SMPDL3b modulates insulin receptor signaling in diabetic kidney disease.

Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in the PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identify SMPDL3b as a modulator of insulin signaling and demonstrate that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

OBJECTIVE: The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. METHODS: We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. RESULTS: DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). CONCLUSION: This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort.

The association between dentition status and sarcopenia in Japanese adults aged ≥75 years.

Sarcopenia is an age-related loss of muscle mass and muscle strength or physical performance. There are limited data on the association between oral health and sarcopenia. To test the hypothesis that impaired dentition status was associated with sarcopenia, we conducted a cross-sectional study. A total of 272 community-dwelling Japanese adults aged ≥75 years for whom data were available from comprehensive health examinations conducted in 2015 were included in this study. During dental examination, the number of natural teeth and occluding pairs of natural teeth was counted. In denture wearers, the fit of the removable dentures was also evaluated. The criteria proposed by the Asian Working Group for Sarcopenia were used to define sarcopenia. A multivariable logistic regression model was used to evaluate the association between dentition status and the presence of sarcopenia. The prevalence of sarcopenia was 25·7% (70/272). Compared to individuals with ≥10 occluding pairs of natural teeth, those with no occluding pairs of natural teeth had significantly higher risk of having sarcopenia (adjusted odds ratio, 3·37; 95% confidence interval, 1·07-10·61), after adjusting for possible confounders. In addition, compared to individuals with well-fitting dentures, those with ill-fitting dentures had significantly higher risk of having sarcopenia (adjusted odds ratio, 5·07; 95% confidence interval, 1·59-16·19). Our findings suggest that impaired dentition status is significantly associated with sarcopenia among community-dwelling Japanese adults aged ≥75 years. Future longitudinal studies with larger, more diverse populations are necessary to validate our findings.

Longitudinal relationship of severe periodontitis with cognitive decline in older Japanese.

BACKGROUND AND OBJECTIVE: Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined the longitudinal relationship of periodontitis with cognitive decline in 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom data were available from comprehensive health examinations conducted in 2010 and 2013. MATERIAL AND METHODS: Based on a baseline full-mouth periodontal examination, severe periodontitis was defined using a Centers for Disease Control and Prevention/American Academy of Periodontology definition. Cognitive decline during the 3-year study period was defined using the results of the Mini-Mental State Examination (MMSE). Information on age, gender, education, depression, body mass index, smoking status, alcohol use, exercise, hypertension, diabetes, history of cardiovascular disease and stroke, and baseline MMSE scores were obtained and tested as potential confounders in the statistical models. RESULTS: Among 85 study participants, 21 (24.7%) were defined as having severe periodontitis. Multivariable Poisson regression analyses revealed that severe periodontitis was significantly associated with an increased risk of cognitive decline [adjusted relative risk = 2.2; 95% confidence interval (95% CI): 1.1-4.5]. Furthermore, multivariable linear regression analyses revealed that participants with severe periodontitis had a 1.8-point greater decrease (95% CI: -3.3 to -0.2) in MMSE score than those without severe periodontitis. CONCLUSION: Within the limitations related to its small sample size, the findings of the present study suggest that severe periodontitis is significantly associated with future decline in cognitive function among community-dwelling older Japanese subjects.

Association between dental status and food diversity among older Japanese.

OBJECTIVE: To investigate the relationship of dental status to food diversity among older Japanese. DESIGN AND SETTING: A community-based cross-sectional study conducted in the town of Tosa, Kochi Prefecture, Japan. METHODS: The study participants were 252 Japanese (84 men and 168 women, average age 81.2 years) and dentate participants were classified into three groups: 1-9 teeth, 10-19 teeth and 20 or more teeth. Food diversity was assessed as a validated measure of dietary quality using the 11-item Food Diversity Score Kyoto (FDSK-11), which evaluates frequency of consumption of 11 main food groups. Multivariable analysis of the differences in FDSK-11 score ranging from 0 to 11, with a higher score indicating greater food diversity, among the three dental status groups was conducted using general linear models. All the performed analyses were stratified by gender. RESULTS: There was no association between dental status and food diversity score in models for men. In contrast, women with ≤ 9 teeth and with 10-19 teeth had significantly lower FDSK-11 scores than women with ≥ 20 teeth after adjusting for confounders (p < 0.001 and p = 0.009, respectively). Additionally, there was a trend toward lower scores for FDSK-11 with fewer teeth (p = 0.001). CONCLUSION: A less varied diet, as indicated by low FDSK-11 score, was observed in female participants with fewer teeth. Tooth loss was associated with poor diet quality among older Japanese women.

