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1.  The dynamic genome of Hydra 
Chapman, Jarrod A. | Kirkness, Ewen F. | Simakov, Oleg | Hampson, Steven E. | Mitros, Therese | Weinmaier, Therese | Rattei, Thomas | Balasubramanian, Prakash G. | Borman, Jon | Busam, Dana | Disbennett, Kathryn | Pfannkoch, Cynthia | Sumin, Nadezhda | Sutton, Granger G. | Viswanathan, Lakshmi Devi | Walenz, Brian | Goodstein, David M. | Hellsten, Uffe | Kawashima, Takeshi | Prochnik, Simon E. | Putnam, Nicholas H. | Shu, Shengquiang | Blumberg, Bruce | Dana, Catherine E. | Gee, Lydia | Kibler, Dennis F. | Law, Lee | Lindgens, Dirk | Martinez, Daniel E. | Peng, Jisong | Wigge, Philip A. | Bertulat, Bianca | Guder, Corina | Nakamura, Yukio | Ozbek, Suat | Watanabe, Hiroshi | Khalturin, Konstantin | Hemmrich, Georg | Franke, André | Augustin, René | Fraune, Sebastian | Hayakawa, Eisuke | Hayakawa, Shiho | Hirose, Mamiko | Hwang, Jung Shan | Ikeo, Kazuho | Nishimiya-Fujisawa, Chiemi | Ogura, Atshushi | Takahashi, Toshio | Steinmetz, Patrick R. H. | Zhang, Xiaoming | Aufschnaiter, Roland | Eder, Marie-Kristin | Gorny, Anne-Kathrin | Salvenmoser, Willi | Heimberg, Alysha M. | Wheeler, Benjamin M. | Peterson, Kevin J. | Böttger, Angelika | Tischler, Patrick | Wolf, Alexander | Gojobori, Takashi | Remington, Karin A. | Strausberg, Robert L. | Venter, J. Craig | Technau, Ulrich | Hobmayer, Bert | Bosch, Thomas C. G. | Holstein, Thomas W. | Fujisawa, Toshitaka | Bode, Hans R. | David, Charles N. | Rokhsar, Daniel S. | Steele, Robert E.
Nature  2010;464(7288):592-596.
The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.
PMCID: PMC4479502  PMID: 20228792
2.  Therapeutic targets in the ASK1-dependent stress signaling pathways 
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.
PMCID: PMC3491083  PMID: 23060232
ASK1; inhibitors; MAP kinase; signal transduction; stress
3.  Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity 
AIMS—To clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA).
METHODS—EEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21-22 weeks PCA, 23-24 weeks PCA, and 25-26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated.
RESULTS—There were three infants at 21-22 weeks PCA, seven at 23-24 weeks PCA, and five at 25-26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA.
CONCLUSIONS—In premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period.

At less than 27 weeks gestational age, the characteristics of background EEG activities were found to be as follows:
PMCID: PMC1721237  PMID: 11320041
4.  Input integration around the dendritic branches in hippocampal dentate granule cells 
Cognitive Neurodynamics  2014;8(4):267-276.
Recent studies have shown that the dendrites of several neurons are not simple translators but are crucial facilitators of excitatory postsynaptic potential (EPSP) propagation and summation of synaptic inputs to compensate for inherent voltage attenuation. Granule cells (GCs)are located at the gateway for valuable information arriving at the hippocampus from the entorhinal cortex. However, the underlying mechanisms of information integration along the dendrites of GCs in the hippocampus are still unclear. In this study, we investigated the input integration around dendritic branches of GCs in the rat hippocampus. We applied differential spatiotemporal stimulations to the dendrites using a high-speed glutamate-uncaging laser. Our results showed that when two sites close to and equidistant from a branching point were simultaneously stimulated, a nonlinear summation of EPSPs was observed at the soma. In addition, nonlinear summation (facilitation) depended on the stimulus location and was significantly blocked by the application of a voltage-dependent Ca2+ channel antagonist. These findings suggest that the nonlinear summation of EPSPs around the dendritic branches of hippocampal GCs is a result of voltage-dependent Ca2+ channel activation and may play a crucial role in the integration of input information.
PMCID: PMC4079902  PMID: 25009669
Hippocampus; Dendrite; Excitatory postsynaptic potentials summation; Uncaging; Supralinear amplification
5.  Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques 
PLoS ONE  2015;10(7):e0132016.
Bitter taste receptors (TAS2R proteins) allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC), in 333 Japanese macaques (Macaca fuscata) from 9 local populations in Japan. We identified a PTC “non-taster” TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area), at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb) from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.
PMCID: PMC4511751  PMID: 26201026
6.  Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2 
Nature Communications  2015;6:7679.
Crosstalk between inflammatory signalling pathways and receptor tyrosine kinases has been revealed as an indicator of cancer malignant progression. In the present study, we focus on EphA2 receptor tyrosine kinase, which is overexpressed in many human cancers. It has been reported that ligand-independent phosphorylation of EphA2 at Ser-897 is induced by Akt. We show that inflammatory cytokines promote RSK-, not Akt-, dependent phosphorylation of EphA2 at Ser-897. In addition, the RSK–EphA2 signalling pathway controls cell migration and invasion of metastatic breast cancer cells. Moreover, Ser-897-phosphorylated EphA2 co-localizes with phosphorylated active form of RSK in various human tumour specimens, and this double positivity is related to poor survival in lung cancer patients, especially those with a smoking history. Taken together, these results indicate that the phosphorylation of EphA2 at Ser-897 is controlled by RSK and the RSK–EphA2 axis might contribute to cell motility and promote tumour malignant progression.
The EphA2 receptor tyrosine kinase is overexpressed in many cancers and is reported to be phosphorylated by Akt. Here, Zhou et al. show that RSK, rather than Akt, phosphorylates EphA2 on Ser-897, and this regulates cell migration and invasion of metastatic cancer cells.
PMCID: PMC4510653  PMID: 26158630
7.  Higher plasma prorenin concentration plays a role in the development of coronary artery disease 
Biomarker Research  2015;3:18.
Prorenin and renin are both involved in atherosclerosis. However, the role of plasma prorenin and renin in the development and progression of coronary artery disease (CAD) is still not clear. Thus, we aimed to examine the relationships among plasma prorenin concentration, CAD and clinical parameters.
We measured plasma prorenin and renin concentrations and other parameters in 85 patients who underwent coronary angiography. Patients were divided into a CAD group (≥75 % stenosis in one or more coronary arteries) and a non-CAD group.
There was a weak correlation between prorenin and plasma renin concentration (r =0.35, p =0.001), and plasma renin activity (r =0.34, p =0.001). There was no significant difference in the plasma prorenin concentration between the CAD group and non-CAD group. However, patients with a high plasma prorenin concentration frequently suffered CAD. Receiver-operating-characteristic curve analysis showed that the optimal cutoff value of plasma prorenin concentration to detect CAD was 1,100 pg/ml, with a positive predictive value of 94 % and a negative predictive value of 36 %.
The plasma prorenin concentration increases with increases in plasma renin concentration. Higher plasma prorenin concentration (>1,100 pg/ml) plays a role in the development of CAD.
PMCID: PMC4499175  PMID: 26167285
Prorenin; Renin; Coronary artery disease
8.  Recurrent Postoperative Spinal Epidural Hematoma in a Patient with Protein S Deficiency 
Case Reports in Orthopedics  2015;2015:536592.
A 71-year-old man underwent cervical laminectomy and developed two symptomatic epidural hematomas during the acute postoperative period. On both occasions, drain obstruction was the predominant cause. Congenital Protein S deficiency was diagnosed postoperatively. Protein S is a vitamin K-dependent natural anticoagulant and is essential for inhibiting thrombosis in microcirculation. We assume that Protein S deficiency followed by perioperative bed-rest and surgical invasiveness led to severe hypercoagulability and subsequent drain obstruction. The present findings suggest that both bleeding disorders and hypercoagulability are risk factors for postoperative symptomatic epidural hematoma.
PMCID: PMC4508477
9.  Incidence and prediction of outcome in hypoxic–ischemic encephalopathy in Japan 
Pediatrics International  2014;56(2):215-221.
Hypoxic–ischemic encephalopathy (HIE) is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological deficits in later life. We investigated the incidence of term infants with moderate or severe HIE in Japan and identified prognostic risk factors for poor outcome in HIE.
Data on 227 infants diagnosed with moderate or severe HIE and born between January and December 2008 were collected via nationwide surveys from 263 responding hospitals. Using logistic regression, we examined the relationship between maternal, antepartum, intrapartum, and neonatal risk factors and clinical outcome at 18 months following birth.
