Depression symptoms during pregnancy and postpartum in patients with recurrent pregnancy loss and infertility: The Japan environment and children's study.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary.

Effects of long working hours and shift work during pregnancy on obstetric and perinatal outcomes: A large prospective cohort study-Japan Environment and Children's Study.

BACKGROUND: The work patterns of pregnant women may be related to adverse obstetric and perinatal outcomes. This study aimed to clarify the effects of weekly working time according to frequencies of night shifts during pregnancy on adverse outcomes in Japan. METHODS: The Japan Environment and Children's Study, a prospective cohort study, was conducted in 15 regions nationwide in Japan. The study population included pregnant women with singleton pregnancies (n = 99 744). The mothers' working hours and frequencies of night shifts during the first and the second/third trimesters were assessed using a self-administered questionnaire. Outcome data were collected from medical transcripts. RESULTS: Compared with nonworking women, women who worked during pregnancy had significantly increased adjusted odds ratios (aORs) of threatened miscarriage (maximum aOR: 1.47, 95% confidence interval [95% CI]: 1.26-1.73) and of threatened preterm labor (maximum aOR: 1.63, 95% CI: 1.41-1.87). Increased aORs were observed for hypertensive disorders of pregnancy (maximum aOR: 2.02, 95% CI: 1.39-2.93) in women working ≥36 hours per week with night shifts, for vacuum/forceps delivery (maximum aOR: 1.34, 95% CI: 1.22-1.48) at ≥36 hours with or without night shifts, and for small-for-gestational-age babies (aOR: 1.32, 95% CI: 1.10-1.59) at ≥46 hours with night shifts. In contrast, lower aORs were observed for gestational diabetes and meconium-stained amniotic fluid in women working without night shifts. CONCLUSIONS: Work during pregnancy slightly increased the risks of threatened miscarriage and threatened preterm labor. Long working hours increased the risks of hypertensive disorders of pregnancy, vacuum/forceps delivery, and small-for-gestational-age babies.

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM. CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A).

PURPOSE: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health. PARTICIPANTS: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children. FINDINGS TO DATE: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas. FUTURE PLANS: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability.

Effects of a Disease Management Program for Preventing Recurrent Ischemic Stroke.

Background and Purpose- Disease management is a healthcare strategy that includes self-management education and treatment coordination. We conducted a randomized controlled trial to determine whether a disease management program intervention could improve risk factor profiles and, thus, reduce the recurrence of stroke and other cardiovascular diseases. Methods- This study is a prospective randomized, open-label, parallel group study involving outpatients with a history of stroke. Between September 2010 and November 2012, we enrolled patients aged between 40 and 80 years who experienced their last ischemic stroke event or transient ischemic attack within 1 year. After stratifying by the ischemic stroke subtype, 321 subjects (67.5±8.5 years, 95 female) were randomly assigned to either the disease management program intervention group (n=156) or the usual care group (n=165). The primary end point of this study was the difference in the Framingham risk score (general cardiovascular disease 10-year risk) from baseline. The secondary end points of this study included stroke recurrence, onset of cardiovascular disease, all-cause mortality, and all vascular events. Results- Regarding the primary end point, there was no significant difference in the changes in the Framingham risk score at any follow-up time between the groups. The incidence of stroke recurrence tended to be lower in the disease management program intervention group, although no significant difference was found (hazard ratio, 0.49; 95% CI, 0.19-1.29). Conclusions- We were unable to demonstrate a clear benefit of disease management program intervention. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02121327.

Endometriosis and Recurrent Pregnancy Loss as New Risk Factors for Venous Thromboembolism during Pregnancy and Post-Partum: The JECS Birth Cohort.

BACKGROUND: Since venous thromboembolism (VTE) is one of the causes of maternal mortality, several guidelines recommend prophylaxis using low molecular weight heparin for women in high-risk groups. The number of large population-based studies examining predictors for VTE has been limited, and there has been no study based on a Japanese population. OBJECTIVE: Our objective was to examine VTE risk factor during the pregnancy and post-partum period. MATERIALS AND METHODS: A nationwide birth cohort study known as the 'Japan Environment and Children's Study (JECS)' was conducted by the Ministry of the Environment. The subjects consisted of 103,070 pregnancies recruited by the JECS between January 2011 and March 2014. Pregnant women completed the questionnaires during the first and second/third trimester. Their medical records were transcribed by physicians or research coordinators at registration, just after delivery and at 1 month after delivery. RESULTS: The frequency of VTE was 7.5 per 10,000 pregnancies (77 of 103,070) during the pregnancy and post-partum period. After the adjustment of multiple covariates for each factor, endometriosis and recurrent pregnancy loss (RPL) were identified as novel independent risk factors for VTE. Adjusted odds ratios were as follows: 2.70 (95% confidence interval, 1.21-6.00) for endometriosis and 6.13 (2.48-15.16) for RPL. Threatened abortion, threatened pre-term birth, pre-term birth and caesarean section were ascertained to be risk factors for VTE. CONCLUSION: Careful attention should be given to novel predictors, such as endometriosis and a history of RPL, to prevent VTE during the pregnancy and post-partum period.