Prevalence and progression of radiographic ossification of the posterior longitudinal ligament and associated factors in the Japanese population: a 3-year follow-up of the ROAD study.

SUMMARY: The prevalence of radiographic cervical ossification of the posterior longitudinal ligament (OPLL) in 1,562 Japanese from a population-based cohort was 1.9 %. The presence of OPLL showed a significant association with the femoral neck bone mineral density (BMD), presence of diffuse idiopathic skeletal hyperostosis (DISH) and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. INTRODUCTION: The purpose of this study was to clarify the prevalence and progression of radiographic OPLL and the associated factors, using the population-based cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: In the ROAD study, 1,690 participants underwent X-ray examination of the entire spine and both knees. Radiographic OPLL, lumbar spondylosis, knee osteoarthritis and DISH were diagnosed by a single, well-experienced orthopaedic surgeon. An interviewer-administered questionnaire and tests for anthropometric measurements were administered, and the BMDs of the lumbar spine and proximal femur were determined. A new OPLL case was considered if heterotopic ossification in the posterior longitudinal ligament was absent at baseline but present during follow-up. Progression was defined as an increase in the maximum length or width of the ossification at follow-up over that at baseline. RESULTS: Radiographic OPLL was detected in 30 (17 men, 13 women) of 1,562 individuals who underwent X-ray examination of the cervical spine (prevalence = 1.9 %). Its prevalence was significantly higher in men than in women (p = 0.007), but no association with age was observed. In a logistic regression analysis, OPLL showed a significant association with the femoral neck BMD, presence of DISH and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. CONCLUSION: This population-based study clarified the prevalence of radiographic OPLL in the Japanese population as well as its progression. OPLL showed significant association with plasma pentosidine levels, BMD and DISH.

Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study.

OBJECTIVES: The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD. DESIGN: This study included 975 participants (324 men, mean age of 67.2 years; 651 women, mean age of 66.0 years) with an age range of 21-97 years in the Wakayama Spine Study. DD on MRI was classified into Pfirrmann's system (grades 4 and 5 indicating DD). We assessed the prevalence of DD at each level in the cervical, thoracic, and lumbar regions and the entire spine, and examined DD-associated factors and symptoms. RESULTS: The prevalence of DD over the entire spine was 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6 (men: 51.5%, women: 46%), T6/7 (men: 32.4%, women: 37.7%), and L4/5 (men: 69.1%, women: 75.8%). Age and obesity were associated with the presence of DD in all regions. Low back pain was associated with the presence of DD in the lumbar region. CONCLUSION: The current study established the baseline data of DD over the entire spine in a large population of elderly individuals. These data provide the foundation for elucidating the causes and mechanisms of DD.

Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study.

OBJECTIVE: Many asymptomatic individuals have radiographic lumbar spinal stenosis (LSS), but the prevalence of symptoms among individuals with radiographic LSS has not yet been established. The purpose of this study was to clarify the association between radiographic LSS and clinical symptoms in the general population. METHODS: In this cross-sectional study, data from 938 participants (308 men, 630 women; mean age, 66.3 years; range, 40-93 years) were analyzed. The severity of radiographic LSS, including central stenosis, lateral stenosis, and foraminal stenosis, was assessed by mobile magnetic resonance imaging and rated qualitatively. Assessment of clinical symptoms was based on the definition of symptomatic LSS in the North American Spine Society guideline. RESULTS: We found that 77.9% of participants had more than moderate central stenosis and 30.4% had severe central stenosis. Logistic regression analysis after adjustment for age, sex, body mass index, and severity of radiographic LSS showed that severe central stenosis was related to clinical symptoms. However, only 17.5% of the participants with severe central stenosis were symptomatic. CONCLUSION: Although radiographic LSS was common in our cohort, which resembled the general Japanese population, symptomatic persons were relatively uncommon.