In Japan, the incidence of moderate or severe HIE was 0.37 per 1000 term live births. Outborn births, low Apgar score at 5 min, use of epinephrine, and low cord blood pH were intrapartum factors significantly associated with neurodevelopmental delay and death at 18 months. Serum lactate, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase (all, P < 0.001) and creatine kinase (P = 0.002) were significantly higher in infants with poor outcome compared to those with favorable outcomes. Abnormal brain magnetic resonance imaging (MRI), an important prognostic factor, was significantly associated with poor outcome (odds ratio, 11.57; 95% confidence interval: 5.66–23.64; P < 0.001).
Risk factors predicting poor outcome in HIE include outborn birth, low Apgar score at 5 min, use of epinephrine, laboratory abnormalities, and abnormal MRI findings.
PMCID: PMC4491348  PMID: 24127879
hypoxic–ischemic encephalopathy; magnetic resonance imaging; neurodevelopmental outcome; risk factor
10.  Rapid computation of the amplitude and phase of tightly focused optical fields distorted by scattering particles 
We develop an efficient method for accurately calculating the electric field of tightly focused laser beams in the presence of specific configurations of microscopic scatterers. This Huygens–Fresnel wave-based electric field superposition (HF-WEFS) method computes the amplitude and phase of the scattered electric field in excellent agreement with finite difference time-domain (FDTD) solutions of Maxwell’s equations. Our HF-WEFS implementation is 2–4 orders of magnitude faster than the FDTD method and enables systematic investigations of the effects of scatterer size and configuration on the focal field. We demonstrate the power of the new HF-WEFS approach by mapping several metrics of focal field distortion as a function of scatterer position. This analysis shows that the maximum focal field distortion occurs for single scatterers placed below the focal plane with an offset from the optical axis. The HF-WEFS method represents an important first step toward the development of a computational model of laser-scanning microscopy of thick cellular/tissue specimens.
PMCID: PMC4213127  PMID: 25121440
11.  Effects of prehospital epinephrine administration on neurological outcomes in patients with out-of-hospital cardiac arrest 
To determine if the effects of epinephrine administration on the outcome of out-of-hospital cardiac arrest (OHCA), patients are associated with the duration of cardiopulmonary resuscitation (CPR) performed by Emergency Medical Service (EMS) personnel.
This retrospective, nonrandomized, observational analysis used the All-Japan Utstein Registry, a prospective, nationwide population-based registry of all OHCA patients transported to the hospital by EMS staff as the data source. We stratified all OHCA patients for quartile of EMSs’ CPR duration. Group 1 consisted of patients who fell under the 25th percentile of EMSs’ CPR duration (under 15 min); group 2, patients who fell into the 25th to 50th percentile (between 15 and 19 min); group 3, patients who fell into the 50th to 75th percentile (between 20 and 26 min); and group 4, patients who fell at or above the 75th percentile (over 26 min). The primary endpoint was a favorable neurological outcome 1 month after cardiac arrest. The secondary endpoints were ROSC before arrival at the hospital and 1-month survival.
A total of 383,811 patients aged over 18 years who had experienced OHCA between 2006 and 2010 in Japan, when stratified for quartile of EMSs’ CPR duration, the epinephrine administration increased the rate of return of spontaneous circulation (ROSC) approximately tenfold in all groups. However, the beneficial effects of epinephrine administration on 1-month survival disappeared in patients on whom EMSs’ CPR had been performed for more than 26 min, and the beneficial effects of epinephrine administration on neurological outcomes were observed only in patients on whom EMSs’ CPR had been performed between 15 and 19 min (odds ratio, 1.327, 95 % confidence intervals, 1.017–1.733 P = 0.037).
Epinephrine administration is associated with an increase of ROSC and with improvement in the neurological outcome on which EMSs’ CPR duration is performed between 15 and 19 min.
PMCID: PMC4478688  PMID: 26110059
Out-of-hospital cardiac arrest; Resuscitation; Epinephrine; Prehospital
12.  Laparoscopic-assisted total gastrectomy for early gastric cancer with situs inversus totalis: report of a first case 
BMC Surgery  2015;15:75.
Situs inversus totalis is a relatively rare condition and is an autosomal recessive congenital defect in which an abdominal and/or thoracic organ is positioned as a “mirror image” of the normal position in the sagittal plane. We report our experience of laparoscopic-assisted total gastrectomy with lymph node dissection performed for gastric cancer in a patient with situs inversus totalis.
Case presentation
A 58-year-old male was diagnosed with cT1bN0N0 gastric cancer. There were no vascular anomalies on abdominal angiographic computed tomography with three-dimensional reconstruction. laparoscopic-assisted total gastrectomy was performed with D1+ lymph node dissection, in accordance with the Japanese Gastric Cancer Treatment Guidelines. There were no intraoperative issues, and no postoperative complications.
This was the first report describing laparoscopic-assisted total gastrectomy with the standard typical lymph node dissection in the English literature. We emphasize that the position of trocars and the standing side of the primary surgeon during the lymph node dissection are critical.
PMCID: PMC4472267  PMID: 26087838
Situs inversus totalis; Gastric cancer; Laparoscopic-assisted total gastrectomy
13.  Activation of the Stimulator of Interferon Genes (STING) adaptor attenuates experimental autoimmune encephalitis 
Cytosolic DNA sensing activates the Stimulator of Interferon Genes (STING) adaptor to induce interferon type I (IFNαβ) production. Constitutive DNA sensing to induce sustained STING activation incites tolerance breakdown leading to autoimmunity. Here we show that systemic treatments with DNA nanoparticles (DNPs) induced potent immune regulatory responses via STING signaling that suppressed experimental autoimmune encephalitis (EAE) when administered to mice after immunization with myelin oligodendrocyte glycoprotein (MOG), at EAE onset, or at peak disease severity. DNP treatments attenuated infiltration of effector T cells into the central nervous system (CNS) and suppressed innate and adaptive immune responses to MOG immunization in spleen. Therapeutic responses were not observed in mice treated with cargo DNA or cationic polymers alone, indicating that DNP uptake and cargo DNA sensing by cells with regulatory functions was essential for therapeutic responses to manifest. Intact STING and IFNαβ receptor genes, but not IFNγ receptor genes, were essential for therapeutic responses to DNPs to manifest. Treatments with cyclic diguanylate monophosphate (c-diGMP) to activate STING also delayed EAE onset and reduced disease severity. Therapeutic responses to DNPs were critically dependent on indoleamine 2,3 dioxygenase (IDO) enzyme activity in hematopoietic cells. Thus DNPs and c-diGMP attenuate EAE by inducing dominant T cell regulatory responses via the STING-IFNαβ-IDO pathway that suppress CNS-specific autoimmunity. These findings reveal dichotomous roles for the STING-IFNαβ pathway in either stimulating or suppressing autoimmunity and identify STING activating reagents as a novel class of immune modulatory drugs.
PMCID: PMC4086255  PMID: 24799564
14.  NADH-dependent glutamate synthase participated in ammonium assimilation in Arabidopsis root 
Plant Signaling & Behavior  2014;9:e29402.
Higher plants have 2 GOGAT species, Fd-GOGAT and NADH-GOGAT. While Fd-GOGAT mainly assimilates ammonium in leaves, which is derived from photorespiration, the function of NADH-GOGAT, which is highly expressed in roots,1 needs to be elucidated. The aim of this study was to clarify the role of NADH-GOGAT in Arabidopsis roots. The supply of ammonium to the roots caused an accumulation of NADH-GOGAT, while Fd-GOGAT 1 and Fd-GOGAT 2 showed no response. A promoter–GUS fusion analysis and immunohistochemistry showed that NADH-GOGAT was located in non-green tissues like vascular bundles, shoot apical meristem, pollen, stigma, and roots. The localization of NADH-GOGAT and Fd-GOGAT was not overlapped. NADH-GOGAT T-DNA insertion lines showed a reduction of glutamate and biomass under normal CO2 conditions. These data emphasizes the importance of NADH-GOGAT in the ammonium assimilation of Arabidopsis roots.
PMCID: PMC4203567  PMID: 25763622
NADH-GOGAT; root; ammonium; glutamate; assimilation; Arabidopsis; CO2; amino acids
15.  Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae 
Epidemiological characteristics of patients with bloodstream infections (BSI) due to extended-spectrum β-lactamase producing (ESBL) and carbapenem-resistant (CRE) strains are often similar. Mortality rates for CRE BSI are 70 %, and mean time to initiation of appropriate therapy is ~5 days. A bedside score was developed to differentiate CRE-BSIs from ESBL-BSIs, in order to help decrease the time to initiation of appropriate therapy for CRE and mortality rates.
Score was developed based of data (2007–2010) abstracted from charts of adult patients from Assaf Harofeh Medical Center (AHMC, Zeriffin, Israel), and validated on a cohort of patients from Detroit Medical Center (DMC, MI, USA). A multivariate model for presence of CRE was generated. A clinical prediction score and ROC curve was derived. 451 patients with ESBL BSIs (285 from AHMC and 166 from DMC) and 74 patients with CRE BSIs (58 from AHMC and 16 from DMC) were included. The prediction score included chemotherapy in the past 3 months (19 points), presence of foreign invasive devices (10 points), no peripheral vascular disease (10 points), reduced consciousness or cognition at time of acute illness (9 points), time in hospital prior to BSI ≥ 3 days (7 points), and age younger than 65 years (6 points). A score of ≥32 to define “high CRE risk” had sensitivity of 59 %, specificity of 76 %, PPV of 34 % and NPV of 90 %.
The score’s 90 % NPV implies it could reduce un-necessary (and toxic) empiric use of anti-CRE therapeutics, but this should be studied prospectively and on broader populations in order to test its potential role in reducing mortality.
PMCID: PMC4460756  PMID: 26041137
CRE; KPC; ESBL; Prediction score; Nosocomial infection; Multidrug resistant
16.  Multi-Pathway Cellular Analysis on Crude Natural Drugs/Herbs from Japanese Kampo Formulations 
PLoS ONE  2015;10(6):e0128872.
Kampo formulations comprise a number of crude natural drugs/herbs as constituents. The crude drugs/herbs have been traditionally classified by their traditional classifications or efficacies in Kampo medicines; however, it has been difficult to establish the scientific link between experimental evidence and traditional classifications in Kampo medicine. To clarify such traditional conceptions, we tested 112 crude drugs/herbs that are major components of Kampo formulations, in the multi-pathway analysis of 10 well-studied transcriptional activities including CREB, ERSF, HIF-1α, IRFs, MYC, NF-κB, p53, SMAD, SOX2, and TCF/LEF in A549 human lung cancer cells. By clustering the results of multi-pathway analysis with the Spearman rank-correlation coefficient and Ward linkage, three distinct traditional categories were significantly enriched in the major groupings, which are heat-clearing and dampness-drying herbs, acrid and warm exterior-resolving herbs, and acrid and cool exterior-resolving herbs. These results indicate that these crude drugs/herbs have similar effects on intracellular signaling and further imply that the traditional classifications of those enriched crude drugs/herbs can be supported by such experimental evidence. Collectively, our new in vitro multi-pathway analysis may be useful to clarify the mechanism of action of crude drugs/herbs and Kampo formulations.
PMCID: PMC4452735  PMID: 26035432
17.  Associations between Depressive State and Impaired Higher-Level Functional Capacity in the Elderly with Long-Term Care Requirements 
PLoS ONE  2015;10(6):e0127410.
Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were <10% which indicated negligible differences in the mean or prevalence of the covariates between non-depressive state and depressive state. The marginal odds ratios were estimated by the logistic models with IPTW using the propensity scores. The marginal odds ratios were 2.17 (95%CI: 1.13–4.19) for men and 2.57 (95%CI: 1.26–5.26) for women. Prevention of depressive state may contribute to not only depressive state but also higher-level functional capacity.
PMCID: PMC4452739  PMID: 26035183
18.  Statistical iterative reconstruction for streak artefact reduction when using multidetector CT to image the dento-alveolar structures 
Dentomaxillofacial Radiology  2014;43(5):20130373.
When metallic prosthetic appliances and dental fillings exist in the oral cavity, the appearance of metal-induced streak artefacts is not avoidable in CT images. The aim of this study was to develop a method for artefact reduction using the statistical reconstruction on multidetector row CT images.
Adjacent CT images often depict similar anatomical structures. Therefore, reconstructed images with weak artefacts were attempted using projection data of an artefact-free image in a neighbouring thin slice. Images with moderate and strong artefacts were continuously processed in sequence by successive iterative restoration where the projection data was generated from the adjacent reconstructed slice. First, the basic maximum likelihood–expectation maximization algorithm was applied. Next, the ordered subset–expectation maximization algorithm was examined. Alternatively, a small region of interest setting was designated. Finally, the general purpose graphic processing unit machine was applied in both situations.
The algorithms reduced the metal-induced streak artefacts on multidetector row CT images when the sequential processing method was applied. The ordered subset–expectation maximization and small region of interest reduced the processing duration without apparent detriments. A general-purpose graphic processing unit realized the high performance.
A statistical reconstruction method was applied for the streak artefact reduction. The alternative algorithms applied were effective. Both software and hardware tools, such as ordered subset–expectation maximization, small region of interest and general-purpose graphic processing unit achieved fast artefact correction.
PMCID: PMC4082265  PMID: 24754471
CT; X-ray; statistical iterative reconstruction; streak artefact reduction; dento-alveolar region
19.  Loiasis in a Japanese Traveler Returning from Central Africa 
Tropical Medicine and Health  2015;43(2):149-153.
We encountered a probable case of loiasis in a returned traveler from Central Africa. A 52-year-old Japanese woman presented to our hospital complaining of discomfort in her eyes and skin. She reported having frequently visited Central Africa over many years and having been extensively exposed to the rainforest climate and ecosystem. Although no microfilariae were found in her blood, there was an elevated level of IgG antibodies against the crude antigens of Brugia pahangi, which have cross-reactivity with Loa loa. She was treated with albendazole for 21 days, after which the antigen-specific IgG level decreased and no relapse occurred.
PMCID: PMC4491493  PMID: 26161033
filarial infection; loiasis; returned traveler
20.  Relationship between social support during pregnancy and postpartum depressive state: a prospective cohort study 
Scientific Reports  2015;5:10520.
Although the association between social support and postpartum depression has been previously investigated, its causal relationship remains unclear. Therefore, we examined prospectively whether social support during pregnancy affected postpartum depression. Social support and depressive symptoms were assessed by Japanese version of Social Support Questionnaire (J-SSQ) and Edinburgh Postnatal Depression Scale (EPDS), among 877 pregnant women in early pregnancy and at one month postpartum. First, J-SSQ was standardized among peripartum women. The J-SSQ was found to have a two-factor structure, with Number and Satisfaction subscales, by exploratory and confirmatory factor analyses. Analysis of covariance was performed to examine how EPDS and J-SSQ scores during pregnancy affected the EPDS score at postpartum. Significant associations were found between postpartum EPDS score and both EPDS and total scores on the Number subscales during pregnancy (β = 0.488 and -0.054, ps < 0.001). Specifically, this negative correlation was stronger in depressive than non-depressive groups. Meanwhile, total score on Satisfaction subscales was not significantly associated with postpartum EPDS score. These results suggest that having a larger number of supportive persons during pregnancy helps protect against postpartum depression, and that this effect is greater in depressive than non-depressive pregnant women. This finding is expected to be vitally important in preventive interventions.
PMCID: PMC4448522  PMID: 26022720
21.  Preparation of Porous Chitosan-Siloxane Hybrids Coated with Hydroxyapatite Particles 
BioMed Research International  2015;2015:392940.
This paper describes the apatite deposition of chitosan-silicate porous hybrids derived from chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) in alkaline phosphate solution. The preparation of porous hybrids with needle-like apatite on their surfaces is described. Following apatite deposition the porous hybrids maintained high porosity. The enzymatic degradation rate was low even after 6 months and the porous hybrids were very flexible and cut easily using surgical scissors.
PMCID: PMC4452833  PMID: 26078948
22.  Pharmacokinetics and the optimal regimen for levofloxacin in critically ill patients receiving continuous hemodiafiltration 
The aim of this study was to establish the pharmacokinetics of levofloxacin (LVFX) and determine the optimal dose of this drug in critically ill patients receiving continuous hemodiafiltration (CHDF). The results of in vivo and in vitro studies showed the pharmacokinetics of LVFX total clearance (CLtotal) according to the creatinine clearance (CLCre), dialysate flow (QD), and ultrafiltrate flow (QF), to be as follows: CLtotal (l/h) = 0.0836 × CLCre (ml/min) + 0.013 × body weight (kg) + 0.94(QD + QF) (l/h). The optimal dose of LVFX was expressed by the following formula: 50 × CLtotal. These results demonstrate that the usual dose of LVFX (500 mg) was sufficient for the patients evaluated in this study.
PMCID: PMC4436099  PMID: 25992293
Levofloxacin; Pharmacokinetics; Continuous hemodiafiltration; Clearance
23.  Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy 
Several studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins.
Materials and Methods
Patients with diabetic nephropathy, selected as those with a serum creatinine level of 0.9–1.5 mg/dL and simultaneously having either microalbuminuria or positive proteinuria, were randomly assigned to one of three groups: a conventional diet therapy group, a group given 10 mg of pravastatin and a group given 10 mg of atorvastatin. Renal function was evaluated before and after a 12-month period of therapy.
The atorvastatin group had a significant decrease in low-density lipoprotein cholesterol at 3 months and thereafter compared with the other groups. The urinary albumin-to-creatinine ratio significantly decreased in the atorvastatin group; the degree of this decrease was significantly greater than that in the diet therapy group. The kidney function estimated with cystatin C (CysC) and the estimated glomerular filtration rate calculated from CysC were significantly preserved in the atorvastatin group compared with the pravastatin group. In a multivariate regression analysis, the use of atorvastatin was the only explanatory variable for the changes in CysC; this was independent of changes in low-density lipoprotein cholesterol.
Atorvastatin is more effective than pravastatin for the prevention of increase in CysC, and this renoprotective effect was considered to a result of the pleiotropic effect of atorvastatin independent of its lipid-lowering effect. This study was registered with UMIN (no. UMIN 000001774).
PMCID: PMC4420568  PMID: 25969721
Early diabetic nephropathy; Renoprotective effects; Statins
24.  A Method for Simultaneous Determination of 20 Fusarium Toxins in Cereals by High-Resolution Liquid Chromatography-Orbitrap Mass Spectrometry with a Pentafluorophenyl Column 
Toxins  2015;7(5):1664-1682.
A high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) method was developed for simultaneous determination of 20 Fusarium toxins (nivalenol, fusarenon-X, deoxynivalenol, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol, HT-2 toxin, T-2 toxin, neosolaniol, diacetoxyscirpenol, fumonisin B1, fumonisin B2, fumonisin B3, fumonisin A1, fumonisin A2, fumonisin A3, zearalenone, α-zearalenol, β-zearalenol, α-zearalanol, and β-zearalanol) in cereals. The separation of 20 Fusarium toxins with good peak shapes was achieved using a pentafluorophenyl column, and Orbitrap MS was able to detect accurately from cereal matrix components within ±0.77 ppm. The samples were prepared using a QuEChERS kit for extraction and a multifunctional cartridge for purification. The linearity, repeatability, and recovery of the method were >0.9964, 0.8%–14.7%, and 71%–106%, respectively. Using this method, an analysis of 34 commercially available cereals detected the presence of deoxynivalenol, 15-acetyl deoxynivalenol, fumonisin B1, fumonisin B2, fumonisin B3, fumonisn A1, fumonisin A2, fumonisin A3, and zearalenone in corn samples with high concentration and frequency. Trichothecenes was detected from wheat samples with high frequency; in particular, the concentration of deoxynivalenol was high. Conversely, α-zearalenol, β-zearalenol, α-zearalanol, and β-zearalanol were not detected in any of the samples.
PMCID: PMC4448167  PMID: 26008230
Fusarium toxins; LC-Orbitrap MS; pentafluorophenyl column; simultaneous determination; cereals
25.  Effect of heel pressure pad attached to ankle-foot orthosis on the energy conversion efficiency in post-stroke hemiplegic gait 
Journal of Physical Therapy Science  2015;27(5):1341-1345.
[Purpose] This study aimed to analyze the effect of heel pads in ankle-foot orthoses on dynamic motion aspects of gait in stroke patients from the viewpoint of energy conversion efficiency. [Subjects] Fourteen chronic stroke patients who were ambulatory and had lower extremity motor function categorized as Brunnstrom stage IV participated in the study. [Methods] A three-dimensional motion analysis system was used to assess the effect of heel pad intervention on dynamic motion gait parameters using a single-system A-B-A design. [Results] The results showed that a heel pad attached to the ankle-foot orthosis caused significant retention of the center-of-pressure at the heel during the heel rocker function and significant increase in the dorsiflexion moment and the height of the center of gravity. [Conclusion] The present study showed that a heel pad attached to the calcaneal region of an ankle-foot orthosis caused slight retention of the center-of-pressure at the heel during the heel rocker function along with center of gravity elevation in the stance phase and improved the energy conversion efficiency, especially on the non-paretic side.
PMCID: PMC4483393  PMID: 26157215
Heel pad; Three-dimensional motion analysis; Hemiplegic gait

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