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Emotional arousal is thought to enhance the consolidation of associated memories by activating the basolateral amygdala (BLA) and its projections to memory-storing regions1–4. Although the importance of both rapid eye movement (REM) and non-REM (NREM) sleep-state specific BLA activity for emotional memory processing has been proposed5–9, how and when the BLA interacts with other brain regions to enhance memory consolidation remains unclear10. Here, by adding emotional information to a perceptual recognition task that relies on top-down inputs from frontal to sensory cortices, we demonstrated that the BLA not only associates emotional information with perceptual information, but also enhances the retention of associated perceptual memory through BLA-frontal projections. Electrophysiological recordings revealed that emotional association increases the reactivation of coordinated activity across the BLA-frontal-sensory region during NREM sleep, but not during REM sleep. Notably, this inter-regional coordinated reactivation during NREM sleep was entrained to the BLA high-frequency oscillations in the emotional condition, suggesting that the BLA triggers inter-regional interaction. Optogenetic silencing of BLA terminals in the frontal cortex during NREM sleep, but not REM sleep, disrupted the enhanced retention of the perceptual memory, but not the association itself or the emotional component of associative memory. Our results indicate that the inter-regional coordination through the BLA-cortical inputs during NREM sleep is causally required for memory enhancement by emotional arousal.

To identify patients at a high risk for primary and secondary osteoporotic fractures using fracture risk assessments performed using the current method and the proposed method, in an acute care hospital and to identify departments where high-risk patients are admitted. This retrospective study included patients aged 40-90 years who were hospitalized at Fujita Health University Hospital. We collated the clinical data and prescriptions of all study participants. We also gathered data pertaining to risk factors according to Fracture Risk Assessment Tool (FRAX). Of the 1595 patients, the mean number of major osteoporotic fracture risk predicted using FRAX was 11.73%. The department of rheumatology showed the highest fracture risk (18.55 ± 16.81) and had the highest number of patients on medications that resulted in reduced bone mineral density (1.07 ± 0.98 medication). Based on the FRAX, the proportion of patients in the high-risk group in this department was significantly higher compared with those in the remaining departments with respect to glucocorticoid administration, rheumatoid arthritis, and secondary osteoporosis. However, the departments included in the high-risk group were not necessarily the same as the departments included in the top group, based on the administered medications. FRAX score is calculated based on various risk factors; however, only glucocorticoid corresponds to medications. We should focus on medication prescription patterns in addition to FRAX to improve fracture risk assessment in hospital-wide surveillance. Therefore, we recommend the use of FRAX along with the prescribed medications to identify departments that admit high-risk patients.

Elderly patients with musculoskeletal disorders are generally expected to receive many prescription drugs for non-musculoskeletal comorbidities and for alleviating chronic musculoskeletal pains. The aims of this study were to review the use of prescription drugs in elderly patients with elective surgeries for musculoskeletal disorders and to identify the factors associated with polypharmacy in elderly patients with musculoskeletal disorders.We retrospectively collected the clinical data of patients aged ≥65 years who underwent knee arthroplasty, total hip arthroplasty, or spinal surgery for lumbar or cervical degenerative disorders at our institution. The following data were evaluated: age, body mass index, sex, surgical site, prescription drugs used, American Society of Anesthesiologists physical status grade, and medical history, including hypertension, hyperlipidemia, diabetes, stroke, malignancy, and smoking. Polypharmacy was defined as the use of six or more drugs.In the present study, 767 consecutive patients were evaluated retrospectively. The prevalence of polypharmacy was50% in the elderly patients with musculoskeletal disorders. The mean numbers of total drugs and pain relief medications were significantly higher in the lumbar surgery group than in the other surgery groups. Multivariable analysis revealed that the factors associated with polypharmacy were lumbar surgery, hypertension, hyperlipidemia, diabetes, and malignancy.This is the first study to cross-sectionally review the drugs prescribed to patients with degenerative musculoskeletal disorders. It clearly identified the factors associated with polypharmacy in elderly patients with degenerative musculoskeletal disorders. Particular attention should be paid to polypharmacy in elderly patients with lumbar degenerative disorders. Geriatr Gerontol Int 2022; 22: 121-126.

Astrocyte- and tanycyte-like neural stem cells (NSCs) were recently detected in the area postrema (AP) and central canal (CC) of the adult medulla oblongata, respectively. The present study aimed to examine dynamical behaviors of the astrocyte- and tanycyte-like NSCs of the mouse medulla oblongata to leptin. The neurosphere assay identified astrocytes in the AP and tanycytes in the CC as NSCs based on their self-renewing neurospherogenic potential. Both NSCs in neurosphere cultures were multipotent cells that generate astrocytes, oligodendrocytes, and neurons. Astrocyte-like NSCs actively proliferated and tanycyte-like NSCs were quiescent under physiologically-relevant in vivo conditions. Chronic leptin treatment promoted proliferation of astrocyte-like NSCs in the AP both in vitro and in vivo. Leptin receptors were expressed in astrocyte-like, but not tanycyte-like NSCs. Food deprivation significantly diminished proliferation of astrocyte-like NSCs. Therefore, the present study indicates that proliferation of astrocyte-like, but not tanycyte-like NSCs is regulated by nutritional conditions.

Background Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. Methods Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. Results There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0–0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1–0.4) and slightly decreased years with activity limitation (0.1–0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3–1.5 years) and decreased years with activity limitation (0.3–1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0–0.8 years) and non-ADL limitations (0.0–0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7–1.1 years) and non-ADL limitations (0.3–0.4). Conclusions These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.

Recent advances in optical bioimaging and optogenetics have enabled the visualization and manipulation of biological phenomena, including cellular activities, in living animals. In the field of neuroscience, detailed neural activity related to brain functions, such as learning and memory, has now been revealed, and it has become feasible to artificially manipulate this activity to express brain functions. However, the conventional evaluation of neural activity by two-photon Ca

Heterotopic ossification (HO) is a pathological condition in which ectopic bone forms within soft tissues such as skeletal muscle. Human platelet-derived growth factor receptor α positive (PDGFRα+) cells, which were proved to be the original cells of HO were incubated in osteogenic differentiation medium with Food and Drug Administration-approved compounds. Alkaline phosphatase activity was measured as a screening to inhibit osteogenic differentiation. For the compounds which inhibited osteogenic differentiation of PDGFRα+ cells, we examined dose dependency of its effect using alizarin red S staining and its cell toxicity using WST-8. In addition, regulation of bone morphogenetic proteins (BMP)-Smad signaling which is the major signal of osteogenic differentiation was investigated by Western blotting to elucidate the mechanism of osteogenesis inhibitory effect by the compound. In vivo experiment, complete transverse incision of Achilles tendons in mice was made and mice were fed the compound by mixing with drinking water after operation. Ten weeks after operation, we assessed and quantified HO by micro-computed tomography scan. Intriguingly, we discovered desloratadine inhibited osteogenic differentiation of PDGFRα+ cells using the drug repositioning method. Desloratadine inhibited osteogenic differentiation of the cells dose dependently without cell toxicity. Desloratadine suppressed phosphorylation of Smad1/5/8 induced by BMP2 in PDGFRα+ cells. In Achilles tenotomy mice model, desloratadine treatment significantly inhibited ectopic bone formation compared with control. In conclusion, we discovered desloratadine inhibited osteogenic differentiation using human PDGFRα+ cells and proved its efficacy using Achilles tenotomy ectopic bone formation model in vivo. Our study paved the way to inhibit HO in early clinical use because of its guaranteed safety.

