Median alveolar cleft and palatal mass without a median upper cleft lip

Median cleft is rare among facial clefts, including bilateral and unilateral clefts. Median upper cleft lip and median alveolar cleft correspond to Type 14 and Type 0, respectively, in Tessier's classification system. Some authors have reported surgical procedures for median cleft. In the case of median alveolar cleft, bone grafting to the cleft side and orthodontics are generally applied, similarly to bilateral or unilateral cleft. Median alveolar cleft is usually accompanied by median upper cleft lip, the degree of which differs in each case. The symptoms include, but are not limited to, median lip defect, wide philtrum, and vermilion notch. However, an isolated alveolar cleft is extremely rare. We encountered a patient with an isolated alveolar cleft who did not have a light median upper cleft lip, such as a wide philtrum or vermilion notch. We herein report this case and describe its treatment

Efficacy, tolerability and safety of once-monthly administration of 75mg risedronate in Japanese patients with involutional osteoporosis: A comparison with a 2.5mg once-daily dosage regimen

AbstractOral risedronate has been shown to be effective in the treatment of osteoporosis when administered once-daily or once-weekly in Japan. This randomized, double-blind, multicenter 12-month study was conducted to compare the efficacy and tolerability of oral risedronate 75mg once-monthly with 2.5mg once-daily in Japanese patients with involutional osteoporosis. Bone mineral density (BMD), biochemical markers of bone metabolism, fractures, and adverse events (AEs) were evaluated. At the end of the study (Month 12, last observation carried forward [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L2–L4) BMD, measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 5.69 (4.00)% in the 2.5mg once-daily group (n=428), and 5.98 (4.54)% in the 75mg once-monthly group (n=422). In the non-inferiority t-test (non-inferiority margin Δ=1.5%), the 75mg once-monthly group was non-inferior to the 2.5mg once-daily group (p<0.0001). The difference between treatment groups was 0.28% (95% CI, −0.31% to 0.88%). Changes in biochemical markers of bone metabolism were generally comparable in the two groups, although decreases in the percent change from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 2.5mg once-daily group than the 75mg once-monthly group. The frequency of new vertebral fractures (including aggravation of prevalent fractures) at the end of the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5mg once-daily group and 1.3% in the 75mg once-monthly group.The incidence of mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5mg once-daily group and 77.7%/8.1%/0.7% in the 75mg once-monthly group. AEs associated with gastrointestinal symptoms occurred in approximately 30% of subjects in each group but with no severe cases. AEs potentially associated with acute phase reaction (including symptoms of influenza-like illness or pyrexia starting within 3days of the first dose of the study drug and with a duration of 7days or less) only occurred in the 75mg once-monthly group (2.1%, 9/422 subjects; influenza-like symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low without any severe cases.In conclusion, risedronate 75mg once-monthly (a dosage which is 30 times higher than risedronate 2.5mg once-daily) had non-inferior efficacy in terms of BMD and was similarly well tolerated compared to the once-daily regimen in Japanese patients with involutional osteoporosis. Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of risedronate 75mg was half that used outside Japan (150mg)

Nanocomposite of silk fibroin nanofiber and montmorillonite: Fabrication and morphology

The purpose of our research is creating a new nanocomposite material. Generally silk fibroin (SF) is regarded as a promising base material for biomedical uses. The incorporation of montmorillonite (MMT) into SF fibers would improve physical properties of the SF fibers. We investigated a new method of combining electospun SF with MMT. Specifically, electrospun silk nanofibers were treated with methanol and dipped in a MMT suspension. We could obtain a nanosheet composite of silk nanofibers and MMT. Their ultrastructures were successfully visualized by high resolution transmission electron microscopy. This compound was comprised of individual silk nanofibers surrounded by thin layers of MMT, each with a thickness of about 1.2 nm. This structure was confirmed by elemental analysis. We also performed IR, NMR and X-ray diffraction analyses in conjunction with morphological data. Conclusively we obtained a new composite of silk nanofiber and MMT, which has never been reported. Using this unique nanocomposite biological tests of its application for a scaffold for tissue engineering are under way.ArticleINTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. 57:124-128 (2013)journal articl

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression

Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin

プロドラッグ型クルクミン注射製剤の抗腫瘍効果及び治療標的の包括的な解析 --安全性の高い抗がん薬としての開発に期待--. 京都大学プレスリリース. 2022-10-21.Curcumin (aglycone curcumin) has antitumor properties in a variety of malignancies via the alteration of multiple cancer-related biological pathways; however, its clinical application has been hampered due to its poor bioavailability. To overcome this limitation, we have developed a synthesized curcumin β-D-glucuronide sodium salt (TBP1901), a prodrug form of aglycone curcumin. In this study, we aimed to clarify the pharmacologic characteristics of TBP1901. In β-glucuronidase (GUSB)-proficient mice, both curcumin β-D-glucuronide and its active metabolite, aglycone curcumin, were detected in the blood after TBP1901 injection, whereas only curcumin β-D-glucuronide was detected in GUSB-impaired mice, suggesting that GUSB plays a pivotal role in the conversion of TBP1901 into aglycone curcumin in vivo. TBP1901 itself had minimal antitumor effects in vitro, whereas it demonstrated significant antitumor effects in vivo. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen disclosed the genes associated with NF-κB signaling pathway and mitochondria were among the highest hit. In vitro, aglycone curcumin inhibited NF-kappa B signaling pathways whereas it caused production of reactive oxygen species (ROS). ROS scavenger, N-acetyl-L-cysteine, partially reversed antitumor effects of aglycone curcumin. In summary, TBP1901 can exert antitumor effects as a prodrug of aglycone curcumin through GUSB-dependent activation

UAV-based exploratory survey of invertebrates on Nishinoshima Island

西之島は2013年以降断続的に噴火を繰り返しており、2017年からは毎年噴火が記録されている。特に2019年12月からの激しい噴火以降は火山活動への警戒により、島のほぼ全てのエリアで上陸調査ができない状況が続いている。しかし、その期間中も西之島では生態系遷移が進むと考えられる。そこで無人航空機（UAV）を活用することにより、遠隔からの生態系モニタリングを実施することとした。小型の無脊椎動物については撮影調査による情報収集が難しいことから、粘着トラップ、吸引機、採水器をUAV で運搬して試料を採集する新規の手法により調査を試みた。粘着トラップではカクレイワガニとシラミバエの1種が捕獲され、採水サンプルの環境DNA解析では軟体動物、棘皮動物のDNA が検出された。生態系遷移の初期段階を明らかにするための調査においては網羅的な生物群の時間的変化を記録することが重要である。火山活動が続く西之島において安全に生態系モニタリングを継続するためにUAVを活用した多様な生物の探索技術は重要な手段となりうる。Nishinoshima Island has been volcanically active since 2013, with eruptions recorded every year since 2017. Especially since the severe eruption in December 2019, almost all areas of the island cannot be surveyed ashore due to the warnings of volcanic activity. However, ecological succession on Nishinoshima Island may continue to progress even during the period. We utilised UAVs to carry out remote ecosystem monitoring. As it is difficult to collect information on small invertebrates by photographing surveys, we tried new methods for collecting samples by transporting a sticky trap, a vacuum cleaner and a water sampler using a UAV. Geograpsus grayi and Olfersia sp. were captured in the sticky traps. Environmental DNA analysis of the collected water samples detected molluscs and echinoderms. It is important to record temporal changes of a comprehensive biological dataset in order to clarify the earliest stages of ecosystem succession on oceanic islands. Various biological survey techniques using UAVs can be important tools for safely conducting continuous implementation of ecosystem monitoring on Nishinoshima Island, where volcanic activity is continuing.departmental bulletin pape

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024