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Genetic screens in Drosophila melanogaster have long been used to identify genes found in a variety of developmental, cellular, and behavioral processes. Here we describe the characterization and mapping of a mutation identified in a conditional screen for genetic regulators of cell growth and cell division. Within a Flp/FRT system, mutant G.3.2 results in a reduction of mutant tissue and a rough eye phenotype. We find that G.3.2 maps to the gene cnk , providing further support that cnk is a critical gene in Drosophila eye development. This mutant was characterized, mapped and sequenced by undergraduate students within the Fly-CURE consortium., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with vascular lesions of the cerebral meninges, port wine spots on the face, and glaucoma of the eyes; it is a congenital, non-genetic disease whose etiology and mechanisms are unknown. In this report, we describe a rare case of SWS with unilateral large odontogenic tumors in the maxilla and mandible. The histopathological diagnosis of the maxillary bone lesion on biopsy was juvenile psammomatoid ossifying fibroma, which is considered a type of ossifying fibroma of craniofacial bone origin. However, the final pathological diagnosis of the excision was cemento-ossifying fibroma derived from periodontal ligament cells, and we discuss the histopathology in detail. In addition, the mandibular lesion was one of the largest odontomas reported to date. Furthermore, in this case, we suggest the possibility that the maxillary and mandibular bone lesions are not separate lesions, but a series of lesions related to SWS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: The present multicenter randomized controlled trial explored the effectiveness of a person-centered care program (intervention group) and a dementia-type-specific program (control group) for nurses in acute-care hospitals., Methods: Seven hospitals in Prefecture A were randomly allocated to two groups (an intervention group and a control group), and a study of these groups was conducted from July 2021 to January 2022., Results: A total of 158 participants were included in the study: 58 in the control group and 100 in the intervention group. In a comparison of assessment values immediately after the course, three months later, and six months later for both the intervention and control groups, "expertise in dementia nursing," "medical expertise in dementia, " and "confidence in nursing older people with dementia" were all significantly higher than before the course. Significant improvements in the intervention group's "knowledge of dementia" and "sense of dignity" on the ethical sensitivity scale were found immediately after the course compared to baseline, three months later, and six months later and were also significantly greater than the control group in terms of the amount of change. In the control group's "unique care tailored to cognitive function and the person," there were significant improvements in the ratings immediately after the course and three and six months after the course compared to baseline, with significantly greater amounts of change than in the intervention group., Conclusion: The person-centered care program for nurses led to improvements in the knowledge about dementia and awareness of the dignity of ethical sensitivity. In addition, the type of dementia program had a significant influence on medical knowledge and unique care tailored to the cognitive function and the individual patient. Further outcome evaluations of physical restraint rates as a quality of care in nursing practice are needed.

Objective: This study aimed to identify factors associated with the response to the SARS-CoV-2 vaccine in people living with HIV (PLWH)., Methods: This study was conducted at the Jikei University School of Medicine, Tokyo, Japan. IgG antibodies against spike and nucleocapsid proteins were detected using Abbott SARS-CoV-2 IgG II Quant assays., Results: During the investigation period, 371 PLWH were enrolled in this study. PLWH with previous COVID-19 infection, untreated or poorly controlled HIV infection, and those whose blood samples were obtained within less than seven days after the second vaccination were excluded. A total of 310 PLWH controlled with anti-retroviral therapy were included in the final analysis. Multivariate analysis demonstrated that chronic kidney disease (CKD) (β = -0.353, p = 0.049) and the duration between the second vaccination and blood sampling (β = -0.005, p < 0.001) were associated with low spike protein IgG titers., Conclusion: Even without hemodialysis or kidney transplant, CKD was associated with vaccine response in PLWH., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to develop a simulation program for physicians and nurses involved in virtual reality (VR) and augmented reality (AR) treatment and care from the perspective of these professionals and older adults with dementia who developed delirium, and to test the effectiveness of the program., Methods: effectiveness of the program was analyzed through free-response statements from 67 nurses (84.8%) and 12 doctors (15.2%) who participated in the program between February 16 and April 18, 2023., Results: Regarding the experience of delirium from the perspective of older adults with dementia (personal experience), the following statements were extracted "1. I do not understand where I am, the situation, and the treatment/care that is about to be given"; "2. I want the situation to be explained to me so that I can understand the reasons for my hospitalization and the treatment/care I am receiving"; "3. The eerie environment of the hospital and the high pressure of the staff made me feel anxious and fearful"; "4. Please respect my existence as I endure pain, anxiety, and loneliness"; "5. I feel relieved when doctors and nurses deal with me from my point of view"; and "6. I feel relieved when there is a familiar presence, such as a family member or the name I am calling on a daily basis"., Conclusion: Specific categories of self-oriented empathy were extracted from the experience of physical restraint at night using VR and the experience of delirium using AR. This suggests the possibility of objective effects on treatment and care in future practice.

Pancreatic tumors grow in an "austerity" tumor microenvironment characterized by nutrient deprivation and hypoxia. This leads to the activation of adaptive pathways in pancreatic cancer cells, promoting tolerance to nutrition starvation and aggressive malignancy. Conventional anticancer drugs are often ineffective against tumors that grow in such austerity condition. Plumbagin, a plant-derived naphthoquinone, has shown potent preferential cytotoxicity against pancreatic cancer cells under nutrient-deprived conditions. Therefore, we synthesized a series of plumbagin derivatives and found that 2-(cyclohexylmethyl)-plumbagin ( 3f ) was the most promising compound with a PC 50 value of 0.11 μM. Mechanistically, 3f was found to inhibit the PI3K/Akt/mTOR signaling pathways, leading to cancer cell death under nutrient-deprived conditions. In vivo studies using pancreatic cancer xenograft mouse models confirmed the efficacy of 3f , demonstrating significant inhibition of tumor growth in a dose-dependent manner. Compound 3f represents a highly promising lead for anticancer drug development based on an antiausterity strategy.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health., (©2023 BMFH Press.)