Sarcopenia is an important health problem associated with adverse outcomes. Although the etiology of sarcopenia remains poorly understood, factors apart from muscle fibers, including humoral factors, might be involved. Here, we used cytokine antibody arrays to identify humoral factors involved in sarcopenia and found a significant increase in levels of milk fat globule epidermal growth factor 8 (MFG‐E8) in skeletal muscle of aged mice, compared with young mice. We found that the increase in MFG‐E8 protein at arterial walls and neuromuscular junctions (NMJs) in muscles of aged mice. High levels of MFG‐E8 at NMJs and an age‐related increase in arterial MFG‐E8 have also been identified in human skeletal muscle. In NMJs, MFG‐E8 is localized on the surface of terminal Schwann cells, which are important accessory cells for the maintenance of NMJs. We found that increased MFG‐E8 at NMJs precedes age‐related denervation and is more prominent in sarcopenia‐susceptible fast‐twitch than in sarcopenia‐resistant slow‐twitch muscle. Comparison between fast and slow muscles further revealed that arterial MFG‐E8 can be uncoupled from sarcopenic phenotype. A genetic deficiency in MFG‐E8 attenuated age‐related denervation of NMJs and muscle weakness, providing evidence of a pathogenic role of increased MFG‐E8. Thus, our study revealed a mechanism by which increased MFG‐E8 at NMJs leads to age‐related NMJ degeneration and suggests that targeting MFG‐E8 could be a promising therapeutic approach to prevent sarcopenia., Milk fat globule epidermal growth factor 8 (MFG‐E8) levels at neuromuscular junctions (NMJs) increase during aging. A genetic deficiency in MFG‐E8 attenuated age‐related denervation of NMJs and muscle weakness, providing evidence of a pathogenic role of increased MFG‐E8. This study revealed a previously unrecognized mechanism of age‐related NMJ denervation associated with sarcopenia.

Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes. Moreover, microglia in the CVOs showed the strong protein expression of the M1 markers CD16/32 and CD86 and M2 markers CD206 and Ym1 without any pathological stimulation. Thus, the present results indicate that microglia in the CVOs of adult mice are morphologically and functionally activated under normal conditions, possibly due to the specialized features of the CVOs, namely, the entry of blood-derived molecules into parenchyma through fenestrated capillaries and the presence of neural stem cells.

Objective.To delineate clinical characteristics of patients with spondyloarthritis (SpA) in Japan in comparison to other areas of the world.Methods.Using the ASAS-COMOSPA (Assessment of Spondyloarthritis international Society–COMOrbidities in SPondyloArthritis) data, an international cross-sectional observational study of patients with SpA, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Japan, other Asian countries (China, Singapore, South Korea, Taiwan), and non-Asian countries (Europe, the Americas, Africa). Patient characteristics, including diagnosis and treatment, were compared.Results.Among 3984 patients included in the study, 161 were from centers in Japan, 933 from other Asian countries, and 2890 from other regions. Of patients with SpA in Japan, 42 (26.1%) had peripheral SpA, substantially more than in other countries. This trend was explained by the predominance of psoriatic arthritis (PsA) among Japanese patients with SpA. In contrast to the relatively low number in Japan, 54% of patients from other Asian countries had pure axial SpA (axSpA) without peripheral features. HLA-B27 testing, considered an integral part of the classification of axSpA, was performed in only 63.6% of Japanese patients with axSpA. More than half of Japanese patients with axSpA were classified using imaging criteria.Conclusion.In our study, there was a more substantial number of peripheral SpA cases observed in Japan compared to other parts of Asia and other regions of the world. Aside from ethnic differences, increasing recognition of PsA in Japan, as well as a potential underdiagnosis of axSpA due to the insufficient use of HLA-B27 testing, may partly explain regional discrepancies.

Background Muscle regenerative capacity reduces during aging. Decline in the muscle stem cell (MuSC) pool is thought to be a cause of age-related muscle regeneration insufficiency. However, why the number of MuSCs decreases with age remains unclear. We previously found that the calcitonin receptor (Calcr) is expressed by MuSCs and plays a pivotal role in maintaining the MuSC pool. In this study, we examined whether Calcr is involved in the age-related decrease in MuSC number. Methods Calcr expression in MuSCs was assessed by immunofluorescence staining using muscle sections during postnatal growth and during aging. The role of Calcr during development, postnatal growth and adult stage was examined using mice conditionally deleted Calcr in myogenic lineage cells. To explore the significance of Calcr signaling on age-related changes in MuSC number, expression levels of endogenous Calcr ligands were examined. Results Immunohistological examination revealed that Calcr expression grew stronger as MuSCs became quiescent. Conditional Calcr deletion in early myogenic lineage cells did not affect the initial capacity of the MuSC pool, but promoted age-dependent MuSC loss. Expression of endogenous Calcr ligands remained unchanged with aging. Calcr expression in MuSCs, however, decreased significantly in aged muscle compared with young muscle in both mice and humans, and this reduction was accompanied by a loss of MuSCs. Conclusions Our study revealed significant reduction of Calcr in MuSCs with age, possibly leading to age-related loss of the MuSC pool. Thus, Calcr signaling could represent a promising target for preventing aging-associated muscle regeneration insufficiency.

