Pericardial fat and myocardial perfusion in asymptomatic adults from the Multi-Ethnic Study of Atherosclerosis

Background

Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals.

Methods

We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF.

Results

Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm³, p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82–1.70) or women (OR, 1.11; 95% CI, 0.68–1.82).

Conclusions

Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden.     

Use of the D-R model to define trends in the emergence of Ceftazidime-resistant Escherichia coli in China

Objective

To assess the efficacy of the D-R model for defining trends in the appearance of Ceftazidime-resistant Escherichia coli.

Methods

Actual data related to the manifestation of Ceftazidime-resistant E. coli spanning years 1996–2009 were collected from the China National Knowledge Internet. These data originated from 430 publications encompassing 1004 citations of resistance. The GM(1,1) and the novel D-R models were used to fit current data and from this, predict trends in the appearance of the drug-resistant phenotype. The results were evaluated by Relative Standard Error (RSE), Mean Absolute Deviation (MAD) and Mean Absolute Error (MAE).

Results

Results from the D-R model showed a rapid increase in the appearance of Ceftazidime-resistant E. coli in this region of the world. These results were considered accurate based upon the minor values calculated for RSE, MAD and MAE, and were equivalent to or better than those generated by the GM(1,1) model.

Conclusion

The D-R model which was originally created to define trends in the transmission of swine viral diseases can be adapted to evaluating trends in the appearance of Ceftazidime-resistant E. coli. Using only a limited amount of data to initiate the study, our predictions closely mirrored the changes in drug resistance rates which showed a steady increase through 2005, a decrease between 2005 and 2008, and a dramatic inflection point and abrupt increase beginning in 2008. This is consistent with a resistance profile where changes in drug intervention temporarily delayed the upward trend in the appearance of the resistant phenotype; however, resistance quickly resumed its upward momentum in 2008 and this change was better predicted using the D-R model. Additional work is needed to determine if this pattern of “increase-control-increase” is indicative of Ceftazidime-resistant E. coli or can be generally ascribed to bacteria acquiring resistance to drugs in the absence of alternative intervention.     

Mining relational paths in integrated biomedical data

Much life science and biology research requires an understanding of complex relationships between biological entities (genes, compounds, pathways, diseases, and so on). There is a wealth of data on such relationships in publicly available datasets and publications, but these sources are overlapped and distributed so that finding pertinent relational data is increasingly difficult. Whilst most public datasets have associated tools for searching, there is a lack of searching methods that can cross data sources and that in particular search not only based on the biological entities themselves but also on the relationships between them. In this paper, we demonstrate how graph-theoretic algorithms for mining relational paths can be used together with a previous integrative data resource we developed called Chem2Bio2RDF to extract new biological insights about the relationships between such entities. In particular, we use these methods to investigate the genetic basis of side-effects of thiazolinedione drugs, and in particular make a hypothesis for the recently discovered cardiac side-effects of Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by recent clinical studies.     

Epidemiology, quality and reporting characteristics of systematic reviews of traditional Chinese medicine interventions published in Chinese journals

Background

Systematic reviews (SRs) of TCM have become increasingly popular in China and have been published in large numbers. This review provides the first examination of epidemiological characteristics of these SRs as well as compliance with the PRISMA and AMSTAR guidelines.

Objectives

To examine epidemiological and reporting characteristics as well as methodological quality of SRs of TCM published in Chinese journals.

Methods

Four Chinese databases were searched (CBM, CSJD, CJFD and Wanfang Database) for SRs of TCM, from inception through Dec 2009. Data were extracted into Excel spreadsheets. The PRISMA and AMSTAR checklists were used to assess reporting characteristics and methodological quality, respectively.

Results

A total of 369 SRs were identified, most (97.6%) of which used the terms systematic review or meta-analysis in the title. None of the reviews had been updated. Half (49.8%) were written by clinicians and nearly half (47.7%) were reported in specialty journals. The impact factors of 45.8% of the journals published in were zero. The most commonly treated conditions were diseases of the circulatory and digestive disease. Funding sources were not reported for any reviews. Most (68.8%) reported information about quality assessment, while less than half (43.6%) reported assessing for publication bias. Statistical mistakes appeared in one-third (29.3%) of reviews and most (91.9%) did not report on conflict of interest.

Conclusions

While many SRs of TCM interventions have been published in Chinese journals, the quality of these reviews is troubling. As a potential key source of information for clinicians and researchers, not only were many of these reviews incomplete, some contained mistakes or were misleading. Focusing on improving the quality of SRs of TCM, rather than continuing to publish them in great quantity, is urgently needed in order to increase the value of these studies.     

Suppression of allograft rejection by Tim-1-Fc through cross-linking with a novel Tim-1 binding partner on T cells

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4(+) effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4(+) T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4(+) T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3(+) cells in splenic CD4(+) T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4(+)CD25(-) T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection.     

In vivo chondrogenesis of adult bone-marrow-derived autologous mesenchymal stem cells

The purpose of this study has been to investigate the possible effects of the normal joint cavity environment on chondrocytic differentiation of bone-marrow-derived mesenchymal stem cells (MSCs). Autologous bone marrow was aspirated from the iliac crest of male sheep. MSCs were purified, expanded, and labeled with the fluorescent dye PKH26. Labeled MSCs were then grown on a three-dimensional porous scaffold of poly (L-lactic-co-glycolic acid) in vitro and implanted into the joint cavity by a surgical procedure. At 4 or 8 weeks after implantation, the implants were removed for histochemical and immunohistochemical analysis. The cells labeled with red fluorescent PKH26 in the implants expressed type II collagen and synthesized sulfated proteoglycans. However, the osteoblast-specific marker, osteocalcin, was not detected by immunohistochemistry indicating that the implanted MSCs had not differentiated into osteoblasts by being directly exposed to the normal joint cavity. To investigate the possible factors involved in chondrocytic differentiation of MSCs further, we co-cultured sheep MSCs with the main components of the normal joint cavity, viz., synovial fluid or synovial cells, in vitro. After 1 or 2 weeks of co-culture, the MSCs in both co-culture systems expressed markers of chondrogenesis. These results suggest that synovial fluid and synovium from normal joint cavity are important for the chondrocytic differentiation of adult bone-marrow-derived MSCs.This work was supported by the National Natural Science Foundation of China (nos. 39900036, 20174006, and 20221402), the National Advanced Technology Programs of China (nos. 2003AA744051, 2003AA205041), the Award Foundation for Young Teachers from the Ministry of Education, 973 project (no. G1999054306-03), and the 248 key innovative project of Beijing (no. H010210190123).     

Confirmation and refinement of a genetic locus of congenital motor nystagmus in Xq26.3-q27.1 in a Chinese family

Congenital motor nystagmus (CMN), a subtype of nystagmus, may reduce vision or be associated with other, more serious, conditions that limit vision. The genetic basis for CMN is still unknown. To identify a locus for CMN, genotyping and linkage analysis were performed in 22 individuals from a Chinese family with X-linked CMN using markers from X chromosome. The maximum LOD score obtained for microsatellite maker DXS1192 linked the CMN locus in this family to Xq. By haplotype construction the locus for CMN was finally localized to an approximately 4.4-cM region at chromosome Xq26.3-q27.1. The SLC9A6 and FGF13 genes in this region, were selected and screened for mutation in this family, but no mutation was detected.B. Zhang and K. Xia contribute to this work equally