Background: Novel therapeutic targets are needed to improve the poor prognosis of patients with advanced gastric cancer. The aim of this study was to identify a novel therapeutic target for the treatment of GC and to investigate the potential therapeutic value of an antibody raised against the target., Methods: We identified gamma-aminobutyric acid type A receptor subunit delta as a candidate therapeutic target by differential transcriptome analysis of metastatic GC tissue and adjacent nontumor tissues. GABRD mRNA levels were analyzed in 230 pairs of gastric tissue by quantitative reverse-transcription polymerase chain reaction. GABRD function was assessed in proliferation, invasion, and apoptosis assays in human GC cell lines expressing control or GABRD-targeting small interfering RNA (siRNA). Mouse anti-human polyclonal GABRD antibodies were generated and assessed for inhibition of GC cell growth in vitro and in a mouse xenograft model of peritoneal GC dissemination., Results: High GABRD mRNA expression level in primary human GC tissue was associated with poor prognosis. Expression of siGABRD in GC cell lines significantly decreased cell proliferation and invasion and increased apoptosis compared with control siRNA expression. Anti-GABRD polyclonal antibodies inhibited GC cell proliferation in vitro and decreased peritoneal tumor nodule size in the mouse xenograft model., Conclusion: We identified GABRD as novel regulator of GC cell growth and function. GABRD is upregulated in GC tissue and is associated with poor prognosis, suggesting that it may be a potential therapeutic target for GC., (© 2022. Society of Surgical Oncology.)

Introduction: In Japan, patients with coronavirus disease 2019 (COVID-19) who do not require medical intervention are provided care in recovery accommodation facilities (RAFs). However, some patients may require hospitalization if their symptoms become more severe during their stay. We conducted an observational study using epidemiological data of patients with COVID-19 admitted to RAFs in Tokyo., Methods: This was an observational cohort study using data from COVID-19 patients admitted to one of the RAFs in Tokyo from December 2020 to November 2021. Admissions to the facilities were limited to patients with asymptomatic or mild COVID-19 with no underlying disease or at least stable underlying disease at the time of admission. Patients were hospitalized when they required oxygen administration or when they had, or persistent fever, or severe respiratory symptoms. We evaluated the association between hospitalization and the risk factors for hospitalization using a Cox regression model., Results: The number of patients with COVID-19 admitted to the RAF was 6176. The number of hospitalized patients was 393 (6.4%), and the median length of stay was 5.50 days (IQR: 4.50, 6.50). In the Cox regression analysis, the hazard ratio increased with age and was significantly higher among patients aged >60 years (HR = 10.23, 95% CI: 6.72-15.57) than those in other age groups. This trend is similar to that observed in the sensitivity analysis., Conclusion: Patients with diabetes, the elderly, obesity, and medications for gout and psychiatric diseases may be at a high risk of hospitalization. In particular, an age over 60 years was strongly associated with hospitalization., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Kinetic vision acuity (KVA) is an index developed in Japan that refers to the capacity to recognize a moving object that moves back and forth against the observer. This review outlines the history of KVA and studies on KVA conducted at the Faculty of Health and Sports Science of Juntendo University, i.e. characteristics of KVA in athletes, factors associated with KVA, sports and age-dependent decline of KVA, and effects of docosahexaenoic acid (DHA) and astaxanthin on KVA. KVA was defined in the early 1960s, and the measurement device was invented in 1968. Studies at the Faculty of Health and Sports Science began in the 1990s. In track-and-field athletics and skeleton, a winter downhill event, higher-ranked athletes had higher KVA than lower-ranked athletes. Although KVA cannot be predicted from static visual acuity or reaction time, a significant correlation was found between KVA and the peak latency of visual-evoked potentials. KVA could not be improved by training and did not change between age of 8 and 17 years. In contrast, habitual practice in kendo may inhibit the age-dependent decline in KVA. DHA may also improve KVA in subjects with low KVA; however, astaxanthin did not improve KVA., Competing Interests: The authors declare that there are no conflicts of interest., (© 2022 The Juntendo Medical Society.)

Background: Metastatic gastric cancer (GC) has a poor prognosis, and elucidating the molecular mechanisms involved in metastasis may lead to the development of novel therapeutic modalities., Methods: Transcriptome analysis of surgically resected metastatic tissue from GC patients and noncancerous tissue was performed to identify novel metastasis-related genes. Analyses of in vitro cell function, apoptosis, the cell cycle and cancer stemness were performed using GC cell lines with a stable knockout of a candidate gene. In vivo percutaneous, peritoneal dissemination and liver metastasis xenograft models were also generated. PCR array and proteome analyses were performed. Expression of the candidate gene was analyzed in GC tissues from 300 patients., Results: Lysosomal Associated Membrane Protein Family Member 5 (LAMP5) was upregulated in the metastatic tissues. LAMP5 knockout significantly suppressed proliferation, invasion, and migration of GC cells and increased apoptosis, cell cycle arrest and cancer stemness. LAMP5 knockout virtually suppressed tumor growth in in vivo percutaneous, peritoneal dissemination and liver metastasis models. EMT- and autophagy-related genes were associated with LAMP5. High LAMP5 mRNA levels were significantly associated with a worse prognosis., Conclusion: LAMP5 plays a vital role in metastasis formation and may be a promising novel target of drug development for metastatic GC in the future., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: The expression of solute carrier (SLC) 7 family genes is reportedly associated with several malignancies. Here, we focused on SLC7A9 and investigated its expression, function, and clinical significance in esophageal squamous cell carcinoma (ESCC)., Methods: SLC7A9 transcription levels were evaluated in 13 ESCC cell lines, and polymerase chain reaction (PCR) array analysis was conducted to detect coordinately expressed genes with SLC7A9. SLC7A9 contributions to proliferation, invasion, and migration were evaluated in ESCC cells subjected to siRNA-mediated gene knockdown and pCMV6-entry plasmid-mediated overexpression. SLC7A9 expression was detected in 189 ESCC tissues by quantitative reverse-transcription (qRT)-PCR and correlated with clinicopathological parameters., Results: The expression levels of SLC7A9 varied widely in ESCC cell lines and correlated with FGFBP1 expression. Knockdown of SLC7A9 significantly suppressed the proliferation, invasion, and migration of the ESCC cell lines. Moreover, overexpression of SLC7A9 enhanced cell proliferation and migration. In analyses of clinical specimens, SLC7A9 mRNA was overexpressed in the ESCC tissues compared with the adjacent normal esophageal tissues. High mRNA expression was significantly associated with high levels of squamous cell carcinoma-related antigen and carcinoembryonic antigen, advanced disease stage, and lymph node metastasis. High SLC7A9 expression was also significantly associated with poor disease-specific and disease-free survival, and lymph node recurrence after radical surgery, but not with the other recurrence patterns. On multivariate analysis, high SLC7A9 expression was an independent predictor of lymph node recurrence., Conclusions: SLC7A9 influences the malignant behavior of ESCC cells. Tumor SLC7A9 expression may serve as a novel biomarker for predicting lymph node metastasis and recurrence in ESCC patients., (© 2021. Society of Surgical Oncology.)

