Maintenance of stemness and optimization of differentiation potentials during in vitro expansion of human adipose-derived stem cells

Adipose-derived stem cells (ADSCs) show similar characteristics to bone marrow-derived stem cells, the gold standard of MSCs, in terms of their characteristics and differentiation potentials. However, ADSCs show sub-optimal functionality compared with the gold standard. In our effort to secure enough number of allogeneic stem cells from healthy donor, FGF2 was pretreated during hADSCs in vitro expansion culture. FGF2 significantly increased the dimension of cell expansion as shown in Figure 1 and 2. Pre-treatment of FGF2 not only induced an increase of cell number – approx. 44-fold at passage 7 - but also potentiated the differentiation potentials of hADSCs. Differentiation potentials of hADSCs expanded in the presence of FGF2 was evaluated in vitro and in vivo. hADSCs pre-treated with FGF2 showed enhanced in vitro osteogenesis and chondrogenesis. Using in vivo ectopic bone model, in vivo osteogenic potential of hADSCs pretreated with FGF2 was also evaluated and abundant osteoid/bone matrix was formed in dose-dependent manner according to the concentration of pre-treated FGF2. Bone matrix formation by control hADSCs was virtually non-existent. FGF2-pre-treated hADSCs also showed enhanced in vitro chondrogenesis. hADSCs expanded with FGF2 showed increased expression of genes associated with early osteogenesis and chondrogenesis. These results shows that FGF2 can exert beneficial effect on in vitro expansion of hADSCs not only in the dimension of the expansion but also in functionality of the expanded cells. Please click Additional Files below to see the full abstract

SNP@Ethnos: a database of ethnically variant single-nucleotide polymorphisms

Inherited genetic variation plays a critical but largely uncharacterized role in human differentiation. The completion of the International HapMap Project makes it possible to identify loci that may cause human differentiation. We have devised an approach to find such ethnically variant single-nucleotide polymorphisms (ESNPs) from the genotype profile of the populations included in the International HapMap database. We selected ESNPs using the nearest shrunken centroid method (NSCM), and performed multiple tests for genetic heterogeneity and frequency spectrum on genes having ESNPs. The function and disease association of the selected SNPs were also annotated. This resulted in the identification of 100 736 SNPs that appeared uniquely in each ethnic group. Of these SNPs, 1009 were within disease-associated genes, and 85 were predicted as damaging using the Sorting Intolerant From Tolerant system. This study resulted in the creation of the SNP@Ethnos database, which is designed to make this type of detailed genetic variation approach available to a wider range of researchers. SNP@Ethnos is a public database of ESNPs with annotation information that currently contains 100 736 ESNPs from 10 138 genes, and can be accessed at and or directly at

Toxicity Studies on Secretio Bufonis: A Traditional Supplement in Asia

AbstractObjectivesThis study was performed to investigate the toxicity of Secretio Bufonis (SB) on male mice and assess its no-observed-adverse-effect-level (NOAEL).Materials and MethodsAfter feeding an aqueous solution of SB extracts to mice for either 1 or 8 weeks, their blood and urine were assayed and their liver and kidney morphology examined. The numerical data was analyzed by the Mann-Whitney U-test and analysis of variance test.ResultsMice administered SB in 50 mg/kg/day for 1 week had higher heart weights and higher aspartate transaminase activities; those administered SB in 0.01 and 0.05 mg/kg/day for 8 weeks had lower creatinine concentrations; and those administered SB in 0.5 mg/kg/day for 8 weeks had higher brain weights and higher blood urea nitrogen.ConclusionsThe extracts of SB had cardiac toxicity in the short term and hepatotoxicity in the long term. The NOAEL of the extract was under 5 mg/kg/day for 1 week and under 0.25 mg/kg/day for 8 weeks

Measuring Anxiety in Patients With Early-Stage Parkinson's Disease: Rasch Analysis of the State-Trait Anxiety Inventory

