160 research outputs found

    An operational information decomposition via synergistic disclosure

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    Abstract: Multivariate information decompositions hold promise to yield insight into complex systems, and stand out for their ability to identify synergistic phenomena. However, the adoption of these approaches has been hindered by there being multiple possible decompositions, and no precise guidance for preferring one over the others. At the heart of this disagreement lies the absence of a clear operational interpretation of what synergistic information is. Here we fill this gap by proposing a new information decomposition based on a novel operationalisation of informational synergy, which leverages recent developments in the literature of data privacy. Our decomposition is defined for any number of information sources, and its atoms can be calculated using elementary optimisation techniques. The decomposition provides a natural coarse-graining that scales gracefully with the system’s size, and is applicable in a wide range of scenarios of practical interest

    Adiponectin Expression from Human Adipose Tissue: Relation to Obesity, Insulin Resistance, and Tumor Necrosis Factor-α Expression

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    Adiponectin is a 29-kDa adipocyte protein that has been linked to the insulin resistance of obesity and lipodystrophy. To better understand the regulation of adiponectin expression, we measured plasma adiponectin and adipose tissue adiponectin mRNA levels in nondiabetic subjects with varying degrees of obesity and insulin resistance. Plasma adiponectin and adiponectin mRNA levels were highly correlated with each other (r = 0.80, P \u3c 0.001), and obese subjects expressed significantly lower levels of adiponectin. However, a significant sex difference in adiponectin expression was observed, especially in relatively lean subjects. When men and women with a BMI2were compared, women had a twofold higher percent body fat, yet their plasma adiponectin levels were 65% higher (8.6 ± 1.1 and 14.2 ± 1.6 μg/ml in men and women, respectively; P \u3c 0.02). Plasma adiponectin had a strong association with insulin sensitivity index (SI) (r = 0.67, P \u3c 0.0001, n = 51) that was not affected by sex, but no relation with insulin secretion. To separate the effects of obesity (BMI) from SI, subjects who were discordant for SI were matched for BMI, age, and sex. Using this approach, insulin-sensitive subjects demonstrated a twofold higher plasma level of adiponectin (5.6 ± 0.6 and 11.2 ± 1.1 μg/ml in insulin-resistant and insulin-sensitive subjects, respectively; P \u3c 0.0005). Adiponectin expression was not related to plasma levels of leptin or interleukin-6. However, there was a significant inverse correlation between plasma adiponectin and tumor necrosis factor (TNF)-α mRNA expression (r = -0.47, P \u3c 0.005), and subjects with the highest levels of adiponectin mRNA expression secreted the lowest levels of TNF-α from their adipose tissue in vitro. Thus, adiponectin expression from adipose tissue is higher in lean subjects and women, and is associated with higher degrees of insulin sensitivity and lower TNF-α expression

    Dorsal hippocampal dopamine receptors are involved in mediating ethanol state-dependent memory

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    In the present study, the effects of bilateral injections of dopaminergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol (EtOH) state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of EtOH (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of EtOH (0.5 g/kg)-induced state-dependent retrieval of the memory acquired under pre-training EtOH (0.5 g/kg) influence. Intra-CA1 administration of the dopamine D1 receptor agonist, SKF 38393 (0.5, 1 and 2 g/mouse) or the dopamine D2 receptor agonist, quinpirole (0.25, 0.5 and 1 μg/mouse) alone cannot affect memory retention. While, pre-test intra-CA1 injection of SKF 38393 (2 μg/mouse, intra-CA1) or quinpirole (0.25, 0.5 and 1 μg/mouse, intra-CA1) improved pre-training EtOH (0.5 g/kg)-induced retrieval impairment. Moreover, pre-test administration of SKF 38393 (0.5, 1 and 2 μg/mouse, intra-CA1) or quinpirole (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of EtOH (0.25 g/kg) significantly restored the retrieval and induced EtOH state-dependent memory. Furthermore, pre-training injection of the dopamine D1 receptor antagonist, SCH 23390 (4 μg/mouse), but not the dopamine D2 receptor antagonist, sulpiride, into the CA1 regions suppressed the learning of a single-trial passive avoidance task. Pre-test intra-CA1 injection of SCH 23390 (2 and 4 μg/mouse, intra-CA1) or sulpiride (2.5 and 5 μg/mouse, intra-CA1) 5 min before the administration of EtOH (0.5 g/kg, i.p.) dose dependently inhibited EtOH state-dependent memory. These findings implicate the involvement of a dorsal hippocampal dopaminergic mechanism in EtOH state-dependent memory and also it can be concluded that there may be a cross-state dependency between EtOH and dopamine. © 2006 Elsevier Inc. All rights reserved

    Psychometric Properties of the Farsi Version of Posttraumatic Growth Inventory for Children-Revised in Iranian Children with Cancer

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    Objective: Coping with childhood cancer, as a stressful incident, can lead to a growth in various aspects of the child's life. Therefore, this study aims to validate Posttraumatic Growth Inventory for Children-Revised (PTGI-C-R) in children with cancer. Methods: This methodological research was carried out in referral children hospitals in Tehran. PTGI-C-R was translated and back-translated. Content and face validity were assessed. Confirmatory factor analysis (CFA) was performed on 200 children with inclusion criteria, using LISREL V8.5. Due to the rejection of the model, an exploratory factor analysis (EFA) was done, using SPSS V21. The correlation of posttraumatic growth (PTG) with the variables, i.e., age and gender, was investigated. Results: Some writing changes were made in phrases in the sections concerning face and content validity. CFA rejected the five-factor model due to the undesirable fit indices. Therefore, an EFA was used and the three-factor model was not approved, either despite the statistical appropriateness or due to the lack of similarity between the items loaded on factors. The results also indicated a significant relationship between PTG and age (r = 0.13, P = 0.05). There is no significant relationship between PTG and gender (z = -1.35, P = 0.83). Conclusions: PTGI-C-R does not have desirable psychometric properties in Iranian children with cancer and may not be able to reflect all the aspects of PTG experienced by them. Therefore, it cannot be used as an appropriate scale, and it is necessary to develop and validate a specific tool through a qualitative study. © 2021 Wolters Kluwer Medknow Publications. All rights reserved

