Talbot-Lau interferometry-based x-ray imaging system with retractable and rotatable gratings for nondestructive testing.

We develop an x-ray imaging system based on Talbot-Lau interferometry equipped with a mechanical structure for retracting and rotating gratings from the optical axis, which enables not only x-ray phase contrast imaging but also conventional x-ray imaging with high-magnification such as microcomputed tomography (µCT). We investigate the characterization of carbon fiber reinforced plastic (CFRP) laminates using this apparatus. Microcracks and fiber orientations are visualized in the dark-field images. Compared with the obtained µCT images, the relationship between the CFRP microstructures and the contrasts in the dark-field images are recognizable.

Menstrual and reproductive factors and risk of vertebral fractures in Japanese women: the Japan Public Health Center-based prospective (JPHC) study.

This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism. INTRODUCTION: This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women. METHODS: Participants were 43,652 women aged 40-69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors. RESULTS: During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24-3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01-2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92-0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51-3.73) in all women, 2.25 (1.35-3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499). CONCLUSIONS: Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.

Plasma levels of natriuretic peptides and year-by-year blood pressure variability: a population-based study.

Augmented blood pressure (BP) variability over various time periods has been recognized as a risk factor for cardiovascular diseases. Both atrial and B-type natriuretic peptides (ANP and BNP) are secreted in response to volume or pressure overload to the heart, exerting natriuretic and vasodilator actions. In this study, we examined the relationships between year-by-year BP variability and plasma levels of ANP and BNP in the general population. Study subjects were local residents receiving an annual heath checkup, who had an estimated glomerular filtration rate of >30 ml min-1 per 1.73 m2 and no history of heart disease. Of those, we selected 314 subjects that received checkups at least five times over the past 6 years. BP variability year-by-year was retrospectively evaluated by s.d., coefficient of variation, average real variability and variation independent of the mean of BP values of 6 or 7 time points. The four parameters of BP variability were each found to significantly correlate with logarithmically transformed ANP and BNP levels by simple regression. When classified by quartiles of s.d. of systolic BP, the highest quartile group showed significantly higher levels of the natriuretic peptides compared with other groups. Multivariate analyses revealed that BP variability was an independent determinant for the ANP and BNP levels. In conclusion, augmented year-by-year BP variability over the past 6 years was associated with elevation of plasma levels of ANP and BNP, suggesting a possible relationship between the BP variability and cardiac load, in the general population.

Jump Squat is More Related to Sprinting and Jumping Abilities than Olympic Push Press.

The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise.

Effects of detraining on neuromuscular performance in a selected group of elite women pole-vaulters: a case study.

AIM: to determine the effects of 28 days of inactivity on neuromuscular performance of elite women pole-vaulters. METHODS: Four athletes undertook measurements of rate of force development (RFD), unloaded and loaded vertical jump tests, drop jumps and a 45 m sprint test before and after a transition period of planned inactivity. RESULTS: The RFD and the ability to accelerate over very short distances (5 m) while sprinting improved after training cessation. Acceleration over longer distances (5-45 m) was impaired, while unloaded and loaded vertical jump tests suffered trivial to small changes. CONCLUSIONS: Therefore, we conclude that detraining periods of approximately one month or even longer may be implemented in elite pole-vaulters without significantly impairing performance. In addition, given that some neuromechanical capacities are enhanced after training reduction, our results can help coaches to implement tapering strategies in order to induce neuromuscular improvements and/or to achieve peak performance.

APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers.

The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. METHODS: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. RESULTS: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. CONCLUSIONS: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia.