The State-Trait Anxiety Inventory (STAI), composed of two 20-item subscales (STAI-state and STAI-trait), has been increasingly used to assess anxiety symptoms in patients with Parkinson's disease (PD). However, the clinimetric attributes of the STAI under the statistical framework of the item-response theory (IRT) have not been fully elucidated within this population to date. We performed an IRT-based Rasch analysis of the STAI outcomes of patients with de novo PD from the Parkinson's Progression Markers Initiative database. The unidimensionality, Rasch model fit, scale targeting, separation reliability, differential item functioning, and response category utility of the STAI were statistically evaluated. A total of 326 (209 males, 117 females) patients without cognitive dysfunction were enrolled in our study. The original versions of the STAI-state and STAI-trait had acceptable separation reliability but lacked appropriate response category functioning, exhibited scale off-targeting, and several items demonstrated poor fit to the Rasch model. The response categories were reduced from four to three, and the rescored three-point TASI-trait demonstrated a marked improvement in clinimetric properties without a significant impact on unidimensionality and separation reliability. The rescored three-point version of the STAI-state required the additional removal of four misfitting items in order to improve the Rasch model fit. To our knowledge, this is the first study to assess the measurement properties based on the IRT of the STAI in patients with PD. Our Rasch analysis identified the components requiring possible amendments in order to improve the clinimetric attributes of the STAI

Deterioration in Global Organization of Structural Brain Networks in Schizophrenia: A Diffusion MRI Tractography Study

Schizophrenia is a heterogenous neuropsychiatric disorder with varying degrees of altered connectivity in a wide range of brain areas. Network analysis using graph theory allows researchers to integrate and quantify relationships between widespread changes in a network system. This study examined the organization of brain structural networks by applying diffusion MRI, probabilistic tractography, and network analysis to 48 schizophrenia patients and 24 healthy controls. T1-weighted MR images obtained from all participants were parcellated into 87 regions of interests (ROIs) according to a prior anatomical template and registered to diffusion-weighted images (DWI) of the same subjects. Probabilistic tractography was performed to obtain sets of white matter tracts between any two ROIs and determine the connection probabilities between them. Connectivity matrices were constructed using these estimated connectivity probabilities, and several network properties related to network effectiveness were calculated. Global efficiency, local efficiency, clustering coefficient, and mean connectivity strength were significantly lower in schizophrenia patients (p = 0.042, p = 0.011, p = 0.013, p = 0.046). Mean betweenness centrality was significantly higher in schizophrenia (p = 0.041). Comparisons of node wise properties showed trends toward differences in several brain regions. Nodal local efficiency was consistently lower in the basal ganglia, frontal, temporal, cingulate, diencephalon, and precuneus regions in the schizophrenia group. Inter-group differences in nodal degree and nodal betweenness centrality varied by region and showed inconsistent results. Robustness was not significantly different between the study groups. Significant positive correlations were found between t-score of color trails test part-1 and local efficiency and mean connectivity strength in the patient group. The findings of this study suggest that schizophrenia results in deterioration of the global network organization of the brain and reduced ability for information processing

Heart Rate Variability and Urinary Catecholamines from Job Stress in Korean Male Manufacturing Workers According to Work Seniority