Physical performance, bone and joint diseases, and incidence of falls in Japanese men and women: a longitudinal cohort study.

SUMMARY: This study examined whether physical performance and bone and joint diseases were risk factors for falls in 745 men and 1,470 women from the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study (mean, 69.7 years). Slower walking speed was a risk factor for falls in men and women. Knee pain was a risk factor for falls in women. INTRODUCTION: The objective of the present study was to clarify the incidence of falls by sex and age and to determine whether physical performance and bone and joint diseases are risk factors for falls in men and women using a large-scale population-based cohort of the ROAD. METHODS: A total of 745 men and 1,470 women were analyzed in the present study (mean age, 68.5 years). A questionnaire assessed the number of falls during 3 years of follow-up. Grip strength and walking speed were measured at baseline. Knee and lumbar spine radiographs were read by Kellgren-Lawrence (KL) grade; radiographic knee osteoarthritis and lumbar spondylosis were defined as KL = 3 or 4. Knee and lower back pain were estimated by an interview. RESULTS: During a mean follow-up of 3 years, 141 (18.9 %) men and 362 (24.6 %) women reported at least one fall. Slower walking speed was a risk factor for falls in men (0.1 m/s decrease; odds ratio [OR], 1.15; 95 % confidence interval [CI], 1.09-1.23) and women (0.1 m/s decrease; OR, 1.05; 95 % CI, 1.01-1.10). Knee pain was also a risk factor for falls (OR, 1.38; 95 % CI, 1.03-1.84) in women, but lower back pain was not. CONCLUSION: We examined the incidence and risk factors for falls in men and women. Slower walking speed was a risk factor for falls in men and women. Knee pain was a risk factor for falls in women.

Eating alone among community-dwelling Japanese elderly: association with depression and food diversity.

UNLABELLED: Eating alone is an emerging social concern these days along with the background of serious aging population growth and increasing number of single-dwellers in Japan. However, little study is focused eating alone and its relation to the health status of community-dwelling elderly. OBJECTIVES: To clarify the relations between eating alone and geriatric functions such as depression, quantitative subjective quality of life (QOL), activities of daily living (ADL) and dietary status of community-dwelling Japanese elderly. DESIGN: A cross-sectional study. SETTINGS: Tosa town, one of the "super-aged" towns in Japan. PARTICIPANTS: The study population consisted of 856 community-dwelling elderly aged ≥65 living in Tosa town. MEASUREMENTS: Eating alone and living arrangement was defined by the questionnaire. Geriatric functions were assessed by measuring activities of daily living (ADL), depressive symptom using 15-item geriatric depression scale (GDS-15), and quality of life (QOL). Food diversity was investigated as a measure of dietary quality using 11-item Food Diversity Score Kyoto (FDSK-11). Body mass index (BMI) was calculated using height and body weight during a medical assessment. RESULTS: The proportion of the elderly who usually eat alone was 33.2% in this study population. Even among 697 elderly subjects who live with others, 136 persons (19.5%) ate alone. The participants who ate alone were significantly depressed according to the assessment using GDS-15 score (5.7±4.3 vs. 4.4±3.8, P<0.001). Those who ate alone have lower scores of QOL items than those who ate with others (Subjective sense of health: 52.5±21.9 vs. 55.7±20.2 P=0.035, Relationship with family: 74.1±23.5 vs. 78.9±18.6 P<0.001, Subjective happiness: 58.5±22.7 vs. 62.2±21.1 P=0.019). A significant close association was found between eating alone and lower food diversity (FDSK-11 score 9.9±1.3 vs. 10.2±1.3, P=0.002). BMI was lower in the elderly subjects who ate alone than those with others. By the multivariate analysis, depression was independently associated with eating alone in the logistic regression model adjusted for age, sex, BMI and food diversity as confounding factors (OR: 1.42, CI: 1.00-2.11, P=0.043). Food diversity was also significantly associated even after the adjustment of these confounding factors. CONCLUSION: Eating alone is an important issue related to depression and QOL as well as dietary status of community-dwellingl elderly in Japan. This study shows the simple and inexpensive way "eating together" may contribute to improve depressive mood of elderly persons, with a strong message that supports of family, friends and neighbors are very important.

