Transforming Teachers’ Attitudes through Experiential Learning in Laos -BENGALA dying workshops and the experience with local teachers-

　ラオスの学校制度は, 初等教育全般において「体験型学習の提供」を求めている。実技教科では体験型の授業が実践されているが, それ以外の教科では座学中心の授業である。その背景には, 体験型学習の行い方がわからないといった教員の課題意識がある。本研究では, 特に教員の授業づくりに対する課題意識を引き受け, ラオスにおいて体験型学習を協働実践し教員意識の変容を明らかにすることとした。具体的には, ラオスの小中学校２校で,体育の授業で使うT シャツをベンガラ染めする体験型学習を行った。教員にも参加してもらいながら, 体験型学習を経験すると同時に協働実践することで, どのように意識が変容するかを検証した。検証方法は, 実践校２校の教員に対する半構造化インタビューである。その結果, 教員らは体験型学習の可能性を理解した一方, 座学中心の授業から体験型学習へ転換の方法がわからないという意見もあり, 今後の課題となった。The Lao school system calls for the "provision of experiential learning" in all aspects of primary education. However, while hands-on learning is practiced in practical subjects, other subjects remain classroom-based. One of the reasons for this is the teachers' awareness that they do not know how to conduct hands-on learning. In this PBL, we took on the problem consciousness of Laotian teachers in particular regarding class creation and clarified how teachers' consciousness would change through the collaborative implementation of experiential learning in Laos. Specifically, we conducted hands-on workshops at two elementary schools in Laos to dye T-shirts for physical education classes as part of the emotional education program. Teachers were also invited to participate in the bengara-dyeing workshop, and we examined how their awareness was changed through the experience of hands-on learning and collaborative practice. Semi-structured interviews were conducted with teachers at the two schools where the workshop was conducted. The results showed that the teachers viewed the workshop positively in regarding the interaction with foreign visitors and enjoyment and fun through learning. While they understood the potential of experiential learning, some of them did not know how to convert their classroom-based courses to include this form of experiential learning, which is an issue to be addressed in the future

Fabrication and Physical Evaluation of Gelatin-Coated Carbonate Apatite Foam

Carbonate apatite (CO3Ap) foam has gained much attention in recent years because of its ability to rapidly replace bone. However, its mechanical strength is extremely low for clinical use. In this study, to understand the potential of gelatin-reinforced CO3Ap foam for bone replacement, CO3Ap foam was reinforced with gelatin and the resulting physical characteristics were evaluated. The mechanical strength increased significantly with the gelatin reinforcement. The compressive strength of gelatin-free CO3Ap foam was 74 kPa whereas that of the gelatin-reinforced CO3Ap foam, fabricated using 30 mass % gelatin solution, was approximately 3 MPa. Heat treatment for crosslinking gelatin had little effect on the mechanical strength of the foam. The gelatin-reinforced foam did not maintain its shape when immersed in a saline solution as this promoted swelling of the gelatin; however, in the same conditions, the heat-treated gelatin-reinforced foam proved to be stable. It is concluded, therefore, that heat treatment is the key to the fabrication of stable gelatin-reinforced CO3Ap foam

ANTITUMOUR EFFECT OF VALPROIC ACID AGAINST SALIVARY GLAND CANCER

Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time-and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC

BORTEZOMIB-ENHANCED RADIOSENSITIZATION IN HUMAN ORAL CANCER CELLS

Oral cancer cells have a significantly augmented nuclear factor-κB (NF-κB) activity and the inhibition of this activity suppresses tumor growth. Bortezomib is a proteasome inhibitor and a drug used for molecular-targeted therapy (targets NF-κB). In this study, we investigated whether bortezomib would be effective as an inhibitor of proliferation and a radiosensitizer for the treatment of oral cancer. We demonstrate that bortezomib inhibits NF-κB activity and cell proliferation. The combined treatment with bortezomib and radiation (RT) suppressed NF-κB activity and cell growth in vitro and in vivo compared with RT treatment alone. To investigate the mechanisms by which bortezomib suppresses tumor growth, the expression of signaling molecules downstream of NF-κB were examined by ELISA. The combined treatment significantly inhibited the radiation‑induced production of angiogenic factors and decreased the number of blood vessels in the tumor tissues. Although the expression of anti‑apoptotic proteins was upregulated by RT, bortezomib downregulated the RT-induced expression of these proteins. Moreover, the expression of cleaved poly(ADP‑ribose) polymerase in vitro and in vivo was enhanced by bortezomib, indicating that bortezomib inhibits tumor growth by inducing apoptosis. This study clearly demonstrates that bortezomib significantly inhibits tumor growth and that the combined treatment with bortezomib and RT results in a significant inhibition of tumor growth. The mechanisms underlying the inhibition of tumor growth by bortezomib include the suppression of angiogenesis and the induction of apoptosis. A novel molecular targeting therapy including bortezomib may be effective in the treatment of oral cancer by suppressing NF-κB activity

Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report

Background The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism. Case presentation A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism. Conclusion All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed

ANTI-TUMOR EFFICACY OF DOCETAXEL AND 5-FLUOROURACIL

Docetaxel (DOC) and 5-fluorouracil (5-FU) are important anticancer agents widely used in the treatment of a variety of cancers including oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the antitumor efficacy of the sequential administration of DOC and 5-FU against OSCC cells (B88 and CAL27 cells) in vitro and in vivo. In in vitro growth inhibition assays, sequential treatment with DOC followed by 5-FU was more effective in inhibiting cancer cell growth than 5-FU followed by DOC, single treatment with DOC or 5-FU, or combined treatment with DOC and 5-FU. Furthermore, DOC followed by 5-FU significantly inhibited tumor growth in vivo compared to 5-FU followed by DOC. To understand the mechanisms underlying the enhanced growth inhibitory effect of the administration sequence, DOC followed by 5-FU, we examined the expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), which were known to regulate the antitumor effect of 5-FU, by real-time RT-PCR and western blot analysis. Downregulation of TS and DPD expression and upregulation of OPRT expression were induced by DOC treatment, suggesting that DOC enhanced the efficacy of 5-FU by altering the expression of its metabolic enzymes. These results indicate that sequential treatment with DOC followed by 5-FU could be a promising therapeutic strategy for oral cancer

Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism

IntroductionWhile it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. Methods Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. Results Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average Delta eGFR of -41.1 mL/min/1.73 m(2)) and an increase in eGFR in hypothyroidism (an average Delta eGFR of 7.1 mL/min/1.73 m(2)). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for Delta eGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. Conclusions We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism

Selective mono-acylation of 1,2-and 1,3-diols using (α,α-difluoroalkyl)amines

In the reaction of N,N-diethyl-α,α-difluorobenzylamine (DFBA) with 1,2- or 1,3-diols, selective mono-benzoylation occurs to afford mono-esters of the diols in good yield. The reaction is completed under mild conditions in a short reaction time. Further, prim-, sec-, and tert-diols and catechol can be converted to the corresponding mono-benzoates. DFBA is used for the protection of the hydroxy group in sugars. The selective mono-nicotinylation, formylation and pivaloylation of diols are also performed by using the corresponding difluoroalkylamines