The aim of this study was to evaluate the relationships between job stress and indicators of autonomic nervous system activity in employees of the manufacturing industry. A total of 140 employees from a company that manufactures consumer goods (i.e., diapers and paper towels) were recruited for participation in this study. Job stress was assessed using Karasek`s Job Content Questionnaire. Heart rate variability (HRV) was measured using a heart rate monitor, and urinary catecholamines were measured by an HPLC-ECD. Information on demographic characteristics, previous job history, smoking status and alcohol consumption was also collected. Job stress did not have a significant effect on HRV or catecholamines. However, low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. Low- and high-frequency HRV were higher in the high-strain group than in the low-strain group, but these differences were not statistically significant. The results of the present study indicate that low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. In addition, the results of this study show that HRV can be used as a potential physiologic indicator of job stress in employees with a short duration of employment.Schubert C, 2009, BIOL PSYCHOL, V80, P325, DOI 10.1016/j.biopsycho.2008.11.005Mitoma M, 2008, PROG NEURO-PSYCHOPH, V32, P679, DOI 10.1016/j.pnpbp.2007.11.011Burr RL, 2007, SLEEP, V30, P913Collins SM, 2005, AM J IND MED, V48, P182, DOI 10.1002/ajim.20204Kang MG, 2004, YONSEI MED J, V45, P838Sztajzel J, 2004, SWISS MED WKLY, V134, P514Towa S, 2004, EXP ANIM TOKYO, V53, P137, DOI 10.1538/expanim.53.137Bunker SJ, 2003, MED J AUSTRALIA, V178, P272Peter R, 2002, J EPIDEMIOL COMMUN H, V56, P294VANGELOVA K, 2002, CENT EUR J PUBL HEAL, V10, P149HA M, 2001, STANDARDIZATION DEVvan Amelsvoort LGPM, 2000, INT ARCH OCC ENV HEA, V73, P255Goldstein IB, 1999, PSYCHOSOM MED, V61, P387PIERCECCHIMARTI MD, 1999, MED LAW, V18, P125Sluiter JK, 1998, OCCUP ENVIRON MED, V55, P407KARASEK R, 1998, J OCCUP HEALTH PSYCH, V3, P322ROVERE MTL, 1998, LANCET, V351, P478Sloan RP, 1996, PSYCHOSOM MED, V58, P25VANDERBEEK AJ, 1995, OCCUP ENVIRON MED, V52, P464HUIKURI HV, 1993, CIRCULATION, V87, P1220PAGANI M, 1991, J AUTONOM NERV SYST, V35, P33PAGANI M, 1991, CIRCULATION, V83, P1143PEASTON RT, 1988, J CHROMATOGR-BIOMED, V424, P263

Improving the predictive potential of diffusion MRI in schizophrenia using normative models-Towards subject-level classification.

Diffusion MRI studies consistently report group differences in white matter between individuals diagnosed with schizophrenia and healthy controls. Nevertheless, the abnormalities found at the group-level are often not observed at the individual level. Among the different approaches aiming to study white matter abnormalities at the subject level, normative modeling analysis takes a step towards subject-level predictions by identifying affected brain locations in individual subjects based on extreme deviations from a normative range. Here, we leveraged a large harmonized diffusion MRI dataset from 512 healthy controls and 601 individuals diagnosed with schizophrenia, to study whether normative modeling can improve subject-level predictions from a binary classifier. To this aim, individual deviations from a normative model of standard (fractional anisotropy) and advanced (free-water) dMRI measures, were calculated by means of age and sex-adjusted z-scores relative to control data, in 18 white matter regions. Even though larger effect sizes are found when testing for group differences in z-scores than are found with raw values (p < .001), predictions based on summary z-score measures achieved low predictive power (AUC < 0.63). Instead, we find that combining information from the different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance (the best predictor achieved AUC = 0.726). Our findings suggest that extreme deviations from a normative model are not optimal features for prediction. However, including the complete distribution of deviations across multiple imaging measures improves prediction, and could aid in subject-level classification

Searching for Logistics and Regulatory Determinants Affecting Overseas Direct Purchase: An Empirical Cross-National Study

Cross-border e-commerce has been very successful in the last decade. Merchants and consumers have been encouraged to participate in e-commerce, including B2C or B2B. B2C is not limited to a domestic market anymore. Consumers across countries are interested in overseas direct purchases. They are willing to purchase products from major online shopping sites such as Amazon and eBay. We aim at gaining a better understanding of overseas direct purchases. Determinants of overseas direct purchases based on cross-national data are identified. Accordingly, we investigate logistics and regulatory determinants. Furthermore, external environments such as regulatory institutions and globalization are discussed in terms of overseas direct purchases. This study incorporates theoretical foundations into empirical findings. Specifically, the institutional theory and the resource-based view are applied to explain the internal and external determinants to increase overseas direct purchases. We conduct an empirical test using panel data for each country to identify the various determinants associated with overseas direct purchases