CO2 レーザーでアパタイトを溶着させたPEEK ディスク上における、ラット骨髄間葉系細胞の骨形成能に関する培養実験

Background: Polyether-ether-ketone (PEEK) is increasingly being used for spinal applications. However, because of its biologically inactive nature, there are risks of false joint loosening and sinking. PEEK materials are coated with apatite to enhance the osteoconductive properties. In this study, we aimed to evaluate whether strontium apatite stimulate osteogenesis on the surface of PEEK by using the CO2 laser technique. Methods: We prepared non-coated disks, laser-exposed disks without apatite, and four types of apatite-coated by laser PEEK disks (hydroxyapatite (HAP), strontium hydroxyapatite (SrHAP), silicate-substituted strontium apatite (SrSiP), and silicate-zinc-substituted strontium apatite (SrZnSiP)). A part of the study objective was testing various types of apatite coatings. Bone marrow mesenchymal cells (BMSCs) of rats were seeded at a density of 2 × 104/cm2 onto each apatite-coated, non-coated, and laser-irradiated PEEK disks. The disks were then placed in osteogenic medium, and alkaline phosphatase (ALP) staining and Alizarin red staining of BMSCs grown on PEEK disks were performed after 14 days of culture. The concentrations of osteocalcin (OC) and calcium in the culture medium were measured on days 8 and 14 of cell culture. Furthermore, mRNA expression of osteocalcin, ALP, runt-related transcription factor 2 (Runx2), collagen type 1a1 (Col1a1), and collagen type 4a1 (Col4a1) was evaluated by qPCR. Results: The staining for ALP and Alizarin red S was more strongly positive on the apatite-coated PEEK disks compared to that on non-coated or laser-exposed without coating PEEK disks. The concentration of osteocalcin secreted into the medium was also significantly higher in case of the SrHAP, SrSiP, and SrZnSiP disks than that in the case of the non-coated on day14. The calcium concentration in the PEEK disk was significantly lower in all apatite-coated disks than that in the pure PEEK disks on day 14. In qPCR, OC and ALP mRNA expression was significantly higher in the SrZnSiP disks than that in the pure PEEK disks. Conclusions: Our findings demonstrate that laser bonding of apatite-along with trace elements-on the PEEK disk surfaces might provide the material with surface property that enable better osteogenesis.博士（医学）・甲第809号・令和4年3月15日© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

ケイ酸/亜鉛置換ストロンチウムアパタイトコーティングによるβ-リン酸カルシウムの骨誘導能促進効果

Background: β-Tricalcium phosphate (β-TCP) is a popular synthetic bone graft substitute with excellent osteoconductive properties and bioabsorbability. However, its osteoinductive properties are inferior to those of autologous or allogeneic bone. Trace elements such as strontium (Sr), silica (Si), and zinc (Zn) have been reported to promote osteogenesis in materials. In this study, we aimed to determine whether a Si/Zn-substituted Sr apatite coating of β-TCP could enhance osteoinductive properties. Methods: The apatite-coated β-TCP disks were prepared using nanoparticle suspensions of silicate-substituted Sr apatite (SrSiP) or silicate- and Zn-co-substituted Sr apatite (SrZnSiP). Bone marrow mesenchymal cells (BMSCs) from rat femur were cultured and subsequently seeded at a density of 1.0 × 106/cm2 onto apatite-coated and non-coated β-TCP disks. In vitro, the β-TCP disks were then placed in osteogenic medium, and lactate dehydrogenase (LDH) activity was measured from supernatants after culture for 2 days. Additionally, after culture for 14 days, the mRNA expression of genes encoding osteocalcin (OC), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was evaluated by qRT-PCR. In vivo, the β-TCP disks were transplanted subcutaneously into rats that were sacrificed after 4 weeks. Then, the harvested disks were evaluated biochemically (ALP activity, OC content, mRNA expression of OC, ALP, BMP-2, and VEGF measured by qRT-PCR), radiologically, and histologically. Results: Significantly higher mRNA expression of almost all evaluated osteogenic and angiogenic genes was observed in the SrZnSiP and SrSiP groups than in the non-coated group, with no significant cytotoxicity elicited by the apatite coating in vitro. Moreover, in vivo, the SrZnSiP and SrSiP groups showed significantly higher osteogenic and angiogenic gene expression and higher ALP activity and OC content than the non-coated group (P < 0.05). Radiological and histopathological findings revealed abundant bone formation in the apatite-coated group. Conclusions: Our findings indicate that apatite coating of β-TCP improves osteoinductive properties without inducing significant cytotoxicity.博士（医学）・甲第805号・令和3年12月21日© 2021. The Author(s).Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

