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Yuki Yamanashi,1,* Mika Ohmichi,2,3,* Yusuke Ohmichi,2,3 Tatsunori Ikemoto,1 Young-Chang Arai,4 Yohei Maruyama,3 Shun Otsuka,3 Shuichi Hirai,3 Munekazu Naito,3 Masataka Deie1 1Department of Orthopedic Surgery, Aichi Medical University, Nagakute, Aichi, Japan; 2Department of Anatomy II, Kanazawa Medical University, Kahoku, Ishikawa, Japan; 3Department of Anatomy, Aichi Medical University, Nagakute, Aichi, Japan; 4Institute of Physical Fitness, Sports Medicine and Rehabilitation, Aichi Medical University, Nagakute, Aichi, Japan*These authors contributed equally to this workCorrespondence: Yusuke OhmichiDepartment of Anatomy II, Kanazawa Medical University, Kahoku, Ishikawa, JapanEmail ohmy@kanazawa-med.ac.jpTatsunori IkemotoDepartment of Orthopedic Surgery, Aichi Medical University, Nagakute, Aichi, JapanEmail tatsunon31-ik@umin.ac.jpObjective: To explore whether methotrexate (MTX) prevents joint destruction and improves pain-related behaviors in the acute phase of knee osteoarthritis (OA) induced by monosodium iodoacetate (MIA) in a rat model.Methods: Twenty of 25 male Wistar rats (10– 14 weeks old) received 3 mg MIA via intra-articular injection into their right knee and were then administered a vehicle control (n=10) or 3 mg/kg MTX orally weekly (n=10). We assessed differences in pain-related behavior, spontaneous lifting behavior, micro-computed tomography (CT), histopathology, and expression of pain- and inflammatory-related genes using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) between the two groups for 4 weeks. Five rats were used as untreated controls to assess pain- and inflammatory-related mRNA expression in the dorsal root ganglia (DRG) and knee joints using RT-qPCR.Results: Joint destruction and mechanical hyperalgesia were observed in the vehicle group. Decreases in mechanical pain thresholds for the knee joint and calf muscles were improved after MTX administration; however, joint damage assessed by micro-CT and histopathology was not significantly inhibited by MTX administration, while upregulation levels of transient receptor potential cation channel, subfamily V, member 1 (TRPV-1) (P< 0.01) and brain-derived neurotrophic factor (BDNF) (P=0.02) mRNA in the DRG and nerve growth factor NGF mRNA (P=0.03) in the affected knee joints were significantly suppressed in the MTX group compared with the vehicle group at week 4.Conclusion: Our results imply that MTX administration improves pain-related behaviors and suppresses expression of pain-related mRNAs in the DRG and knee joint; however, MTX is not expected to prevent cartilage degeneration in MIA-induced OA in rat knee.Keywords: knee osteoarthritis, methotrexate, monosodium iodoacetate, inflammation

Background: Thoracic epidural analgesia (TEA) and intravenous patient‐controlled analgesia (IV‐PCA) are widely used to mitigate immediate postoperative pain; however, their effects on long‐term disability‐free survival are poorly documented. This study aimed to compare the effects of postoperative TEA and IV‐PCA on disability‐free survival in patients who underwent thoracic or abdominal surgery. Methods: This post hoc analysis of a prospective observational study included 845 inpatients aged ≥55 years that underwent elective thoracic and abdominal surgery between 1 April 2016 and 28 December 2018 in a tertiary care hospital. Inverse probability of treatment weighted (IPTW) using stabilized inverse propensity scores was adopted to minimize bias. The primary outcome in this study was disability‐free survival, defined as survival with a 12‐item World Health Organization Disability Assessment Schedule 2.0 score of <16%, assessed at 3 months and 1 year after surgery. Results: The final analysis included 601 patients who received TEA and 244 who received IV‐PCA. After IPTW, the weighted incidence of disability‐free survival at 3 months and 1 year was 60.5% and 61.4% in the TEA group and 78.3% and 66.2% in the IV‐PCA group, respectively. The adjusted OR for disability‐free survival at 3 months and 1 year was 0.84 (95% confidence interval [CI]: 0.50–1.39) and 1.21 (95% CI: 0.72–2.05), respectively, for the TEA group. Conclusion: No significant differences were observed in the disability‐free survival at 3 months and 1 year after elective thoracic and abdominal surgery in patients aged ≥55 years who received TEA or IV‐PCA. Significance statement: This study is the first in our setting to document the long‐term effects of patient‐controlled analgesia. In a post hoc analysis of our prospective cohort study, we show that although differences in chronic postsurgical pain exist at 3 months post‐surgery, disability‐free survival rates at 1 year do not differ irrespective of the choice of patient‐controlled analgesia. The findings of this study highlight the need for shared decision‐making between clinicians and patients. [ABSTRACT FROM AUTHOR]

During dissolution of liquid or gaseous C[O.sub.2] into the ocean, a potential process for C[O.sub.2] ocean sequestration to offset global warming, a hydrate film forms at the C[O.sub.2]--water interface and limits the C[O.sub.2] dissolution rate. By experimentally studying the conditions under which such a C[O.sub.2] gas hydrate film maintains a constant thickness, we determined the processes that control C[O.sub.2] hydrate growth rates. A constant film thickness cannot be maintained when the decomposition rate exceeds a certain critical value. The decomposition rate was varied by adjusting the flow velocity of a water stream directed perpendicular to the hydrate film. An increase of the flow speed increased the decomposition rate, which decreased the steady-state film thickness. However, at a critical value, net decomposition occurs and the hydrate film completely dissolves. The critical decomposition rates are roughly proportional to pressure and relatively independent of temperature from 274.6 to 278.7 K. The transport of [H.sub.2]O through the hydrate layer to the growth sites near the C[O.sub.2]--hydrate interface controls the growth rate when it is relatively small, but the supply of C[O.sub.2] molecules limits it at relatively high growth rates.