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Epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is a rare benign condition that occasionally mimic malignant pancreatic neoplasms. We present a case of ECIPAS in a 53-year-old asymptomatic male, initially discovered incidentally during imaging for a suspected hepatic hemangioma. The lesion, located in the pancreatic tail, demonstrated characteristic imaging features on contrast-enhanced computed tomography and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI), including a cystic component with peripheral solid tissue exhibiting splenic enhancement patterns. Despite these typical ECIPAS findings, the lesion increased in size from 38 × 33 mm to 50 × 45 mm over 12 months, accompanied by a significant rise in serum carbohydrate antigen 19-9 (CA19-9) from 21 to 330 U/mL. This clinical progression raised concerns about potential malignancy, leading to a robot-assisted spleen-preserving distal pancreatectomy. Histopathological examination confirmed the diagnosis of ECIPAS. Postoperatively, the patient's serum CA19-9 levels normalized. This case highlights that ECIPAS can complicate clinical decision-making through size increase and CA19-9 elevation, complicating preoperative diagnosis. However, careful analysis of imaging characteristics, particularly on SPIO-enhanced MRI, can aid in accurate diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Research Ethics Committee of the University of Tokyo issued approval 2561-(23). Written informed consent was waived due to the retrospective noninvasive nature of the study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsujimoto et al.)

Peliosis hepatis (PH) is a rare benign vascular condition characterized by sinusoidal dilatation and the presence of blood-filled spaces within the liver. PH is often clinically asymptomatic and is discovered incidentally. It presents a clinical challenge as its imaging findings frequently mimic other pathologies, including primary or secondary malignancies and abscesses. In this article, we present a case of a 73-year-old woman with a history of recurrent tongue cancer treated by surgery and chemoradiotherapy, and concurrent multiple myeloma, in whom PH was incidentally discovered. Based on computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging findings prior to biopsy, PH was diagnosed, and pathologically confirmed. Follow-up computed tomography five months after the discontinuation of raloxifene hydrochloride, a selective estrogen receptor modulator and a suspected drug causing PH, the regression of PH lesions was observed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The University of Tokyo research ethics committee issued approval 2561-(23). Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yamada et al.)

Background: Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women., Methods: We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass., Results: Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p<0.001). The multiple linear regression analysis showed that grip strength (p = 0.001), chair stand time (p = 0.004), and functional reach (p = 0.048) were significantly associated with the stiffness index after adjusting for age, body mass index, smoking, drinking, and exercise., Conclusions: Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suiko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have beneficial effects on the renal function of chronic kidney disease (CKD) patients, although the types of patients suitable for this treatment remain unclear., Methods: A retrospective observational study was conducted on CKD patients who were treated with SGLT2I in our department from 2020 to 2023. The estimated glomerular filtration rate (eGFR) just before treatment was defined as the baseline and the difference between pre-and post-treatment eGFR slopes were used to compare the improvement of renal function. Logistic regression analysis was used to evaluate the independent factors for its improvement., Results: A total of 128 patients were analyzed (mean age: 67.2 years; number of women: 28 [22%]). The mean eGFR was 42.1 mL/min/1.73 m2, and urine protein was 0.66 g/gCr. The eGFR slopes of patients with an eGFR &lt;30 mL/min/1.73 m2 were improved significantly after treatment (-0.28 to -0.14 mL/min/1.73 m2/month, p &lt; 0.001) but were worsened in patients with an eGFR ≥30 mL/min/1.73 m2. Logistic analysis for the improvement in eGFR slopes showed that women (odds ratio [OR], 5.63; 95% confidence interval [CI], 1.16-27.3; p = 0.03), use of mineralocorticoid receptor antagonists (OR, 11.79; 95% CI, 1.05-132.67; p = 0.012) and rapid decline of eGFR before treatment (OR, 12.8 per mL/min/1.73 m2/month decrease in eGFR; 95% CI, 3.32-49.40; p &lt; 0.001) were significant independent variables., Conclusion: SGLT2Is may have beneficial effects, especially for rapid decliners of eGFR, including advanced CKD., (© 2024 S. Karger AG, Basel.)

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1β (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 μM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation ( p < 0.01) under IL-1β stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

Background: It is possible that increased synthesis of metallothioneins (MTs), Zn 2+ -binding proteins is linked with the protective effect of Ninjin-yoei-to (NYT) on Zn 2+ toxicity ferried by amyloid β 1-42 (Aβ 1-42 )., Methods: Judging from the biological half-life (18-20 h) of MTs, the effective period of newly synthesized MT on capturing Zn 2+ is estimated to be approximately 2 days. In the present paper, a diet containing 3% NYT was administered to mice for 2 days and then Aβ 1-42 was injected into the lateral ventricle of mice., Results: MT level in the dentate granule cell layer was elevated 2 days after administration of NYT diet, while the administration reduced intracellular Zn 2+ level increased 1 h after Aβ 1-42 injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aβ 1-42 injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aβ 1-42 into the dentate granule cell layer of rats., Conclusion: The present study indicates that pre-administration of NYT diet for 2 days increases synthesis of MTs, which reduces intracellular Zn 2+ toxicity ferried by extracellular Aβ 1-42 , resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aβ 1-42 ., (© 2022. The Author(s).)

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1β (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1β stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.

On the basis of amyloid β (Aβ) peptides as triggers in atrophy of structures in the limbic system, here we postulated that Aβ 1-42 -induced intracellular Zn 2+ toxicity in the basolateral amygdala contributes to conditioned fear memory. Aβ 1-42 increased intracellular Zn 2+ level in the amygdala after local injection of Aβ 1-42 into the basolateral amygdala, resulting in conditioned fear memory deficit via attenuated LTP at perforant pathway-basolateral amygdala synapses. Co-injection of isoproterenol, a beta-adrenergic receptor agonist, reduced Aβ 1-42 -mediated increase in intracellular Zn 2+ , resulting in rescue of the memory deficit and attenuated LTP. The present study suggests that beta-adrenergic activity induced by isoproterenol in the basolateral amygdala rescues the impairment of conditioned fear memory by Aβ 1-42 . The rescuing effect may be linked with reducing Aβ 1-42 -induced intracellular Zn 2+ toxicity. Furthermore, Aβ 1-42 injection into the basolateral amygdala also attenuated LTP at perforant pathway-dentate granule cell synapses, while co-injection of isoproterenol rescued it, suggesting that Aβ 1-42 toxicity in the basolateral amygdala also affects hippocampus-dependent memory. It is likely that beta-adrenergic receptor activation in the basolateral amygdala rescues the limbic system exposed to Aβ 1-42 toxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Regarding epidemiological studies, the role of vitamin D in musculoskeletal functionality (muscle weakness and physical performance) among elderly people is still controversial. The purpose of the present study was to investigate the associations between 25-hydroxyvitamin D [25(OH)D] and physical performance among community-dwelling middle-aged and old Japanese men and women., Methods: The subjects were community-dwelling 297 men and 415 women aged 50 years and over. Data on height (m) and weight (kg) were collected. Serum 25(OH)D, parathyroid hormone, calcium, and albumin levels were measured. Serum 25(OH)D was classified into deficiency group: < 20 ng/mL, insufficiency group: 20-30 ng/mL, and sufficiency group: ≧ 30 ng/mL. Physical performance was assessed by grip strength, chair stand time, and functional reach. Information on current smoking, alcohol drinking, regular exercise, any comorbidities (hypertension, heart disease, diabetes mellitus, lung disease, and stroke), and pain (lumbar and knee) was collected., Results: Vitamin D deficiency and insufficiency based on serum 25(OH)D levels were observed in 15.2% and 56.9% of men and 52.0% and 43.6% of women, respectively. In men, higher serum 25(OH)D levels were associated with better grip strength (p for trend = 0.003), chair stand time (p for trend = 0.042), and functional reach (p for trend <0.001). On the other hand, these parameters were not associated with serum 25(OH)D levels in women., Conclusion: A higher level of serum 25(OH)D was associated with better physical performance in men but not in women., Competing Interests: The authors have declared that no competing interests exist.

We showed an association between serum concentrations of vitamin D and bone health among community-dwelling adults in Japan after adjustment for confounding factors, with 730 participants in a city, with concentrations of 25(OH) vitamin D, and with parameters of quantitative ultrasound., Purpose: The primary objective of this study was to examine the correlation between serum 25-hydroxyvitamin D (25(OH)D) concentration and bone indicators as measured by quantitative ultrasound in middle-aged and older Japanese adults living in low-latitude seaside areas during summer and autumn., Methods: We conducted a cross-sectional study, the Unzen study, on community-dwelling Japanese adults who participated to periodic health examinations between 2011 and 2013 (during the months of May to November)., Results: A total of 301 men (mean (SD) age, 67.9 (8.2) years; range, 50-92 years) and 429 women (mean (SD) age, 67.9 (7.7); range, 50-89 years) participated in this study. Serum 25(OH)D levels and quantitative ultrasound parameters (broadband ultrasound (BUA), speed of sound (SOS), and stiffness index of the calcaneus were measured for the participants. We excluded two men and 28 women from the 730 participants because they were on medication for osteoporosis. So, 299 men and 401 women were included in the final data analysis. The prevalence of vitamin D insufficiency (< 30 ng/ml) was very high: 71.9% in men and 95.5% in women. In women, the log(25(OH)D) positively and significantly correlated with SOS (p = 0.011) and stiffness index (p = 0.028) but not with BUA (p = 0.176). In men, the log(25(OH)D) did not correlate with the BUA, SOS, or stiffness index (p = 0.218, 0.420, and 0.262, respectively)., Conclusions: Serum 25(OH)D levels were associated with SOS or stiffness index in women but not in men., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

The loss of nucleus pulposus (NP) notochordal cells is one of the key initial hallmarks of age-related intervertebral disc degeneration. Although the transmembrane mechanoreceptor integrin α5β1 is important in the process of disc degeneration, the relationship between integrin α5β1 and notochordal cell disappearance remains unclear. The purpose of this study was to elucidate the role of integrin α5β1 in the homeostasis of notochordal cells using an ex-vivo dynamic loading culture system that we developed. Rat tail functional spinal units (n = 80 from 40 rats) were cultured under unloading or 1.3-MPa, 1.0-Hz dynamic compressive loading for 48 or 144 h with or without an integrin α5β1 inhibitor. Disc histomorphology, cell viability, apoptosis, senescence, and phenotypic expression were investigated. Consequently, histological degenerative disc changes with decreased cell viability and increased cell apoptosis and senescence were observed with an extended loading duration. Immunofluorescence revealed that the expression of notochordal cell markers, CD24 and brachyury, and chondrocyte markers, collagen type II and SRY-box 9, declined with loading. In particular, reduction in notochordal cell marker expression was more dramatic than that in chondrocyte marker expression. Apoptotic terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was also higher in brachyury-positive notochordal cells. Furthermore, all these changes were delayed by inhibiting integrin α5β1. Findings of our dynamic loading regimen with a relatively high pressure suggest reproducibility of the cellularity and phenotypic disappearance of NP notochordal cells during adolescence, the susceptibility of notochordal cells to mechanical stimuli partially through the integrin α5β1 pathway, and future potential treatment of integrin regulation for intervertebral disc disease., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Although central hemodynamics are known to be closely associated with microvascular damage, their association with lesions in the small renal arteries has not yet been fully clarified. We focused on arterioles in renal biopsy specimens and analyzed whether their structural changes were associated with noninvasive vascular function parameters, including central blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV). Forty-four nondiabetic patients (18-50 years of age) with preserved renal function underwent renal biopsy. Wall thickening of arterioles was analyzed based on the media/diameter ratio, and hyalinosis was analyzed by semiquantitative grading. Associations of these indexes (arteriolar wall remodeling grade index (RG index) and arteriolar hyalinosis index (Hyl index)) with clinical variables were analyzed. Multiple regression analyses demonstrated that the RG index was significantly associated with central systolic BP (β = 0.97, p = 0.009), serum cystatin C-based estimated glomerular filtration rate (β = -0.36, p = 0.04), and high-density lipoprotein cholesterol levels (β = -0.37, p = 0.02). The Hyl index was significantly associated with baPWV (β = 0.75, p = 0.01). Our results indicate that aortic stiffness and abnormal central hemodynamics are closely associated with renal microvascular damage in young to middle-aged, nondiabetic kidney disease patients with preserved renal function., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Few studies have addressed the impact of palliative surgery for cervical spine metastasis on patients' performance status (PS) and quality of life (QOL). We investigated the surgical outcomes of patients with cervical spine metastasis and the risk factors for a poor outcome with a focus on the PS and QOL., Methods: We prospectively analyzed patients with cervical spine metastasis who underwent palliative surgery from 2013 to 2018. The Eastern Cooperative Oncology Group PS (ECOGPS) and EuroQol 5-Dimension (EQ5D) score were assessed at study enrollment and 1, 3, and 6 months postoperatively. Neurological function was evaluated with Frankel grading. Univariate and multivariate analyses were performed to identify the risk factors for a poor surgical outcome, defined as no improvement or deterioration after improvement of the ECOGPS or EQ5D score within 3 months., Results: Forty-six patients (mean age, 67.5 ± 11.7 years) were enrolled. Twelve postoperative complications occurred in 11 (23.9%) patients. The median ECOGPS improved from PS3 at study enrolment to PS2 at 1 month and PS1 at 3 and 6 months postoperatively. The mean EQ5D score improved from 0.085 ± 0.487 at study enrolment to 0.658 ± 0.356 at 1 month and 0.753 ± 0.312 at 3 months. A poor outcome was observed in 18 (39.1%) patients. The univariate analysis showed that variables with a P value of < 0.10 were sex (male), the revised Tokuhashi score, the new Katagiri score, the level of the main lesion, and the Frankel grade at baseline. The multivariate analysis identified the level of the main lesion (cervicothoracic junction) as the significant risk factor (odds ratio, 5.00; P = 0.025)., Conclusions: Palliative surgery for cervical spine metastasis improved the PS and QOL, but a cervicothoracic junction lesion could be a risk factor for a poor outcome.

Purpose to examine the accuracy and reproducibility of the femoral axial offset measured from the retrocondylar plane by computed tomography (CT). Bone specimens of the femur of 15 males and 15 females were analyzed. CT imaging was performed and data of the coordinates were collected (center of femoral head, center of an ellipse around greater trochanter, center of an ellipse around the base of femoral neck, posterior edge of great trochanter, and both posterior condyles). The angle between the line connecting center of the femoral head and center of an ellipse around greater trochanter and the line connecting both posterior condyles was set as anteversion 1. The angle between the line connecting the center of femoral head and center of an ellipse around base of the femoral neck and the line connecting both posterior condyles was set as anteversion 2. The femoral axial offset was measured from the retrocondylar plane. Measurements were performed three times on the same subject, and intrarater reliability (ICC) was determined. In addition, interrater reliability (ICC) was determined by comparing data from three raters. The mean value for anteversion 1 was 20.1° for males and 22.7° for females. The values for anteversion 2 were 16.0° and 19.9° for males and females, respectively. Offset was 34.0 and 33.4 mm in males and females, respectively. Intrarater ICC and interrater ICC exceeded 0.81 for both methods, suggesting that the method of measurement was reliable. Accuracy and reproducibility of the measurement of femoral axial offset from the retrocondylar plane were high., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM-CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM-CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA-MB-231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM-CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p < 0.05). Local administration of GM-CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM-CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. DESIGN; CROSS-SECTIONAL STUDY: Setting and Participants; The survey population included 1008 postmenopausal women 50-92 years of age residing in rural communities., Methods: Self-reported walking speed was ascertained by asking the participants: "Is your walking speed faster than others of the same age and sex?" to which participants responded "yes (faster)" or "no (moderate/slower)." Calcaneal stiffness index was measured., Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p <  0.001)., Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women.

Background: Proteasomes are found in both the cell nucleus and cytoplasm and play a major role in the ubiquitin-dependent and -independent non-lysosomal pathways of intracellular protein degradation. Proteasomes are also involved in the turnover of various regulatory proteins, antigen processing, cell differentiation, and apoptosis. To determine the diagnostic value of serum proteasome in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we investigated patients with AAV at various stages of the disease., Methods: Serum 20S-proteasome was measured by ELISA in 44 patients with MPO-ANCA-associated microscopic polyangiitis (MPA) and renal involvement. Thirty of the patients provided serum samples before the initial treatment, and 30 provided samples during remission; 16 provided samples at both time points., Results: The mean serum 20S-proteasome level was significantly higher in the active-vasculitis patients (3414.6 ± 2738.9 ng/mL; n  = 30) compared to the inactive-vasculitis patients (366.4 ± 128.4 ng/mL; n  = 30; p  <  0.0001) and 40 controls (234.9 ± 90.1 ng/mL; p  <  0.0001). There were significant positive correlations between the serum 20S-proteasome level and the Birmingham Vasculitis Activity Score (BVAS) ( r  = 0.581, p  <  0.0001), the ANCA titer ( r  = 0.384, p  <  0.0001), the white blood cell (WBC) count ( r  = 0.284, p  = 0.0042), the platelet count ( r  = 0.369, p  = 0.0002), and the serum C-reactive protein (CRP) level ( r  = 0.550, p  < 0.0001). There were significant negative correlations between the serum 20S-proteasome level and both the hemoglobin concentration ( r  = - 0.351, p  = 0.0003) and the serum albumin level ( r  = - 0.460, p  < 0.0001). In a multiple regression analysis, there was a significant positive correlation between the serum 20S-proteasome level and only the BVAS results ( β  = 0.851, p  = 0.0009). In a receiver operating curve analysis, the area under the curve for the serum 20S-proteasome level was 0.996, which is higher than those of the WBC count (0.738) and the serum CRP level (0.963)., Conclusion: The serum level of 20S-proteasome may be a useful marker for disease activity in AAV., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Introduction: In children, the pelvis contains a large amount of cartilage components; therefore, when traumatic hip dislocation spontaneously reduces, it can be impossible to see on X-ray or computed tomography (CT) images in some cases, which can delay its detection., Case Presentation: We report the case of a 10-year-old boy who was injured by being hit by a car while walking. Upon diagnosis of pelvic ring fracture, the patient received conservative treatment. Seven months after injury, the patient was referred to our department with the chief complaint of limping., Diagnosis: Marked limitation was observed in the left hip with extension of -40°, abduction of 10°, and internal rotation of 20°. X-ray revealed narrowing of the left hip joint space, with deformity of the femoral head, obturator foramen narrowing, and the break in the Shenton line. CT revealed proximal dislocation of the posterior acetabular wall and posterior subluxation of the femoral head. Magnetic resonance imaging (MRI) revealed necrosis of the femoral head., Intervention: Operation was performed with soft tissue dissection, varus-extension-internal rotation femoral osteotomy, greater trochanteric epiphysiodesis, and pelvic osteotomy (incomplete periacetabular osteotomy: IPO). After operation, complete paralysis of the sciatic nerve was observed., Outcomes: At 1 year after operation, the patient's limited range of motion (ROM) and femoral head necrosis had improved. The sciatic nerve paralysis had fully recovered., Conclusion: If hip extension, abduction, and internal rotation are limited and X-ray reveals a break in the Shenton line., subluxation of the hip should be suspected., Competing Interests: None., (© 2020 The Authors.)

