes severe and prolonged gastric bleeding. Although GAVE has been described in adult patients treated with hematopoietic stem cell transplantation (HSCT), a few cases involving pediatric patients have also been reported. A 5-year-old boy with neuroblastoma (NB) developed severe hematemesis after undergoing tandem HSCT, i.e. autologous peripheral blood stem cell transplantation (auto-PBSCT), followed by allogeneic cord blood transplantation (allo-CBT). The patient suffered oral feeding difficulties because of the effects of chemotherapy and an unbalanced diet. Intravenous Busulfan (ivBU) was used as a conditioning regimen for the auto-PBSCT. The diagnosis of GAVE was made based on endoscopy of the upper gastrointestinal tract on day 31 after the allo-CBT. Argon plasma coagulation (APC) was performed twice, and the complete resolution of GAVE was confirmed by an endoscopic re-evaluation, conducted on day 87. GAVE in this case might have been associated with ivBU treatment. Atrophy of the gastric mucosa due to loss of appetite might also have contributed to GAVE. NB was treated using high-doses of alkylating agents, such as BU. Such treatment can cause significant mucositis of the oral cavity as well as vascular lesions and is associated with GAVE. Therefore, GAVE should be considered when gastrointestinal bleeding occurs in NB patients treated with HSCT. APC might be effective against HSCT-GAVE.

Physical Activity Earlier in Life Is Inversely Associated With Insulin Resistance Among Adults in Japan.

BACKGROUND: It is known that physical activity affects glucose metabolism. However, there have been no reports on the influence of physical activity earlier in life on subsequent glucose metabolism. Therefore, we analyzed the influence of physical activity in earlier decades of life on insulin resistance in middle aged and older residents in Japan. METHODS: The subjects were 6,883 residents of Okazaki City between the ages of 40 and 79 years who underwent physical examinations at the Okazaki City Medical Association Public Health Center from April 2007 through August 2011. They gave informed consent for participation in the study. Data on individual characteristics were collected via a questionnaire and from the health examination records. Fasting blood glucose and insulin levels were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). HOMA-IR >1.6 was considered to indicate insulin resistance for the purpose of logistic regression models. RESULTS: The study sample included 3,683 men and 3,200 women for whom complete information was available. For those who exercised regularly throughout their teens to their 30s-40s, the odds ratio for having insulin resistance was 0.75 (95% confidence interval [CI], 0.58-0.96) for men and 0.76 (95% CI, 0.58-0.99) for women after adjusting for other variables, including age, body mass index, and present physical activity. A linear trend was also observed in both men and women. CONCLUSIONS: Subjects who have exercised regularly in the early decades of life are less likely to have insulin resistance later in life.

Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.

[This retracts the article DOI: 10.3892/ol.2018.8225.].

Prophylactic recombinant thrombomodulin treatment prevents hepatic sinusoidal obstruction syndrome in high-risk pediatric patients that undergo hematopoietic stem cell transplants.

Hepatic SOS is a potentially life-threatening complication of conditioning for allogeneic HSCT. rTM is a new drug for treating DIC. We report our experience of the use of rTM as a prophylaxis against SOS in high-risk pediatric patients that underwent HSCT. We evaluated the cases of 19 pediatric hematology and oncology patients who underwent HSCT at our institution between 2007 and 2016. The patients who received HSCT after 2012 (n = 8) were treated with rTM as a prophylaxis against SOS together with UDCA and LMWH, whereas the others (n = 11) were only treated with UDCA and LMWH. Although SOS occurred by post-HSCT day 35 in 3 (27%) patients in the control group, SOS was not seen in the rTM group. Two of the former three patients suffered severe SOS, and one died of the condition. The mean peak level of PAI-1 (a marker of endothelial damage) was significantly lower in the rTM group. rTM appears to be a safe prophylaxis for SOS. The present findings suggest that prophylactic rTM after HSCT might help to prevent SOS.

Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.

Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 (BAP1) and neurofibromatosis type 2 (NF2). Previously, the utility of detecting the loss of BAP1 by immunohistochemistry (IHC) and p16-deletion by fluorescence in situ hybridization has been identified in several studies. However, NF2-associated examinations have not been performed. The present study aimed to evaluate the expression of yes-associated protein 1 (YAP1) and tafazzin (TAZ) protein, which are associated with NF2 gene mutations, in malignant mesothelioma (MM) and reactive mesothelial cells (RMCs). Formalin-fixed paraffin-embedded tissues from 31 MM and 33 RMC samples were analyzed. The expression of YAP1 and TAZ protein were examined by IHC. Positivity for YAP1 was identified 27/31 MM and 15/33 RMC samples. Positivity for TAZ was identified in 28/31 MM and 18/33 RMC samples. Using the optimal cutoff points determined by the receiver operating characteristic curve, a positive IHC result for YAP1 and TAZ was 74% sensitive and 94% specific for detecting MM. The results indicate that increased expression of YAP1 and TAZ may be associated with mesothelial tumorization, and aid in the diagnosis of MM.

The presence of children in households was associated with dietary intake among Japanese married women: the POTATO study.

A growing body of evidence from Western countries shows that the presence of children in households is associated with the dietary intake of adults, but little is known about this relationship in non-Western countries with different food cultures. Our aim was to examine whether dietary intake was different with respect to the presence of young children in the home among Japanese married women. Subjects were Japanese married women (aged 23-44 years) living with children aged less than 5 years (n 73) and married women who did not have children (n 85). Data regarding habitual dietary intake were obtained using a validated, self-administered diet history questionnaire. A cross-sectional comparison between women with young children and women without children was conducted using ANCOVA adjusted for potential confounding factors. Women with young children had a significantly greater intake of protein, carbohydrates, Na, Zn and Cu than did women without children. Intake of cereals, pulses and sugar was significantly higher among mothers than among non-mothers. Intake of both alcoholic and non-alcoholic beverages was significantly higher among non-mothers than among mothers. Thus, the presence of young children at home might influence women's intake of macronutrients and some minerals, especially Na, and beverages among Japanese married women. Our findings suggest that effective dietary interventions among Japanese mothers with young children may differ from those of married women without children.

Immunohistochemical CD73 expression status in gastrointestinal neuroendocrine neoplasms: A retrospective study of 136 patients.

The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC). The incidences of lymphatic and venous invasions were higher in the NEC group compared with in the NET group (P<0.0001 and P=0.0021, respectively). The immunohistochemical staining of cluster of differentiation 73 (CD73) was evaluated in GI-NENs. CD73 is a potentially useful molecule in tumor immunity. In general, CD73 on the tumor cell membrane converts adenosine monophosphate to adenosine, which restrains the production of interferon-γ and cytocidal activity. Although the association between stem cells of pancreatic NENs and CD73 has been reported, few studies have reported on CD73 expression in GI-NENs. Immunohistochemical CD73 expression on the cytomembrane of neuroendocrine cells was detected in 27.2% (37/136) of the GI-NENs. The positive ratio of CD73 was significantly higher in the NEC group compared with in the NET group (P=0.0015). CD73 is also considered as a potential biomarker of anti-programmed death-1 (PD-1) therapy. The expression of programmed death-ligand 1 (PD-L1) on the cytomembrane of GI-NENs was assessed. The positive ratio of PD-L1 was higher in the NEC group compared with in the NET group (P=0.0011). Furthermore, CD73 expression status was significantly correlated with PD-L1 expression (P<0.0001). These results indicate that CD73 may be an interesting candidate for a biomarker for certain prognostic factors and therapeutics concerning PD-1 therapy.