Background: Although the incidence of symptomatic pulmonary thromboembolism after elective surgery for musculoskeletal degenerative disorders is comparatively low, it is extremely detrimental to both patients and health-care providers. Therefore, its prevention is mandatory. We aimed to perform a cross-sectional analysis of deep venous thrombosis (DVT) before elective surgery for degenerative musculoskeletal disorders, including total knee arthroplasty (TKA), total hip arthroplasty (THA), and spinal surgery, and identify the factors associated with the incidence of preoperative DVT.Methods: The clinical data of patients aged ≥30 years who underwent TKA or THA, and spine surgery for lumbar or cervical degenerative disorders at our institution were retrospectively collected. D-dimer levels were measured preoperatively in all the patients scheduled for surgery. For the patients with D-dimer levels ≥ 1 μg/mL or who were determined by their physicians to be at high risk of DVT, the lower extremity vein was preoperatively examined for DVT on ultrasonography.Results: Overall, we retrospectively evaluated 1236 consecutive patients, including 701 men and 535 women. Of the patients, 431 and 805 had D-dimer levels ≥ 1 and < 1 μg/mL, respectively. Of 683 patients who underwent lower extremity ultrasonography, 92 had proximal (n = 7) and distal types (n = 85) of DVT. The preoperative prevalence of DVT was 7.4%. One patient (0.08%) had the incidence of postoperative symptomatic venous thromboembolism. A multivariate analysis revealed that age ≥80 years (odds ratio [OR], 95% confidence interval [CI]: 2.8, 1.1–7.3), knee surgery (2.1, 1.1–4.0), American Society of Anesthesiologists (ASA) grade 2 (2.8, 1.2–6.8), ASA grades 3 or 4 (3.1, 1.0–9.4), and malignancy (1.9, 1.1–3.2) were significantly associated with DVT incidence.Conclusions: This is the first study to conduct a cross-sectional analysis of preoperative DVT data of patients scheduled for elective surgery for degenerative musculoskeletal disorders. Although whether screening for preoperative DVT is needed to prevent postoperative symptomatic pulmonary thromboembolism remains to be clarified, our data suggested that DVT should be noted before surgery in the patients with advanced age, knee surgery, high ASA physical status, and malignancy.

Background Although the incidence of symptomatic pulmonary thromboembolism after elective surgery for degenerative musculoskeletal disorders is comparatively low, it is extremely detrimental to both patients and health-care providers. Therefore, its prevention is mandatory. We aimed to perform a cross-sectional analysis of deep venous thrombosis (DVT) before elective surgery for degenerative musculoskeletal disorders, including total knee arthroplasty (TKA), total hip arthroplasty (THA), and spinal surgery, and identify the factors associated with the incidence of preoperative DVT. Methods The clinical data of patients aged ≥ 30 years who underwent TKA or THA, and spine surgery for lumbar or cervical degenerative disorders at our institution were retrospectively collected. D-dimer levels were measured preoperatively in all the patients scheduled for surgery. For the patients with D-dimer levels ≥ 1 µg/mL or who were determined by their physicians to be at high risk of DVT, the lower extremity vein was preoperatively examined for DVT on ultrasonography. Results Overall, we retrospectively evaluated 1236 consecutive patients, including 701 men and 535 women. Of the patients, 431 and 805 had D-dimer levels ≥ 1 and Conclusions This is the first study to conduct a cross-sectional analysis of preoperative DVT data of patients scheduled for elective surgery for degenerative musculoskeletal disorders. Although whether screening for preoperative DVT is needed to prevent postoperative symptomatic pulmonary thromboembolism remains to be clarified, our data suggested that DVT should be noted before surgery in the patients with advanced age, knee surgery, high ASA physical status, and malignancy.

Age-related sarcopenia constitutes an important health problem associated with adverse outcomes. Sarcopenia is closely associated with fat infiltration in muscle, which is attributable to interstitial mesenchymal progenitors. Mesenchymal progenitors are non-myogenic in nature but are required for homeostatic muscle maintenance. However, the underlying mechanism of mesenchymal progenitor-dependent muscle maintenance is not clear, nor is the precise role of mesenchymal progenitors in sarcopenia. Here, we show that mice genetically engineered to specifically deplete mesenchymal progenitors exhibited phenotypes markedly similar to sarcopenia, including muscle weakness, myofiber atrophy, alterations of fiber types, and denervation at neuromuscular junctions. Through searching for genes responsible for mesenchymal progenitor-dependent muscle maintenance, we found that Bmp3b is specifically expressed in mesenchymal progenitors, whereas its expression level is significantly decreased during aging or adipogenic differentiation. The functional importance of Bmp3b in maintaining myofiber mass as well as muscle-nerve interaction was demonstrated using knockout mice and cultured cells treated with Bmp3b. Furthermore, the administration of recombinant BMP3B in aged mice reversed their sarcopenic phenotypes. These results reveal previously unrecognized mechanisms by which the mesenchymal progenitors ensure muscle integrity and suggest that age-related changes in mesenchymal progenitors have a considerable impact on the development of sarcopenia.

Tanycyte is a subtype of ependymal cells which extend long radial processes to brain parenchyma. The present study showed that tanycyte-like ependymal cells in the organum vasculosum of the lamina terminalis, subfornical organ and central canal (CC) expressed neural stem cell (NSC) marker nestin, glial fibrillar acidic protein and sex determining region Y. Proliferation of these tanycyte-like ependymal cells was promoted by continuous intracerebroventricular infusion of fibroblast growth factor-2 and epidermal growth factor. Tanycytes-like ependymal cells in the CC are able to form self-renewing neurospheres and give rise mostly to new astrocytes and oligodendrocytes. Collagenase-induced small medullary hemorrhage increased proliferation of tanycyte-like ependymal cells in the CC. These results demonstrate that these tanycyte-like ependymal cells of the adult mouse brain are NSCs and suggest that they serve as a source for providing new neuronal lineage cells upon brain damage in the medulla oblongata.

Membrane dynamics in the presynaptic region of the neuron is a key process of neuronal signal transduction. Dynamin plays a central part during endocytosis participating in the deformation of membrane structure and constriction. During the study of molecular interaction of presynaptic proteins, we found that dynamin fraction prepared from brain extract contains several lipid components. Fractionation of lipids with thin layer chromatography and mass-analysis showed the presence of phosphatidylcholine, phosphatidylethanolamine, cerebroside, cholesterol and its-derivatives, and triacylglycerol. Since the GTPase activity of bacterially expressed dynamin was activated by the extracted lipid fraction, lipid components that affect the GTPase activity of dynamin was screened and cerebroside, hydroxycholesterols, cholesterol, and triacylglycerol were found to activate the GTPase activity. This result not only suggests the possibility that several neutral lipids participate in the membrane dynamics, but also revealed the possibility that a protein fraction contains lipid components even if its purity was confirmed with SDS-PAGE.

Neurons have well-developed membrane microdomains called “rafts” that are recovered as a detergent-resistant low-density membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM and localizes in the presynaptic region. In order to know the role of NAP-22 in the synaptic transmission, NAP-22 binding proteins in the cytosol were searched with an affinity screening with NAP-22 as a bait and several protein bands were detected. Using mass-analysis and western blotting, one of the main band of ∼90 kDa was identified as dynamin I. The GTPase activity of dynamin I was partly inhibited by NAP-22 expressed in bacteria and this inhibition was recovered by the addition of calmodulin, a NAP-22 binding protein. The GTPase activity of dynamin was known to be activated with acidic membrane lipids such as phosphatidylserine and the addition of NAP-22, a phosphatidylserine binding protein, inhibited the activation of the GTPase by this lipid. Since NAP-22 localizes on the presynaptic plasma membrane and on synaptic vesicles, these results suggest the participation of NAP-22 in the membrane cycling through binding to dynamin and acidic membrane lipids at the presynaptic region.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or