The far-field pattern of an optical wave radiating from a grating coupler integrated in a directional coupler is discussed based on the coupled mode theory. It is shown that there are two types of intensity distributions with respect to the radiation angle. One type shows a simple single lobe, while the other has a deformed lobe or two lobes. Far-field patterns are discussed along with near-field patterns. They are determined by directional coupling strength as well as radiation decay strength. A parameter is introduced to indicate the type. The indicator is useful as a key parameter for device design.

Introduction: The treatment strategies for residual deformity of Perthes disease are not established., Case Presentation: This is a case report of a 15-year-old boy. He developed right Perthes disease (lateral pillar classification group B) when he was 10 years old and underwent varus femoral osteotomy of the right side. At 12 years of age, he developed left Perthes disease (lateral pillar classification group B) and underwent varus femoral osteotomy of the left side. Postoperatively, he was treated with partial weight bearing of the left leg with crutches. At 15 years, range of motion (ROM) of his left hip was markedly limited at 30° flexion, 10° abduction, 70° external rotation, and -20° internal rotation, and he was having difficulty maintaining a sitting position., Diagnosis: Stulberg group V was noted on plain radiography. Computed tomography (CT) showed collapse of the load-bearing part of the femoral head on the coronal plane, but the ball-shape was maintained in the posterior femoral head on sagittal and transverse sections., Intervensinos: Valgus-flexion-internal rotation osteotomy was performed to improve ROM., Outcomes: Left hip ROM improved to 90° flexion, 20° abduction, 50° external rotation, and 40° internal rotation immediately after the surgery. He was able to sit 10 months postoperatively but was left with a limp and limited ROM in the left hip at 60° flexion. Chondroplasty was performed during the plate removal surgery at 10 months postoperatively, which improved hip flexion to 100° immediately after the surgery. The patient was left with limited ROM of 60° flexion of the left hip at the final observation., Conclusion: Femoral osteotomy to improve ROM could be an option for residual deformity of Perthes disease., Competing Interests: The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Background: An increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women., Methods: The subjects were community-dwelling men (n = 358) and women (n = 503) aged ≥ 40 years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected., Results: Serum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ≥ 80 years than those in the age groups of 40-49, 50-59, and 60-69 years. Serum ucOC concentrations in women were higher in the age groups of 50-59 and 60-69 years than those at 40-49 years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men., Conclusions: Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.

Back pain is a global health problem with a high morbidity and socioeconomic burden. Intervertebral disc herniation and degeneration are its primary cause, further associated with neurological radiculopathy, myelopathy, and paralysis. The current surgical treatment is principally discectomy, resulting in the loss of spinal movement and shock absorption. Therefore, the development of disc regenerative therapies is essential. Here we show reduced disc damage by a new collagen type I-based scaffold through actinidain hydrolysis-Low Adhesive Scaffold Collagen (LASCol)-with a high 3D spheroid-forming capability, water-solubility, and biodegradability and low antigenicity. In human disc nucleus pulposus and annulus fibrosus cells surgically obtained, time-dependent spheroid formation with increased expression of phenotypic markers and matrix components was observed on LASCol but not atelocollagen (AC). In a rat tail nucleotomy model, LASCol-injected and AC-injected discs presented relatively similar radiographic and MRI damage control; however, LASCol, distinct from AC, decelerated histological disc disruption, showing collagen type I-comprising LASCol degradation, aggrecan-positive and collagen type II-positive endogenous cell migration, and M1-polarized and also M2-polarized macrophage infiltration. Reduced nucleotomy-induced disc disruption through spontaneous spheroid formation by LASCol warrants further investigations of whether it may be an effective treatment without stem cells and/or growth factors for intervertebral disc disease., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P  < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P  < .01), indicating bone absorption. This showed no significant difference between the HA spacers ( P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers ( P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.)

The RDT population, initially at 215 patients, exceeded 300,000 in 2011, with a total of 329,609 patients at the end of December 2016. In our Institute, the number of patients with destructive spondylosis is increasing with the increase in the number of dialysis patients in Japan. We had 14 Cases in the 1990s, and then 82 cases in the 2000s and have already had 131 cases in the 2010s. The purpose of this study was to investigate the incidence of dialysis-related amyloidosis (DRA) such as destructive spondyloarthropathy (DSA), dialysis amyloid arthropathy (DAA), and carpal tunnel syndrome (CTS). In addition, another purpose was to examine the risk factors of the DRA. DAA made its own assessment on radiographs based on stage. Survey items were patient's basic data, laboratory data and X-ray view. Patient's basic data included such as sex, age, height, and weight and RDT-related factors such as kidney disease that led to RDT, age at start of RDT, RDT history, medical history (past and present), and history of surgery. The frequency of DRA was examined by medical history and radiological examination in 199 dialysis patients who obtained informed consent. The patients were divided into two groups according to the presence or absence of DRA, and risk factors of DRA were investigated from the medical history, basic data of patients, and blood tests. Of the 199 patients on regular dialysis therapy, 41 (20.6%) showed DRA. Based on the X-ray images, 21 patients (10.6%) showed DSA, while 22 patients (11.1%) showed DAA. Sixteen patients (8.0%) had CTS, determined through a history of surgery. Regarding overlap of conditions, 14 had both DSA and DAA, 3 had both DSA and CTS, and 2 had both DAA and CTS. There were statistically significant differences between the two groups in the cause of disease in Chronic glomerulonephritis and Diabetic Nephropathy, age at the start of RDT, period of RDT, body weight, blood platelet count, and blood Ca level. When multivariate analysis was performed on these items, statistical differences were recognized only during the dialysis period. In conclusion, long dialysis period was a risk factor for DRA.

Introduction Recently, although there are many reports showing that serum magnesium concentration is a predictor of mortality in dialysis patients, the observation periods of those reports were of short duration, typically around 12 months. Thus, we investigated this relationship over a longer follow-up period. Methods This retrospective, observational study included a total of 83 non-diabetic hemodialysis patients. The follow-up period was 120 months. Patients were divided into two groups, those with serum magnesium ≥2.5 mg/dL (Mg ≥2.5 mg/dL group) and serum magnesium <2.5 mg/dL (Mg <2.5 mg/dL group), and Kaplan-Meier analysis and Cox proportional hazards analysis were conducted. In addition to the above analysis, single and multiple regression analysis were performed at baseline to reveal the relationship between serum magnesium and clinical parameters. Findings During the follow-up period, 31 out of 83 patients died. Kaplan-Meier analysis showed a significantly higher incidence of death in the Mg <2.5 mg/dL group (log-rank test 4.951, P = 0.026). Multivariate Cox proportional hazards analysis showed a 62% decreased risk of mortality in the Mg ≥2.5 mg/dL group compared to the Mg <2.5 mg/dL group after adjustment for several confounding factors. Simple correlation coefficient analysis showed positive correlations of serum magnesium levels with serum creatinine, phosphorus, high-density lipoprotein, ankle-brachial index and KT/V, and a negative correlation with age. Multiple linear regression analysis showed that the ankle-brachial index was the only parameter that had a positive and significant correlation with the serum magnesium level. Conclusion Our study demonstrated that higher serum magnesium levels were associated with improved survival in non-diabetic hemodialysis patients., (© 2019 International Society for Hemodialysis.)

