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INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.

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Aim: To evaluate the costs associated with healthcare and long-term care during the last 24 months before death according to major disease groups. Methods: Individual data regarding healthcare and long-term care costs according to public insurance schemes during the last 24 months before death among all decedents older than 75 years reported in a city in Japan between April 1, 2010 and March 31, 2014 were identified; the data for nine major diseases were then analyzed. Results: For the 2149 decedents studied, the average healthcare costs per capita in the last 24 months of life for moderately-old (75 to 84 years) and extremely-old (85 years and older) decedents was 4,135,467 JPY and 2,493,001 JPY, respectively, while the average long-term care costs per capita for 24 months was 1,300,710 JPY and 2,723,239 JPY, respectively. The total costs (healthcare and long-term care combined) ranged from 9,169,547 JPY for chronic kidney disease to 5,023,762 JPY for ischemic heart disease. In all the diseases studied, the moderately-old decedents incurred higher healthcare costs while the extremely-old decedents incurred higher long-term care costs. However, for the care costs of chronic lower respiratory diseases, this pattern was not observed. Conclusion: A shift in expenditure from healthcare to long-term care as the decedents' age increased was observed in major diseases, with some exceptions.

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Dysregulation of Ras guanyl nucleotide-releasing protein 1 (RasGRP1) in mice results in a systemic lupus erythematosus (SLE)-like disorder. We therefore looked for defective isoforms and/or diminished levels of human RasGRP1 in a cohort of SLE patients. PBMCs were collected from twenty healthy individuals and thirty-two patients with SLE. mRNA was isolated and five RasGRP1 cDNAs from each subject were sequenced. T cell lysates from healthy controls and SLE patients also were evaluated for their levels of RasGRP1 protein. The accumulated data led to the identification of 13 new splice variants of the human RasGRP1 gene. Not only did our SLE patients have increased levels and types of these defective transcripts relative to normal individuals, two SLE patients were identified whose PBMCs and T cells contained very little, if any, functional RasGRP1 mRNA and protein. The presence of aberrantly spliced RasGRP1 transcripts also was correlated with lower levels of RasGRP1 protein in the patients' T cells. The lack of the normal isoform of RasGRP1 in some SLE patients and the increased prevalence of defective isoforms of RasGRP1 in others raise the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.

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