DRU classificationに基づく特発性側弯症の適切な観察間隔の設定 多施設研究

Purpose: To determine the capability of the distal radius and ulna (DRU) classification for predicting the scoliosis progression risk within 1 year in patients with adolescent idiopathic scoliosis (AIS) and to develop simple recommendations for follow-up durations. Methods: Medical records of patients with AIS at two tertiary scoliosis referral centers were retrospectively reviewed for their DRU classification and major curve Cobb angles. Baseline DRU grades and Cobb angles with subsequent 1-year follow-up curve magnitudes were studied for scoliosis progression, which was defined as exacerbation of the Cobb angle by ≥ 6°. The relationship between DRU classification and scoliosis progression risk within 1 year was investigated. Patients were divided into three groups according to the Cobb angle (10°-19°, 20°-29°, ≥ 30°). Results: Of the 205 patients with 283 follow-up visits, scoliosis progression occurred in 86 patients (90 follow-up visits). Radius and ulna grades were significantly related to scoliosis progression (p 80% of patients within 1 year. Curve progression was less likely for grades R9 and U7. Most patients with more mature DRU grades did not experience progression, even with Cobb angles ≥ 30°. Conclusion: With R6, R7, and U5, scoliosis may progress within a short period; therefore, careful follow-up with short intervals within 6 months is necessary. R9 and U7 may allow longer 1-year follow-up intervals due to the lower progression risk.博士（医学）・甲第771号・令和3年3月15日© Springer-Verlag GmbH Germany, part of Springer Nature 2020This is a post-peer-review, pre-copyedit version of an article published in European spine journal. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00586-020-06441-4

脊椎手術中のMonophasic刺激下での経頭蓋刺激筋誘発電位における定電流刺激と定電圧刺激での比較検討

Constant-voltage and constant-current stimulators may be used for transcranial electrical stimulation of motor evoked potentials (TES-MEP). However, no previous report has determined whether the two monophasic stimulation methods lead to similar responses during intra-operative monitoring. We studied differences in the lateralities of compound muscle action potentials (CMAPs) during intra-operative spinal cord monitoring via TES-MEP using monophasic constant-current and constant-voltage stimulations. CMAPs were bilaterally recorded from the upper and lower limb muscles in 95 patients who underwent elective spine and spinal cord surgery. We used two monophasic stimulation patterns: pattern 1, right anode and left cathode; pattern 2, right cathode and left anode. There were no statistically significant differences between the right and left sides with respect to success rates, wave amplitudes, and efficiencies, with constant-voltage stimulation, however, there were statistically significant differences between the right and left sides with constant-current stimulation. In case of our stimulation condition, there were no statistically significant differences between the right and left sides with respect to CMAPs with constant-voltage stimulation; constant-current stimulation was influenced by the type of monophasic stimulation, which necessitates the switch the polarity of the stimulation to bilaterally record CMAPs.博士（医学）・甲第725号・令和元年12月5日© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

