Impaired myocardial deformation and ventricular vascular coupling in obese adolescents with dysglycemia

Patients with Diabetes mellitus (DM) are susceptible to coronary artery disease (CAD). However, the impact of DM on plaque progression in the non-stented segments of stent-implanted patients has been rarely reported. This study aimed to evaluate the impact of DM on the prevalence, characteristics and severity of coronary computed tomography angiography (CCTA) verified plaque progression in stented patients. A comparison between diabetic and non-diabetic patients was performed. A total of 98 patients who underwent clinically indicated serial CCTAs arranged within 1 month before and at least 6 months after percutaneous coronary intervention (PCI) were consecutively included. All the subjects were categorized into diabetic group (n = 36) and non-diabetic groups (n = 62). Coronary stenosis extent scores, segment involvement scores (SIS), segment stenosis scores (SSS) at baseline and follow-up CCTA were quantitatively assessed. The prevalence, characteristics and severity of plaque progression was evaluated blindly to the clinical data and compared between the groups. During the median 1.5 year follow up, a larger number of patients (72.2% vs 40.3%, P = 0.002), more non-stented vessels (55.7% vs 23.2%, P < 0.001) and non-stented segments (10.3% vs 4.4%, P < 0.001) showed plaque progression in DM group, compared to non-DM controls. More progressive lesions in DM patients were found to be non-calcified plaques (31.1% vs 12.8%, P = 0.014) or non-stenotic segments (6.6% vs 3.0%, p = 0.005) and were more widely distributed on left main artery (24.2% vs 5.2%, p = 0.007), the right coronary artery (50% vs 21.1%, P = 0.028) and the proximal left anterior artery (33.3% vs 5.1%, P = 0.009) compared to non-DM patients. In addition, DM patients possessed higher numbers of progressive segments per patient, ΔSIS and ΔSSS compared with non-DM individuals (P < 0.001, P = 0.029 and P < 0.001 respectively). A larger number of patients with at least two progressive lesions were found in the DM group (P = 0.006). Multivariate logistic regression analysis demonstrated that DM (OR: 4.81; 95% CI 1.64–14.07, P = 0.004) was independently associated with plaque progression. DM is closely associated with the prevalence and severity of CCTA verified CAD progression. These findings suggest that physicians should pay attention to non-stent segments and the management of non-stent segment plaque progression, particularly to DM patients.     

Carbimazole embryopathy-bilateral choanal atresia and patent vitello-intestinal duct: a case report and review of literature

BACKGROUND: In utero exposure to carbimazole for maternal hyperthyroidism has been reported to cause choanal atresia. There are case reports of patent vitello‐intestinal duct and Meckel's diverticulum in similar association. CASE: We report another such instance of an infant who was exposed to carbimazole in utero, presenting with bilateral choanal atresia and patent vitello‐intestinal duct. CONCLUSIONS: As there seems to be no reports of a possible association between propylthiouracil and congenital malformations, it may be safer to use propylthiouracil instead of carbimazole. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Mercury Volatilization by R Factor Systems in <Emphasis Type="Italic">Escherichia coli</Emphasis> Isolated from Aquatic Environments of India

Ten Escherichia coli strains isolated from five different aquatic environments representing three distinct geographical regions of India showed significantly high levels of tolerance to the inorganic form of mercury, i.e., mercuric chloride (HgCl₂). MRD14 isolated from the Dal Lake (Kashmir) could tolerate the highest concentration of HgCl₂, i.e., 55 g/mL, and MRF1 from the flood water of the Yamuna River (Delhi) tolerated the lowest concentration, i.e., 25 g/mL. All ten strains revealed the presence of a plasmid of approximately 24 kb, and transformation of the isolated plasmids into the mercury-sensitive competent cells of E. coli DH5 rendered the transformants resistant to the same concentration of mercury as the wild-type strains. Mating experiments were performed to assess the self-transmissible nature of these promiscuous plasmids. The transfer of mercury resistance from these wild-type strains to the mercury-sensitive, naladixic acid-resistant E. coli K12 (F^–lac⁺) strain used as a recipient was observed in six of the nine strains tested. Transconjugants revealed the presence of a plasmid of approximately 24 kb. An evaluation of the mechanism of mercury resistance in the three most efficient strains (MRG12, MRD11, and MRD14) encountered in our study was determined by cold vapor atomic absorption spectroscopy (CV-AAS), and it was noted that resistance to HgCl₂ was conferred by conversion of the toxic ionic form of mercury (Hg⁺⁺) to the nontoxic elemental form (Hg⁰) in all three strains. MRD14 volatilized mercury most efficiently.     

Abnormal V(D)J recombination of T cell receptor beta locus in SMAR1 transgenic mice

Scaffold/matrix-associated region-1-binding protein (SMAR1) specifically interacts with the MARbeta sequence, which is located 400-bp upstream of the murine TCRbeta enhancer and is highly expressed during the DP stage of thymocyte development. To further analyze the functions of SMAR1, transgenic mice were generated that express SMAR1 in a tissue-independent manner. SMAR1-overexpressing mice exhibit severely altered frequency of the T cells expressing commonly used Vbetas (Vbeta5.1/5.2 and Vbeta8.1/8.2/8.3). The rearrangements of Vbeta5.1/5.2, Vbeta8.1/8.2/8.3 loci are also reduced in SMAR1 transgenic mice. The T cells in SMAR1 transgenic mice exhibit a mild perturbation at the early DN stage. SMAR1 transgenic mice exhibit hypercellular lymph nodes and spleen accompanied with prominent architectural defects in these organs. These results indicate that SMAR1 plays an important role in the regulation of T cell development as well as V(D)J recombination besides maintaining the architecture of the lymphoid organs.     

Sequential Substrate Removal in a Dilute System by Heterogeneous Microbial Populations

The sequential metabolism of substrates by heterogeneous bacterial populations has been previously reported from this laboratory in studies with high substrate concentrations. This phenomenon has now been shown to occur at very dilute substrate concentrations, i.e., 5 mg/liter of glucose plus 5 mg/liter of sorbitol, in studies conducted under the conditions of the standard biochemical oxygen demand (BOD) test. Sequential metabolism of these substrates resulted in a diphasic curve of accumulated oxygen uptake wherein the two phases were separated by a discernible plateau. These findings illustrate one possible explanation for the generation of discontinuity in the kinetic course of carbonaceous BOD exertion.     

Elemental and biochemical markers of stigma receptivity in sunflower

Stigma development in sunflower is accompanied with an accumulation of calcium (33 %), potassium (37 %) and boron (62 %) in mature stigma as compared to stigma at bud stage, thereby demonstrating their essential roles in attaining receptivity. Membrane-bound calcium accumulation is enhanced on the pellicle and is also evident in the cytoplasm accompanying stigma maturation. Total soluble carbohydrate content increases in the staminate stage (55 %) as compared to bud stage. Glucose and fructose are the major monosaccharides and their contents are maximum in the staminate stage. Total lipid content also increases with the passage of stigma development. Erucic acid (22:1) is expressed specifically in the bud and staminate stages. A variation in the contents of triacylglycerides and free fatty acids, and expression of fatty acyl esterases in mature stigma have been correlated with biochemical events associated with signalling mechanisms. Lastly, enhanced expression of two hydrolytic enzymes, namely β-1,3 glucanase and fatty acyl ester hydrolase, has been observed to correlate with stigma maturation. Present findings, thus, provide new information on the structural and biochemical changes marking various signalling events associated with successful pollen–stigma interaction.     

Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods

Hepatitis C virus (HCV) is a global health challenge, affecting approximately 200 million people worldwide. In this study we developed SAR models with advanced machine learning classifiers Random Forest and k Nearest Neighbor Simulated Annealing for 679 small molecules with measured inhibition activity for NS5B genotype 1b. The activity was expressed as a binary value (active/inactive), where actives were considered molecules with IC₅₀ ?0.95 μM. We applied our SAR models to various drug-like databases and identified novel chemical scaffolds for NS5B inhibitors. Subsequent in vitro antiviral assays suggested a new activity for an existing prodrug, Candesartan cilexetil, which is currently used to treat hypertension and heart failure but has not been previously tested for anti-HCV activity. We also identified NS5B inhibitors with two novel non-nucleoside chemical motifs.