Background:Clinical characteristics of nonradiographic axial spondyloarthritis (nr-ax-SpA) are highly variable across patients, and may potentially vary across patient populations, particularly due to differing distributions of human leukocyte antigens (HLA) and other genetic factors. The majority of nr-ax-SpA studies have been conducted in Europe, the United States, and small studies are reported from Asia [1].Objectives:To delineate clinical characteristics of patients with nr-ax-SpA in Asian countries in comparison to other areas of the world.Methods:Utilizing the ASAS-COMOSPA data, an international cross-sectional observational study of SpA patients, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Asia (China, Japan, Singapore, South Korea, and Taiwan), and non-Asian countries (Europe, Americas, and Africa); patient characteristics, including diagnosis and treatment, were compared.Results:Among 3984 SpA patients included in the study, 1094 were from centers in Asian countries, and 2890 from other regions. 112/780 (14.4%) of axial SpA patients in Asian countries were nr-ax-SpA, substantially less than in other countries (486/1997, 24.3%). Nr-ax-SpA patients in Asian countries compared to nr-ax-SpA in other countries were more likely male (75.9 vs 47.1%), have onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years) at younger age, and experience less diagnostic delay (1.88 vs 2.92 years) (Table 1). Nr-ax-SpA patients in Asian countries have higher prevalence of positive HLA-B27 (90.6% vs 61.9%) and fewer peripheral signs such as arthritis, enthesitis, or dactylitis (53.6% vs 66.3%) but have similar rate of extra-articular manifestations (psoriasis, IBD, or uveitis) and co-morbidities. Disease activity, functional impairment, and inflammation on MRI were less in nr-ax-SpA patients in Asian countries. NSAIDs response was higher and use of methotrexate and b-DMARDs were lower among nr-ax-SpA in Asian countries.Conclusion:Among axial SpA patients, substantially lower frequency of nr-ax-SpA was observed in Asian countries compared to other regions of the world. Nr-ax-SpA patients in Asian countries were predominantly male, and had younger disease onset with higher HLA-B27 positivity rate and less peripheral signs, and better response to NSAIDs. These results offer an opportunity to improve both early diagnosis and treatment of nr-ax-SpA patients in Asian countries.Table 1.Characteristics of nonradiographic axial SpA in Asia versus non-Asian regionsVariablesAsianon-Asian regionsp valueN112486Age at disease diagnosis, yrs27.2 [21.1, 39.6]34.5 [27.7, 41.7]Diagnostic delay, yrs1.88 [0.27, 5.56]2.92 [0.59, 9.58]0.011Male (%)85 (75.9)229 (47.1)Sacroiliitis on MRI among tested (%)49 (67.1)341 (82.2)0.005HLA B27 positivity among measured (%)96 (90.6)273 (61.9)Inflammatory Back Pain (%)107 (95.5)478 (98.4)0.076Arthritis, enthesitis, or dactylitis (%)60 (53.6)322 (66.3)0.016Psoriasis (%)12 (10.7)82 (16.9)0.142Uveitis (%)20 (17.9)81 (16.7)0.870Inflammatory bowel disease (%)5 (4.5)27 (5.6)0.817Elevated CRP (%)37 (33.0)213 (43.8)0.048Physician global assessment (0-10)2.0 [1.0, 5.0]2.0 [1.0, 4.0]0.741Patient global assessment (0-10)3.0 [1.0, 6.0]4.0 [2.0, 6.0]0.012ASDAS-CRP1.40 [0.95, 2.08]1.97 [1.21, 2.78]BASFI0.8 [0.05, 2.65]2.9 [0.8, 5.6]Good response to NSAIDs (%)80 (71.4)272 (56.0)0.004Methotrexate use (%)18 (16.1)134 (27.6)0.016Biological DMARDs use (%)27 (24.1)191 (39.3)0.004References:[1]López-Medina C, Ramiro S, van der Heijde D, et al. Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis. RMD Open. 2019 Nov 21;5(2): e001108.Acknowledgements:This study was conducted under the umbrella of the International Society for Spondyloarthritis Assessment (ASAS) and COMOSPA study was supported by unrestricted grants from Pfizer, AbbVie and UCB.Disclosure of Interests:Keisuke Ono: None declared, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Sho Fukui: None declared, Satoshi Kawaai: None declared, Gautam A. Deshpande: None declared, Kazuki Yoshida Consultant of: OM1, Inc., Grant/research support from: Corrona, LLC, Naomi Ichikawa: None declared, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB, Taku Kawasaki: None declared, Kazuo Matsui: None declared, Mitsuhiro Morita: None declared, Kurisu Tada: None declared, Naoho Takizawa: None declared, Naoto Tamura: None declared, Atsuo Taniguchi: None declared, Yoshinori Taniguchi: None declared, Shigeyoshi Tsuji: None declared, Shigeto Kobayashi: None declared, Masato Okada: None declared, Clementina López-Medina: None declared, Anna Moltó Consultant of: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Grant/research support from: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Imaging Rheumatology bv. (Director), Maxime Dougados: None declared, Yoshinori Komagata: None declared, Tetsuya Tomita: None declared, Shinya Kaname: None declared.

