Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques

Gliomas express mutant isocitrate dehydrogenases producing excessive amounts of D 2-hydroxyglutarate (D2HG) and releasing some of it into the environment. The immune surveillance is reduced as a result, however, the mechanisms behind lymphocyte suppression by the D2HG stereoisomer remain unknown. I incubated Jurkat T cells with D2HG at concentrations present within and surrounding gliomas, or its obverse L2HG stereoisomer, and quantified 2HG isomers within washed cells by TSPC derivatization with stable isotope-labeled D2HG and L2HG internal standards, HPLC separation, and mass spectrometry. D2HG was found in quiescent cells in double the amount of L2HG. External D2HG or L2HG increased the level of the provided stereoisomer in a transient, concentration-dependent process. IL-2 expression, even when maximally elicited by A23187 and PMA, was inhibited and ultimately abolished by exogenous D2HG in a concentration-dependent manner. Notably, a significant reduction occurred at just twice its basal intracellular level. In contrast, L2HG was only moderately inhibitory. IL-2 expression is regulated by increased intracellular Ca++ that stimulates Calcineurin to dephosphorylate cytoplasmic phospho-NFAT to enable its nuclear translocation. Besides, to induce IL-2, AP-1 complex which is downstream of ERK needs to ligate. D2HG inhibited p-ERK in Jurkat T cells, impairing the AP-1 complex. D2HG abolished expression of a stably-integrated NFAT-driven luciferase reporter, and this concentration-dependent inhibition precisely paralleled inhibition of IL-2. D2HG did not affect intracellular Ca++. Rather, surface Plasmon resonance showed D2HG, but not L2HG, bound Calcineurin. D2HG, but not L2HG, inhibited Ca++-dependent Calcineurin phosphatase activity. Thus, D2HG is a stereoselective Calcineurin phosphatase inhibitor that prevents NFAT dephosphorylation, and so abolishes IL-2 transcription in stimulated Jurkat cells. This occurs at D2HG concentrations found within and adjacent to gliomas independent of delayed epigenetic modulation of transcription

Comparative study of the performance of Supercritical Fluid Extraction, Microwave assisted Hydro-distillation and Hydro-distillation of Lemongrass (Cymbopogon Citratus): A Review

This review study deals with the collocation of the performance of three different separation techniques for the extraction of essential oil of Lemongrass (Cymbopogon Citratus) accordant with yield produced, time utilized for extraction, and overall cost of production. The system of Supercritical CO2 extraction (SFC), Microwave-assisted Hydro-distillation (MAHD), and conventional hydro-distillation (HD) method were juxtaposed from the yield and time point of view. SFE is a modern extraction technology that uses a Supercritical phase of CO2for the isolation of essential oil from lemongrass (Cymbopogon Citratus) and is a green process because of the use of natural and climate-friendly solventCO2. MAHD is a microwave-powered extraction procedure that provides efficient and effective heating to the plant material and uses deionized water as a solvent. A lab-scale apparatus of conventional hydro-distillation was used. SFE and MAHD were found to be superior green technology when compared with HD producing high quality of oil, in a short period with negligible environmental degradation

Reliable extraction of energy landscape properties from critical force distributions

The structural dynamics of a biopolymer is governed by a process of diffusion through its conformational energy landscape. In pulling experiments using optical tweezers, features of the energy landscape can be extracted from the probability distribution of the critical force at which the polymer unfolds. The analysis is often based on rate equations having Bell-Evans form, although it is understood that this modeling is inadequate and leads to unreliable landscape parameters in many common situations. Dudko et al. [Phys. Rev. Lett. 96, 108101 (2006)PRLTAO0031-900710.1103/PhysRevLett.96.108101] have emphasized this critique and proposed an alternative form that includes an additional shape parameter (and that reduces to Bell-Evans as a special case). Their fitting function, however, is pathological in the tail end of the pulling force distribution, which presents problems of its own. We propose a modified closed-form expression for the distribution of critical forces that correctly incorporates the next-order correction in pulling force and is everywhere well behaved. Our claim is that this new expression provides superior parameter extraction and is valid even up to intermediate pulling rates. We present results based on simulated data that confirm its utility