外側環軸関節の関節症性変化のリスク増加に関連する要因; 後ろ向き研究

Purpose Atlantodens osteoarthritis and atlantoaxial osteoarthritis cause neck pain and suboccipital headaches. Currently, knowledge on the risk factors for atlantoaxial osteoarthritis is lacking. This study aimed to investigate the factors related to the increased risk of atlantoaxial osteoarthritis. Methods We analyzed computed tomography (CT) images of the upper cervical spine of 1266 adult trauma patients for whom upper cervical spine CT was performed at our hospital between 2014 and 2019. The degree of atlantoaxial osteoarthritis was quantified as none-to-mild (not having osteoarthritis) or moderateto- severe (having osteoarthritis). Risk factors associated with atlantoaxial osteoarthritis were identified using univariate and multivariable logistic regression analyses. Results The study group included 69.4% men, and the overall average age of the study population was 54.9 ± 20.4 years. The following factors were independently and significantly associated with atlantoaxial osteoarthritis in the multivariable logistic regression analysis: age in the sixth decade or older (odds ratio [OR], 20.5; 95% confidence interval [CI], 6.2‒67.2, p < 0.001), having calcific synovitis (OR, 4.9; 95% CI, 2.4‒9.9, p < 0.001), women sex (OR, 3.3; 95% CI, 1.9‒5.7, p = 0.002), and not having atlantodens osteoarthritis (OR, 2.1; 95% CI, 1.2‒3.8, p = 0.014). Conclusion In the multivariable logistic regression analysis, age in the sixth decade or older, calcification of the transverse ligament, being women, and not having atlantodens osteoarthritis were found to be significantly associated with atlantoaxial osteoarthritis. Delayed diagnosis and treatment can be avoided by focusing on these risk factors.博士（医学）・甲第873号・令和5年3月15

Tobacco Root Endophytic Arthrobacter Harbors Genomic Features Enabling the Catabolism of Host-Specific Plant Specialized Metabolites

Plant roots constitute the primary interface between plants and soilborne microorganisms and harbor microbial communities called the root microbiota. Recent studies have demonstrated a significant contribution of plant specialized metabolites (PSMs) to the assembly of root microbiota. However, the mechanistic and evolutionary details underlying the PSM-mediated microbiota assembly and its contribution to host specificity remain elusive. Here, we show that the bacterial genus Arthrobacter is predominant specifically in the tobacco endosphere and that its enrichment in the tobacco endosphere is partially mediated by a combination of two unrelated classes of tobacco-specific PSMs, santhopine and nicotine. We isolated and sequenced Arthrobacter strains from tobacco roots as well as soils treated with these PSMs and identified genomic features, including but not limited to genes for santhopine and nicotine catabolism, that are associated with the ability to colonize tobacco roots. Phylogenomic and comparative analyses suggest that these genes were gained in multiple independent acquisition events, each of which was possibly triggered by adaptation to particular soil environments. Taken together, our findings illustrate a cooperative role of a combination of PSMs in mediating plant species-specific root bacterial microbiota assembly and suggest that the observed interaction between tobacco and Arthrobacter may be a consequence of an ecological fitting process

Higher Order Corrections to the Primordial Gravitational Wave Spectrum and its Impact on Parameter Estimates for Inflation

We study the impact of the use of the power series expression for the primordial tensor spectrum on parameter estimation from future direct detection gravitational wave experiments. The spectrum approximated by the power series expansion may give large deviation from the true (fiducial) value when it is normalized at CMB scale because of the large separation between CMB and direct detection scales. We derive the coefficients of the higher order terms of the expansion up to the sixth order within the framework of the slow-roll approximation and investigate how well the inclusion of higher order terms improves the analytic prediction of the spectrum amplitude by comparing with numerical results. Using the power series expression, we consider future constraints on inflationary parameters expected from direct detection experiments of the inflationary gravitational wave background and show that the truncation of the higher order terms can lead to incorrect evaluation of the parameters. We present two example models; a quadratic chaotic inflation model and mixed inflaton and curvaton model with a quartic inflaton potential.Comment: 25 pages, 7 figures, revised version accepted by JCA