Purpose: The number of hospitalizations of older patients with dementia who require medical treatment has increased and delirium or physical restriction have become problems in the acute care setting. Dementia nursing intervention ability developing program by e-learning assumed the quality improvement of dementia medical care and the nursing of older patients with dementia based on person-centered aimed at reduction of body restriction. The purpose of this study was to validate the effectiveness of the developed e-learning programs for nurses in the acute care setting of seven to one nursing standards., Method: This study was conducted between April and December 2020. This study was introduced to the floor nurse of the hospital for suitable application. Interested nurses were asked to attend "Developing programs for Dementia nursing intervention ability (4 weeks)" at four different time points (1) before attendance (baseline), post-attendance (1 month later), (3) practiced 3 months post-attendance, and (4) practiced 6 months post-attendance. A questionnaire to evaluate program effectiveness asked about consciousness of the dementia nursing with four items on "Interest in nursing of people with dementia and so on (four items)".In the evaluation on the person-centered dementia care, using the Self-assessment Scale of Nursing Practice for Elderly Patients with Cognitive Impairment, the Approach to Dementia Questionnaire - Japanese Edition (19 items). In the evaluation of ethics, ethical sensitivity scale for clinical nurses (19 items), self-efficacy on reduction of the physical restriction (six items). A statistical analysis was conducted using the Bonferroni test as the multiple test method to compare baseline values with the values obtained 1, 3, and 6 months later., Results: A total of 70 subjects were analyzed in this study. They belonged to different wards including the surgical and internal wards from where 60 subjects (85.7%) were recruited. The average clinical experience of the nurses was 13.5±9.5 years. The degree of self-efficacy was assessed in terms of attaching mitten type gloves as a physical restraint to avoid the pulling of tubes used for intravenous feeding, central veins, normal feeding, etc. by the patients and so on. Most patients had cognitive functional disorder, including dementia [n = 30 (42.9%)]. The self-assessed scale of nursing practice for elderly people with cognitive impairment, which aimed to promote person-centered care in an acute care hospital, revealed that the total score of each of the Approaches to Dementia Questionnaire - Japanese Edition significantly increased just after intervention (1 month) in comparison to baseline, and 3 months and 6 months after intervention., Conclusion: This study indicated that the program developed to improve dementia nursing intervention ability significantly increased the above-mentioned evolution and consciousness of nurses after the intervention program (1 month), followed by 3 months and 6 months later. Along with ethical sensitivity, practice aimed at person-centered care was also found to improve. It was suggested that the intervention program of this study was effective and that nurses could easily learn using their respective free time and practice.

Here, we evaluated the therapeutic potential of antibodies (Abs) targeting cholinergic receptor nicotinic beta 2 subunit (CHRNB2) in gastric cancer. To investigate the effects of these Abs on malignant phenotypes in vitro and in mouse xenograft models, we generated gene knockouts through genome editing, performed RNA interference-mediated knockdown of gene expression, and ectopically expressed CHRNB2 in gastric cancer cells. The effects of anti-CHRNB2 Abs on the proliferation of cancer cells were evaluated both in vitro and in vivo. We determined the effects of Chrnb2 deficiency on mice and the clinical significance of CHRNB2 expression in gastric cancer clinical specimens. Knockdown of CHRNB2 attenuated gastric cancer cell proliferation, whereas forced overexpression of CHRNB2 increased cell proliferation. Knockout of CHRNB2 significantly influenced cell survival and functions associated with metastasis. The effects of polyclonal Abs targeting the C- and N-termini of CHRNB2 guided the development of anti-CHRNB2 monoclonal Abs that inhibited the growth of gastric cancer cells in vitro and in vivo. Pathway analysis revealed that CHRNB2 interfered with signaling through the PI3K-AKT and JAK-STAT pathways. Chrnb2-deficient mice exhibited normal reproduction, organ functions, and motor functions. CHRNB2 regulates multiple oncological phenotypes associated with metastasis, and blockade of CHRNB2 expression using specific Abs shows promise for controlling metastasis in gastric cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The liver is the most common site for haematogenous metastasis of gastric cancer, and liver metastasis is fatal., Methods: We conducted a transcriptomic analysis between metastatic foci in the liver, primary tumour and adjacent tissues from gastric cancer patients with metastasis limited to the liver. We determined mRNA expression levels in tumour tissues of 300 patients with gastric cancer via quantitative RT-PCR. The oncogenic phenotypes of GNG4 were determined with knockdown, knockout and forced expression experiments. We established and compared subcutaneous and liver metastatic mouse xenograft models of gastric cancer to reveal the roles of GNG4 in tumorigenesis in the liver., Results: GNG4 was upregulated substantially in primary gastric cancer tissues as well as liver metastatic lesions. High levels of GNG4 in primary cancer tissues were associated with short overall survival and the likelihood of liver recurrence. Functional assays revealed that GNG4 promoted cancer cell proliferation, the cell cycle and adhesiveness. Tumour formation by GNG4-knockout cells was moderately reduced in the subcutaneous mouse model and strikingly attenuated in the liver metastasis mouse model., Conclusions: GNG4 expression may provide better disease monitoring for liver metastasis, and GNG4 may be a novel candidate therapeutic target for liver metastasis., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

The clinical manifestations of COVID-19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID-19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID-19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID-19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID-19 severity. Strikingly, we identified three distinct groups of markers (antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs) with the potential to serve as early predictive biomarkers for COVID-19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID-19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00-1.00)). The validation set included 40 COVID-19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73-0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID-19 therapy., Competing Interests: Yu Fujita is a chief science advisor, Mitsuru Miyato is a chief executive officer, and Takahiro Ochiya is a technical executive officer of International Space Medical Co., Ltd. The other authors have declared that no conflict of interest exists., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Coenzyme Q10 (CoQ10) is the electron transporter in oxidative phosphorylation and an endogenous antioxidant. Recent researches have indicated that doses of 200-300 mg/day are needed to recognize effects to prevent oxidative damage in athletes, and the reduced form of CoQ10, ubiquinol-10, is more bioavailable than its oxidized form. Therefore, we hypothesized that higher doses of ubiquinol-10 could elevate plasma CoQ10 levels rapidly and exert physiological benefits in athletes. Therefore, a placebo controlled, double blinded test was carried out to determine the effects of ubiquinol-10 on the extravasate enzymes and fatigue levels of distance runners. Methods: Sixteen male collegiate distance runners were allocated to two groups receiving 300 mg/day of ubiquinol-10 (19.8 ± 1.7 years) or a placebo (20.1 ± 1.6 years) for 12 days during summer training that comprised 25- and 40-km runs on days 7 and 9, respectively. Results: Ubiquinol-10 elevated plasma CoQ10 concentration to 5.62 μg/mL and significantly decreased activities of the serum extravasate enzymes, CK, ALT, LDH (P < 0.01), and AST (P < 0.05) on day 6. Subjective fatigue status was significantly elevated on day 10 (the day after the 45-km run) in the placebo group (P < 0.001), but did not significantly change in the group given ubiquinol-10. Therefore, ubiquinol-10 could mitigate tissue damage and alleviate fatigue status in distance runners during summer training. Conclusions: Ubiquinol-10 (300 mg/day) supplementation elevated plasma CoQ10 concentrations almost to plateau levels, decreased extravasate enzymes within six days, and suppressed the subjective fatigue in male distance runners.

Background: Gastric cancer (GC) with hepatic metastasis has a poor prognosis. Understanding the molecular mechanisms involved in hepatic metastasis may contribute to the development of sensitive diagnostic biomarkers and novel therapeutic strategies., Methods: We performed transcriptome analysis of surgically resected specimens from patients with advanced GC. One of the genes identified as specifically associated with hepatic metastasis was selected for detailed analysis. GC cell lines with knockout of the candidate gene were evaluated in vitro and in vivo. Expression of the candidate gene was analysed in GC tissues from 300 patients., Results: Ethanolamine kinase 2 (ETNK2) was differentially upregulated in GC patients with hepatic metastasis. ETNK2 expression was elevated in GC cell lines derived from haematogenous metastases. ETNK2 knockout significantly suppressed proliferation, invasion, and migration; increased apoptosis; reduced Bcl-2 protein expression; and increased phosphorylated p53 expression. In mouse xenograft models, ETNK2 knockout virtually abolished hepatic metastasis. Stratification of GC patients based on ETNK2 mRNA level revealed significant associations between high ETNK2 tumour expression and both hepatic recurrence and worse prognosis., Conclusions: Upregulation of ETNK2 in GC enhances hepatic metastasis, possibly via dysregulation of p53-Bcl-2-associated apoptosis. ETNK2 expression may serve as a biomarker for predicting hepatic recurrence and a therapeutic target.

Purpose: This study aimed to clarify the effects of dementia care mapping (DCM) for one year in a healthcare center for older adults. DCM was conducted between September 2016 and August 2017. The care staff include nurses and caregivers in a narrow sense, medical staff, such as a physician, physical therapists, and occupational therapists worked on DCM as care staff in this study., Results: There were 24 participants, with an average work experience of 7.21 (±4.74) years. In comparison to the baseline evaluation, the final assessment of self-efficacy through person-centred care showed significant improvement in 'Forecasting and Problem Solving on the Job' within 'Perceived Job Competence of Care Workers'. Six main categories of content were extracted from focus group interviews: 'Awareness,' 'Change of Elderly People under the Care of Staff throughout the Development of Mapping', 'Affirmative Feelings of Care Staff for Mapping', 'Negative Feelings for Mapping', 'Need for the Efficacy and Efficiency of the Mapping', and 'Mapping Based on the Age of the Participant and Future Prospects for Mapping'. The results of person-centred care showed that both the older patients and the staff noticed changes through the development of mapping., Conclusion: The developmental evaluation, based on collaboration by medical and welfare staff can improve self-efficacy through the practice of person-centred care and improves the ability to solve problems during the provision of care.

Patients with peritoneal metastasis of gastric cancer have dismal prognosis, mainly because of inefficient systemic delivery of drugs to peritoneal tumors. We aimed to develop an intraperitoneal treatment strategy using amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting synaptotagmin XIII ( SYT13 ) and to identify the function of SYT13 in gastric cancer cells. We screened 71 candidate oligonucleotide sequences according to SYT13 -knockdown efficacy, in vitro activity, and off-target effects. We evaluated the effects of SYT13 knockdown on cellular functions and signaling pathways, as well as the effects of intraperitoneal administration to mice of AmNA-modified anti-SYT13 ASOs. We selected the ASOs (designated hSYT13-4378 and hSYT13-4733) with the highest knockdown efficiencies and lowest off-target effects and determined their abilities to inhibit cellular functions associated with the metastatic potential of gastric cancer cells. We found that SYT13 interfered with focal adhesion kinase (FAK)-mediated intracellular signals. Intraperitoneal administration of hSYT13-4378 and hSYT13-4733 in a mouse xenograft model of metastasis inhibited the formation of peritoneal nodules and significantly increased survival. Reversible, dose- and sequence-dependent liver damage was induced by ASO treatment without causing abnormal morphological and histological changes in the brain. Intra-abdominal administration of AmNA-modified anti-SYT13 ASOs represents a promising strategy for treating peritoneal metastasis of gastric cancer., (© 2020 The Author(s).)

Background: Despite advances in our understanding on the pathogenesis of gastric cancer (GC), patients face a poor prognosis. To improve clinical outcomes, effective approaches to diagnosis and treatment employing new diagnostic biomarkers are required to achieve early detection and predict recurrence and prognosis., Materials and Methods: Transcriptome analysis was conducted using surgically resected gastric tissues from four patients with metastatic GC. A total of 228 pairs of primary GC tissues and corresponding normal adjacent tissues were subjected to mRNA expression analysis. To validate our findings, we accessed an integrated microarray dataset and RNA sequencing data of GC cell lines., Results: We identified stimulated by retinoic acid 6 (STRA6) as a differentially overexpressed gene, which encodes a transmembrane protein that mediates the cellular uptake of retinol. To investigate how STRA6 contributes to the malignant phenotype of GC cells, we mined public datasets and found the mRNA encoding retinol binding protein 1 (RBP1), which is associated with retinoid metabolism, was co-expressed with STRA6. Furthermore, STRA6 mRNA levels were significantly higher in GC tissues compared to the corresponding noncancerous adjacent tissues of 228 surgically resected gastric tissue samples. Moreover, patients with high levels of STRA6 mRNA experienced significantly shorter disease-free survival and overall survival. Multivariate analysis revealed that high levels of STRA6 served as a significant risk factor., Conclusion: Patients with high levels of STRA6 mRNA experienced significantly worse clinical outcomes, indicating that STRA6 may serve as a diagnostic and prognostic biomarker of GC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: β-1,4-N-Acetyl-galactosaminyltransferase 4 (B4GALNT4), an enzyme involved in ganglioside synthesis, is upregulated in many cancers. We examine B4GALNT4 expression and its relationship to prognosis in esophageal squamous cell carcinoma (ESCC)., Patients and Methods: Expression of B4GALNT4 mRNA and B4GALNT4 protein was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively, in 17 human ESCC cell lines and/or clinical specimens from two independent cohorts of 147 and 159 ESCC patients. The contributions of B4GALNT4 to proliferation, invasion, migration, and adhesion was evaluated in ESCC cells subjected to siRNA-mediated gene knockdown. Correlations between clinicopathological parameters and B4GALNT4 expression in clinical specimens were analyzed in both patient cohorts., Results: B4GALNT4 mRNA expression levels varied widely in ESCC cell lines, regardless of differentiation status or the originating tissue. Knockdown of B4GALNT4 significantly suppressed the proliferation, invasion, migration, and adhesion of ESCC cell lines compared with control cells. B4GALNT4 mRNA was overexpressed in ESCC tissues compared with adjacent normal esophageal tissues. High mRNA expression was significantly associated with poor disease-free survival and hematogenous recurrence, and high B4GALNT4 protein expression was also significantly related to poor disease-specific survival. On multivariable analysis, high B4GALNT4 expression was an independent predictor of poor prognosis. In both patient cohorts, high B4GALNT4 expression did not correlate with known prognostic factors, such as disease stage, lymphovascular invasion, or squamous cell-carcinoma-related antigen level., Conclusions: B4GALNT4 influences the malignant behavior of ESCC cells. B4GALNT4 expression may serve as a novel prognostic marker, independent of established risk factors, for ESCC patients.

Background: Controlling metastasis is essential for improving the prognosis of patients with gastric cancer (GC). Here, we aimed to identify a molecule required for GC metastasis and to investigate its potential utility as a target for the development of therapeutic antibodies (Abs)., Methods: Transcriptome and bioinformatics analyses of human GC cell lines identified the neuronal pentraxin receptor (NPTXR) as a candidate molecule. NPTXR function was probed by modulating its expression in GC cells and assessing the effects on intracellular signaling and malignant behaviors in vitro and in mouse xenograft models. We also generated anti-NPTXR Abs and Nptxr -/- mice, and assessed the clinical significance of NPTXR expression in GC specimens., Results: NPTXR mRNA expression in clinical specimens was associated with disease progression and was significantly higher in tissues from GC patients with distant metastasis compared with those without. NPTXR regulated expression of genes involved in metastatic behaviors as well as activation of the PI3K-AKT-mTOR, FAK-JNK, and YAP signaling pathways. NPTXR silencing promoted caspase-mediated apoptosis and attenuated GC cell proliferation, cell cycle progression, migration, invasion, adhesion, stem cell-like properties, and resistance to 5-fluorouracil in vitro, and also inhibited the tumorigenicity of GC cells in vivo. Anti-NPTXR Abs inhibited GC peritoneal metastasis in mice. Nptxr -/- mice showed no abnormalities in reproduction, development, metabolism, or motor function., Conclusions: NPTXR plays an essential role in controlling the malignant behavior of GC cells in vitro and in vivo. NPTXR-targeting Abs may thus have utility as novel diagnostic tools and/or treatment modalities for GC.

Background: The three dominant recurrence patterns of gastric cancer are peritoneal, hematogenous, and nodal recurrence. Correlation between initial recurrence site and prognosis is poorly understood, particularly after standardization of postoperative S-1 adjuvant chemotherapy., Methods: We analyzed a multi-institutional database of 3484 patients who underwent gastrectomy for gastric cancer between 2010 and 2014. Patients who experienced recurrences after curative gastrectomy classified into peritoneal, hematogenous, or nodal recurrence groups, according to their initial recurrence sites, and their prognoses were compared., Results: We included 313 patients in the analysis, of whom 190 patients (63%) were treated with postoperative adjuvant chemotherapy. Pathological disease states were stage I: n = 20 (6%), stage II: n = 62 (20%), and stage III: n = 231 (74%). Patients were categorized into groups by peritoneal (n = 127), hematogenous (n = 123), and nodal (n = 63) recurrence. The peritoneal recurrence group tended to have longer recurrence-free survival, but shorter post-recurrence survival, than the other two groups. Median disease-specific survival after curative resection by group were peritoneal: 25.8 months, hematogenous: 29.0 months, and nodal: 27.8 months (peritoneal vs hematogenous, P = .152; hematogenous vs nodal, P = .955; peritoneal vs nodal, P = .213)., Conclusions: Prognoses after curative resection for gastric cancer were similar among patients with peritoneal, hematogenous, or nodal recurrences., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: To investigate the function of chromobox 2 (CBX2) in oesophageal squamous cell carcinoma (OSCC)., Materials and Methods: We used real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry to determine CBX2 expression levels in 13 human OSCC cell lines and clinical specimens of two independent cohorts of patients with OSCC., Results: PCR array analysis revealed that CBX2 was co-ordinately expressed with WNT5B in OSCC cell lines. RT-qPCR analysis of clinical samples revealed a high tumour-specific CBX2 expression compared with normal oesophageal tissues. High CBX2 expression was significantly associated with shorter disease-specific survival, hematogenous recurrence, and overall recurrence. Analysis of tissue microarrays of one cohort revealed that patients with higher CBX2 levels tended to have a shorter disease-specific survival., Conclusion: CBX2 overexpression in OSCC tissues may serve as a novel biomarker for predicting survival and hematogenous recurrence., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Liver metastasis of gastric cancer (GC) is highly associated with poor prognosis. The development of sensitive biomarkers for detecting and predicting liver metastasis is required for better clinical outcome., Objective: In this study, we aimed to identify novel genes associated with liver metastasis of GC., Methods: Global expression profiling of 57,749 genes was performed using surgically resected gastric tissues from four patients with liver metastasis to identify candidate genes. The mRNA expression levels of the selected candidate gene were analyzed in the resected gastric tissues of 300 GC patients and correlated with clinicopathological parameters. Fourteen GC cell lines were subjected to mRNA expression and polymerase chain reaction (PCR) array analysis., Results: Among 25 candidate genes identified by transcriptome analysis, preferentially expressed antigen of melanoma (PRAME) was selected for subsequent analyses. mRNA expression analysis of clinical samples revealed the aberrant expression of PRAME in GC tissues, and its high expression was significantly related to differentiated phenotype and vessel invasion, as well as liver metastasis. High PRAME expression was significantly associated with hepatic recurrence after curative surgery, and cumulative incidences of hepatic recurrence were significantly greater in patients with high PRAME expression compared with patients with low PRAME expression. In an in vitro analysis, overexpression was observed in all GC cell lines compared with a normal epithelial cell line. PCR array analysis revealed the coordinate expression of MMP9, OCLN, IL1RN, and MST1R., Conclusions: PRAME is related to the malignant potential of GC and could serve as a novel biomarker for the detection and prediction of liver metastasis.

HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p < 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p < 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/aim: To investigate the function of preferentially expressed antigen of melanoma (PRAME) in esophageal squamous cell carcinoma (ESCC)., Materials and Methods: mRNA expression levels of PRAME were analyzed in resected esophageal tissues of 150 ESCC patients and correlated with clinicopathological parameters. We also investigated the potential function of PRAME by analyzing coordinately expressed genes in 13 ESCC cell lines., Results: RT-qPCR analysis of clinical samples revealed aberrantly high PRAME expression in tumors compared with normal esophageal tissues. High PRAME expression was significantly associated with shorter disease-specific survival and hematogenous recurrence, but not with overall recurrence. The cumulative incidence of hematogenous recurrence was significantly greater for patients with high compared to those with low PRAME expression. In vitro, PCR array analysis revealed that PRAME was coordinately expressed with EGFR, ITGB, and TCF3., Conclusion: PRAME is overexpressed in ESCC tissues and may serve as a novel biomarker for predicting hematogenous recurrence., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The aim of the study was to identify novel biomarkers that are vital for improving management of patients with gastric cancer (GC)., Materials and Methods: An RNA-sequencing analysis was conducted using gastric tissue from patients with metastatic GC. In vitro cell functions were evaluated by siRNA-mediated knockdown assays. A total of 230 pairs of gastric tissue were subjected to expression analysis of mRNA and protein in situ. The serum levels of the candidate biomarker were determined by ELISA., Results: MELTF was identified as a candidate biomarker. Inhibition of MELTF expression suppressed the invasion ability of GC cells. Increased tissue MELTF mRNA expression was associated with shorter survival. Furthermore, staining intensity of tissue MELTF protein was linked to recurrence rates. Serum MELTF levels gradually were increased from healthy controls to advanced GC. Patients with high serum MELTF levels had poor prognosis., Conclusion: Both tissue and serum MELTF levels may serve as biomarkers of GC progression., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gastric cancer (GC) exhibits heterogeneous clinical and molecular features, requiring the development of new biomarkers to further understand this disease. Our transcriptomic analysis detected overexpression of melanoma-associated antigen A6 (MAGEA6) in metastatic GC, leading us to determine the clinical significance of MAGEA6 in GC., Materials and Methods: Fourteen GC cell lines and 230 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. Polymerase chain reaction array analysis was performed to identify coordinately expressed cancer-related genes, and immunohistochemistry (IHC) was used to detected MAGEA6 expression in situ., Results: MAGEA6 mRNA levels were positively correlated with the expression of matrix metallopeptidase 9 mRNA. MAGEA6 mRNA levels were higher in GC tissues compared with those in normal adjacent tissues. Patients with high MAGEA6 expression had significantly worse prognosis. MAGEA6 protein levels in primary lesions predicted the likelihood of recurrence., Conclusion: Overexpression of MAGEA6 in GC tissues represents a promising biomarker for assessing the malignant phenotype of GC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Between January and May in 2018, 17 male cases of hepatitis A were reported in Yokohama, Japan. Of these, 14 identified as men who have sex with men. The viral sequence in this outbreak was same as that of the recent European and Taiwanese outbreaks strain.

Introduction: Gastric cancer (GC) is the leading cause of cancer-related death worldwide. Despite recent advances in diagnosis and therapy, the prognosis of patients with GC is poor. Many patients have inoperable disease upon diagnosis or experience recurrent disease after curative gastrectomy. Unfortunately, tumor markers for GC, such as serum carcinoembryonic antigen and carbohydrate antigen 19-9, lack sufficient sensitivity and specificity. Therefore, effective biomarkers are required to detect early GC and to predict tumor recurrence and chemosensitivity. Areas covered: Here we aimed to review recent developments in techniques that improve the detection of aberrant expression of GC-associated molecules, including protein coding genes, microRNAs, long noncoding RNAs, and methylated promoter DNAs. Expert commentary: Detection of genetic and epigenetic alterations in gastric tissue or in the circulation will likely improve the diagnosis and management of GC to achieve significantly improved outcomes.

Background: Although peritoneal metastasis is a serious concern in patients with gastric cancer, no acceptable and specific biomarker is available. We aimed to identify a candidate biomarker to predict peritoneal metastasis of gastric cancer., Methods: Metastatic pathway-specific transcriptome analysis was conducted by comparison of patient groups with no recurrence and with peritoneal, hepatic, and nodal recurrence. Fifteen cell lines and 262 pairs of surgically resected gastric tissues were subjected to messenger RNA (mRNA) expression analysis. Polymerase chain reaction array analysis was performed to explore coordinately expressed cancer-related genes. To evaluate the in situ protein localization and expression patterns, immunohistochemical staining was performed., Results: From transcriptome data, troponin I2 (TNNI2) was identified as a candidate molecule specifically overexpressed in gastric cancer prone to peritoneal metastasis. TNNI2 mRNA was expressed at differential levels, independent of differentiated phenotype of cell lines. Epithelial to mesenchymal transition-related genes, tumor inhibitor of metalloproteinase 1 (TIMP1), and vacuolar protein sorting 13 homolog A (VPS13A) were expressed with TNNI2 at correlation coefficient > 0.7. The optimal cutoff of TNNI2 expression was determined as 0.00017. High TNNI2 expression was significantly and specifically associated with peritoneal metastasis and served as an independent risk marker for peritoneal recurrence after curative gastrectomy. Prevalence of peritoneal recurrence increased in parallel with staining intensity of TNNI2., Conclusions: TNNI2 expression in gastric tissues may serve as a specific biomarker for prediction of peritoneal metastasis of gastric cancer and contribute to improvement of patient management.