A clinical study of factors predicting prognosis in acute ischemic stroke in a tertiary care center in north Kerala

Background: Stroke is the second most common cause of death and third most common cause of disability in the world. Knowledge of prognostic factors is necessary for the clinician to make a reasonable prediction of outcome for individual patients, to provide rational approach to management and to help patients and their families understand course of the disease. Hence, this study to determine the prognostic factors in acute ischemic stroke with special emphasis on atrial fibrillation, hyperglycemia and fever was undertaken.Methods: This is a prospective and hospital based observational study of 70 patients with acute ischemic stroke. The diagnosis of acute ischemic stroke was based on history, physical examination and CT imaging. The severity was assessed based on Scandinavian Stroke Scale (SSS). The prognostic factors with special emphasis on atrial fibrillation, hyperglycemia and fever were studied based on the standard diagnostic criteria.Results: Prevalence of Atrial Fibrillation was 20% in present study. Mortality and dependency rates were significantly higher in AF group. Fever during the first few days of acute ischemic stroke was a statistically significant predictor of poor outcome. Neuronal damage in brain is directly proportional to its temperature. The results of the study confirm that hyperglycemia at stroke onset is an adverse prognostic factor with 33.33% mortality in hyperglycemic stroke.Conclusions: Atrial fibrillation, hyperglycemia and fever were found to be poor prognostic factors in acute ischemic stroke. Prompt recognition and correction of these poor prognostic factors improve the outcome for such patients

CONCORDANCE BETWEEN FREE T4 AND T4 IN THYROID FUNCTION TESTS

Background: Thyroid hormones regulate the metabolism of virtually all cells in the body. The frequency of thyroid dysfunction in our population compels every physician to be skilled in the diagnosis of thyroid disease. Direct measurement of serum concentration of TSH, T4 and T3 is used to establish the diagnosis of primary hypothyroidism and hyperthyroidism. The free unbound fraction of T4 (FT4) and T3 (FT3) which is less than 0.03% is the active form of the hormone. Free T4 (the biologically active T4) is less sensitive to changes in serum binding proteins and hence FT4 levels could best represent the thyroid functional status Aim: To evaluate the concordance between total T4, T3 levels and free T4 levels in patients with abnormal thyroid function test reports where the full panel of TFT has been ordered. Materials & Methods: Consecutive TFT reports of patients in whom the full panel of TFT have been ordered over a two month period were included in the analysis. The results obtained were statistically analyzed by the help of Microsoft Excel and SPSS software. Results: In the hypothyroid group, the median TSH was 6.89 microIU/ml (Mean=21.25) with a mean T4 of 6.75 microgm/dl and mean FT4 of 1.03 ng/ml .In this group, the mean T3 was 0.91 ng/ml a range 0.195-1.95. In the hyperthyroid group, the mean TSH was 0.049 microIU/ml with a mean T4 and FT4 of 11.01 microgm/dl and 2.07 ng/ml and the mean T3 was 1.3 ng/ml with a range of 0.62 to 4.33. Statistical analysis using Karl Pearson's method showed a significant correlation (r = 0.8) between T4 and FT4 values. It was also found that T3 also had a significant positive correlation with FT4 and T4. No significant influence of age and gender on TFT was found. 14% of the T4 values in the hypothyroid group and 40 % of T4 values in the hyperthyroid group were in the normal range while Free T4 alone showed changes consistent with the corresponding thyroid dysfunction. Conclusion: FT4 correlates highly with T4 in both primary hypothyroidism and hyperthyroidism, and in conjugation with TSH its measurement serves as a better tool than total T4 in the diagnosis of thyroid disorders. KEYWORDS: Thyroid function test correlation; Free T4 concordance