Bone is continuously remodeled by bone resorption and formation and, accordingly, bone metabolism is tightly regulated to maintain homeostasis. Deviation from the normal conditions of bone resorption can result in bone diseases. Lipid rafts are specialized plasma membrane microdomains that are enriched with glycosphingolipids, sphingomyelin and cholesterol. Lipid rafts are important for the transport of select membranes and relay stations involved in intracellular signaling.To investigate the role of lipid rafts in RAW264 cells signaling, lipid rafts were disrupted by depleting cholesterol through the introduction of methyl-β-cyclodextrin (MβCD). We found that sRANKL-induced differentiation into osteoclasts was markedly inhibited by MβCD in a dose-dependent manner. MβCD enhanced the sRANKL-induced phosphorylation of ERK1/2 MAP kinase. In contrast, MβCD blocked the phosphorylation of IκB. These findings suggest that cholesterol might play a crucial role in the regulation of the sRANKL-mediated signaling pathway and in osteoclast differentiation of RAW264 cells, thereby reflecting its importance in the formation of plasma membrane lipid rafts.

We participated in TIPS-FM (Toronto International Program to Strengthen Family Medicine and Primary Care) for two weeks in Toronto in June 2019. This program enabled us to learn many important factors for developing family medicine. Based on Canadian family medicine, which has a long history, we were able to review the missions of family medicine in Japan, and gained further insight into multilayered essentials on the patient-, community-, and global-levels.

The two basic scripts of the Korean writing system, Hanja (the logography of the traditional Korean character) and Hangul (the more newer Korean alphabet), have been used together since the 14th century. While Hanja character has its own morphemic base, Hangul being purely phonemic without morphemic base. These two, therefore, have substantially different outcomes as a language as well as different neural responses. Based on these linguistic differences between Hanja and Hangul, we have launched two studies; first was to find differences in cortical activation when it is stimulated by Hanja and Hangul reading to support the much discussed dual-route hypothesis of logographic and phonological routes in the brain by fMRI (Experiment 1). The second objective was to evaluate how Hanja and Hangul affect comprehension, therefore, recognition memory, specifically the effects of semantic transparency and morphemic clarity on memory consolidation and then related cortical activations, using functional magnetic resonance imaging (fMRI) (Experiment 2). The first fMRI experiment indicated relatively large areas of the brain are activated by Hanja reading compared to Hangul reading. The second experiment, the recognition memory study, revealed two findings, that is there is only a small difference in recognition memory for semantic transparency, while for the morphemic clarity was much larger between Hanja and Hangul. That is the morphemic clarity has significantly more effect than semantic transparency on recognition memory when studies by fMRI in correlation with behavioral study.
Adult ; Brain/*physiology ; Brain Mapping/*methods ; Brain Waves/*physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neurolinguistic Programming ; Recognition (Psychology)/physiology ; Writing

OBJECTIVE: To evaluate the efficacy and toxicity of paclitaxel plus carboplatin (TC)-based concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIB/IVA cervical cancer patients. METHODS: We reviewed the medical records of FIGO stage IIIB/IVA cervical cancer patients (n=30) who had been intended to be treated with TC-based CCRT followed by consolidation chemotherapy (TC-CCRT-group) from April 2012–May 2016. Patients who had been treated with CCRT involving a single platinum agent (CCRT-group; n=52) or definitive radiotherapy alone (RT-group; n=74) from January 1997–September 2012 were also identified and used as historical controls. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of the 30 patients included in the TC-CCRT-group, 22 patients (73.3%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up of 35 months, 9 patients (30.0%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 67.9% and 90.8%, respectively. In comparisons with historical control groups, the survival outcomes of TC-CCRT-group was significantly superior to CCRT-group in terms of OS (p=0.011) and significantly superior to RT-group in terms of both PFS (p=0.009) and OS (p<0.001). CONCLUSION: TC-based CCRT followed by consolidation chemotherapy is safe and effective. A randomized controlled study needs to be conducted to further evaluate the efficacy of this multimodal approach in this patient population.
Carboplatin* ; Chemoradiotherapy* ; Consolidation Chemotherapy* ; Diarrhea ; Disease-Free Survival ; Follow-Up Studies ; Gynecology ; Humans ; Leukopenia ; Medical Records ; Methods ; Neutropenia ; Obstetrics ; Paclitaxel* ; Platinum ; Prognosis ; Radiotherapy ; Uterine Cervical Neoplasms*