Adverse pregnancy and perinatal outcome in patients with recurrent pregnancy loss: Multiple imputation analyses with propensity score adjustment applied to a large-scale birth cohort of the Japan Environment and Children's Study.

PROBLEM: Several studies have reported the increased risk of preterm birth, premature rupture of membranes, and low birth weight in patients with recurrent pregnancy loss (RPL). There have been a limited number of large population-based studies examining adverse pregnancy and perinatal outcome after RPL. Multiple-imputed analyses (MIA) adjusting for biases due to missing data is also lacking. METHOD OF STUDY: A nationwide birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted by the Ministry of the Environment. The subjects consisted of 104 102 registered children (including fetuses or embryos). RESULTS: No increased risk of a congenital anomaly, aneuploidy, neonatal asphyxia, or a small for date infant was observed among the children from women with a history of RPL. A novel increased risk of placental adhesion and uterine infection was found. The adjusted ORs using MIA in women with three or more PL were 1.76 (95% CI, 1.04-2.96) for a stillbirth, 1.68 (1.12-2.52) for a pregnancy loss, 2.53 (1.17-5.47) for placental adhesion, 1.87 (1.37-2.55) and 1.60 (.99-2.57) for mild and severe hypertensive disorders of pregnancy, respectively, 1.94 (1.06-3.55) for uterine infection, 1.28 (1.11-1.47) for caesarean section and .86 (.76-.98) for a male infant. CONCLUSION: MIA better quantified the risk, which could encourage women who might hesitate to attempt a subsequent pregnancy.

Spatial Allocation and Specification of Cardiomyocytes during Zebrafish Embryogenesis.

Incomplete development and severe malformation of the heart result in miscarriage of embryos because of its malfunction as a pump for circulation. During cardiogenesis, development of the heart is precisely coordinated by the genetically-primed program that is revealed by the sequential expression of transcription factors. It is important to investigate how spatial allocation of the heart containing cardiomyocytes and other mesoderm-derived cells is determined. In addition, the molecular mechanism underlying cardiomyocyte differentiation still remains elusive. The location of ectoderm-, mesoderm-, and endoderm-derived organs is determined by their initial allocation and subsequent mutual cell-cell interactions or paracrine-based regulation. In the present work, we provide an overview of cardiac development controlled by the germ layers and discuss the points that should be uncovered in future for understanding cardiogenesis.

Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors.

Multiwalled carbon nanotubes (MWCNT) have a fibrous structure and physical properties similar to asbestos and have been shown to induce malignant mesothelioma of the peritoneum after injection into the scrotum or peritoneal cavity in rats and mice. For human cancer risk assessment, however, data after administration of MWCNT via the airway, the exposure route that is most relevant to humans, is required. The present study was undertaken to investigate the carcinogenicity of MWCNT-N (NIKKISO) after administration to the rat lung. MWCNT-N was fractionated by passing it through a sieve with a pore size of 25 µm. The average lengths of the MWCNT were 4.2 µm before filtration and 2.6 µm in the flow-through fraction; the length of the retained MWCNT could not be determined. For the present study, 10-week-old F344/Crj male rats were divided into five groups: no treatment, vehicle control, MWCNT-N before filtration, MWCNT-N flow-through and MWCNT-N retained groups. Administration was by the trans-tracheal intrapulmonary spraying (TIPS) method. Rats were administered a total of 1 mg/rat during the initial 2 weeks of the experiment and then observed up to 109 weeks. The incidences of malignant mesothelioma and lung tumors (bronchiolo-alveolar adenomas and carcinomas) were 6/38 and 14/38, respectively, in the three groups administered MWCNT and 0/28 and 0/28, respectively, in the control groups. All malignant mesotheliomas were localized in the pericardial pleural cavity. The sieve fractions did not have a significant effect on tumor incidence. In conclusion, administration of MWCNT to the lung in the rat induces malignant mesothelioma and lung tumors.

Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.

Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.

Baseline feature of a randomized trial assessing the effects of disease management programs for the prevention of recurrent ischemic stroke.

BACKGROUND: Comprehensive and long-term patient education programs designed to improve self-management can help patients better manage their medical condition. Using disease management programs (DMPs) that were created for each of the risk factor according to clinical practice guidelines, we evaluate their influence on the prevention of stroke recurrence. METHODS: This is a randomized study conducted with ischemic stroke patients within 1 year from their onset. Subjects in the intervention group received a 6-month DMPs that included self-management education provided by a nurse along with support in collaboration with the primary care physician. Those in the usual care group received ordinary outpatient care. The primary end point is a difference of the Framingham risk score-general cardiovascular disease 10-year risk [corrected]. Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6-month education period (total of 30 months). RESULTS: A total of 321 eligible subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects (6.5%) with transient ischemic attack, were enrolled in this study. Regarding risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney disease. There were no significant differences between the 2 groups with respect to subject characteristics. CONCLUSIONS: This article describes the rationale, design, and baseline features of a randomized controlled trial that aimed to assess the effects of DMPs for the secondary prevention of stroke. Subject follow-up is in progress and will end in 2015.

Multifactorial analysis of factors affecting recurrence of stroke in Japan.

Data on factors affecting stroke recurrence are relatively limited. The authors examined potential factors affecting stroke recurrence, retrospectively. The study participants were 1087 patients who were admitted to stroke centers suffering from first-ever ischemic stroke and returned questionnaires with usable information after discharge. The authors analyzed the association between clinical parameters of the patients and their prognosis. Recurrence rate of during an average of 2 years after discharge was 21.3%, and there were differences among stroke subtypes. It was found that the disability level of the patients after discharge correlated well with the level at discharge (r s = 0.66). Multivariate logistic regression analysis of the data shows that modified Rankin Scale score, National Institute of Health Stroke Scale score, gender, age, and family history had statistically significant impacts on stroke recurrence, and the impact was different depending on subtypes. These findings suggest that aggressive and persistent health education for poststroke patients and management of risk factors are essential to reduce stroke recurrence.

[Causes and prevalence of visual impairment in Japan].

PURPOSE: To investigate the causes of visual impairment in Japan. METHODS: The documents of 4,852 individuals with authorization of visual impairment registered between April 2007 and March 2010 in 7 randomly selected regions were reviewed. RESULTS: The major causes of visual impairment were glaucoma (21.0%), diabetic retinopathy (15.6%), retinitis pigmentosa (12.0%), macular degeneration (9.5%) and chorioretinal atrophy (8.4%). Individuals over 70 years of age were predominant for glaucoma, those aged 50-69 years for diabetic retinopathy and those under 40 years of age for retinitis pigmentosa. Sixty-one percent of persons affected by glaucoma were severely handicapped. Macular degeneration increased with age especially in individuals over 80 years of age. CONCLUSION: There was no difference in the order of major causes as compared with a previous report in 2001-2004. It is important to establish a central database system so that the data can be surveyed to provide more relevant information to understand current issues for handicapped persons and develop new prophylactic and therapeutic modalities.

Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes.

Multiwalled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L; l = 8 µm, d = 150 nm), and a smaller sized MWCNT (MWCNT-S; l = 3 µm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT-L and MWCNT-S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT-L, but not MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT-L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development.

Nanosized zinc oxide particles do not promote DHPN-induced lung carcinogenesis but cause reversible epithelial hyperplasia of terminal bronchioles.

Zinc oxide (ZnO) is known to induce lung toxicity, including terminal bronchiolar epithelial hyperplasia, which gives rise to concerns that nanosized ZnO (nZnO) might lead to lung carcinogenesis. We studied the tumor promoting activity of nZnO by an initiation-promotion protocol using human c-Ha-ras proto-oncogene transgenic rats (Hras128 rats). The rats were given 0.2 % N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water for 2 weeks and then treated with 0.5 ml of 250 or 500 µg/ml nZnO suspension by intra-pulmonary spraying once every 2 weeks for a total of 7 times. Treatment with nZnO particles did not promote DHPN-induced lung carcinogenesis. However, nZnO dose-dependently caused epithelial hyperplasia of terminal bronchioles (EHTB) and fibrosis-associated interstitial pneumonitis (FAIP) that were independent of DHPN treatment. Tracing the fate of EHTB lesions in wild-type rats indicated that the hyperplastic lesions almost completely disappeared within 12 weeks after the last nZnO treatment. Since nZnO particles were not found in the lung and ZnCl2 solution induced similar lung lesions and gene expression profiles, the observed lesions were most likely caused by dissolved Zn(2+). In summary, nZnO did not promote carcinogenesis in the lung and induced EHTB and FAIP lesions that regressed rapidly, probably due to clearance of surplus Zn(2+) from the lung.

Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats.

Multi-walled carbon nanotubes have a fibrous structure similar to asbestos and induce mesothelioma when injected into the peritoneal cavity. In the present study, we investigated whether carbon nanotubes administered into the lung through the trachea induce mesothelial lesions. Male F344 rats were treated with 0.5 mL of 500 µg/mL suspensions of multi-walled carbon nanotubes or crocidolite five times over a 9-day period by intrapulmonary spraying. Pleural cavity lavage fluid, lung and chest wall were then collected. Multi-walled carbon nanotubes and crocidolite were found mainly in alveolar macrophages and mediastinal lymph nodes. Importantly, the fibers were also found in the cell pellets of the pleural cavity lavage, mostly in macrophages. Both multi-walled carbon nanotube and crocidolite treatment induced hyperplastic proliferative lesions of the visceral mesothelium, with their proliferating cell nuclear antigen indices approximately 10-fold that of the vehicle control. The hyperplastic lesions were associated with inflammatory cell infiltration and inflammation-induced fibrotic lesions of the pleural tissues. The fibers were not found in the mesothelial proliferative lesions themselves. In the pleural cavity, abundant inflammatory cell infiltration, mainly composed of macrophages, was observed. Conditioned cell culture media of macrophages treated with multi-walled carbon nanotubes and crocidolite and the supernatants of pleural cavity lavage fluid from the dosed rats increased mesothelial cell proliferation in vitro, suggesting that mesothelial proliferative lesions were induced by inflammatory events in the lung and pleural cavity and likely mediated by macrophages. In conclusion, intrapulmonary administration of multi-walled carbon nanotubes, like asbestos, induced mesothelial proliferation potentially associated with mesothelioma development.

Soy isoflavones for osteoporosis: an evidence-based approach.

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.

Is salt intake an independent risk factor of stroke mortality? Demographic analysis by regions in Japan.

We reported a remarkable regional difference within Japan in the incidence of end-stage renal disease. Regional differences were also well-known for salt intake, blood pressure (BP), and mortality from stroke, which remains one of the leading causes of death. Noting these regional differences, we examined mutual relationships among salt intake, BP, and stroke mortality in 12 regions of Japan. Data of salt intake, BP, and stroke mortality in 12 regions were collected from National Nutrition Survey (NNS-J), reanalysis of NNS-J, and Vital Statistics of National Population Dynamic Survey (Ministry of Health, Labor and Welfare), respectively. Significant regional differences were found in salt intake (P < .0001), mean arterial BP (P = .0001), and stroke mortality (P < .0001). Although annual changes in these parameters were also significant, their regional differences persisted. Salt intake had positive relationships with both mean arterial BP (r = 0.26, P = .0009) and stroke mortality (r = 0.26, P < .0001) across 12 regions, whereas mean arterial BP was not correlated with stroke mortality. Multiple regression analysis further identified salt intake as an independent factor to increase stroke mortality, but mean arterial BP was not a determinant. Compared with the four regions with lowest salt intake, odds ratios of stroke mortality adjusted by mean arterial BP were 1.04 (95% CI, 1.03-1.06) for the intermediate four regions and 1.25 (95% CI, 1.23-1.27) for the four regions with highest salt intake. These findings suggest that salt intake may have an adverse effect on stroke mortality independently of BP.

Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials.

This study was conducted to clarify the effect of ingesting soy isoflavone extracts (not soy protein or foods containing isoflavones) on bone mineral density (BMD) in menopausal women. PubMed, CENTRAL, ICHUSHI, CNKI, Wanfang Data, CQVIP, and NSTL were searched for randomized controlled trials published in English, Japanese, or Chinese reporting the effects of soy isoflavone extracts on lumbar spine or hip BMD in menopausal women. Trials were identified and reviewed for inclusion and exclusion eligibility. Data on study design, participants, interventions, and outcomes were extracted. Eleven, seven, five, and five trials were finally selected for estimation of the effects on spine, femoral neck, hip total, and trochanter BMD, respectively. Meta-analysis including data from1240 menopausal women revealed that daily ingestion of an average of 82 (47-150) mg soy isoflavones (aglycone equivalent) for 6-12 months significantly increased spine BMD by 22.25 mg/cm2 (95% CI: 7.62, 32.89; p=0.002), or by 2.38% (95% CI: 0.93, 3.83; p=0.001) compared with controls (random-effects model). Subgroup analyses indicated that the varying effects of isoflavones on spine BMD across trials might be associated with study characteristics of intervention duration (6 vs. 12 months), region of participant (Asian vs. Western), and basal BMD (normal bone mass vs. osteopenia or osteoporosis). No significant effects on femoral neck, hip total, and trochanter BMD were found. Soy isoflavone extract supplements increased lumbar spine BMD in menopausal women. Further studies are needed to address factors affecting the magnitudes of effect on spine and to verify the effect on hip.