Since nitrogenase is extremely vulnerable to oxygen, aerobic or micro-aerobic nitrogen-fixing organisms need to create anaerobic microenvironments in the cells for diazotrophic growth, which would be one of the major barriers to express active nitrogenase in plants in efforts to create nitrogen-fixing plants. Numerous cyanobacteria are able to fix nitrogen with nitrogenase by coping with the endogenous oxygen production by photosynthesis. Understanding of the molecular mechanisms enabling to the coexistence of nitrogen fixation and photosynthesis in nonheterocystous cyanobacteria could offer valuable insights for the transfer of nitrogen fixation capacity into plants. We previously identified the cnfR gene encoding the master regulator for the nitrogen fixation ( nif ) gene cluster in the genome of a nonheterocystous cyanobacterium Leptolyngbya boryana , in addition to initial characterization of the nif gene cluster. Here we isolated nine mutants, in which the nif and nif -related genes were individually knocked out in L. boryana to investigate the individual functions of (1) accessory proteins (NifW, NifX/NafY, and NifZ) in the biosynthesis of nitrogenase metallocenters, (2) serine acetyltransferase (NifP) in cysteine supply for iron-sulfur clusters, (3) pyruvate formate lyase in anaerobic metabolism, and (4) NifT and HesAB proteins. ΔnifW , ΔnifXnafY , and ΔnifZ exhibited the most severe phenotype characterized by low nitrogenase activity (<10%) and loss of diazotrophic growth ability. The phenotypes of ΔnifX , ΔnafY , and ΔnifXnafY suggested that the functions of the homologous proteins NifX and NafY partially overlap. ΔnifP exhibited significantly slower diazotrophic growth than the wild type, with lower nitrogenase activity (22%). The other four mutants ( ΔpflB , ΔnifT , ΔhesA , and ΔhesB ) grew diazotrophically similar to the wild type. Western blot analysis revealed a high correlation between nitrogenase activity and NifD contents, suggesting that NifD is more susceptible to proteolytic degradation than NifK in L. boryana . The phenotype of the mutants lacking the accessory proteins was more severe than that observed in heterotrophic bacteria such as Azotobacter vinelandii , which suggests that the functions of NifW, NifX/NafY, and NifZ are critical for diazotrophic growth of oxygenic photosynthetic cells. L. boryana provides a promising model for studying the molecular mechanisms that produce active nitrogenase, to facilitate the creation of nitrogen-fixing plants.

Objectives　This study aimed to explore the association of difficulties in activities of daily living (ADL) (activities related to bending, spine extension, standing endurance, and walking) with fear of falling among community-dwelling older adults.Methods　We recruited 642 older adults (men, n=267; women, n=375) aged 65 years and over. The mean age was 72.2±5.1 years. Fear of falling, falls in the previous year, pain (low back pain or knee pain), comorbidity, and cataracts were assessed using a self-administered questionnaire. ADL difficulties were assessed individually, such as activities related to bending (getting in or out the car, picking up a lightweight object, putting on socks or stockings, and lifting a 5 kg object from the floor), spine extension (reaching an object above your head), standing endurance (standing on your feet for 2 h), and walking (walking 100 m on a level surface, climbing 10 steps without stopping, and walking down 10 steps). The independent association between fear of falling and each ADL difficulties was assessed using logistic regression analysis.Results　Participants with fear of falling, compared with those without fear of falling, had an older age (74.8 and 71.6 in men, 73.3 and 71.0 in women, respectively; P<0.01), more falls in the previous year (21% and 9% in men, 28% and 11% in women, respectively; P<0.05), pain (80% and 61% in men, 82% and 64% in women, respectively; P<0.01), and comorbidity (23% and 15% in women, respectively; P<0.05). Multivariate logistic regression analysis identified each ADL difficulties except walking 100 m on a level surface as being independently associated with fear of falling after adjusting for age, body mass index, sex, falls in the previous year, pain, and comorbidity.Conclusion　ADL difficulties, such as activities related to bending, spine extension, standing endurance, and walking, except for walking 100 m on a level surface, were associated with fear of falling.

Introduction: The most cases of excessive femoral anteversion may be asymptomatic, because the he hip joint is a ball joint. However, when the hip, knee, or ankle joint is in a pathological state, excessive femoral anteversion may not be compensated for and induce symptoms., Case Report: A 16-year-old female with achondroplasia. Medullary compression by the odontoid process caused right hemiplegia at 10 months after birth and equinus foot concomitantly developed. At 14 years old, right knee pain developed during walking. For treatment, firstly, tenodesis of medial collateral ligament of the knee joint (MCL) was performed. Oblique osteotomy was applied to the proximal MCL attachment site over the distal tibial tuberosity, followed by simple limb lengthening, which improved knee instability. To prevent recurrence of knee instability, varus and derotationosteotomy of the femur and Vulpius procedure (triceps surae muscle lengthening) were additionally performed, and gait stabilized after surgery., Discussion: Regarding the pathogenesis, her gait was originally in-toeing because of excessive femoral anteversion, but the lower leg did not internally rotate during walking because of equinus foot, and the foot grounded in an externally rotated position, loading burdens on the MCL. This condition may have gradually caused instability of the knee over the years., Conclusion: We surgically treated the patient with knee joint valgus instability caused by excessive femoral anteversion and equinus foot and achieved a favorable outcome.

Background: Patients with end-stage renal disease undergoing hemodialysis (HD) have an elevated risk of cardiovascular disease-related morbidity and mortality. To prevent from such a life-threatening event, the continuous blood pressure (BP) monitoring system may contribute to detect BP decline in early stages and may help to do appropriate disposal. Our research team has introduced an electronic stethoscope (Asahi Kasei Co, Ltd., Tokyo, Japan), which translates sound intensity of Arteriovenous Fistula (AVF) to BP data using the technique of Fourier transformation that can predict continuous BP non-invasively. This study, we investigated whether electronic stethoscope-guided estimated BP (e-BP) would actually reflect systolic BP measured by sphygmomanometer (s-BP), and whether e-BP could predict fall of BP during HD., Methods: Twenty-six patients who underwent HD treatment in our hospital were evaluated prospectively. We obtained sound intensity data from the electronic stethoscope which was equipped with the return line of HD. Then, the data were translated into e-BP data to be compared with s-BP. Correlation of total of 315 data sets obtained from each method was examined. An accuracy of diagnosis of intra-dialytic hypotension (IDH) was evaluated., Results: Total of 315 data sets were obtained. A close correlation was observed between e-BP and s-BP (r = 0.887, p < 0.0001). Sensitivity and positive predictive value of predicted-BP for detection of IDH was 90 and 81.3%, respectively., Conclusions: Electronic stethoscope-guided BP measurement would be helpful for real-time diagnosis of BP fall in HD patients. Further investigations are needed.