The myelin sheath is critical in maintaining normal functions of the adult central nervous system (CNS) and the loss of the myelin sheath results in various neurological diseases. Although remyelination is the intrinsic repair system against demyelination that new myelin sheath is formed around axons in the adult CNS, little has been reported on remyelination system in the medulla oblongata. In the present study, we showed that the proliferation of oligodendrocyte progenitor cells (OPCs) was increased in the medulla oblongata by lysophosphatidylcholine (LPC)-induced focal demyelination, but that of NSCs was not changed. The inhibition of vascular endothelial growth factor (VEGF)- and platelet-derived growth factor (PDGF)-signaling suppressed the proliferation of OPCs by LPC-induced demyelination. Thus, the present study indicates that resident OPCs contribute to focal remyelination and VEGF and PDGF signaling is required for the proliferation of OPCs in the medulla oblongata of the adult mouse.

We propose a nonscanning three-dimensional (3-D) fluorescence imaging technique using the transport of intensity equation (TIE) and free-space Fresnel propagation. In this imaging technique, a phase distribution corresponding to defocused fluorescence images with a point-light-source-like shape is retrieved by a TIE-based phase retrieval algorithm. From the obtained phase distribution, and its corresponding amplitude distribution, of the defocused fluorescence image, various images at different distances can be reconstructed at the desired plane after Fresnel propagation of the complex wave function. Through the proposed imaging approach, the 3-D fluorescence imaging can be performed in multiple planes. The fluorescence intensity images are captured with the help of an electrically tunable lens; hence, the imaging technique is free from motion artifacts. We present experimental results corresponding to microbeads and a biological sample to demonstrate the proposed 3-D fluorescence imaging technique.

Experimental autoimmune encephalomyelitis (EAE) is primarily used as an animal model of autoimmune demyelinating disease, multiple sclerosis. In this study, we found the proliferative rate of oligodendrocyte progenitor cells (OPCs) in the medulla elevated twofold above control levels during EAE and new generation of mature oligodendrocytes was increased as well. Although astrocytes showed hypertrophic reactive phenotype, a new generation of them was rare. Astrocyte- and tanycyte-like neural stem cells (NSCs), multipotent NSCs, did not augment their low proliferative rate. Thus, the present study demonstrates that resident OPCs derived from NSCs contribute to remyelination in the medulla oblongata in EAE mice.

Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function. In this study, we screened the effect of several membrane lipid-derived molecules on the CaN activity and found sphingosine and some sphingosine-derived metabolites such as sphingosylphosphorylcholine, galactosylsphingosine (psychosine), and glucosylsphingosine, have inhibitory effect on CaN through the interaction with calmodulin.