Leukocyte-Endothelium Interaction in the Sublingual Microcirculation of Coronary Artery Bypass Grafting Patients

Objective: The aim of this study was to apply an innovative methodology to incident dark-field (IDF) imaging in coronary artery bypass grafting (CABG) patients for the identification and quantification of rolling leukocytes along the sublingual microcirculatory endothelium. Methods: This study was a post hoc analysis of a prospective study that evaluated the perioperative course of the sublingual microcirculation in CABG patients. Video images were captured using IDF imaging following the induction of anesthesia (T-0) and cardiopulmonary bypass (CPB) (T-1) in 10 patients. Rolling leukocytes were identified and quantified using frame averaging, which is a technique that was developed for correctly identifying leukocytes. Results: The number of rolling leukocytes increased significantly from T-0 (7.5 {[}6.4-9.1] leukocytes/capillary-postcapillary venule/4 s) to T-1 (14.8 {[}13.2-15.5] leukocytes/capillary-postcapillary venule/4 s) (p < 0.0001). A significant increase in systemic leukocyte count was also detected from 7.4 +/- 0.9 x 10(9)/L (preoperative) to 12.4 +/- 4.4 x 10(9)/L (postoperative) (p < 0.01). Conclusion: The ability to directly visualize leukocyte-endothelium interaction using IDF imaging facilitates the diagnosis of a systemic inflammatory response after CPB via the identification of rolling leukocytes. Integration of the frame averaging algorithm into the software of handheld vital microscopes may enable the use of microcirculatory leukocyte count as a real-time parameter at the bedside.1JAN8-155

Skewed X-chromosome inactivation in scleroderma

Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3-20.6, P 90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8-70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma. © 2007 Humana Press Inc

Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies

Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of anti-norovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection

Enhancing crop resilience through thiamine: implications for sustainable agriculture in drought-stressed radish

During 21st century, abiotic stress has adversely affected the agriculture crop production around the globe. Keeping in view the food requirement under water shortage condition, a study was planned to investigate the effect of thiamine application on radish crop under drought stress conditions on plant. For study purpose, two varieties of locally available radish (‘Early-Milo’ and ‘Laal-Pari’) were grown with normal water application as well as thiamine (100 mg L-1) application while maintaining a stress condition (60% field capacity). Increasing water deficit stress linearly reduced plant growth, yield and biomass in both varieties by reducing water use efficiency, while significantly enhanced these attributes with thiamine application. Thiamine application under drought stress exerted significant impacts on physiological attributes in both varieties, including enhanced osmolytic attribute in drought conditions and improvements in superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), H2O2, and malondialdehyde (MDA) activities in plant leaves. Antioxidant and osmoprotectant upregulation positively linked to radish crop's drought tolerance. Moreover, PCA and heatmap analysis revealed a significant interdependence among various traits and interconnected in determining the crop's capacity to sustain growth under conditions of drought stress. In crux, thiamine application conclusively enhances radish growth, yield, biomass, physio-chemical and osmolytic attributes, ionic composition and enzymatic antioxidant potential. Therefore, it is recommended to consider the application of thiamine in commercial agriculture practices to mitigate the negative effects of drought stress on radish crop production

Extreme Clonality in Lymphoblastoid Cell Lines with Implications for Allele Specific Expression Analyses

Lymphoblastoid cell lines (LCL) are being actively and extensively used to examine the expression of specific genes and genome-wide expression profiles, including allele specific expression assays. However, it has recently been shown that approximately 10% of human genes exhibit random patterns of monoallelic expression within single clones of LCLs. Consequently allelic imbalance studies could be significantly compromised if bulk populations of donor cells are clonal, or near clonal. Here, using X chromosome inactivation as a readout, we confirm and quantify widespread near monoclonality in two independent sets of cell lines. Consequently, we recommend where possible the use of bulk, non cell line, ex vivo cells for allele specific expression assays

Intraoperative Imaging Techniques to Visualize Hepatic (Micro)Perfusion: An Overview

The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, ass

How do water users perceive the quality of their irrigation services?: Report on a Training Course in the Use of Participatory Rural Appraisal for Irrigation Management Research, December 1994

Irrigation managementWater usersWater supplyIrrigation operationPerformanceParticipatory rural appraisalTraining

Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder - Possible Role for Methoxyindole Pathway

10.1371/journal.pone.0068283PLoS ONE87-POLN