    Metformin inhibits polyphosphate-induced hyper-permeability and inflammation

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    Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic shortand systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/ anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases.Peer reviewe

    Bone mineral density, body mass index and cigarette smoking among Iranian women: implications for prevention

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    BACKGROUND: While risk factors of osteoporosis in Western populations have been extensively documented, such a profile has not been well studied in Caucasians of non-European origin. This study was designed to estimate the modifiable distribution and determinants of bone mineral density (BMD) among Iranian women in Australia. METHODS: Ninety women aged 35 years and older completed a questionnaire on socio-demographic and lifestyle factors. BMD was measured at the lumbar spine (LS) and femoral neck (FN) using DXA (GE Lunar, WI, USA), and was expressed in g/cm(2 )as well as T-score. RESULTS: In multiple regression analysis, advancing age, lower body mass index (BMI), and smoking were independently associated with LS and FN BMD, with the 3 factors collectively accounting for 30% and 38% variance of LS and FN BMD, respectively. LS and FN BMD in smokers was 8% lower than that in non-smokers. Further analysis of interaction between BMI and smoking revealed that the effect of smoking was only observed in the obese group (p = 0.029 for LSBMD and p = 0.007 for FNBMD), but not in the overweight and normal groups. Using T-scores from two bone sites the prevalence of osteoporosis (T-scores ≤ -2.5) was 3.8% and 26.3% in pre-and post-menopausal women, respectively. Among current smokers, the prevalence was higher (31.3%) than that among ex-smokers (28.6%) and non-smokers (7.5%). CONCLUSION: These data, for the first time, indicate that apart from advancing age and lower body mass index, cigarette smoking is an important modifiable determinant of bone mineral density in these Caucasians of non-European origin

    The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study

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    BACKGROUND: The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. METHODS: The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. RESULTS: 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively). CONCLUSION: our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco

    A Novel Role of Peripheral Corticotropin-Releasing Hormone (CRH) on Dermal Fibroblasts

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    Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh−/−) had higher proliferation and migration rates and compromised production of IL-6 and TGF-β1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF1 antagonist antalarmin recapitulated the findings in the Crh−/− cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis

    Global survey of the roles, satisfaction, and barriers of home healthcare nurses on the provision of palliative care

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    Background: the World Health Assembly urges members to build palliative care (PC) capacity as an ethical imperative. Nurses provide PC services in a variety of settings, including the home and may be the only health care professional able to access some disparate populations. Identifying current nursing services, resources, and satisfaction and barriers to nursing practice are essential to build global PC capacity. Objective: to globally examine home health care nurses' practice, satisfaction, and barriers, regarding existing palliative home care provision. Design: needs assessment survey. Setting/Subjects: five hundred thirty-two home health care nurses in 29 countries. Measurements: a needs assessment, developed through literature review and cognitive interviewing. Results: nurses from developing countries performed more duties compared with those from high-income countries, suggesting a lack of resources in developing countries. Significant barriers to providing home care exist: personnel shortages, lack of funding and policies, poor access to end-of-life or hospice services, and decreased community awareness of services provided. Respondents identified lack of time, funding, and coverages as primary educational barriers. In-person local meetings and online courses were suggested as strategies to promote learning. Conclusions: it is imperative that home health care nurses have adequate resources to build PC capacity globally, which is so desperately needed. Nurses must be up to date on current evidence and practice within an evidence-based PC framework. Health care policy to increase necessary resources and the development of a multifaceted intervention to facilitate education about PC is indicated to build global capacity

    The role of GLI-SOX2 signaling axis for gemcitabine resistance in pancreatic cancer

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    Pancreatic cancer, mostly pancreatic ductal adenocarcinomas (PDAC), is one of the most lethal cancers, with a dismal median survival around 8 months. PDAC is notoriously resistant to chemotherapy. Thus far, numerous attempts using novel targeted therapies and immunotherapies yielded limited clinical benefits for pancreatic cancer patients. It is hoped that delineating the molecular mechanisms underlying drug resistance in pancreatic cancer may provide novel therapeutic options. Using acquired gemcitabine resistant pancreatic cell lines, we revealed an important role of the GLI-SOX2 signaling axis for regulation of gemcitabine sensitivity in vitro and in animal models. Down-regulation of GLI transcriptional factors (GLI1 or GLI2), but not SMO signaling inhibition, reduces tumor sphere formation, a characteristics of tumor initiating cell (TIC). Down-regulation of GLI transcription factors also decreased expression of TIC marker CD24. Similarly, high SOX2 expression is associated with gemcitabine resistance whereas down-regulation of SOX2 sensitizes pancreatic cancer cells to gemcitabine treatment. We further revealed that elevated SOX2 expression is associated with an increase in GLI1 or GLI2 expression. Our ChIP assay revealed that GLI proteins are associated with a putative Gli binding site within the SOX2 promoter, suggesting a more direct regulation of SOX2 by GLI transcription factors. The relevance of our findings to human disease was revealed in human cancer specimens. We found that high SOX2 protein expression is associated with frequent tumor relapse and poor survival in stage II PDAC patients (all of them underwent gemcitabine treatment), indicating that reduced SOX2 expression or down-regulation of GLI transcription factors may be effective in sensitizing pancreatic cancer cells to gemcitabine treatment
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