BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy

Bone morphogenetic protein 7 (BMP7) has been reported to confer renoprotective effects in acute and chronic kidney disease models, but its potential role in Type 2 diabetic nephropathy remains unknown. In cultured human proximal tubular epithelial cells (PTECs), exposure to advanced glycation end-products (AGEs) induced overexpression of intercellular adhesion molecule 1 (ICAM1), monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL-8) and interleukin 6 (IL-6), involving activation of p44/42 and p38 mitogen-activated protein kinase (MAPK) signalling. BMP7 dose-dependently attenuated AGE-induced up-regulation of ICAM1, MCP1, IL-8 and IL-6 at both mRNA and protein levels. Moreover, BMP7 suppressed AGE-induced p38 and p44/42 MAPK phosphorylation and reactive oxygen species production in PTECs. Compared with vehicle control, uninephrectomized db/db mice treated with BMP7 for 8 weeks had significantly lower urinary albumin-to-creatinine ratio (3549±816.2 μg/mg compared with 8612±2037 μg/mg, P=0.036), blood urea nitrogen (33.26±1.09 mg/dl compared with 37.49±0.89 mg/dl, P=0.006), and renal cortical expression of ICAM1 and MCP1 at both gene and protein levels. In addition, BMP7-treated animals had significantly less severe tubular damage, interstitial inflammatory cell infiltration, renal cortical p38 and p44/42 phosphorylation and lipid peroxidation. Our results demonstrate that BMP7 attenuates tubular pro-inflammatory responses in diabetic kidney disease by suppressing oxidative stress and multiple inflammatory signalling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule in diabetic nephropathy warrants further investigation.postprin

Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-alpha, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-kappaB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and alpha-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFalpha-stimulating gene (TSG)-6 via P38 and NF-kappaB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-alpha overexpression were suppressed by recombinant HGF treatment, while the upregulation of alpha-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, alpha-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.published_or_final_versio

Speaking and Listening with the Eyes: Gaze Signaling during Dyadic Interactions

Cognitive scientists have long been interested in the role that eye gaze plays in social interactions. Previous research suggests that gaze acts as a signaling mechanism and can be used to control turn-taking behaviour. However, early research on this topic employed methods of analysis that aggregated gaze information across an entire trial (or trials), which masks any temporal dynamics that may exist in social interactions. More recently, attempts have been made to understand the temporal characteristics of social gaze but little research has been conducted in a natural setting with two interacting participants. The present study combines a temporally sensitive analysis technique with modern eye tracking technology to 1) validate the overall results from earlier aggregated analyses and 2) provide insight into the specific moment-to-moment temporal characteristics of turn-taking behaviour in a natural setting. Dyads played two social guessing games (20 Questions and Heads Up) while their eyes were tracked. Our general results are in line with past aggregated data, and using cross-correlational analysis on the specific gaze and speech signals of both participants we found that 1) speakers end their turn with direct gaze at the listener and 2) the listener in turn begins to speak with averted gaze. Convergent with theoretical models of social interaction, our data suggest that eye gaze can be used to signal both the end and the beginning of a speaking turn during a social interaction. The present study offers insight into the temporal dynamics of live dyadic interactions and also provides a new method of analysis for eye gaze data when temporal relationships are of interest

Loneliness of Older Immigrant Groups in Canada: Effects of Ethnic-Cultural Background

This study aimed to explore the loneliness of several groups of older immigrants in Canadacompared to native-born older adults. Data from the Canadian General Social Survey, Cycle 22 (Nolder adults = 3,692) were used. The dependent variable is the 6 item De Jong Gierveld lonelinessscale. Determinants of loneliness included country of birth, ethnic background (cultural context);belongingness (community context) and social networks (social context). Results showed that onlysome immigrant groups are significantly lonelier than older adults born in Canada. Immigrants withsimilar language and culture are not lonelier; while those from countries that differ in nativelanguage/culture are significantly higher on loneliness. Multivariate analyses showed the importanceof cultural background, of composition of the network of relatives and friends, and of localparticipation and feelings of belonging to the Canadian society in explaining loneliness of olderimmigrants

Identifying Sources of Health Care Underutilization Among California’s Immigrants

Many studies show that immigrants face significant barriers in accessing health care. These barriers may be particularly pronounced for newer immigrants, who may face additional obstacles in navigating the health care system. Understanding the sources of health care disparities between recent and non-recent immigrants may allow for better design of policies and interventions to address the vulnerabilities unique to different subgroups of immigrants defined by their length of residency. This study employs descriptive analyses and multivariate logistic regression to estimate the likelihood of accessing and utilizing health care services based on immigration-related factors after controlling for predisposing, enabling, and health care need factors. We also employ a regression-based decomposition method to determine whether health care differences between recent and non-recent immigrants are statistically significant and to identify the primary drivers of healthcare differences between recent and non-recent immigrants. The findings support the hypothesis that significant disparities in health care access and utilization exist between recent and non-recent immigrants. We found that health care access and utilization differences between recent and non-recent immigrants were driven primarily by enabling resources, including limited English proficiency (LEP), insurance status, public assistance usage, and poverty level. These results indicate that not only are newer immigrants more likely to underutilize health care, but also that their underutilization is driven primarily by their lack of insurance, lack of adequate financial resources, and inability to navigate the health care system due to LEP. The results further indicate that immigrants with prolonged LEP may be less likely to have a usual source of care and more likely to report delays in obtaining medical treatments, than even recent immigrants with LEP

Scaffolding in teacher-student interaction: a decade of Research

Although scaffolding is an important and frequently studied concept, much discussion exists with regard to its conceptualizations, appearances, and effectiveness. Departing from the last decade’s scaffolding literature, this review scrutinizes these three areas of scaffolding. First, contingency, fading, and transfer of responsibility are discerned in this review as the three key characteristics of scaffolding. Second, an overview is presented of the numerous descriptive studies that provided narratives on the appearances of scaffolding and classifications of scaffolding strategies. These strategies are synthesized into a framework for analysis, distinguishing between scaffolding means and intentions. Third, the small number of effectiveness studies available is discussed and the results suggest that scaffolding is effective. However, more research is needed. The main challenge in scaffolding research appears to be its measurement. Based on the encountered and described measurement problems, suggestions for future research are made

Density-based Place Clustering in Geo-social Networks

Spatial clustering deals with the unsupervised grouping of places into clusters and finds important applications in urban planning and marketing. Current spatial clustering models disregard information about the people who are related to the clustered places. In this paper, we show how the density-based clustering paradigm can be extended to apply on places which are visited by users of a geo-social network. Our model considers both spatial information and the social relationships between users who visit the clustered places. After formally defining the model and the distance measure it relies on, we present efficient algorithms for its implementation, based on spatial indexing. We evaluate the effectiveness of our model via a case study on real data; in addition, we design two quantitative measures, called social entropy and community score to evaluate the quality of the discovered clusters. The results show that geo-social clusters have special properties and cannot be found by applying simple spatial clustering approaches. The efficiency of our index-based implementation is also evaluated experimentally

Auto-optimisation for three-dimensional conformal radiotherapy of nasopharyngeal carcinoma

Purpose: The purpose of this study was to evaluate the application of auto-optimisation in the treatment planning of three-dimensional conformal radiotherapy (3DCRT) of nasopharyngeal carcinoma (NPC). Methods: Twenty-nine NPC patients were planned by both forward planning and auto-optimisation methods. The forward plans, which consisted of three coplanar facial fields, were produced according to the routine planning criteria. The auto-optimised plans, which consisted of 5-15 (median 9) fields, were generated by the planning system after prescribing the dose requirements and the importance weightings of the planning target volume and organs at risk. Plans produced by the two planning methods were compared by the dose volume histogram, tumour control probability (TCP), conformity index and normal tissue complication probability (NTCP). Results: The auto-optimised plans reduced the average planner's time by over 35 min. It demonstrated better TCP and conformity index than the forward plans (P = 0.03 and 0.04, respectively). Besides, the parotid gland and temporo-mandibular (TM) joint were better spared with the mean dose reduction of 31.8 and 17.7%, respectively. The slight trade off was the mild dose increase in spinal cord and brain stem with their maximum doses remaining within the tolerance limits. Conclusions: The findings demonstrated the potentials of auto-optimisation for improving target dose and parotid sparing in the 3DCRT of NPC with saving of the planner's time. © 2003 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

The impact of pandemic-related life stress on internet gaming : social cynicism and gaming motivation as serial mediators

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