Transfer of nitrogen fixation ability to plants, especially crops, is a promising approach to mitigate dependence on chemical nitrogen fertilizer and alleviate environmental pollution caused by nitrogen fertilizer run-off. However, the need to transfer a large number of nitrogen fixation (nif) genes and the extreme vulnerability of nitrogenase to oxygen constitute major obstacles for transfer of nitrogen-fixing ability to plants. Here we demonstrate functional expression of a cyanobacterial nitrogenase in the non-diazotrophic cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803). A 20.8-kb chromosomal fragment containing 25 nif and nif-related genes of the diazotrophic cyanobacterium Leptolyngbya boryana was integrated into a neutral genome site of Synechocystis 6803 by five-step homologous recombination together with the cnfR gene encoding the transcriptional activator of the nif genes to isolate CN1. In addition, two other transformants CN2 and CN3 carrying additional one and four genes, respectively, were isolated from CN1. Low but significant nitrogenase activity was detected in all transformants. This is the first example of nitrogenase activity detected in non-diazotrophic photosynthetic organisms. These strains provide valuable platforms to investigate unknown factors that enable nitrogen-fixing growth of non-diazotrophic photosynthetic organisms, including plants.

To determine the prevalence of fear of falling and associated factors among Japanese community-dwelling older adults.Cross-sectional study between 2011 and 2013.Community in which residents voluntarily attended a health examination.We recruited 844 older adults (male, n = 350; female, n = 494) aged 60 to 92 years from among those who presented at the health examination.We assessed fear of falling, falls in the previous year, pain, comorbidity, and cataracts. Five times chair stand time was applied as an indicator of physical performance.The prevalence of fear of falling was 26.9% and 43.3% among the men and women, respectively. Men and women who feared falling were older (P < .01), had longer 5 times chair stand time (P < .01), and more falls in the previous year (P < .05), pain (P < .01), and comorbidity (P < .05). Multivariate logistic regression analysis identified advanced age (odds ratios [OR], 1.57; 95% confidence interval [CI], 1.03-2.39), falls in the previous year (OR, 2.44; 95%CI, 1.29-4.64), and pain (OR, 1.82; 95%CI, 1.03-3.22) in men, and advanced age (OR, 1.59; 95%CI, 1.13-2.24), longer 5 times chair stand times (OR, 1.28; 95%CI, 1.04-1.59), falls in the previous year (OR, 2.59; 95%CI, 1.54-4.34), and pain (OR, 1.65; 95%CI, 1.06-2.55) in women as being independently associated with fear of falling.The prevalence of fear of falling was similar to previous reports. Advanced age, falls in previous year, and pain were associated with fear of falling in men. A longer 5 times chair stand time was also associated with fear of falling among older adult women. Maintenance of physical function and pain management might be important for older adults with fear of falling.

Residual renal function (RRF) is a strong prognostic factor of morbidity and mortality in patients undergoing peritoneal dialysis (PD). We determined predictors of the RRF rate of decline using both baseline values and time-averaged ones. We retrospectively analyzed 94 patients being treated with PD at the Japanese Red Cross Medical Center. The decline rate of RRF was calculated by a diminution in the weekly renal Kt/V between the first and last follow up divided by follow-up years. The mean follow-up period was 2.28 years, and the mean decline rate of weekly renal Kt/V was 0.25 per year. A multivariate analysis using baseline parameters identified dialysis-to-plasma ratios of creatinine at 4 h (P = 0.02), urinary protein (P = 0.02), and mean blood pressure (MBP) (P < 0.01) as being positively associated with the RRF rate of decline, while the use of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) had a negative correlation (P = 0.03). When using time-averaged values as independent variables, a lower weekly total renal Kt/V (P < 0.0001), higher urinary protein (P < 0.0001), and higher MBP (P = 0.04) independently predicted a faster RRF rate of decline. We demonstrated that PD patients with a lower MBP and lower urinary protein both at baseline and throughout their PD duration had a slower RRF rate of decline. We recommend strict control of blood pressure and anti-proteinuric therapy for PD patients., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Aim: The purposes of the present study were to investigate risk factors for incident disability in activities of daily living (ADL) among middle-aged and older women, and to determine whether there are differences in risk factors according to age groups., Methods: The participants were 264 Japanese women aged 40 years and older. A self-administered questionnaire was used to survey participants about difficulty in carrying out selected basic and instrumental ADL at baseline and at follow up. ADL disability was defined as difficulty carrying out three or more ADL. Information on knee joint or back pain and comorbidities (heart disease, lung disease, stroke or diabetes mellitus) was obtained using a self-administered questionnaire at baseline. Physical performance measurements (grip strength, chair stand time, rapid walking speed and functional reach) were also carried out at baseline., Results: The prevalence of incident ADL disability was 44 (27.5%) in women aged 40-64 years, and 57 (54.8%) in women aged ≥65 years (P < 0.001). Multiple logistic regression analysis showed that decreased grip strength and having pain were significantly associated with a higher risk for incident ADL disability among women aged 40-64 years. For women aged ≥65 years, decreased rapid walking speed, having a comorbidity and having pain were associated with incident ADL disability., Conclusions: The present study showed that a different set of risk factors was associated with incident ADL disability among women aged 40-64 years and women aged ≥65 years. Age-specific screening and intervention strategies are necessary for effective prevention of incident ADL disability. Geriatr Gerontol Int 2017; 17: 1096-1101., (© 2016 Japan Geriatrics Society.)