UNLABELLED: Essentials Two groups recently reported GFI1B as a novel causative gene for congenital macrothrombocytopenia. We performed functional analysis of a novel GFI1B mutation and previous mutations. An immunofluorescence analysis of the platelet CD34 expression can be useful as a screening test. Mutant-transduced megakaryocytes produced enlarged proplatelet tips which were reduced in number. SUMMARY: Background GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. Two groups have recently identified GFI1B as a novel causative gene for congenital macrothrombocytopenia associated with α-granule deficiency. Methods We performed whole exome sequencing and identified a novel GFI1B p.G272fsX274 mutation in a family with macrothrombocytopenia, and a decreased number of platelet α-granules and abnormally shaped red blood cells. p.G272fsX274 and the previous two mutations all predicted disruption of an essential DNA-binding domain in GFI1B. We therefore performed functional studies to characterize the biochemical and biological effects of these three patient-derived mutations. Results An immunofluorescence analysis revealed decreased thrombospondin-1 and increased CD34 expression in platelets from our patient. Consistent with the previous studies, the three patient-derived mutants were unable to repress the expression of the reporter gene and had a dominant-negative effect over wild-type GFI1B. In addition, the three mutations abolished recognition of a consensus-binding site in gel shift assays. Furthermore, transduction of mouse fetal liver-derived megakaryocytes with the three GFI1B mutants resulted in the production of abnormally large proplatelet tips, which were reduced in number. Conclusions Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.

Increased level of tumour necrosis factor-alpha (TNF-α) on the skin of Japanese obese males: measured by quantitative skin blotting.

OBJECTIVE: A state of chronic inflammation, characterized by an increased level of tumour necrosis factor-alpha (TNF-α), is often found in the obese population. The negative effects of elevated TNF-α are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF-α in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF-α on the skin and to find the relationship between obesity and the level of TNF-α detected on the skin. METHODS: We used a novel, non-invasive method called quantitative skin blotting. Fifty-nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF-α detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis. RESULTS: Significant positive correlations were found between the levels of TNF-α detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating. CONCLUSION: We found that high levels of TNF-α were detected on the skin of Japanese obese males, which implied the higher TNF-α in the skin. The elevation of skin TNF-α may be one factor related to skin fragility that is often found in obese individuals.

A Correlational Analysis of Tethered Swimming, Swim Sprint Performance and Dry-land Power Assessments.

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and -0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers.

Pre-Transplant Erythropoiesis-Stimulating Agent Hypo-Responsiveness and Post-Transplant Anemia.

BACKGROUND: At the time of kidney transplantation (KT), almost all patients have anemia caused by low levels of endogenous erythropoietin (EPO), along with several other factors. After KT, anemia improves because of secretion of EPO from the allograft. But some recipients have persistent anemia. Whether or not erythropoiesis-stimulating agent (ESA) hypo-responsiveness before KT affects post-transplant anemia (PTA) remains unknown. METHODS: Sixty-eight patients received KT between January 2007 and July 2012 through the Department of Urology at Kobe University Hospital, and 35 of these patients were enrolled. Exclusion criteria included age <18 years, unknown ESA dosage at transplantation, ESA start within 1 year after transplantation, and other criteria. We evaluated post-transplant hemoglobin (Hb) levels from the pre-transplant ESA responsive index (ERI): pre-transplant ESA dosage/Hb × body weight at 1 year after transplantation. RESULTS: The mean (± SD) Hb of all patients rose from 11.3 ± 1.0 mg/dL to 12.7 ± 1.4 mg/dL at 1 year after transplantation (P < .01). The pre-transplant low ERI group (<10) showed significantly higher hemoglobin levels compared with the pre-transplant high ERI group (≥ 10; 12.9 ± 1.14 mg/dL versus 11.8 ± 1.76 mg/dL, respectively; P = .03). CONCLUSIONS: ESA hypo-responsiveness before KT carried over after KT. Low pre-transplant ERI might be a sentinel marker for PTA.

Effects of macrophage-dependent peroxisome proliferator-activated receptor γ signalling on adhesion formation after abdominal surgery in an experimental model.

BACKGROUND: The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator-activated receptor (PPAR) γ stimulation on adhesion formation in an animal model. METHODS: Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10(-/-) ), IL-4-deficient (IL-4(-/-) ) and CD11b-Cre/PPARγ(fl) (/fl) mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR-γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression. RESULTS: Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL-4(-/-) and IL-10(-/-) mice were not affected, whereas CD11b-Cre/PPARγ(fl) (/fl) mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild-type but not CD11b-Cre/PPARγ(fl) (/fl) mice. Pioglitazone had no effect on anastomotic healing. CONCLUSION: Endogenous macrophage-specific PPAR-γ signalling affected arginase activity and macrophage polarization, and counter-regulated peritoneal adhesion manifestation. Pharmacological PPAR-γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage-dependent manner. Surgical relevance Postoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation. In an experimental model, macrophage M2 marker expression was associated with reduced peritoneal adhesion formation and involved PPAR-γ-mediated arginase activity. Macrophage-specific PPAR-γ deficiency resulted in reduced arginase activity and aggravated adhesion formation. Pioglitazone, a PPAR-γ agonist, induced M2 polarization and reduced postoperative adhesion formation without compromising anastomotic healing in mice. Pioglitazone ameliorated postoperative adhesion formation without compromising intestinal wound healing. Therefore, perioperative PPAR-γ agonism might be a promising strategy for prevention of adhesion formation after abdominal surgery.

Randomized study of orally administered fluorinated pyrimidines (capecitabine versus S-1) in women with metastatic or recurrent breast cancer: Japan Breast Cancer Research Network 05 Trial.

PURPOSE: Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer (MBC). This randomized, multicenter, phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. METHODS: Patients with MBC were randomly assigned to receive capecitabine 825 g/m(2) twice daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body surface area, on days 1-28 every 6 weeks. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 142 patients were enrolled and randomized to either capecitabine (N = 73) or S-1 (N = 69). Median PFS (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1, with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI] 0.52-1.38) (P = 0.48 by log-rank). The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 (P = 0.938). The most common treatment-related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %, capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P = 0.029). CONCLUSIONS: The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC, while their adverse events were different. They are both convenient, orally administered drugs, making them attractive agents for use in outpatient treatment.

Prolonged occupational activity and 6-year changes in postural sway in elderly women.

OBJECTIVES: Prolonged occupational work such as farm work has been reported to adversely affect mobility in elderly women. The purpose of this study was to investigate possible relationships between prolonged occupational work and 6-year changes in postural sway in elderly women. METHODS: Subjects were 392 women aged ≥ 69 years who participated in a 6-year follow-up examination of the Muramatsu Cohort Study. Handgrip strength and postural sway, measured as gravity-center velocity (cm/s), were evaluated at baseline and 6-year follow-up. Interviews were conducted to determine the time spent on moderate occupational activity (3-5 metabolic equivalents) such as farm work. Activity levels were defined as: 1, no-activity; 2, 'short' (>0, ≤ 17.75 h/wk); and 3, 'long' ( ≥ 17.75 h/wk). RESULTS: At baseline, mean values for age, handgrip strength, and postural sway were 73.3 years (SD 3.7), 20.3 kg (SD 4.1), and 2.0 cm/s (SD 0.8), respectively, and 32.5% of participants engaged in occupational activity. The change in postural sway was significantly greater in the long-activity group (median, 35.0 h/wk) than the no-activity group (0.56 vs. 0.27 cm/s, P=0.021). CONCLUSIONS: Prolonged occupational work may be detrimental to the control of body balance. Accordingly, elderly individuals are not recommended to engage in prolonged occupational activity.

Development of an improved method for quantitative analysis of skin blotting: increasing reliability and applicability for skin assessment.

OBJECTIVE: A novel skin assessment tool named 'skin blotting' has been recently developed, which can easily predict the skin status to avoid its deterioration. The aim of this study was to propose a normalization method for skin blotting to compensate for individual differences that can hamper the quantitative comparisons and clinical applications. METHODS: To normalize individual differences, we utilized a total protein as a 'normalizer' with calibration curves. For evaluation, we performed a simple simulation experiment, in which the same concentration of a protein of interest [tumour necrosis factor (TNF)-α] was applied at different volumes as a virtual individual difference. Moreover, to demonstrate the applicability of this normalization, male volunteers were recruited for skin blotting followed by the estimation of TNF-α with normalization. RESULTS: We obtained good calibration curves for total protein (R(2)  = 0.995) and TNF-α (R(2)  = 0.997), both of which were necessary for an exact quantification. In the simulation experiment, we estimated the exact concentration of TNF-α regardless of the applied volume, demonstrating the applicability of this normalization method in skin blotting. Further, skin blotting on human subjects showed a wide range of variation in the total protein content, although the normalization was thought to reduce such individual variations. CONCLUSION: This study has proposed total protein normalization for skin blotting with calibration curves. This method may strengthen the quantitative performance of skin blotting, which may expand the applicability of this method as a skin assessment tool in broader fields, such as nursing and cosmetology.

Impact of demographic, environmental, and lifestyle factors on vitamin D sufficiency in 9084 Japanese adults.

BACKGROUND: Little is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38°13') in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population. METHODS: This study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011-2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration ≥ 75 nmol/L. RESULTS: The prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration ≥ 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P<0.0001; OR=2.37, 95% CI: 1.84-3.05), older age (P for trend <0.0001), lower BMI (P for trend <0.0001), higher METs score (P for trend=0.0138), higher vitamin D intake (P for trend=0.0467), summer season (P for trend <0.0001), longer duration outdoors (P for trend=0.0026), no sunscreen use (P=0.0135; OR=1.40, 95% CI: 1.07-1.82), higher salmon consumption (P for trend <0.0001), higher alcohol consumption (P for trend <0.0001), and lower coffee consumption (P for trend=0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age. CONCLUSIONS: The prevalence of vitamin D sufficiency (i.e., 25[OH]D ≥ 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency.

Developmental increase in hyperpolarization-activated current regulates intrinsic firing properties in rat vestibular ganglion cells.

The primary vestibular neurons convey afferent information from hair cells in the inner ear to the vestibular nuclei and the cerebellum. The intrinsic firing properties of vestibular ganglion cells (VGCs) are heterogeneous to sustained membrane depolarization, and undergo marked developmental changes from phasic to tonic types during the early postnatal period. Previous studies have shown that low-voltage-activated potassium channels, Kv1 and Kv7, play a critical role in determining the firing pattern of VGCs. In the present study, we explored the developmental changes in the properties of hyperpolarization-activated current (Ih) in rat VGCs and the role played by Ih in determining the firing properties of VGCs. Tonic firing VGCs showed a larger current density of Ih as compared to phasic firing VGCs, and tonic firing VGCs became phasic firing in the presence of ZD7288, an Ih channel blocker, indicating that Ih contributes to control the firing pattern of VGCs. The amplitude of Ih increased and the activation kinetics of Ih became faster during the developmental period. Analysis of developmental changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels revealed that expression of HCN1 protein and its mRNA increased during the developmental period, whereas expression of HCN2-4 protein and its mRNA did not change. Our results suggest that HCN1 channels as well as Kv1 channels are critical in determining the firing pattern of rat VGCs and that developmental up-regulation of HCN1 transforms VGCs from phasic to tonic firing phenotypes.

Physical activity and 10-year incidence of self-reported vertebral fractures in Japanese women: the Japan Public Health Center-based Prospective Study.

UNLABELLED: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. INTRODUCTION: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. METHODS: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. RESULTS: The 10-year cumulative incidence of vertebral fractures was 0.67%. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95% CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95% CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures (P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not (P for trend = 0.0729 and 0.4341, respectively). CONCLUSIONS: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures.