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Background: Epidemiological evidence of dyslipidemia in Pacific Island countries is limited despite the knowledge that non-communicable diseases have a high burden in the region. We aimed to examine the prevalence and correlates of dyslipidemia among residents of Palau., Methods: The Palau STEPwise approach to Surveillance (STEPS), which was conducted from 2011 through 2013, comprised three parts: behavioral risk factors; physical measurements; and biochemical tests, covering areas such as blood lipids. We used STEPS-generated data to perform a cross-sectional study of 2,184 randomly selected Palau residents, comprising Palauans and non-Palauans aged 25-64 years., Results: The age-adjusted mean BMI was 29.3 kg/m 2 in men and 29.9 kg/m 2 in women; age-adjusted mean triglycerides value was 182 mg/dL in men and 166 mg/dL in women; and age-adjusted mean cholesterol was 178 mg/dL in men and 183 mg/dL in women. The prevalence of overweight/obesity (BMI ≥25 kg/m 2 ) was 75% in men and 76% in women, and those of hypertriglyceridemia (triglycerides ≥150 mg/dL) and hypercholesterolemia (total cholesterol ≥200 mg/dL) were 48% in men and 41% in women and 18% in men and 23% in women, respectively. Mean values of total cholesterol were 177 mg/dL in Palauan men and 182 mg/dL in non-Palauan men. Mean values of triglycerides were 171 mg/dL in Palauan women and 150 mg/dL in non-Palauan women. Women living in rural areas showed a higher mean value of total cholesterol than those in urban areas., Conclusion: We found a high mean BMI and high prevalence of overweight/obesity and hypertriglyceridemia, but low mean total cholesterol and a low prevalence of hypercholesterolemia in Palau. Lipid profiles varied by age, ethnicity, and living area.

The mechanical strength of metal-organic frameworks (MOFs) is highly relevant for their practical applications. In this research, we show that encapsulation of polymer chains into MOF nanochannels can effectively restrain the breakage of coordination bonding in MOFs and inhibit the amorphization under high physical pressure. The hardness of single MOF crystals was greatly improved, which depended on the direction of the inserted polymers, as revealed by nanoindentation analysis. Insertion of polymer chains did not influence the crystal structure of MOFs, which indicates that this approach should be highly promising for improving the mechanical properties of MOFs.

Background: Broader autism phenotype (BAP) refers to the expression of behavioral and cognitive dispositions similar to autism spectrum disorder. The present study investigated whether mothers' BAP was prospectively associated with maternal attachment, and if postpartum depression modified this association., Methods: The Japan Environment and Children's Study (JECS) is a national and government-funded birth cohort study that began in January 2011. Among the 103,099 mothers enrolled, 87,369 mothers without a history of depression were included in the analysis. Self-administered questionnaires were used. These included: the Japanese version of the Autism Spectrum Quotient, the Mother to Infant Bonding Scale, and the Edinburgh Postnatal Depression Scale. Logistic regression analyses were performed., Results: The BAP during the second or third trimester of pregnancy was linearly associated with an increased risk of postpartum depression and insecure maternal attachment when infants were one month old (p for trend < 0.001), after adjusting for confounding variables. When stratified by postpartum depression, among the BAP subscales, deficiencies in social skills and communication were associated with an increased risk of insecure maternal attachment in mothers without postpartum depression. The relationships between the BAP subscales and maternal attachment were attenuated among mothers with postpartum depression., Limitations: Only five items of the Mother to Infant Bonding Scale were used in the present study, and thus the results should be interpreted with caution., Conclusions: Mothers' BAP was predictive of insecure maternal attachment toward their infant. Postpartum depression partially moderated the associations between mothers' BAP and insecure maternal attachment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Superior mesenteric artery ischemia and nonocclusive mesenteric ischemia are representative diseases of the vascular emergency known as irreversible transmural intestinal necrosis (ITIN). The receptor for advanced glycation end-products (RAGE) belongs to the immunoglobulin superfamily of extracellular ligands, which also includes high-mobility group box 1 (HMGB-1) and proteins of the S100 family. The HMGB-1 ligands have been implicated in the pathogenesis of various inflammatory disorders. This study was designed to investigate the relation between RAGE and ITIN in a murine acute intestinal ischemic model., Materials and Methods: ITIN was induced by clipping the cranial mesenteric artery and the peripheral blood vessels. Mucosal and blood samples were collected and analyzed by reverse-transcription PCR and immunohistochemistry for mucosal inflammation and levels of RAGE-related proteins. The influence of RAGE signaling on intestinal cell reproduction was investigated using the cell scratch test, an in vitro wound-healing assay. Finally, RAGE-related proteins and their respective inhibitors were administered intraperitoneally to ITIN model mice to determine their effects., Results: RAGE-expressing cells were located at the base of the intestinal crypts at day 0. As ITIN progressed, most of the damaged intestinal cells expressed RAGE, and ligands of RAGE such as HMGB-1, S100 A8/A9, and S100β were present in the crypt cells from the bottom to the top. The quantities of S100 A8/A9 and S100β were particularly high, above the levels found in other diseases. When S100 A8/A9 and S100β were applied to small intestinal epithelial cells in vitro, regeneration was significantly impeded. Inflammatory Gr1+ neutrophils and F4/80+ macrophages are involved in tissue ischemia. S100 A8/A9 enhances inflammatory myeloid cell influx., Conclusions: RAGE-related proteins are elevated in ITIN model mice and impede intestinal regeneration in vitro. RAGE-related proteins may be a new therapeutic target or a new marker for ITIN., (© 2020 S. Karger AG, Basel.)

There are many psychosocial and biomedical risk factors for postpartum depression (PPD). However, associations between co-resident family members and PPD risk have not been examined. This study investigated whether co-resident family members were associated with risk for PPD during 1 month postpartum among Japanese women, and if these associations were modified by household income and their perceived partner's involvement in childcare. The sample comprised 86,490 women. Data were drawn from the Japan Environment and Children's Study, a large-scale national cohort study started in 2011. Our major predictor was co-resident family members when they registered around the first trimester of the women's pregnancy: partner, parent(s), parent(s)-in-law, or child(ren). The outcome was PPD at 1 month after delivery, assessed by the Edinburgh Postnatal Depression Scale. Adjusted odds ratios (OR) for family members and PPD incidence were calculated using multivariable logistic regression analysis. Subgroup analyses were conducted by household income and perceived partner's involvement in childcare. Adjusted ORs (95% confidence interval) for PPD for those not living with their partner, parent(s), parent(s)-in-law, or child(ren) compared with those who lived with these family members were 1.21 (1.07-1.37), 1.13 (1.03-1.24), 0.91 (0.84-0.98), and 1.42 (1.31-1.53), respectively. The level of perceived partner's involvement in childcare changed the identified association between family member and PPD. We found that "who a pregnant woman lives with" affects the risk of PPD in the first month postpartum, and high levels of perceived partner's involvement in childcare reduced harmful effects/increased protective effect of family members on PPD incidence. These findings suggested that interventions to increase perceived partner's support for childcare may be effective in preventing PPD, regardless of living situation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Appendiceal intussusception is a rare disease in which the appendix invaginates into the cecum. It is often caused by organic diseases. The present case involved an appendiceal intussusception without an organic disease, and laparoscopic resection of part of the cecum was performed. Appendiceal intussusception has various causes, including malignant diseases. Therefore, diagnosis and selection of operative method are complex and could potentially lead to an excessively invasive option. By performing SILS with a multiuse single-site port, we were able to provide an appropriate, non-invasive treatment that had a good esthetic outcome., (© 2017 The Authors. Asian Journal of Endoscopic Surgery published by John Wiley & Sons Ltd on behalf of Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force.)

A comprehensive understanding of the molecular machinery important for nociception is essential to improving the treatment of pain. Here, we show that the BMP signaling pathway regulates nociception downstream of the E3 ubiquitin ligase highwire (hiw). hiw loss of function in nociceptors caused antagonistic and pleiotropic phenotypes with simultaneous insensitivity to noxious heat but sensitized responses to optogenetic activation of nociceptors. Thus, hiw functions to both positively and negatively regulate nociceptors. We find that a sensory reception-independent sensitization pathway was associated with BMP signaling. BMP signaling in nociceptors was up-regulated in hiw mutants, and nociceptor-specific expression of hiw rescued all nociception phenotypes including the increased BMP signaling. Blocking the transcriptional output of the BMP pathway with dominant negative Mad suppressed nociceptive hypersensitivity that was induced by interfering with hiw. The up-regulated BMP signaling phenotype in hiw genetic mutants could not be suppressed by mutation in wallenda suggesting that hiw regulates BMP in nociceptors via a wallenda independent pathway. In a newly established Ca2+ imaging preparation, we observed that up-regulated BMP signaling caused a significantly enhanced Ca2+ signal in the axon terminals of nociceptors that were stimulated by noxious heat. This response likely accounts for the nociceptive hypersensitivity induced by elevated BMP signaling in nociceptors. Finally, we showed that 24-hour activation of BMP signaling in nociceptors was sufficient to sensitize nociceptive responses to optogenetically-triggered nociceptor activation without altering nociceptor morphology. Overall, this study demonstrates the previously unrevealed roles of the Hiw-BMP pathway in the regulation of nociception and provides the first direct evidence that up-regulated BMP signaling physiologically sensitizes responses of nociceptors and nociception behaviors., Competing Interests: The authors have declared that no competing interests exist.

Background: There is little longitudinal evidence on the impact of specific living arrangements (ie, who individuals live with) on mental health among older adults, and no studies have examined the modifying effect of residential social cohesion level on this association. We aimed to examine the association between living arrangements and depressive symptoms and whether this association varies with residential neighborhood social cohesion level among 19,656 men and 22,513 women aged 65 years and older in Japan., Methods: We analyzed the association between baseline living arrangements in 2010 and depressive symptoms in 2013. We calculated gender-specific odds ratios (ORs) of living arrangements for depressive symptoms using a logistic regression and conducted subgroup analyses by neighborhood social cohesion level., Results: Among men (but not women), living alone (OR 1.43; 95% confidence intervals [CI], 1.18-1.73) and living with spouse and parent (OR 1.47, 95% CI, 1.09-1.98) were associated with increased odds of depressive symptoms compared with living with a spouse only. Living with spouse and child was a risk for men in the young age group but a protective factor for women. We also identified that the negative impact of living arrangements on depressive symptoms was attenuated in neighborhoods with higher levels of social cohesion., Conclusions: Living arrangements are associated with risk of depressive symptoms among men and women; these associations differ by gender and neighborhood social cohesion level. Our results suggest the need to pay more attention to whether individuals live alone, as well as who individuals live with, to prevent depressive symptoms among older adults.

The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER + ) MCF-7 cells but also highly expressed in ER - SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells. In SK-BR-3 cells but not in MCF-7 cells, PCP4/PEP19 knockdown by siRNA silencing decreased the aromatase expression in gene transcriptional level. When PCP4/PEP19 was overexpressed by CMV promoter-driven PCP4/PEP19 expressing plasmid transfection, aromatase gene transcription increased in SK-BR-3 cells. This aromatase gene transcription is mainly mediated through promoter region PI.1, which is usually active in the placental tissue but not in the breast cancer tissue. These results indicate a new function of PCP4/PEP19 that would enhance aromatase gene upregulation to supply estrogens in heterogeneous cancer microenvironment., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Despite established guidelines for population-level assessments of immunity after vaccination, standard methods for individual-level analyses have not been established, limiting the ability to optimize vaccination strategies within a particular season. In this study, we evaluated changes in cell-mediated immunity (CMI) with respect to the number of influenza vaccine doses. In particular, the influenza vaccine was administered to 21 adults during the 2015-2016 season. IFN-γ production induced by the influenza vaccine antigens [A (H1N1), A (H3N2), B (Yamagata lineage), and B (Victoria lineage)] increased after the first dose of vaccination in 11, 10, 10, and 11 subjects, respectively. In 5 of 10 (H1N1), 4 of 10 (H3N2), 3 of 9 (Yamagata lineage), and 3 of 8 (Victoria lineage) subjects who did not exhibit an increase in IFN-γ production after the first dose, CMI was enhanced after the second dose. The production of IFN-γ increased after the first or second dose of the vaccine in 16, 14, 13, and 14 of the 21 subjects, respectively. The results of this study showed that two doses of the influenza vaccine effectively enhance CMI in subjects with primary vaccine failure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivity (LM1-RM1 rs-connectivity) is a measure of its functional integrity. CST Injury and LM1-RM1 rs-connectivity each individually correlate with motor outcome post-stroke, but less is understood about the relationship between these biomarkers. Thus, this study investigates the relationship between CST Injury and LM1-RM1 rs-connectivity, individually and together, with motor outcome. Twenty-seven participants with upper limb motor deficits post-stroke completed motor assessments and underwent MRI at one time point. CST Injury and LM1-RM1 rs-connectivity were derived from T1-weighted and resting state functional MRI scans, respectively. We performed hierarchical multiple regression analyses to determine the contribution of each biomarker in explaining motor outcome. The interaction between CST Injury and LM1-RM1 rs-connectivity does not significantly contribute to the variability in motor outcome. However, inclusion of both CST Injury and LM1-RM1 rs-connectivity explains more variability in motor outcome, than either alone. We suggest both biomarkers provide distinct information about an individual's motor outcome.

Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects., Methods: Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO., Results: Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79)., Conclusions: A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music-supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty-eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10-week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke-McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well-being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community-dwelling chronic-stage survivors., (© 2018 New York Academy of Sciences.)

Background: There are few reports of metastases from colon cancer to an inguinal hernia sac, and few reports of colon cancer originating in diverticula. We report a patient with carcinoma of the sigmoid colon arising in two diverticula, who presented with peritoneal seeding to an inguinal hernia sac, and a review of the literature., Case Presentation: A 55-year-old male underwent open herniorrhaphy for a left inguinal hernia. At operation, a nodule in the inguinal hernia sac was resected and histologic examination revealed adenocarcinoma, which was suspected to be a metastasis from a distant primary lesion. Postoperative evaluation included colonoscopy and positron emission tomography which showed two suspected lesions in sigmoid diverticula. Laparoscopic subtotal colectomy was performed, and pathology revealed adenocarcinoma in two sigmoid diverticula., Conclusions: If a nodule is found in an inguinal hernia sac, especially in older patients, peritoneal metastases should be considered. Resection of the nodule with histopathologic evaluation is essential. Colon cancer arising in a diverticulum should be considered as a possible site of the primary lesion.

After the severe nuclear disaster in Fukushima, which was triggered by the Great East Japan earthquake in March 2011, nuclear power plants in Japan were temporarily shut down for mandatory inspections. To prevent large-scale blackouts, the Japanese government requested companies and households to reduce electricity consumption in summer and winter. It is reported that the domestic electricity demand had a structural decrease because of the electricity conservation effect (ECE). However, quantitative analysis of the ECE is not sufficient, and especially time variation of the ECE remains unclear. Understanding the ECE is important because Japan's NDC (nationally determined contribution) assumes the reduction of CO2 emissions through aggressive energy conservation. In this study, we develop a time series model of monthly electricity demand in Japan and estimate time variation of the ECE. Moreover, we evaluate the impact of electricity conservation on CO2 emissions from power plants. The dynamic linear model is used to separate the ECE from the effects of other irrelevant factors (e.g. air temperature, economic production, and electricity price). Our result clearly shows that consumers' electricity conservation behavior after the earthquake was not temporary but became established as a habit. Between March 2011 and March 2016, the ECE on industrial electricity demand ranged from 3.9% to 5.4%, and the ECE on residential electricity demand ranged from 1.6% to 7.6%. The ECE on the total electricity demand was estimated at 3.2%-6.0%. We found a seasonal pattern that the residential ECE in summer is higher than that in winter. The emissions increase from the shutdown of nuclear power plants was mitigated by electricity conservation. The emissions reduction effect was estimated at 0.82 MtCO2-2.26 MtCO2 (-4.5% on average compared to the zero-ECE case). The time-varying ECE is necessary for predicting Japan's electricity demand and CO2 emissions after the earthquake.

Purpose: To investigate the relationship between the meiotic spindle size in human metaphase II oocytes and embryo developmental potential after intracytoplasmic sperm injection (ICSI)., Methods: Analyzed were 1302 oocytes with a visible meiotic spindle from 281 patients aged under 40 years undergoing ICSI cycles. The meiotic spindle was imaged by using PolScope before ICSI. The oocytes were classified into three groups, according to spindle size: group A (<90 μm 2 ), group B (90-120 μm 2 ), and group C (>120 μm 2 )., Results: Overall, 389 (29.9%) oocytes were classified into group A, 662 (50.8%) into group B, and 251 (19.3%) into group C. The fertilization rate of the group B oocytes was significantly higher than for the A and C oocytes. The blastocyst formation rate in group B was significantly higher than in group A. In addition, the pregnancy rate in group B was significantly higher than in the other two groups., Conclusion: The oocytes with a spindle size of 90-120 μm 2 showed higher fertilization, blastocyst formation, and clinical pregnancy rates than those with larger or smaller spindles. The measurement of the meiotic spindle size thus has a positive predictive value for identifying human embryo developmental potential clinically.

Rapid and efficient escape behaviors in response to noxious sensory stimuli are essential for protection and survival. Yet, how noxious stimuli are transformed to coordinated escape behaviors remains poorly understood. In Drosophila larvae, noxious stimuli trigger sequential body bending and corkscrew-like rolling behavior. We identified a population of interneurons in the nerve cord of Drosophila , termed Down-and-Back (DnB) neurons, that are activated by noxious heat, promote nociceptive behavior, and are required for robust escape responses to noxious stimuli. Electron microscopic circuit reconstruction shows that DnBs are targets of nociceptive and mechanosensory neurons, are directly presynaptic to pre-motor circuits, and link indirectly to Goro rolling command-like neurons. DnB activation promotes activity in Goro neurons, and coincident inactivation of Goro neurons prevents the rolling sequence but leaves intact body bending motor responses. Thus, activity from nociceptors to DnB interneurons coordinates modular elements of nociceptive escape behavior., Competing Interests: AB, KH, TO, CQ, GS, DG, MS, WT, MZ, AC, WG No competing interests declared, (© 2018, Burgos et al.)

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain networks implicated in the damage. The aim of this study is to investigate how resting state connectivity (rs-connectivity) within and between motor and frontoparietal networks are affected post-stroke in correlation with motor outcome. Twenty-seven participants with chronic stroke with unilateral upper limb deficits underwent motor assessments and magnetic resonance imaging. Participants completed the Chedoke-McMaster Stroke Assessment as a measure of arm (CMSA-Arm) and hand (CMSA-Hand) impairment and the Action Research Arm Test (ARAT) as a measure of motor function. We used a seed-based rs-connectivity approach defining the motor (seed=contralesional primary motor cortex (M1)) and frontoparietal (seed=contralesional dorsolateral prefrontal cortex (DLPFC)) networks. We analyzed the rs-connectivity within each network (intra-network connectivity) and between both networks (inter-network connectivity), and performed correlations between: a) intra-network connectivity and motor assessment scores; b) inter-network connectivity and motor assessment scores. We found: a) Participants with high rs-connectivity within the motor network (between M1 and supplementary motor area) have higher CMSA-Hand stage (z=3.62, p=0.003) and higher ARAT score (z=3.41, p=0.02). Rs-connectivity within the motor network was not significantly correlated with CMSA-Arm stage (z=1.83, p>0.05); b) Participants with high rs-connectivity within the frontoparietal network (between DLPFC and mid-ventrolateral prefrontal cortex) have higher CMSA-Hand stage (z=3.64, p=0.01). Rs-connectivity within the frontoparietal network was not significantly correlated with CMSA-Arm stage (z=0.93, p=0.03) or ARAT score (z=2.53, p=0.05); and c) Participants with high rs-connectivity between motor and frontoparietal networks have higher CMSA-Hand stage (r s =0.54, p=0.01) and higher ARAT score (r s =0.54, p=0.009). Rs-connectivity between the motor and frontoparietal networks was not significantly correlated with CMSA-Arm stage (r s =0.34, p=0.13). Taken together, the connectivity within and between the motor and frontoparietal networks correlate with motor outcome post-stroke. The integrity of these regions may be important for an individual's motor outcome. Motor-frontoparietal connectivity may be a potential biomarker of motor recovery post-stroke., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A clinical trial of a quadrivalent split influenza vaccine was performed in the 2014/15 season. Sixty-four subjects aged 6 months to 18 years were enrolled in order to investigate the relationship between cellular and humoral immune responses. Subjects were categorized into two groups by measuring neutralizing antibodies: non-primed naïve/primed or seroconverted/non-seroconverted groups. Whole-blood cultures were stimulated with the H1N1 split antigen before immunization and one month after the first and second immunizations for subjects < 13 years and before and one month after the first dose for those ≥ 13 years in order to investigate cytokine production. Significant amounts of IL-2, IL-12, IL-13, MCP-1, MIP-1β, and TNF-α were detected from one month after the first dose in the naïve group. In addition to these cytokines, the production of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, G-CSF, and IFN-γ was enhanced one month after the second dose. No significant increase was noted in the primed group, except in the production of IL-10. In seroconverted subjects, the production of IL-2, IL-4, IL-8, IL-10, G-CSF, MCP-1, TNF-α, and IFN-γ increased one month after the first dose, which was earlier than in the naïve group, whereas no significant cytokine response was noted in subjects without seroconversion. Subjects ≥ 13 years were primed and the production of G-CSF, IL-4, and IL-1β increased in subjects with seroconversion. Whole-blood cultures were also stimulated with the H3N2 split antigen and similar cytokine profiles were obtained. Many cytokines and chemokines, including inflammatory cytokines, were produced in seroconverted, but not non-seroconverted subjects.

Background: The aim of this study was to elucidate the influence of insular infarction on blood pressure (BP) variability and outcomes according to the region of the insular cortex affected., Methods: A total of 90 patients diagnosed with acute unilateral ischemic stroke were registered. The BP variability was calculated over 24 h after admission (hyperacute) and for 2-3 days after admission (acute). Patients were classified into groups of right and left, and then right anterior, right posterior, left anterior, and left posterior insular infarction., Results: Patients with insular infarction showed a significantly larger infarct volume, higher modified Rankin scale scores, and lower SD and coefficient of variation (CV) of -systolic BP in the hyperacute phase than shown by patients without insular infarction (p < 0.01, p < 0.01, p = 0.02, and p = 0.03, respectively). The SD and CV of systolic BP in the hyperacute phase showed significant differences among the 3 groups with right insular infarction, with left insular infarction, and without insular infarction (p < 0.05 and p < 0.05, respectively). There was a tendency for the systolic BP variability to be lower in patients with right anterior insular infarction than in patients with infarcts in other areas., Conclusion: The right insular cortex, especially the anterior part, might be a hub for autonomic nervous regulation., (© 2018 S. Karger AG, Basel.)

Originally identified at the breakpoint of a (1;11)(q42.1; q14.3) chromosomal translocation in a Scottish family with a wide range of mental disorders, the DISC1 gene has been a focus of intensive investigations as an entry point to study the molecular mechanisms of diverse mental dysfunctions. Perturbations of the DISC1 functions lead to behavioral changes in animal models, which are relevant to psychiatric conditions in patients. In this work, we have expressed the human DISC1 gene in the fruit fly (Drosophila melanogaster) and performed a genetic screening for the mutations of psychiatric risk genes that cause modifications of DISC1 synaptic phenotypes at the neuromuscular junction. We found that DISC1 interacts with dnrx1, the Drosophila homolog of the human Neurexin (NRXN1) gene, in the development of glutamatergic synapses. While overexpression of DISC1 suppressed the total bouton area on the target muscles and stimulated active zone density in wild-type background, a partial reduction of the dnrx1 activity negated the DISC1-mediated synaptic alterations. Likewise, overexpression of DISC1 stimulated the expression of a glutamate receptor component, DGLURIIA, in wild-type background but not in the dnrx1 heterozygous background. In addition, DISC1 caused mislocalization of Discs large, the Drosophila PSD-95 homolog, in the dnrx1 heterozygous background. Analyses with a series of domain deletions have revealed the importance of axonal localization of the DISC1 protein for efficient suppression of DNRX1 in synaptic boutons. These results thus suggest an intriguing converging mechanism controlled by the interaction of DISC1 and Neurexin in the developing glutamatergic synapses.

This study developed flexible light-emitting diodes (LEDs) with warm white and neutral white light. A simple ultraviolet flip-chip sticking process was adopted for the pumping source and combined with polymer and quantum dot (QD) films technology to yield white light. The polymer-blended flexible LEDs exhibited higher luminous efficiency than the QD-blended flexible LEDs. Moreover, the polymer-blended LEDs achieved excellent color-rendering index (CRI) values (Ra = 96 and R9 = 96), with high reliability, demonstrating high suitability for special applications like accent, down, or retrofit lights in the future. In places such as a museum, kitchen, or surgery room, its high R9 and high CRI characteristics can provide high-quality services.

Purpose: Medial patellofemoral ligament (MPFL) reconstruction has become a common form of treatment for recurrent patellar dislocation. This study was performed using open-MRI to compare the length change pattern of MPFL in patients with a history of patellar dislocation to that in healthy subjects., Methods: The subjects comprised 10 knees of 8 males and 13 knees of 12 females with a history of one or more patellar dislocations. The length of the MPFL was measured using open-MRI in both the leg-extended position and knee-flexed positions to analyse the length change pattern., Results: The average MPFL lengths were 58.6 ± 6.5 mm and 52.0 ± 4.6 mm for males and females in the extended knee position, respectively. The length change pattern of the MPFL showed slight variation up to a flexion angle of 30° and a clear decrease above 30°. This pattern differed from that of normal MPFL. In terms of morphology, the fibre bundle of the damaged MPFL followed a convex course towards the side of the patellofemoral joint surface at a knee flexion angle of 60°, whereas that of the normal MPFL followed a straight course., Conclusion: The in vivo damaged MPFL length change pattern was specific and differed distinctly from that of normal MPFL. The results of the present study suggested that MPFL fibres with a history of patellar dislocation lack sufficient tension at knee flexion angles of 0°-60°. However, further studies are needed to obtain a better understanding of cases with a patellar dislocation or postsurgical cases of MPFL reconstruction., Level of Evidence: III.

Thermal ring-opening polymerization of the unsymmetrically substituted [1]ferrocenophane was performed in one-dimensional nanochannels of porous coordination polymers (PCPs). In contrast to conventional thermal polymerization in bulk, formation of cyclic polymer was inhibited in the channels. In addition, the tacticity of the resulting polymer was dependent on the pore size of PCPs.

Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1 ) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat -/- and Serpine1 -/- In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275. Some animals were treated with clodronate to deplete macrophages. Epidermal growth factor (EGF) experiments were performed to understand the role of macrophages and how EGF contributes to adhesion. In the early phase of adhesive small bowel obstruction, increased PAI-1 activity was observed in the peritoneal cavity. Genetic and pharmacologic PAI-1 inhibition prevented progression of adhesion and increased circulating plasmin. Whereas Serpine1 -/- mice showed intra-abdominal bleeding, mice that were treated with TM5275 did not. Mechanistically, PAI-1, in combination with tissue plasminogen activator, served as a chemoattractant for macrophages that, in turn, secreted EGF and up-regulated the receptor, HER1, on peritoneal mesothelial cells, which led to PAI-1 secretion, further fueling the vicious cycle of impaired fibrinolysis at the adhesive site. Controlled inhibition of PAI-1 not only enhanced activation of the fibrinolytic system, but also prevented recruitment of EGF-secreting macrophages. Pharmacologic PAI-1 inhibition ameliorated adhesion formation in a macrophage-dependent manner.-Honjo, K., Munakata, S., Tashiro, Y., Salama, Y., Shimazu, H., Eiamboonsert, S., Dhahri, D., Ichimura, A., Dan, T., Miyata, T., Takeda, K., Sakamoto, K., Hattori, K., Heissig, B. Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice., (© FASEB.)

Background and Purpose: Because of limited evidence, we investigated a long-term impact of changes in employment status on risk of stroke., Methods: This was a prospective study of 21 902 Japanese men and 19 826 women aged 40 to 59 years from 9 public health centers across Japan. Participants were followed up from 1990 to 1993 to the end of 2009 to 2014. Cox proportional hazard ratio of stroke (incidence and mortality) and its types (hemorrhagic and ischemic) was calculated according to changes in the employment status within 5 years interval between 1990 to 1993 and 1995 to 1998 (continuously employed, job loss, reemployed, and continuously unemployed)., Results: During the follow-up period, 973 incident cases and 275 deaths from stroke in men and 460 cases and 131 deaths in women were documented. Experiencing 1 spell of unemployment was associated with higher risks of morbidity and mortality from total, hemorrhagic, and ischemic stroke in both men and women, even after propensity score matching. Compared with continuously employed subjects, the multivariable hazard ratio (95% confidence interval) for total stroke incidence in job lost men was 1.58 (1.18-2.13) and in job lost women was 1.51 (1.08-2.29), and those for total stroke mortality were 2.22 (1.34-3.68) in men and 2.48 (1.26-4.77) in women. The respective hazard ratio (95% confidence interval) in reemployed men was 2.96 (1.89-4.62) for total stroke incidence and 4.21 (1.97-8.97) for mortality, whereas those in reemployed women were 1.30 (0.98-1.69) for incidence and 1.28 (0.76-2.17) for mortality., Conclusions: Job lost men and women and reemployed men had increased risks for both hemorrhagic and ischemic stroke incidence and mortality., (© 2017 American Heart Association, Inc.)

The rise of noncommunicable diseases is a serious health burden for Palau. This study described the prevalence of hypertension, and assessed its association with obesity. Surveys following the WHO STEPwise approach to surveillance were conducted in 2529 adults. Multivariate prevalence ratios (PR) of hypertension for body mass index (BMI) categories were calculated by logistic regression models using conditional standardization procedure. Age- and sex-specified analyses were performed. Overall prevalence of obesity and hypertension were 40.4% and 46.8%, respectively. Prevalence of hypertension was positively associated with BMI. However, overweight men had as high prevalence of hypertension as the obese (multivariable-adjusted PR was 1.84 for overweight and 1.91 for obese compared with nonoverweight). The association between hypertension and BMI was similar across age groups. The prevalence of hypertension in women increased gradually with the increase of BMI whereas that in men reached a plateau already in the overweight.

Previous studies have suggested associations of family composition with morbidity and mortality; however, the evidence of associations with risk of stroke is limited. We sought to examine the impact of changes in the household composition on risk of stroke and its types in Japanese population. Cox proportional hazard modelling was used to assess the risk of incident stroke and stroke types within a cohort of 77,001 Japanese men and women aged 45-74 years who experienced addition and/or loss of family members [spouse, child(ren), parent(s) and others] to their households over a five years interval (between 1990-1993 and 1995-1998). During 1,043,446 person-years of the follow-up for 35,247 men and 41,758 women, a total of 3,858 cases of incident stroke (1485 hemorrhagic and 2373 ischemic) were documented. When compared with a stable family composition, losing at least one family member was associated with 11-15% increased risk of stroke in women and men; hazard ratios (95% confidence interval) were 1.11 (1.01-1.22) and 1.15 (1.05-1.26), respectively. The increased risk was associated with the loss of a spouse, and was evident for ischemic stroke in men and hemorrhagic stroke in women. The addition of any family members to the household was not associated with risk of stroke in men, whereas the addition of a parent (s) to the household was associated with increased risk in women: 1.49 (1.09-2.28). When the loss of a spouse was accompanied by the addition of other family members to the household, the increased risk of stroke disappeared in men: 1.18 (0.85-1.63), but exacerbated in women: 1.58 (1.19-2.10). In conclusion, men who have lost family members, specifically a spouse have higher risk of ischemic stroke, and women who gained family members; specifically a parent (s) had the higher risk of hemorrhagic stroke than those with a stable family composition.

Polymerization of monosaccharide monomers usually suffers from the production of polysaccharides with ill-defined structures because of the uncontrolled random reactions among many reactive hydroxyl groups on saccharide monomers. In particular, rational synthesis of polysaccharides with porosity approximating molecular dimensions is still in its infancy, despite their usefulness as drug carriers. Here, we disclose an efficient synthetic methodology for the preparation of polysaccharides with controllable mesoporosity in the structure, utilizing [Cu 3 (benzene-1,3,5-tricarboxylate)] n (HKUST-1; 1) as templates. Cationic ring-opening polymerization of 1,6-anhydro glucose was performed in nanochannels of 1, followed by removal of the host frameworks, giving polysaccharide particles as replicas of the original molds. Nitrogen adsorption measurement revealed that the obtained polysaccharide particles contained high mesoporosity in the structure, which could be controlled systematically depending on the polymerization conditions. Because of the large specific surface area, tunable porosity and particle size, we could also demonstrate the capabilities of our polysaccharides for loading and releasing of a drug molecule and protein.

To examine associations between work-family conflict and self-rated health among Japanese workers and to determine whether the associations differed by household income. Data was derived from the Japan Public Health Center-based Prospective Study for the Next Generation in Saku area in 2011-2012 (7,663 men and 7,070 women). Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for poor self-rated health by work-family conflict consisting of two dimensions (work-to-family and family-to-work conflicts) were calculated by gender and household income. Multivariate ORs of high work-to-family and family-to-work conflicts for poor self-rated health were 2.46 (95% CI; 2.04-2.97) for men and 3.54 (95% CI; 2.92-4.30) for women, with reference to the low work-to-family and family-to-work conflicts (p-value for gender interaction = 0.02). Subgroup analysis indicated that health effects of work-family conflict were likely to be more evident in the low income group only among women. Work-family conflict was associated with poor self-rated health among middle-aged Japanese men and women; its health impact was relatively stronger among women, and particularly economically disadvantaged women.

Non-communicable diseases have been recognized as a serious threat to public health in Palau. To tackle the problem, different strategies might be necessary for populations with different ethnic backgrounds. This study aims to find the differences in the prevalence of metabolic risk factors of non-communicable diseases between Palauans and Filipinos living in Palau, and examine possible determinants of the differences. We selected data of 2,032 participants, including native Palauans and Filipinos, from the Palau STEPS Survey 2011-2013 for this study. Logistic regression models were used to inspect the association of each metabolic risk factor with ethnicity by calculating odds ratios adjusted for potential confounding factors. Palauans had higher age-standardized prevalence of overweight or obesity (84% vs. 45%), hypertension (50% vs. 38%) and diabetes (19% vs. 13%) than Filipinos. However, after adjusting for BMI and various lifestyle related factors, there are no statistical significant differences in the prevalence of hypertension and diabetes between these two ethnic groups. Palauan men were less likely to have elevated total cholesterol, especially after adjusting for BMI (odds ratio=0.55, 95% confidence interval: 0.33-0.91), while Palauan women were more likely to have elevated triglycerides than their Filipino counterparts (odds ratio=1.45, 95% confidence interval: 1.02-2.06). Our findings suggested that Palauans' higher BMI distribution might be able to explain their higher prevalence of hypertension and partially explain their higher diabetes prevalence. Palauans were not consistently more likely to have all metabolic risk factors, namely dyslipidemia were less likely to be observed in Palauan men.

We examined the effect of education level on the association between healthy lifestyle behaviors and cardiovascular mortality in the Japanese population. A total of 42,647 community-based men and women aged 40-79 years were enrolled at baseline (1988-1990), followed through 2009. The components of the healthy lifestyle score included the intake of fruits, fish, and milk; body mass index; exercise; avoidance of smoking; moderate alcohol intake; and moderate sleep duration. During the 19.3 years of follow-up, 8,314 all-cause and 2,377 total cardiovascular mortality cases were noted. Inverse associations were observed between healthy lifestyle scores and total cardiovascular disease (CVD) for both the lower and higher education level groups. Multivariable hazard ratios (95% confidence interval) for CVD mortality from the highest to the lowest healthy lifestyle scores, and the population attributable fraction (95% CIs) without healthy lifestyle scores of 7-8 were 0.51 (0.33-0.52) and 42% (24-58%), and 0.38 (0.27-0.47) and 55% (36-69%) for the higher and lower education levels, respectively. Our findings suggest that the association between higher CVD mortality and lower education level can be explained by the individuals' lower adherence to a healthy lifestyle; hence, lifestyle modification would be beneficial for the prevention of cardiovascular mortality, irrespective of the education level.

Since the bona fide Fc receptor for IgM antibody (FcµR) was identified eight years ago, much progress has been made in defining its biochemical nature, cellular distribution, and effector function. However, there are clearly conflicting results, especially about the cellular distribution and function of murine FcµR. In this short article, we will discuss recent findings from us and other investigators along with our interpretations and comments that may help to resolve the existing puzzles and should open new avenues of investigation.

We aimed to investigate the prevalence and predictors of diabetes and prediabetes among adults in Palau. We used data of 1915 adults, aged 25 to 64 years, who participated in the World Health Organization's (WHO) STEPwise Approach to Risk Factor Surveillance (STEPS) study in Palau. Information on behavioral risk factors of NCDs and physical and biochemical measurements were obtained using standard methods of the WHO. The diagnosis of diabetes and prediabetes was based on the recent American Diabetes Association criteria. Predictors of the prevalence of diabetes and prediabetes were identified using multinomial logistic regression analysis. The overall age-standardized prevalence of prediabetes and diabetes were 40.4% (43.6% for men, 37.4% for women) and 17.7% (18.6% for men, 17% for women), respectively. Old age, overall obesity (high BMI), central obesity (large waist circumference or waist-hip ratio), hypertension and hypertriglyceridemia were significant predictors of prediabetes and/or diabetes. Diabetes occurred at a younger age in "obese" individuals than that of their "non-obese" counterparts. We confirmed that prediabetes and diabetes are highly prevalent in Palau affecting 40% and 18% adults, respectively. Introducing public health interventions to reduce and prevent obesity as early as possible could prove useful to curb the problem.

Generation of osteoblasts from human somatic cells may be applicable in an effective transplantation therapy against bone diseases. Recently we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some transcription factor genes via retroviral vectors. However, retroviral vector-mediated transduction may potentially cause tumor formation from the infected cells, thus a non-viral gene transfection method may be more preferable for preparation of osteoblasts to be used for transplantation therapy. Here, we constructed a plasmid vector encoding Oct4, Osterix, and L-Myc that were an appropriate combination of transcription factors for this purpose. Osteoblast-like phenotypes including high alkaline phosphatase (ALP) activity, bone matrix production and osteoblast-specific gene expression were induced in normal human fibroblasts that were transfected with the plasmid followed by culturing in osteogenic medium. The plasmid-driven directly converted osteoblasts (p-dOBs) were obtained even in the absence of a xenogenic protein. The plasmid vector sequence had fallen out of the p-dOBs. The cells formed deposition of calcified bodies in situ after transplantation into mice. These results strongly suggest that p-dOBs can be put into practical use for a novel cell-based therapy against bone diseases. J. Cell. Biochem. 117: 2538-2545, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Health disparities in Japan are attracting increasing attention. Temporal trends in health disparities should be continuously monitored using multiple indices of socioeconomic status (SES) and health-related outcomes. We explored changes in socioeconomic differences in the health of Japanese adults during 2000-2010. The data was taken from the Japanese General Social Surveys, the cross-sectional surveys for nationally representative samples of Japanese adults. We used 14,193 samples (individuals of 20-64 years of age) in our analysis. We estimated age-adjusted prevalence ratios of the lowest SES group in comparison with the highest SES group using Poisson regression models with robust error variance. Relative index of inequality (RII) and slope index of inequality (SII) were also calculated. We examined the changes in the association between health-related outcomes (self-rated health (SRH), smoking, and physical activity) and SES indices (income, education, occupation, and subjective social class identification). The results showed temporally expanding trends for the associations of current smoking with SES, especially among women, in both relative and absolute measures. In contrast, no expanding trends were seen for SRH and physical activity. Although the smoking rates declined through the first decade of the 21st century, the socioeconomic disparities in smoking prevalence among Japanese adults expanded, especially among women. Researchers and policymakers should continuously monitor the trends that may cause future disparities in smoking-related morbidity and mortality.

Originally found in a Scottish family with diverse mental disorders, the DISC1 protein has been characterized as an intracellular scaffold protein that associates with diverse binding partners in neural development. To explore its functions in a genetically tractable system, we expressed the human DISC1 in fruit flies (Drosophila melanogaster). As in mammalian neurons, DISC1 is localized to diverse subcellular domains of developing fly neurons including the nuclei, axons and dendrites. Overexpression of DISC1 impairs associative memory. Experiments with deletion/mutation constructs have revealed the importance of amino-terminal domain (46-290) for memory suppression whereas carboxyl domain (598-854) and the amino-terminal residues (1-45) including the nuclear localization signal (NLS1) are dispensable. DISC1 overexpression also causes suppression of axonal and dendritic branching of mushroom body neurons, which mediate a variety of cognitive functions in the fly brain. Analyses with deletion/mutation constructs reveal that protein domains 598-854 and 349-402 are both required for the suppression of axonal branching, while amino-terminal domains including NLS1 are dispensable. In contrast, NLS1 was required for the suppression of dendritic branching, suggesting a mechanism involving gene expression. Moreover, domain 403-596 is also required for the suppression of dendritic branching. We also show that overexpression of DISC1 suppresses glutamatergic synaptogenesis in developing neuromuscular junctions. Deletion/mutation experiments have revealed the importance of protein domains 403-596 and 349-402 for synaptic suppression, while amino-terminal domains including NLS1 are dispensable. Finally, we show that DISC1 functionally interacts with the fly homolog of Dysbindin (DTNBP1) via direct protein-protein interaction in developing synapses., Competing Interests: The authors declare no conflict of interest.

Here, we describe a targeted reverse genetic screen for thermal nociception genes in Drosophila larvae. Using laser capture microdissection and microarray analyses of nociceptive and non-nociceptive neurons, we identified 275 nociceptor-enriched genes. We then tested the function of the enriched genes with nociceptor-specific RNAi and thermal nociception assays. Tissue-specific RNAi targeted against 14 genes caused insensitive thermal nociception while targeting of 22 genes caused hypersensitive thermal nociception. Previously uncategorized genes were named for heat resistance (i.e., boilerman, fire dancer, oven mitt, trivet, thawb, and bunker gear) or heat sensitivity (firelighter, black match, eucalyptus, primacord, jet fuel, detonator, gasoline, smoke alarm, and jetboil). Insensitive nociception phenotypes were often associated with severely reduced branching of nociceptor neurites and hyperbranched dendrites were seen in two of the hypersensitive cases. Many genes that we identified are conserved in mammals., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Quantitative evaluation of vascular ingrowth to the bone tunnel walls and tendon graft after anterior cruciate ligament reconstruction for up to two years post-surgery using magnetic resonance angiography (MRA)., Methods: The study population consists of 100 patients that underwent reconstruction with multi-stranded semitendinosus tendons. The patients were retrospectively divided into those that underwent MRA two, three, four to six, and ≥ seven months after surgery (46, 17, 16, and 21 patients, respectively). Digital imaging and communication in medicine (DICOM) MRA images were imported into image processing software (OsiriX®), and the mean signal-to-noise ratio (SNR) of the bone tunnel walls in the femur and tibia and tendon graft parenchyma in the bone tunnels were measured., Results: On MRA, the signal intensities of the bone tunnel walls in the femur and tibia (12.6 ± 3.41 and 10.7 ± 3.04) were greater than that in the tendon graft (2.65 ± 1.94 and 2.50 ± 2.02, respectively) at two months after surgery. At three months after surgery, the intensities of the tendon grafts (6.25 ± 2.18 and 5.77 ± 1.57, respectively) were greater than those of the bone tunnel wall (2.56 ± 1.29 and 2.50 ± 1.11, respectively). At four to six months, the intensities in the bone tunnel wall were 1.76 ± 0.73 and 1.62 ± 0.72, respectively, and those in the tendon graft were 5.01 ± 2.11 and 4.01 ± 2.35, respectively. At ≥ seven months after surgery, the intensities in the bone tunnel wall were 1.36 ± 0.63 and 1.21 ± 0.87, respectively, and those in the tendon graft were 4.25 ± 1.87 and 3.44 ± 1.99, respectively., Conclusion: Blood flow was seen around the bone tunnel on the femoral and tibial sides two months after ACL reconstruction and in the tendon graft parenchyma three months after surgery. The remodeling process continued after seven months.

The larval brain of Drosophila melanogaster provides an excellent system for the study of the neurocircuitry mechanism of memory. Recent development of neurogenetic techniques in fruit flies enables manipulations of neuronal activities in freely behaving animals. This protocol describes detailed steps for artificial induction of olfactory associative memory in Drosophila larvae. In this protocol, the natural reward signal is substituted by thermogenetic activation of octopaminergic neurons in the brain. In parallel, the odor signal is substituted by optogenetic activation of a specific class of olfactory receptor neurons. Association of reward and odor stimuli is achieved with the concomitant application of blue light and heat that leads to activation of both sets of neurons in living transgenic larvae. Given its operational simplicity and robustness, this method could be utilized to further our knowledge on the neurocircuitry mechanism of memory in the fly brain.

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses.

Background: Suicide rates have been related to educational level and other socioeconomic statuses. However, no prospective study has examined the association between educational level and the risk of suicide in Japan., Methods: We examined the association of education level and suicide risk in a population-based cohort of Japanese men and women aged 40-59 years in the Japan Public Health Center-based Prospective Study Cohort I. In the baseline survey initiated in 1990, a total of 46 156 subjects (21 829 men and 24 327 women) completed a self-administered questionnaire, which included a query of educational level, and were followed up until the end of December 2011. Educational levels were categorized into four groups (junior high school, high school, junior or career college, and university or higher education). During a median follow-up of 21.6 years, the hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide according to educational level were estimated using the Cox proportional hazards regression model adjusted for age; study area; previous history of stroke, ischemic heart disease, or cancer; self-reported stress; alcohol consumption; smoking; living with spouse; and employment status. A total of 299 deaths attributed to suicide occurred., Results: The HR for university graduates or those with higher education versus junior high school graduates was 0.47 (95% CI, 0.24-0.94) in men, and that for high school graduates versus junior high school graduates was 0.44 (95% CI, 0.24-0.79) in women., Conclusions: High educational levels were associated with a reduced risk of suicide for both Japanese men and women.

We demonstrate a feasible method for the preparation of polyglucose (PGlc) with controlled structures, where the polymerization of glucose monomers was performed using one-dimensional nanochannels of [La(1,3,5-benzenetrisbenzoate)(H2O)]n (1). Cationic ring-opening polymerization of 1,6-anhydro-β-D-glucose (levoglucosan) using 1 gave a quasi-linear PGlc, which contrasts highly with the results obtained from conventional polymerizations in bulk and solution. The regulated structure of PGlc prepared using the PCP led to a remarkable improvement in the processability and thermal stability of PGlc, which is useful in applications as a bioplastic.

Background and Purpose: There have been consistent findings reported that marital transition (ie, change in marital status during a given time period) is associated with risk of cardiovascular disease; however, few studies have been conducted on stroke risk, particularly stroke subtypes. Moreover, no studies have examined the moderating effect of living arrangement and employment status on the association between marital transition and stroke risk., Methods: We examined sex-specific associations between marital transition and stroke risk using data from Japan Public Health Center-based Prospective Study. We included 24 162 men and 25 626 women who were married at prebaseline (5 years before baseline). Marital transition was determined by marital status at baseline. Weighted hazard ratios of stroke risk were estimated by Cox proportional regression analysis with inverse probability of weighting using a propensity score., Results: An increased risk of stroke, particularly hemorrhagic stroke, was observed among men and women with marital transition (ie, married to unmarried); weighted hazard ratios (95% confidence interval [CI]) for men and women were 1.26 (1.13-1.41) and 1.26 (1.09-1.45), respectively. Participants with marital transition and lived with children had increased stroke risk. Living with parents buffered the increased stroke risk owing to marital transition among men; however, no such effect was identified among women. Elevated stroke risk owing to marital transition was magnified among women if they were unemployed; weighted hazard ratio=2.98 (95% CI, 1.66-5.33)., Conclusions: Living arrangement and employment status modified the positive associations between marital transition and stroke risk, which differed by sex., (© 2016 American Heart Association, Inc.)

Spontaneous osteonecrosis of the knee (SPONK) usually involves a single condyle, most often the medial femoral condyle (MFC). Involvement of the medial tibial plateau (MTP) is less common, occurring in about 2% of knees with SPONK. Early onset SPONK on the ipsilateral side of the medial compartment is very rare, with, to our knowledge, only four cases reported to date. We describe a very rare case of SPONK with early simultaneous development in the MFC and MTP. Serial plain radiographs and magnetic resonance imaging showed that SPONK in both condyles followed a similar progressive course. The pathological findings in these lesions were similar to those observed in subchondral insufficiency fractures.

Although many reports have been published on the functional roles of periodontal ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis of PDL have not been determined. We investigated the effects of biomechanical force on growth factor production, phosphorylation of MAPKs, and intracellular transduction pathways for growth factor production in human periodontal ligament (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of MAPKs was measured using BD™ CBA Flex Set. In addition, MAPKs inhibitors were used to identify specific signal transduction pathways. Application of biomechanical force (equivalent to occlusal force) increased the synthesis of VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The growth factors induced by biomechanical force may play a role in the mechanisms of homeostasis of PDL.