Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration

Introduction. Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle. Methods. We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24§ssup§-/-§esup§) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function. Results: Our results indicate that MDSPCs isolated from Zmpste24§ssup§-/- §esup§mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24§ssup§-/- §esup§MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24§ssup§-/- §esup§MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro. Conclusions: These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells. © 2013 Song et al.; licensee BioMed Central Ltd

Advanced Quantitative Risk Assessment of Offshore Gas Pipeline Systems

This research has reviewed the current status of offshore and marine safety. The major problems identified in the research are associated with risk modelling under circumstances where the lack of data or high level of uncertainty exists. This PhD research adopts an object-oriented approach, a natural and straightforward mechanism of organising information of the real world systems, to represent the Offshore Gas Supply Systems (OGSSs) at both the component and system levels. Then based on the object-oriented approach, frameworks of aggregative risk assessment and fault tree analysis are developed. Aggregative risk assessment is to evaluate the risk levels of components, subsystems, and the overall OGSS. Fault trees are then used to represent the cause-effect relationships for a specific risk in the system. Use of these two assessment frameworks can help decision makers to obtain comprehensive view of risks in the OGSS. In order to quantitatively evaluate the framework of aggregative risk, this thesis uses a fuzzy aggregative risk assessment method to determine the risk levels associated with components, subsystems, and the overall OGSS. The fuzzy aggregative risk assessment method is tailored to quantify the risk levels of components, subsystems, and the OGSS. The proposed method is able to identify the most critical subsystem in the OGSS. As soon as, the most critical subsystem is identified, Fuzzy Fault Tree Analysis (FFTA) is employed to quantitatively evaluate the cause-effect relationships for specific undesired event. These results can help risk analysts to select Risk Control Options (RCOs) for mitigating risks in an OGSS. It is not financially possible to employ all the selected RCOs. Therefore, it is necessary to rank and select the best RCO. A decision making method using the Fuzzy TOPSIS (FTOPSIS) is proposed to demonstrate the selection of the best RCOs to control the existing risks in the system. The developed models and frameworks can be integrated to formulate a platform which enables to facilitate risk assessment and safety management of OGSSs without jeopardising the efficiency of OGSSs operations in various situations where traditional risk assessment and safety management techniques cannot be effectively applied

Platelet-Rich Plasma Promotes the Proliferation of Human Muscle Derived Progenitor Cells and Maintains Their Stemness

Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs. © 2013 Li et al

The relation between evolutionary life strategy, temperament and character in individuals with opioid use disorder

Background: Although many risk factors have been proposed for the etiology of the addiction, little research has been conducted from the perspective of evolutionary psychology. The theory of life strategies (with respect to evolutionary causes) has led to a new understanding of addiction. While researchers have shown that Cloninger's bio-psychological model is one of the most important personality factors in the etiology of addiction, there is no research about the relationship between life strategy and the temperament-character component of addiction. Objectives: The main objective of this study was to examine the relationship between these two variables in individuals with opioid use disorder in comparison with the normal group. Patients and Methods: This correlational study included 96 participants with opioid use disorder selected by convenience sampling from the Iranian national center for addiction studies (INCAS) and 97 participants without any substance use disorder, who were matched to the opioid-use group. After administering the mini-form of Arizona life history battery (ALHB) and the temperament and character inventory (TCI), data were analyzed with Pearson's correlation coefficient and multivariate regression. Results: Results showed a relationship between fast-life strategy and novelty seeking in the group with opioid use disorder and a positive relationship between slow-life strategy and co-operation in the control group. The regression analysis indicated that novelty seeking was able to predict fast-life strategy in the opioid use group and co-operation could predict slow-life strategy in the control group. Conclusions: Life strategy could be a new variable in understanding and planning addiction prevention programs. © 2018, International Journal of High Risk Behaviors and Addiction

The relation between evolutionary life strategy, temperament and character in individuals with opioid use disorder

Background: Although many risk factors have been proposed for the etiology of the addiction, little research has been conducted from the perspective of evolutionary psychology. The theory of life strategies (with respect to evolutionary causes) has led to a new understanding of addiction. While researchers have shown that Cloninger's bio-psychological model is one of the most important personality factors in the etiology of addiction, there is no research about the relationship between life strategy and the temperament-character component of addiction. Objectives: The main objective of this study was to examine the relationship between these two variables in individuals with opioid use disorder in comparison with the normal group. Patients and Methods: This correlational study included 96 participants with opioid use disorder selected by convenience sampling from the Iranian national center for addiction studies (INCAS) and 97 participants without any substance use disorder, who were matched to the opioid-use group. After administering the mini-form of Arizona life history battery (ALHB) and the temperament and character inventory (TCI), data were analyzed with Pearson's correlation coefficient and multivariate regression. Results: Results showed a relationship between fast-life strategy and novelty seeking in the group with opioid use disorder and a positive relationship between slow-life strategy and co-operation in the control group. The regression analysis indicated that novelty seeking was able to predict fast-life strategy in the opioid use group and co-operation could predict slow-life strategy in the control group. Conclusions: Life strategy could be a new variable in understanding and planning addiction prevention programs. © 2018, International Journal of High Risk Behaviors and Addiction

Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells

Background: A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers' attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2'-chloro-5'-nitrobenzenesulfonyl)-2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells.Results: In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells.Conclusion: CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition

Assessing mastery through psychotherapy: Psychometric properties of the persian version of the mastery scale

Background: Considering the importance of assessing the range of phenomena that can change in psychodynamic therapy, and lack of appropriate assessment scale in Persian language, the present study assessed the reliability of the Persian mastery scale. The mastery scale is a comprehensive research tool for assessing a patient's mastery of transference-related interpersonal conflicts during the treatment process. Objectives: The aim of this research was to examine the psychometric properties of the Persian version of the Mastery Scale. Methods: After preparing the Persian version of the mastery scale through the forward-backward translation process, a sample of 36 relationship episodes was rated by three independent judges. Data were collected in Mashhad, Iran in 2015. The psychometric properties of the instrument, including inter-rater reliability and test-retest analysis were assessed. Results: The test-retest correlations of the 3 judges were (0.80, 0.91 and 0.95), highly significant at P < 0.0001 and the inter-rater reliability indicated a good level of agreement (The ICC (3, 3) 0.84, 95 CI 0.72, 0.90). Conclusions: The current study has provided evidence that the Persian mastery scale is a reliable instrument for assessing changes in inner capacities and resources through psychodynamic treatments. However, further studies are required to investigate the validity of this scale. ©2018, Iranian Journal of Psychiatry and Behavioral Sciences

Phase 2 prospective open label study of neoadjuvant nab‐paclitaxel, trastuzumab, and pertuzumab in patients with HER2‐positive primary breast cancer

BackgroundThe objective of this study was to evaluate the safety and efficacy of nab-paclitaxel, trastuzumab, and pertuzumab as neoadjuvant therapy (NAT) in patients with human epidermal growth factor receptor 2 HER2+ breast cancer (HER2+ BC) to determine pathologic complete response (pCR), invasive disease-free survival (iDFS), and overall survival.MethodsForty-five patients with HER2+ BC Stages II-III were to be enrolled from 2013 to 2017. Patients were treated with weekly nab-paclitaxel (100&nbsp;mg/m2 intravenously), weekly trastuzumab (4&nbsp;mg/kg loading dose, then 2&nbsp;mg/kg), and six cycles of pertuzumab (840&nbsp;mg loading dose, then 420&nbsp;mg intravenously day 1 every 21&nbsp;days).ResultsMedian follow-up was 60&nbsp;months (95% CI, 32.3-55.6) and pCR was 29/45 (64%). The 5-year iDFS for patients who achieved pCR (N&nbsp;=&nbsp;29) was 96.3% (95% CI, 76.5-99.5) and non-pCR patients (N&nbsp;=&nbsp;16) was 74.3% (95% CI, 39.1-91.0). The 5-year overall survival (N&nbsp;=&nbsp;45) was 94.1% (95% CI, 77.6-98.5). Based on hormonal status, the 5-year iDFS for HR+ pCR patients (N&nbsp;=&nbsp;14) was 92.3% (95% CI, 56.6-98.9) and for HR- (N&nbsp;=&nbsp;15) was 100% (p&nbsp;=&nbsp;.3).ConclusionsThis anthracycline/carboplatin-free regimen with nab-paclitaxel achieved a pCR rate of 64% in patients with HER2+ BC. The 5-year iDFS in patients with and without pCR was 96.3% and 74.3%, respectively. The pCR rate is comparable with docetaxel, carboplatin, trastuzumab, and pertuzumab therapy in the NAT setting, but with fewer treatment-associated toxicities. This finding suggests the possibility of safe avoidance of anthracyclines and carboplatin as components of NAT in patients with HER2+ BC

Fuzzy evidence theory and Bayesian networks for process systems risk analysis

YesQuantitative risk assessment (QRA) approaches systematically evaluate the likelihood, impacts, and risk of adverse events. QRA using fault tree analysis (FTA) is based on the assumptions that failure events have crisp probabilities and they are statistically independent. The crisp probabilities of the events are often absent, which leads to data uncertainty. However, the independence assumption leads to model uncertainty. Experts’ knowledge can be utilized to obtain unknown failure data; however, this process itself is subject to different issues such as imprecision, incompleteness, and lack of consensus. For this reason, to minimize the overall uncertainty in QRA, in addition to addressing the uncertainties in the knowledge, it is equally important to combine the opinions of multiple experts and update prior beliefs based on new evidence. In this article, a novel methodology is proposed for QRA by combining fuzzy set theory and evidence theory with Bayesian networks to describe the uncertainties, aggregate experts’ opinions, and update prior probabilities when new evidences become available. Additionally, sensitivity analysis is performed to identify the most critical events in the FTA. The effectiveness of the proposed approach has been demonstrated via application to a practical system.The research of Sohag Kabir was partly funded by the DEIS project (Grant Agreement 732242)