Quantification and Localization of Mast Cells in Periapical Lesions

Background: Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Aim: Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. Materials and Methods: A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t‑test.Results: Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females.Conclusion: Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions. Keywords: Mast cells, Periapical granuloma, Radicular cyst, Toluidine blu

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC‐16, sRAGE, ICAM‐1, IL‐8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC‐16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p < 0.001). CC‐16 was associated with PGD in nonidiopathic pulmonary fibrosis (non‐IPF) subjects (OR for highest quartile of CC‐16: 2.87, 95% CI: 1.37, 6.00, p = 0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p = 0.59). After adjustment, preoperative CC‐16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p = 0.013) in non‐IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients. The authors demonstrate a relationship between perioperative CC‐16 blood levels and an increased risk of primary lung allograft dysfunction, particularly in those without idiopathic pulmonary fibrosis as a pretransplant diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102697/1/ajt12541.pd

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21

Meta-AnalysisThis is the final version of the article. Available from the American Diabetes Association via the DOI in this record.Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.The major funding for this work comes from Council for Scientific and Industrial Research, Government of India, in the form of the grant “Diabetes mellitus—New drug discovery R&D, molecular mechanisms, and genetic and epidemiological factors” (NWP0032-19). R.T. received a postdoctoral fellowship from the Fogarty International Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (D43-HD-065249)

Implementation of Dual-Source RF Excitation in 3 T MR-Scanners Allows for Nearly Identical ADC Values Compared to 1.5 T MR Scanners in the Abdomen

Background: To retrospectively and prospectively compare abdominal apparent diffusion coefficient (ADC) values obtained within in a 1.5 T system and 3 T systems with and without dual-source parallel RF excitation techniques. Methodology/Principal Findings: After IRB approval, diffusion-weighted (DW) images of the abdomen were obtained on three different MR systems (1.5 T, a first generation 3 T, and a second generation 3 T which incorporates dual-source parallel RF excitation) on 150 patients retrospectively and 19 volunteers (57 examinations total) prospectively. Seven regions of interest (ROI) were throughout the abdomen were selected to measure the ADC. Statistical analysis included independent two-sided t-tests, Mann-Whitney U tests and correlation analysis. In the DW images of the abdomen, mean ADC values were nearly identical with nonsignificant differences when comparing the 1.5 T and second generation 3 T systems in all seven anatomical regions in the patient population and six of the seven in the volunteer population (p.0.05 in all distributions). The strength of correlation measured in the volunteer population between the two scanners in the kidneys ranged from r = 0.64–0.88 and in the remaining regions (besides the spleen), r.0.85. In the patient population the first generation 3 T scanner had different mean ADC values with significant differences (p,0.05) compared to the other two scanners in each of the seven distributions. In the volunteer population, the kidneys shared similar ADC mean values in comparison to the other two scanners with nonsignificant differences

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure