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Bone-modifying agents (BMAs) are indispensable to cancer therapy. However, the number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing according to the BMA administration. Oral factors predisposing to development of MRONJ are receiving attention, and oral management is recommended for prevention of MRONJ; however, the strategy and criteria have not yet been established. Therefore, we investigated the oral risk factors associated with MRONJ development in this study. A retrospective study was carried out on 398 cancer patients who had received oncological-dose BMAs between 2007 and 2018; general health factors, demographic, and dental factors were examined along with MRONJ development in all the patients. The cumulative occurrence rate of MRONJ was calculated using a Kaplan–Meier analysis. Clinical factors were analyzed using the Cox regression analysis. MRONJ occurred in 42 of the 398 patients. The cumulative MRONJ incidence rates were 4.5, 12.9, 17.7, and 21.6% at 1, 2, 3, and 4 years, respectively. Age (p = 0.038), male sex (p = 0.002), initiation of dental interventions before BMA administration (p = 0.020), alveolar bone loss involving more than half the root (p

High-dose bone–modifying agents (BMAs), such as bisphosphonates and denosumab, are essential for the treatment of cancer patients with bone metastases. The incidence of medication-related osteonecrosis of the jaw (MRONJ) is increasing. Inflammatory dental diseases could lead to MRONJ, and hence, they should be managed appropriately. Tooth extractions are commonly advised to prevent dental inflammation; however, the accurate indications for tooth extractions before starting BMA therapy have not been established. Hence, we assessed teeth with inflammatory dental diseases to identify indicators for prophylactic extraction before starting BMA therapy. We included 745 teeth with inflammatory dental diseases of 212 cancer patients on high-dose BMA therapy. We assessed the relationship between inflammatory dental disease and risk of MRONJ development. Multivariate Cox regression analysis was used for statistical analysis. The cumulative occurrence rate of MRONJ was calculated using the Kaplan–Meier method. MRONJ occurred in 43 of 745 teeth. Teeth characteristics significantly correlated with MRONJ occurrence were mandible (p = 0.009), molar region (p = 0.005), radiopaque changes in bone surrounding the root on orthopantograms obtained at patients’ first visits (p < 0.001), and tooth extractions after starting BMA therapy (p < 0.001). Radiopaque changes in bone surrounding the root are an important radiographic finding that indicates the need for prophylactic tooth extractions before starting BMA therapy. Our results suggest that the prophylactic extraction of teeth with radiopaque changes in bone surrounding the root before starting BMA therapy could prevent the onset of MRONJ.

Postoperative pneumonia is one of the major complications after esophageal cancer surgery. The risk factors associated with postoperative pneumonia are poor general health, smoking, decreased pulmonary function, diabetes mellitus, surgical stress, old age, postoperative aspiration, and oral hygiene. In this study, we examined the effect of perioperative oral care on reducing postoperative pneumonia since the evidence to-date is not clear. A multicenter, retrospective investigation of the relationship between perioperative oral care and incidence of postoperative pneumonia in patients undergoing esophageal cancer surgery was conducted. A total of 775 patients who underwent thoracoscopic esophageal resection at 25 hospitals between 2016 and 2017 were enrolled in the study. Various factors were examined for correlation with development of postoperative pneumonia. Multivariate analysis showed that old age, smoking habit, lower hemoglobin, higher creatinine, postoperative dysphagia, and lack of oral care intervention were independent risk factors for pneumonia. Oral care was more effective in preventing pneumonia in hospitals in which the incidence of postoperative pneumonia was lower than 20%, while it was not effective in hospitals in which the incidence was higher than 20%. Results of the study suggest that it is recommended to carry out perioperative oral care in esophageal cancer surgery.

In this rapidly changing society, it has been widely acknowledged that education needs to happen continuously, lifelong and lifewide. The concept of lifelong learning is well established and the need for learning at many intervals throughout one’s life is well recognized. Lifewide learning refers to the learning which takes place in a variety of different environments and situations covering formal, non-formal, and informal learning. Ideally learning for an individual should be holistic, not separating different contexts of his/her life. Learning can occur at many different places including schools, homes, communities, workplaces, and public places, but often times individuals lack awareness of their own learning when it comes to learning outside of formal schooling. In this age of open educational resources (OER) and massive open online courses (MOOCs), the materials for learning are ubiquitous and knowledge access is easy. Potentials for linking informal or non-formal learning to formal learning have become salient. However, the means to assess and visualize one’s own lifewide and lifelong learning paths organizing all those learning resources are rarely discussed. With the current tremendous power of cloud computing, digital storage and mobile devices, technologies afford us to keep all the personal learning records throughout our lives as well as across different contexts of our lives. These technologies also give the possibility of integrating and visualizing all the disparate learning and recognizing it throughout one’s life. This paper discusses potentials of the technologies to assist actualizing the vision.

Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin-eosin staining and immunohistochemistry with protein-gene product 9.5.In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg(-1) day(-1) S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2-20 mg kg(-1) day(-1) were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg(-1) day(-1) corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT.The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine.Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.

A case of metastatic sarcomatoid renal cell carcinoma to the mandible treated with Sorafenib is reported. A 76-year-old man consulted us for hyposthesia of the right lower lip. Panorama X-ray film showed a ra-diolucent lesion in the right mandibular body. A diagnosis of metastatic tumor to the mandible from the left kidney was made after evaluation by computed tomography and positron emission tomography, which also revealed multiple bone metastases. After radiotherapy for mandibular and thoracic lesions, nephrectomy was performed. Histological diagnosis was sarcomatoid renal cell carcinoma. Interferon therapy was performed but was not effective; therefore, a molecular targeted drug, Sorafenib, was administered. Sorafenib effectively inhibited the growth of oral and other metastatic lesions for 10 months. Quality of life was relatively well maintained with tolerable adverse effects. The patient survived for as long as 2 years after appearance of the first symptom.

Background: Large amounts of unusual bile acids are synthesized by the fetal liver in late gestation. These compounds are mostly transferred from fetus to mother, although some are excreted into the amniotic fluid. We investigated the role of placental transfer of bile acids in fetal bile acid metabolism, particularly with respect to the unusual bile acids (1β-hydroxylated and ketonic bile acids). Methods: We measured concentrations of bile acids in umbilical cord blood and urine of newborn infants, and in perinatal maternal serum and urine, using gas chromatography-mass spectrometry. Serum and urine specimens from healthy non-pregnant women were used as controls. Results: In newborn infants at delivery, cord blood and urine contained mostly primary and 1β-hydroxylated bile acids, respectively. We also detected large amounts of ketonic bile acids in their urine, and the urinary concentration of total bile acids was elevated. Main maternal bile acids at 30 and 35 weeks of gestation and at delivery were 1β-hydroxylated bile acids. After delivery, main bile acids changed from 1β-hydroxylated bile acids to primary bile acids (P < 0.03), which also predominated in healthy non-pregnant women. Conclusion: Fetally synthesized unusual bile acids were transported from fetus to mother. Pregnant women appear to excrete these bile acids into the urine, lowering both fetal and maternal serum bile acid concentrations.

口腔癌では，初回治療後から再発や転移がなく5年以上経過すれば臨床的に治癒したとみなされる。治療成績も5年生存率で検討されることが多いが，5年以上の経過後に再発する症例もみられる。我々は，根治手術をおこなった進行口腔扁平上皮癌症例の治療成績および経過観察の期間と再発時期との関連について検討を行った。対象は1994年11月から2004年10月までに経験した口腔扁平上皮癌症例312例のうち，Stage III・IVの進行癌で，Stage IIIが76例，Stage IVが40例であり，平均年齢は63.0歳であった。10年累積生存率は77.8%であった。原発巣累積再発率は10年で20.1%であり，頸部累積再発率は10年で12.9%であった。局所再発率は2年で19.0%と最も高く，5年以降で3.4%であった。5年以上経過した症例においても再発症例が存在することから，長期の経過観察の必要性が示唆された。

In this study, a questionnaire on learning preferences was administered to students who were enrolled in e-learning courses offered by the collaborative project among several higher education institutions and we extracted factors in learning preferences. A strong correlation between the factor loadings (the preference for asynchronous learning and the one for the use of ICT) and the adaptability to e-learning courses was found. As a result of multiple regression analyses, it was found that, to some extent, we could predict the student's adaptability to an e-learning course by measuring his/her preferences for asynchronous learning and the use of ICT. Furthermore, based on these analyses, the paper discusses an effective e-learning system that offers learning courses and learning objects that are suitable for particular students.

本稿では、学習支援員（チューター）制度が、効果的な遠隔教育プログラムの提供に欠かせないものであると考える。様々な学習支援員制度が様々な遠隔教育プログラムで採用されている。本稿では、まず、英国、米国、メキシコ、韓国、ドイツ、オランダ、スペイン、ギリシャの11の遠隔教育大学における学習支援制度を、（1）チューターの役割、（2）チューターの管理体制、（3）チューターと学生のコミュニケーション手段、の3つの観点からまとめる。最後に、学生・教員・教材・チューターの4要素の関係性から学習支援員制度の4つのモデルを提示する。

Background Bile acid metabolism in preterm infants is yet to be fully characterized. We compared the developmental pattern of urinary bile acid profiles in ten infants born at gestational ages from 25 to 33 weeks with previous data from full-term infants from birth to about 7 months of age. Methods Gas chromatography-mass spectrometry was performed on serial samples. Results Total urinary bile acid concentrations gradually increased until 1 to 2 months of age. After this peak of excretion (30 to 60 micromol/mmol creatinine), total urinary bile acid concentrations gradually decreased to less than 20 micromol/mmol creatinine. The percentage of usual bile acids (mainly cholic acid) relative to total urinary total bile acids gradually deceased from approximately 30% at birth to less than 15% at 7 months of age. On the other hand, 1beta-hydroxylated bile acids (mainly 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acid) relative to total urinary bile acids were increased gradually from 60% at birth to reach 70% to 80% at 1 month of age. The percentage of 1beta-hydroxylated bile acids relative to total urinary bile acids then remained stable at a high percentage (70% to 90%) until the age of 7 months. Conclusion Physiological cholestasis in preterm infants persists longer than in full-term infants. Moreover, as large amounts of cholic and 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acids were detected in urine from preterm infants during this study, the 25-hydroxylation pathway may be particularly important for bile acid synthesis in early preterm infants.

WOS: 000257550200004, Japan and Korea have highly developed information and communications technology infrastructures and have recently reformed their higher education systems and encouraged e-transformation. However, Japanese universities have not embraced e-learning as wholeheartedly as their Korean counterparts. The paper concludes that this is due to governmental and institutional failure to develop a cogent vision and strategic plan for e-learning, to recognise the need for fundamental shifts in organisational cultures and structures and pedagogy and to provide training, funding, recognition and reward for such development. It attributes this to differences in the cultural perspectives, values and customs of the two countries' policy makers, managers and faculty members. The findings are seen to hold important lessons for other countries embarking on e-transformation.

We report a case of glandular odontogenic cyst (GOC) arising in the mandible. The patient was a 55-year-old woman who presented with a painful swelling of the right premolar region of the mandible.Roentgenographic examination revealed a multilocular radiolucent lesion from the right first molar across themidline to the left second premolar region. The clinical diagnosis was a mandibular cyst. Enucleation of the cystand extraction of the teeth were performed with the patient under general anesthesia. Histological examinationshowed a multicystic lesion partially lined by non-keratinized epithelium with focal plaque-like thickening. Thesurface epithelium included eosinophilic cuboidal and ciliated cells. Cyst-like spaces and glandular structureswere also observed within the epithelium. Epithelial islands were also seen in connective tissue of the cyst.Immunohistochemically, epithelial cells were strongly positive for cytokeratin (CK) 13 and 19, but almost negativefor CK18. The histological diagnosis was GOC. The postoperative course was satisfactory, and no recurrencehas been noted 4 years 6 months after the operation.

An odontoma is an odontogenic, tumor composed of enamel, dentine, and cementum, commonly less than 30 mm in diameter. We describe a large compound odontoma arising in the left anterior region of the mandible.A 16-year-old boy was referred by an orthopedist to our hospital for evaluation of a radiopaque lesion in the left side of the mandible. Clinical examination revealed a bony-hard swelling in the left anterior region of the mandible at presentation. The left mandibular canine and lateral incisor were not erupted. Radiographic and CT examinations showed a large, circumscribed, radiopaque lesion, measuring 30×40×28mm and surrounded by a thin radiolucent area accompanied by two impacted teeth. There were many small tooth-like structures within the lesion. The clinical diagnosis was odontoma. The tumor and the impacted teeth were surgically removed by an intraoral approach under general anesthesia. The tumor was covered by a thin capsule and consisted of 321 small tooth-like structures. The histopathological diagnosis was a compound odontoma. The clinical course has been uneventful for 4 years 3 months after surgery.

In recent years, the curability of oral cancers has increased because of improvements in cancer treatments, including radiotherapy, surgery, and chemotherapy. However, these treatments frequently cause dental and oral adverse events, including oral dysfunction, mucositis, salivary dysfunction, rampant dental caries, and osteonecrosis of jaws. Such dental and oral adverse events do not only lead to patient discomfort but also to decreased overall survival rate of patients owing to the required change of treatment regimen. Further, patients’ quality of life is negatively influenced because of pain and oral dysfunction, along with concerns regarding adverse events and recurrence of cancer following cancer treatment. Therefore, the prevention and alleviation of such adverse events is paramount in maintaining oral health of patients with oral cancer. This chapter outlines planning and management procedures required to maintain an oral cancer patient’s oral health.

We previously reported that mice lacking bombesin receptor subtype-3 (BRS-3) exhibit mild late-onset obesity and glucose intolerance [Nature 390 (1997) 160]. To examine the mechanism by which glucose intolerance is developed in these mice, we studied insulin release and proinsulin biosynthesis in isolated pancreatic islets and glucose uptake and facilitative glucose transporter (GLUT)-4 translocation in adipose tissues. Although islet insulin contents and the size and number of islets of Langerhans in BRS-3-deficient mice decreased, there was no difference in glucose-stimulated insulin release and proinsulin biosynthesis between BRS-3-deficient and wild-type control mice. In contrast, adipose tissues exhibited a marked difference: the uptake of [ 14 C]2-deoxy- d -glucose by adipocytes isolated from BRS-3-deficient mice was not stimulated by 10 −7 M insulin addition, and membrane fractionation analysis showed that GLUT4 was barely detected in the fraction of plasma membrane in BRS-3-deficient mice in the presence of 10 −7 M insulin. Quantitative reverse transcription-PCR (RT-PCR) showed that mRNA levels of GLUT4, insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2, syntaxin 4, SNAP23, and VAMP-2 in adipose tissues of BRS-3-deficient mice were unchanged compared with those in wild-type control mice. We concluded that impaired glucose metabolism observed in BRS-3-deficient mice was mainly caused by impaired GLUT4 translocation in adipocytes.

Relationships between the distribution of fungal sclerotium grains and soil chemical properties were studied in forest soils of Podsole, Braunfahlerde, and Braunerde-Podsoles in Harz Mts., Germany. Development of sclerotium grains ns was dominant in surface horizons (Ah, E horizons) within a 10-cm depth and weight density of grains ranged from 0.01 to 4.99 g kg-1 soil. The SEMI-EDX analysis proved that the weight percentage (excluding C and N) of Al2O3 was 39.8–63.9% inside the grains. The content of elgosterol, a biomarker of viable fungal biomes, showed good correlations with weight density of sclerotium grains in grain-detected soils. The sclerotium. grains were likely to be formed in soils with high ratios (>0.6) of organic bonding Al (Alp) to amorphous Al (Alo), and with high contents of exchangeable Al (Al3+) (>0.54 g kg-1). The content and state of active Al were believed to be responsible for the development of sclerotium because sclerotium grains were not detected in acid soils which had...

Neurotensin (NT) is a neuropeptide that induces a wide range of biological activities including hypothermia and analgesia. Such effects are mediated by the NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in specific NT functions remains unknown. To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM). The mutant and control mice were subjected to the examination of thermal nociception, and in the hot plate test, a significant alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1-deficient or wild-type control mice. Latencies of tail flick and hind paw licking of the mutant mice were not affected compared to control mice. These results suggest that Ntsr2 has an important role in thermal nociception compared to Ntsr1, and that these mutant mice may represent a useful tool for the development of analgesic drugs.

Cell phones are a pervasive new communication technology, especially among college students. This paper examines college students' cell phone usage from a behavioral and psychological perspective. Utilizing both qualitative (focus groups) and quantitative (survey) approaches, the study suggests these individuals use the devices for a variety of purposes: to help them feel safe, for financial benefits, to manage time efficiently, to keep in touch with friends and family members, et al. The degree to which the individuals are dependent on the cell phones and what they view as the negatives of their utilization are also examined. The findings suggest people have various feelings and attitudes toward cell phone usage. This study serves as a foundation on which future studies will be built.

Rat cytokine-induced neutrophil chemoattractants (CINCs), which belong to the interleukin-8 family, are known to be induced by treatment with lipopolysaccharide (LPS). Recently, CINCs were grouped into four subtypes-CINC-1, CINC-2alpha, CINC-2beta, and CINC-3-and CINC-1 was considered to be a major isoform among the four CINCs in LPS-induced acute lung inflammation in rats. The purpose of this study was to investigate the change in location of CINCs with chronic inflammation induced by experimental pulmonary silicosis. Administration of silica particles induced lung granulomas. Immunohistochemical staining for CINCs showed that the number of cells positive for CINC-2alpha, CINC-2beta, and CINC-3 was increased, peaking at 1 day after treatment with silica particles, whereas CINC-1 was almost undetectable. We suggest that CINC-2alpha, CINC-2beta, and CINC-3 are the most important chemoattractants in the formation of granulomas in chronic inflammation.