Prevalence of symptomatic lumbar spinal stenosis and its association with physical performance in a population-based cohort in Japan: the Wakayama Spine Study.

OBJECTIVE: The purpose of this study was to investigate the prevalence of symptomatic lumbar spinal stenosis (LSS) and to clarify the association between symptomatic LSS and physical performance using magnetic resonance imaging (MRI) in a population-based cohort. DESIGN: This cross-sectional study was performed as a part of the research on osteoarthritis/osteoporosis against disability (ROAD) in Japan and 1,009 subjects (335 men, 674 women, mean age 66.3 years, age range 21-97 years) were analyzed. An experienced orthopedic surgeon obtained the medical history and performed the physical testing for all participants. Symptomatic LSS diagnostic criteria required the presence of both symptoms and radiographic LSS findings. A 6-m walking time, chair standing time, and one-leg standing time were obtained from all participants. RESULTS: The prevalence of symptomatic LSS was 9.3% (95% confidence interval [CI]: 7.7-11.3) overall, 10.1% (CI: 7.4-13.8) in men and 8.9% (CI: 7.0-11.3) in women. There was a difference in the prevalence with increasing age by gender. The LSS prevalence showed little difference with age greater than 70 years for men, but the LSS prevalence for women was higher with increasing age. Among physical performance measures, 6-m walking time at a maximal pace was significantly associated with symptomatic LSS (P = 0.03). CONCLUSION: The prevalence of symptomatic LSS was approximately 10% in a cohort resembling the general Japanese population. A 6-m walking time at a maximal pace was a more sensitive index than walking at a usual pace in assessing decreased physical performance associated with symptomatic LSS.

Incidence and risk factors for radiographic lumbar spondylosis and lower back pain in Japanese men and women: the ROAD study.

OBJECTIVE: To determine the incidence of radiographic lumbar spondylosis (LS)and lower back pain, and their risk factors in Japan using a large-scale population from the nationwide cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD) Study. METHODS: Participants in the ROAD study who had been recruited between 2005 and 2007 were followed up with lumbar spine radiography for 3 years. A total of 2,282 paired radiographs (75% of the original sample) were scored using Kellgren and Lawrence (KL) grades, and the incidence and progression rate of radiographic LS was analyzed. The incidence of lower back pain was also examined. In addition, associations between risk factors and incident and progressive radiographic LS as well as incident lower back pain were tested. RESULTS: Given a 3.3-year follow-up, the incidence of KL≥2 radiographic LS was 50.0% and 34.4% (15.3% and 10.5% per year), while that of KL≥3 LS was 15.3% and 23.7% (4.6% and 7.2% per year) in men and women, respectively. The progression rate of LS was 20.5% and 27.4% (6.2% and 8.3% per year) in men and in women, respectively. In addition, the incidence of lower back pain was 28.3% and 31.2% (8.6% and 9.5% per year) in men and women. Lower back pain was not significantly associated with incident radiographic LS, while a more severe KL grade at baseline was associated with incident lower back pain. CONCLUSION: The present longitudinal study revealed a high incidence of radiographic LS in Japan.

Spectrocolorimetric evaluation of human articular cartilage.

OBJECTIVE: The aim of this study was to investigate whether human articular cartilage can be quantitatively evaluated using a spectrocolorimeter. MATERIALS AND METHODS: Human articular cartilage specimens were analyzed using a spectrocolorimeter after macroscopic evaluation using the Outerbridge classification. The cartilage characteristics were examined, the L*, a*, b* colorimetric system, the spectral reflectance distribution and the yellow/red spectral reflectance percentage (Y/R SRP). Moreover, the results of the spectrocolorimetric evaluation were compared with the histological score described by Mankin et al. RESULTS: There were significant differences among the macroscopic four grades in the L*, a* and Y/R SRP values. The spectral reflectance distribution of grade 1 cartilage exhibited a gradual increase in the spectral reflectance ratio as the wavelength increased. The spectral reflectance curves of grades 2 to 4 cartilage had dips at a wavelength of around 580 nm. Across all the measured wavelengths, there were lower reflectance ratios with the progression of cartilage degeneration. Moreover, correlations were observed between the spectrocolorimetric values and Mankin score. A strong relationship existed between Mankin score and he Y/R SRP values. CONCLUSIONS: The present study is the first to clearly demonstrate the relationship between spectrocolorimetric evaluation and the degeneration of human articular cartilage. The spectrocolorimeter may be a new quantitative evaluation tool for articular cartilage with clinical potential.