Background: Lumbar spondylosis is more prevalent among the middle-aged and elderly, but few population-based studies have been conducted, especially in Japan. The purpose of this study was to explore the prevalence of lumbar spondylosis and its associations with low back pain among community-dwelling Japanese women., Methods: Lateral radiographs of the lumbar spine were obtained from 490 Japanese women ≥ 40 years old, and scored for lumbar spondylosis using the Kellgren-Lawrence (KL) grade at lumbar intervertebral level from L1/2 to L5/S1. Height and weight were measured, and body mass index (BMI) was calculated. Low back pain in subjects was assessed using a self-administered questionnaire. Stiffness index (bone mass) was measured at the calcaneal bone using quantitative ultrasound., Results: Prevalence of radiographic lumbar spondylosis for KL ≥ 2, KL ≥ 3 and low back pain were 76.7%, 38.8% and 20.0%, respectively. Age was positively associated with radiographic lumbar spondylosis (KL = 2, KL ≥ 3) and low back pain. Greater BMI was associated with lumbar spondylosis with KL = 2, but not with KL ≥ 3. Stiffness index was associated with neither radiographic lumbar spondylosis nor low back pain. Multiple logistic regression analysis identified radiographic lumbar spondylosis (KL ≥ 3) at L3/4, L4/5 and L5/S1 was associated with low back pain, independent of age, BMI and stiffness index., Conclusion: Severe lumbar spondylosis at the middle or lower level may contribute to low back pain.

The filamentous cyanobacterium Leptolyngbya boryana has the ability to fix nitrogen without any heterocysts under microoxic conditions. Previously, we identified the cnfR gene for a master transcriptional activator for nitrogen fixation (nif) genes in a 50-kb gene cluster containing nif and nif-related genes in L. boryana. We showed that CnfR activates the transcription of nif genes in response to low oxygen conditions, which allows the oxygen-vulnerable enzyme nitrogenase to function. However, the regulatory mechanism that underlies regulation by CnfR remains unknown. In this study, we identified a conserved cis-acting element that is recognized by CnfR. We established a reporter system in the non-diazotrophic cyanobacterium Synechocystis sp. PCC 6803 using luciferase genes (luxAB). Reporter analysis was performed with a series of truncated and modified upstream regulatory regions of nifB and nifP. The cis-element can be divided into nine motifs I-IX, and it is located 76 bp upstream of the transcriptional start sites of nifB and nifP. Six motifs of them are essential for transcriptional activation by CnfR. This cis-acting element is conserved in the upstream regions of nif genes in all diazotrophic cyanobacteria, including Anabaena and Cyanothece, thereby suggesting that the transcriptional regulation by CnfR is widespread in nitrogen-fixing cyanobacteria., (© 2016 John Wiley & Sons Ltd.)

Chlorophyll a (Chl) is a light-absorbing tetrapyrrole pigment that is essential for photosynthesis. The molecule is produced from glutamate via a complex biosynthetic pathway comprised of at least 15 enzymatic steps. The first half of the Chl pathway is shared with heme biosynthesis, and the latter half, called the Mg-branch, is specific to Mg-containing Chl a. Bilin pigments, such as phycocyanobilin, are additionally produced from heme, so these light-harvesting pigments also share many common biosynthetic steps with Chl biosynthesis. Some of these common steps in the biosynthetic pathways of heme, Chl and bilins require molecular oxygen for catalysis, such as oxygen-dependent coproporphyrinogen III oxidase. Cyanobacteria thrive in diverse environments in terms of oxygen levels. To cope with Chl deficiency caused by low-oxygen conditions, cyanobacteria have developed elaborate mechanisms to maintain Chl production, even under microoxic environments. The use of enzymes specialized for low-oxygen conditions, such as oxygen-independent coproporphyrinogen III oxidase, constitutes part of a mechanism adapted to low-oxygen conditions. Another mechanism adaptive to hypoxic conditions is mediated by the transcriptional regulator ChlR that senses low oxygen and subsequently activates the transcription of genes encoding enzymes that work under low-oxygen tension. In diazotrophic cyanobacteria, this multilayered regulation also contributes in Chl biosynthesis by supporting energy production for nitrogen fixation that also requires low-oxygen conditions. We will also discuss the evolutionary implications of cyanobacterial tetrapyrrole biosynthesis and regulation, because low oxygen-type enzymes also appear to be evolutionarily older than oxygen-dependent enzymes.

Although cyanobacteria are photoautotrophs, they have the capability for heterotrophic metabolism that enables them to survive in their natural habitat. However, cyanobacterial species that grow heterotrophically in the dark are rare. It remains largely unknown how cyanobacteria regulate heterotrophic activity. The cyanobacterium Leptolyngbya boryana grows heterotrophically with glucose in the dark. A dark-adapted variant dg5 isolated from the wild type (WT) exhibits enhanced heterotrophic growth in the dark. We sequenced the genomes of dg5 and the WT to identify the mutation(s) of dg5. The WT genome consists of a circular chromosome (6,176,364 bp), a circular plasmid pLBA (77,793 bp) and two linear plasmids pLBX (504,942 bp) and pLBY (44,369 bp). Genome comparison revealed three mutation sites. Phenotype analysis of mutants isolated from the WT by introducing these mutations individually revealed that the relevant mutation is a single adenine insertion causing a frameshift of cytM encoding Cyt c(M). The respiratory oxygen consumption of the cytM-lacking mutant grown in the dark was significantly higher than that of the WT. We isolated a cytM-lacking mutant, ΔcytM, from another cyanobacterium Synechocystis sp. PCC 6803, and ΔcytM grew in the dark with a doubling time of 33 h in contrast to no growth of the WT. The respiratory oxygen consumption of ΔcytM grown in the dark was about 2-fold higher than that of the WT. These results suggest a suppressive role(s) for Cyt cM in regulation of heterotrophic activity., (© The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Little research has been done on the prevalence of Kienböck's disease, and there is no consensus on the relationship between Kienböck's disease and negative ulnar variance. The goal of this cross-sectional study was to determine the prevalence of Kienböck's disease in middle-aged and elderly Japanese women and to clarify the relationship between Kienböck's disease and negative ulnar variance. The authors analyzed plain radiographs of both hands in women 40 years and older residing in the community to investigate the prevalence of Kienböck's disease and the relationship between Kienböck's disease and negative ulnar variance. Kienböck's disease was seen in 7 of the 572 participants. In the group with Kienböck's disease, ulnar variance did not differ significantly between affected (0.3 mm; SD, 1.5) and unaffected (0.3 mm; SD, 1.0; P=.285) sides. No significant difference was seen in ulnar variance values between the affected side in the group with Kienböck's disease and the normal group (P=.118). The number or proportion of participants with negative ulnar variance did not differ significantly between the affected side in the group with Kienböck's disease (3 of 7) and the unaffected side in the group with Kienböck's disease (1 of 7; P=.237) and between the affected side in the group with Kienböck's disease and the normal group (111 of 504; P=.189) by chi-square test. The prevalence of Kienböck's disease was 1.2% in middle-aged and elderly Japanese women. Negative ulnar variance is not a contributing factor to Kienböck's disease., (Copyright 2015, SLACK Incorporated.)

Acute arterial occlusions are a rare complication of total knee arthroplasty (TKA). However, in revision TKA, the risk of such complications is higher and these complications can lead to amputation if not adequately treated. We describe a case of acute popliteal artery occlusion 4 hours after second revision TKA in a patient with a history of several surgical procedures because of periprosthetic infection at a previous hospital. Revascularization was achieved via bypass grafting and amputation was narrowly avoided despite time lag after symptom onset to revascularization. In this case, it was possible that the arterial disease that accompanied the vascular endothelium injury such as pseudoaneurysm had existed since the previous surgery at another hospital and was destroyed by the surgical procedure, which led to the formation of thrombosis and arterial occlusion. Preoperative evaluation of the arterial condition should be considered to avoid acute arterial occlusive disease, especially in patients who had several previous surgical procedures.

Leptolyngbya boryana (Plectonema boryanum) is a diazotrophic cyanobacterium lacking heterocysts. How nitrogen fixation is regulated in filamentous nonheterocystous cyanobacteria remains unclear. Here we describe a large 50-kb nitrogen fixation (nif) gene cluster in L. boryana containing 50 genes. This gene cluster contains 14 nif genes (nifBSUHDKVZT and nifPENXW), two genes encoding transcriptional regulators showing high similarity to ChlR (chlorophyll regulator) and PatB, three genes encoding ferredoxin, three genes encoding cytochrome oxidase subunits, and 28 genes encoding nif-related proteins and proteins with putative or unknown functions. Eleven mutants lacking one gene or a subset of genes were isolated. Five of them did not grow under diazotrophic conditions, including two mutants lacking the transcriptional regulators. Although the chlR homolog-lacking mutant showed a normal level of nitrogenase activity, various intermediates of chlorophyll biosynthesis were accumulated under micro-oxic conditions. The phenotype suggested that ChlR activates the expression of the genes responsible for anaerobic chlorophyll biosynthesis to support energy supply for nitrogen fixation. In another mutant lacking the patB homolog, no transcripts of any nif genes were detected under nitrogen fixation conditions, which was consistent with no activity. Constitutive expression of patB in a shuttle vector resulted in low but significant nitrogenase activity even under nitrate-replete conditions, suggesting that the PatB homolog is the master regulator of nitrogen fixation. We propose to rename the patB homolog as cnfR, after cyanobacterial nitrogen fixation regulator.

Nitrogen is the most important macronutrient in plants and its supply induces responses in gene expression, metabolism and developmental processes. However, the molecular mechanisms underlying the nitrogen responses remain poorly understood. Here we show that the supply of nitrate but not ammonium immediately induces the expression of a transcriptional repressor gene in rice, designated NIGT1 (Nitrate-Inducible, GARP-type Transcriptional Repressor 1). The results of DNA-binding site selection experiments and electrophoretic mobility shift assays indicated that NIGT1 binds to DNA containing either of two consensus sequences, GAATC or GAATATTC. In transient reporter assays, NIGT1 was found to repress transcription from the promoters containing the identified NIGT1-binding sequences in vivo. Furthermore, NIGT1 repressed the activity of its own promoter, suggesting an autorepression mechanism. Consistently, nitrate-induced NIGT1 expression was found to be down-regulated after a transient peak during nitrate treatment, and the nitrate-induced expression of NIGT1 decreased in transgenic rice plants in which this gene was constitutively overexpressed. Furthermore, the chlorophyll content that could be a marker of nitrogen utilization was found to be decreased in NIGT1 overexpressors of rice grown with nitrate medium but not with ammonium medium. Thus, we propose NIGT1 as a nitrate-inducible and autorepressible transcriptional repressor that may play a role in the nitrogen response in rice. Taken together with the fact that the NIGT1-binding sites are conserved in promoter sequences of Arabidopsis NIGT1 homologs, our findings imply the presence of a time-dependent complex system for nitrate-responsive transcriptional regulation that is conserved in both monocots and dicots.

HtrA1, a member of the mammalian HtrA serine protease family, has a highly conserved protease domain followed by a PDZ domain. Because HtrA1 is a secretory protein and has another functional domain with homology to follistatin, we examined whether HtrA1 functions as an antagonist of Tgfbeta family proteins. During embryo development, mouse HtrA1 was expressed in specific areas where signaling by Tgfbeta family proteins plays important regulatory roles. The GST-pulldown assay showed that HtrA1 binds to a broad range of Tgfbeta family proteins, including Bmp4, Gdf5, Tgfbetas and activin. HtrA1 inhibited signaling by Bmp4, Bmp2, and Tgfbeta1 in C2C12 cells, presumably by preventing receptor activation. Experiments using a series of deletion mutants indicated that the binding activity of HtrA1 required the protease domain and a small linker region preceding it, and that inhibition of Tgfbeta signaling is dependent on the proteolytic activity of HtrA1. Misexpression of HtrA1 near the developing chick eye led to suppression of eye development that was indistinguishable from the effects of noggin. Taken together, these data indicate that HtrA1 protease is a novel inhibitor of Tgfbeta family members.

Fatty acids of Ophiuroidea (brittle star) Ophiura sarsi have been investigated by gas-liquid chromatography (GLC). About 2-13% of four unidentified fatty acids were found in total fatty acids from a sample caught at a depth of 1,100 m. Structural analyses were undertaken after partial hydrogenation of their concentrates with hydrazine hydrate and subsequent isolation of the monoenoate products by argentation thin-layer chromatography. The structures of the unidentified fatty acids were determined as 7E,13E-eicosadienoic (20:2), 7E,13E,17Z-eicosatrienoic (20:3), 9E,15E,19Z-docosatrienoic (22:3), and 4Z,9E,15E,19Z-docosatetraenoic (22:4) acids by gas chromatography-mass spectrometry of dimethyl disulfide adducts and GLC of the monoenoates on a polar column. These fatty acids belong to a family of nonmethylene-interrupted (NMI) polyunsaturated fatty acids frequently observed in marine invertebrates and conifer seeds. As far as the authors know, however, these NMI fatty acid types with mixed geometry of ethylenic bonds have not been reported previously.

This paper discusses a new type of comparison group for research on adult survivors of child sexual abuse (CSA). A No Sexual Trauma Comparison Group excludes women who have experienced, during adulthood, a sexual trauma similar in impact to CSA. Using this type of comparison group increases sensitivity to (i.e., the likelihood of detecting) clinically relevant characteristics of CSA survivors.