Phagosome formation and maturation are essential innate immune mechanisms to engulf and digest foreign particles. To analyze these processes quantitatively, we established a specific Escherichia coli probe expressing a tandem fluorescent protein, comprising glutathione S-transferase fused with monomeric Cherry (mCherry) and monomeric Venus (mVenus). We demonstrated that mVenus was more susceptible to bleaching in an acidic environment than mCherry, and that the mVenus:mCherry fluorescence intensity ratio can be used to monitor phagosomal pH changes during maturation. Using this probe, we revealed that synaptosomal-associated protein of 23 kDa, a plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein, actively regulated phagocytosis of E. coli and subsequent phagosome maturation in macrophages. Our results indicated that this probe has the potential to be a powerful tool in understanding the molecular mechanisms of phagosome formation and maturation., (© The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Background: The major types of commercially available gelatin hydrolysates are prepared from mammals or fish. Dietary gelatin hydrolysates from mammals were reported to improve bone mineral density (BMD) in some animal models. In contrast, there is limited study showing the effects of dietary gelatin hydrolysates from fish on BMD. The quantity and structure of peptides in the plasma after oral administration of gelatin hydrolysates depend on the gelatin source, which suggests that the biological activity of gelatin hydrolysates depend on the gelatin source. This study examined the effects of fish-derived gelatin hydrolysate (FGH) or porcine-derived gelatin hydrolysate (PGH) intake on BMD and intrinsic biomechanical properties in magnesium (Mg)-deficient rats as a model showing the decrease in both BMD and intrinsic biomechanical properties., Methods: Four-week-old male Wistar rats were assigned into four groups: a normal group was fed a normal diet (48 mg Mg/100 g diet), a Mg-deficient (MgD) group was fed a MgD diet (7 mg Mg/100 g diet), a FGH group was fed a MgD + FGH diet (5% FGH), and a PGH group was fed a MgD + PGH diet (5% PGH) for 8 weeks. At the end of the study, BMD and intrinsic biomechanical properties of the femur were measured., Results: The MgD group showed significantly lower Young's modulus, an intrinsic biomechanical property, and trabecular BMD of the femur than the normal group; however, the MgD diet did not affect cortical BMD and cortical thickness. Both the FGH and the PGH groups showed significantly higher cortical thickness and ultimate displacement of the femur than the normal group, but neither type of gelatin hydrolysate affected Young's modulus. Furthermore, the FGH group, but not the PGH group, showed significantly higher trabecular BMD than the MgD group., Conclusions: This study indicates that FGH and PGH increase cortical thickness but only FGH prevents the decrease in trabecular BMD seen in Mg-deficient rats, while neither type of gelatin hydrolysate affect intrinsic biomechanical properties.

Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state; however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-α, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-α and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly; therefore, nanoformulations should be optimized before extending studies into the in vivo environment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Human intestinal microbiota are influenced by various factors viz. diet, environment, age, gender, geographical, and socioeconomic situation, etc. among which diet has the most profound impact. However, studies investigating this impact have mostly included subjects from diverse geographic/socioeconomic backgrounds and hence the precise effects of dietary factors on gut microbiota composition remain largely confounded. Herein, with an aim to evaluate the association between dietary habits, specifically yogurt consumption, and the gut microbiota in healthy young adults sharing similar age, lifestyle routine, geographical setting, etc., we conducted a cross-sectional study wherein 293 collegiate freshmen answered a questionnaire about their frequency of yogurt consumption over the last 2 months and provided stool specimens for microbiota analysis. Fecal microbiota were analyzed by highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial 16S rRNA molecules. Fecal organic acids were measured by HPLC. Overall, the gut microbiota were predominated (97.1 ± 8.6%) by Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium and Atopobium cluster. Interestingly, after adjusting the data for yogurt consumption, females were found to have higher total bacterial ( P = 0.013) and Bifidobacterium ( P = 0.046) count and fecal pH ( P = 0.007) and lower fecal concentration of total organic acids ( P = 0.030), succinic acid ( P = 0.007) and formic acid ( P = 0.046) as compared to males. Altogether, yogurt consumption showed positive linear association with Lactobacillus and Lactobacillus gasseri subgroup in both male and female subjects; however, several gender-specific disparities were also detected in this yogurt-microbiota association. Yogurt consumption demonstrated a negative association with L. sakei subgroup, Enterobacteriaceae and Staphylococcus in males but shared a positive association with L. casei subgroup and succinic acid in female subjects. The study manifests the association between yogurt consumption and gut microbiota in a healthy homogeneous cohort and show how this association can differ by host gender. The findings should be helpful for prospective studies investigating the diet-microbiome interaction in human health and disease.

Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.

Medication-related osteonecrosis of the jaw (MRONJ) is developed even in the patients who are edentulous and treated with short-term bisphosphonate therapy and oral administration. It sometimes causes lethal sepsis in patients who have multiple health problems such as diabetes, cirrhosis, steroid use for interstitial pneumonia, sepsis, and spinal disk herniation.

Objectives: Ease of denture cleaning is of paramount importance in geriatric patients and those with limited dexterity. We have previously investigated methods of coating dentures with titanium dioxide (TiO 2 ) and reported the effects (self-cleaning and antibacterial) of such treatments in in vitro studies. This study was to verify the biocompatibility of a TiO 2 -coated acrylic resin produced by the new coating method with spray-coating technique., Methods: Specimens were prepared from denture base acrylic resin and polished up to grit #1000. The TiO 2 -coating agent was sprayed onto the specimens using an airbrush gun. Specimens were then divided into 'polymethyl methacrylate (PMMA)', 'primer-coated PMMA' and 'TiO 2 -coated PMMA' groups to be evaluated for biological safety using a hamster oral mucosa irritation test, a guinea pig skin sensitisation test and a rabbit intracutaneous test. The biological reaction was scored., Results: Reaction scores were considerably <1.0, the acceptable limit set by the ISO, in all three tests. Indeed, in most samples, there was no deleterious effect at all., Conclusion: These results tested on animals demonstrate that denture base resin coated with TiO 2 by this method does not cause irritation or sensitisation of the oral mucosa, skin or intracutaneous tissue and is therefore good biocompatibility for use in close proximity to oral mucosa and skin., (© 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.)

Background: Krill oil is an edible oil extracted from krill, a small red-colored crustacean found in the Antarctic Ocean. The administration of krill oil is reported to mitigate inflammation in patients with cardiac disease, rheumatoid arthritis, or osteoarthritis. However, the effect of krill oil on mild knee pain has not yet been determined., Objective: To assess the effect of krill oil on mild knee pain., Design: A randomized, double-blind, parallel-group, placebo-controlled trial of fifty adults (38-85 years old) with mild knee pain attending the Fukushima Orthopedic Clinic (Tochigi, Japan) between September 2014 and March 2015., Interventions: Participants were randomized to receive 2 g per day of either krill oil or an identical placebo for 30 days., Outcomes: The primary outcome was improvement in subjective symptoms of knee pain as assessed by the Japanese Knee Osteoarthritis Measure (JKOM) and Japanese Orthopaedic Association score (JOA). Secondary outcomes included blood and urine biochemical parameters., Results: Both the placebo and krill oil groups showed significant improvements in the questions in the JKOM and JOA questionnaires after administration. After the intervention, krill oil group showed more improvements than placebo group in two questions regarding the pain and stiffness in knees in JKOM. Controlling for age, sex, weight, and smoking and drinking habits, krill oil significantly mitigated knee pain in sleeping (P < 0.001), standing (P < 0.001) and the range of motion of both right and left knees (both P = 0.011) compared to placebo. Krill oil administration raised plasma EPA (P = 0.048) and EPA/AA ratio (P = 0.003)., Conclusion: This study indicates that krill oil administration (2 g/day, 30 days) improved the subjective symptoms of knee pain in adults with mild knee pain., Trial Registration: UMIN-CTR; ID UMIN000014413., Competing Interests: This study was funded by Sunsho Pharmaceutical Co., Ltd. (Fuji, Shizuoka, Japan). This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the authors was employed by the funder, gave consultancy to the funder, obtained patents with the funder, or developed or marketed products for the funder. This work was also supported by the Grant of Cross-Ministerial Strategic Innovation Promotion Program (SIP). The authors have declared that no competing interests exist.

Objective: It is sometimes difficult to determine during the preoperative period whether patients have oral infections; these patients need treatment to prevent oral infection-related complications from arising during medical therapies, such as cancer therapy and surgery. One of the reasons for this difficulty is that basic medical tests do not identify oral infections, including periodontitis and periapical periodontitis. In this report, we investigated the potential of positron emission tomography/computerized tomography (PET/CT) as a diagnostic tool in these patients., Study Design: We evaluated eight patients during the preoperative period. All patients underwent PET/CT scanning and were identified as having the signs of oral infection, as evidenced by (18)F-fludeoxyglucose (FDG) localization in the oral regions. Periodontal examination and orthopantomogram evaluation showed severe infection or bone resorption in the oral regions., Results: (18)F-FDG was localized in oral lesions, such as severe periodontitis, apical periodontitis, and pericoronitis of the third molar. The densities of (18)F-FDG were proportional to the degree of inflammation., Conclusions: PET/CT is a potential diagnostic tool for oral infections. It may be particularly useful in patients during preoperative staging, as they frequently undergo scanning at this time, and those identified as having oral infections at this time require treatment before cancer therapy or surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We synthesized a novel cyclooctyne-based clickable fluorescent probe with versatile properties such as high cell-membrane permeability and free diffusibility in the cell. Our probe "FC-DBCO" was conjugated to an azide-modified mannose via a Cu-free click reaction in living HeLa cells and displayed intracellular specific fluorescence imaging with low background signals.

The 14-helix structure of oligo-β-peptides was significantly stabilized by direct attachment of CF3 groups to their backbones. Our studies indicate that this stabilization originates from the CF3-promoted increase in the intramolecular hydrogen-bonding ability of their backbone amides, leading to a novel strategy to stabilize peptide folding.

Acute promyelocytic leukemia (APL) is characterized by the occurrence of translocations between chromosomes 15 and 17, resulting in generation of a fusion protein of promyelocytic leukemia (PML) and retinoid A receptor (RAR) α. APL cells are unable to differentiate into mature granulocytes since PML-RARα functions as a strong transcriptional repressor for a gene involved in granulocyte differentiation. All-trans retinoic acid (ATRA) is the first agent that has been developed to target specific disease-causing molecules, i.e., ATRA suppresses abnormal functions of oncogenic proteins. Moreover, ATRA facilitates the differentiation of APL cells toward mature granulocytes by changing epigenetic modifiers from corepressor complexes to co-activator complexes on target genes after binding to the ligand-binding domain at the RARα moiety of the PML-RARα oncoprotein. On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARα protein, causing oxidation and multimerization. ATO enhances the conjugation of small ubiquitin-like modifiers to PML-RARα, followed by ubiquitination and degradation, relieving the genes associated with granulocytic differentiation from suppressive restraint by the oncoprotein. Recent clinical studies have demonstrated that combination therapy with both ATRA and ATO is useful to achieve remission.

Wheat gluten hydrolysate (WGH) is a food ingredient, prepared by partial enzymatic digestion of wheat gluten, which has been reported to suppress exercise-induced elevation of serum creatinine kinase (CK) activity. However, its effects on athletic performance have not yet been elucidated. This is the presentation of an experiment performed on five female college triathletes who completed an Olympic distance triathlon with or without ingestion of 21 g of WGH during the cycling leg. The experiment was performed in a crossover double-blind manner. The race time of the running leg and thus the total race time was significantly shorter when WGH was ingested. However, serum CK levels exhibited no apparent differences between the two WGH or placebo groups.

Hydrogen peroxide acts as a signaling molecule mediating the acquisition of tolerance to both biotic and abiotic stresses. Identification of marker genes for H2O2 response could help to intercept the signaling network of stress response of plants. Here, we describe application of marker genes for H2O2 responses to monitoring several abiotic stress responses. Arabidopsis plants were treated with UV-B, high light, and cold stresses, where involvement of H2O2-mediated signaling is known or suggested. Monitoring of these stress responses with molecular markers using quantitative real-time RT-PCR can detect landmark events in the sequential stress responses. These methods can be used for analysis of mutants and transgenic plants to examine natural H2O2 responses that are involved in environmental adaptation., (Copyright © 2013 Elsevier Inc. All rights reserved.)