Effect of interaction shape on the condensed toroid of the semiflexible chain.

We investigate how different microscopic interactions between semiflexible chain segments can qualitatively alter the physical properties of the condensed toroid. We propose a general form of the Hamiltonian of the toroid and discuss its analytic properties. For different interactions, the theory predicts different scaling behaviors of the mean toroidal and cross sectional radii, rc and rcross, as functions of the contour length L: (rc,rcross) approximately Lnu(Nc), with nu=(1/5,2/5) for the van der Waals-type, nu=(-1/3,2/3) for the Coulomb-type, and nu=(-1,1) for the delta-function-type attractions in the asymptotic limit. For the toroids with finite winding number Nc=100-400, we find nu approximately 0 for the Yukawa interaction with screening parameter kappa=0.5-1.0 and nu=0.1-0.13 for the van der Waals-type interactions. These findings could provide a possible explanation for the experimentally well known observation nu approximately 0 of the condensed DNA toroids. Conformational transitions are also discussed.

Attenuation by dietary taurine of dextran sulfate sodium-induced colitis in mice and of THP-1-induced damage to intestinal Caco-2 cell monolayers.

The effects of dietary taurine on the experimental colitis induced by dextran sulfate sodium (DSS) in mice were evaluated. C57BL/6 female mice were given 3% DSS in drinking water for 5 d to induce acute colitis. Taurine at 2% was added to the drinking water 5 d before and during the DSS-treatment to investigate its preventive effect. Taurine supplementation significantly attenuated the weight decrease, diarrhea severity, colon shortening, and the increase in the colonic tissue myeloperoxidase activity induced by DSS. Taurine also significantly inhibited the increase in the expression of a pro-inflammatory chemokine, macrophage inflammatory protein 2 (MIP-2), but not of interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha mRNA. Furthermore, taurine significantly protected the intestinal Caco-2 cell monolayers from the damage by macrophage-like THP-1 cells in an in vitro coculture system. These results suggest that taurine prevented DSS-induced colitis partly in association with (1) its inhibitory effects on the secretion of MIP-2 from the intestinal epithelial cells and on the infiltration of such inflammatory cells as neutrophils and (2) its cytoprotective functions on the epithelial barrier from the direct toxicity of DSS and from the inflammatory cell-induced injury.

[Extraabdominal desmoid tumor of the chest wall].

We report a rare case of desmoid tumor of the chest wall. A 75-year-old female visited our hospital due to a feeling of oppression in the left chest. A chest X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large mass in the left thorax. Surgical resection of the tumor was performed under the left standard thoracotomy. The tumor was 90 x 80 x 75 mm in size and diagnosed pathologically as desmoid tumor which showed proliferation of spindle shape cells and collagen fibers. Immunohistochemistry revealed that the tumor cells were positive for vimentin, alpha-smooth muscle actin and negative for CD34. The patient has been well without recurrence for 2 years and 2 months after surgery.

Low-energy states of a semiflexible polymer chain with attraction and the whip-toroid transitions.

We establish a general model for the whip-toroid transitions of a semiflexible homopolymer chain using the path integral method and the O3 nonlinear sigma model on a line segment with the local inextensibility constraint. We exactly solve the energy levels of classical solutions and show that some of its classical configurations exhibit toroidal forms, and the system has phase transitions from a whip to toroidal states with a conformation parameter c = (W2l)(L2pi)2. We also discuss the stability of the toroid states and propose the low-energy effective Green's function. Finally, with the finite size effect on the toroid states, predicted toroidal properties are successfully compared to experimental results of DNA condensation.