12,402 research outputs found
Association of Thyroid Stimulating Hormone and Lipid Profile in Pregnancy
No full textABSTRACT
Introduction: Thyroid hormones have significant functions in embryogenesis and fetal development. Evidence suggests that thyroid stimulating hormone (TSH) may exert extra-thyroidal effects and modify the profile of blood lipids.
Aim: To determine the association between maternal blood lipid profile and thyroid stimulating hormone in second and third trimester of pregnancy.
Methods & Materials: The present study was carried out at MGM Hospital, Navi Mumbai, India. 200 antenatal cases from October, 2012 to October 2014 were enrolled after taking an informed consent. The blood samples for Thyroid stimulating hormone and lipid profile were taken at 16th and 32nd weeks.
Results: The mean TSH level in second trimester was 1.53 mIU/L, with a standard deviation of 1.147 mIU/L. In third trimester, the mean TSH level was increased to 2.60 mIU/L with a standard deviation of 0.836mIU/L. The t-stat value was found to be -10.649 (p < 0.001). In third trimester, TSH was negatively correlated with Cholesterol (r= -0.214, p < 0.01) and VLDL (r= -0.148, p < 0.05). With increase in TSH level, cholesterol level will decrease.
Conclusion: TSH levels rises according to the gestational age, being higher in third trimester as compared to second trimester. There is a significant negative correlation between TSH levels and cholesterol & VLDL in third trimester of the pregnancy. Hence, TSH levels should be looked for, especially in third trimester, in order to keep the thyroid related problems in check.
Keyword: Lipid Profile, Cholesterol, VLDL, HDL, TSH, Thyroid
Rodin: an open toolset for modelling and reasoning in Event-B
No full textEvent-B is a formal method for system-level modelling and analysis. Key features of Event-B are the use of set theory as a modelling notation, the use of refinement to represent systems at different abstraction levels and the use of mathematical proof to verify consistency between refinement levels. In this article we present the Rodin modelling tool that seamlessly integrates modelling and proving. We outline how the Event-B language was designed to facilitate proof and how the tool has been designed to support changes to models while minimising the impact of changes on existing proofs. We outline the important features of the prover architecture and explain how well-definedness is treated. The tool is extensible and configurable so that it can be adapted more easily to different application domains and development methods
Seasonal Variation in Onset of Pulmonary Embolism is Independent of Patients' Underlying Risk Comorbid Conditions
No full textAs for many cardiovascular events, pulmonary embolism (PE) is not randomly distributed over time, but shows rhythmic patterns. The purpose of this study was to investigate whether such temporal pattern of occurrence varied in subgroups of patients according to different risk comorbid conditions. All cases of PE observed at the Hospital of Ferrara, Italy, from 1998 to 2001, were considered. After determination of the day of onset, the population was grouped by gender and the most common underlying risk comorbid conditions, e.g., deep vein thrombosis (DVT), neoplasms, cardiomyopathies, traumas/surgical operations, diabetes mellitus, pulmonary diseases, hypertension, cerebrovascular diseases, heart failure, hematologic diseases. For statistical analysis, chi-square test for goodness of fit and partial Fourier series were used. A total of 784 cases (mean age 71 +/- 14 years) were included. Frequency of onset was higher in winter for total population (p = 0.002), men (p = 0.004), DVT (p = 0.001), pulmonary disease (p = 0.008), cardiomyopathies (p = 0.011), and major traumas/surgical operations (p = 0.049). Chronobiologic analysis identified a winter peak for total population (p = 0.008), men (p < 0.001), DVT (p = 0.006), pulmonary diseases (p = 0.017), and hypertension (p = 0.026). This study confirms the winter peak of PE and provides evidence that it is not influenced by the underlying clinical conditions, but probably by endogenous variations
Genetic and Biochemical Studies with Chinese Hamster Ovary Cell Mutants Resistant to the Purine Nucleoside Analogs: Toyocamyin, Formycin A and Formycin B
No full textThe aim of this study was to investigate the mechanism of cellular resistance and toxicity to the purine nucleoside analogs toyocamycin, formycin A and formycin B by using genetic, biochemical and immunological approaches. To investigate the similarity or differences in the mechanism of action of various pyrrolopyrimidine nucleosides, second-step toyocamycin resistant mutants (Toyʳᴵᴵ mutants) of Chinese hamster ovary cells were isolated from a cell line which exhibited similar degree of resistance to toyocamycin and tubercidin. These second-step mutants exhibited a further 8- to 9-fold increase in resistance to toypcamycin but no concurrent increase in their resistance towards tubercidin. The Toyʳᴵᴵ mutants were found to be very similar to the first-step mutants in their levels of adenosine kinase activity ( The genetic and biochemical approach was also used to investigate the mechanism of resistance and metabolism to another group of nucleoside analogs in which the base is linked to ribose moiety by a C-C linkage. Studies presented showed that stable mutants which are approximately 3- and 8-fold resistant to the C-nucleoside, formycin A (Fomᴿ mutants) could be obtained in a single step in CHO cells. In cell extracts, the Fomᴿ mutants contained no measurable activity of the enzyme adenosine kinase. In cell hybrids formed between formycin A resistant and sensitive cells (Fomˢ) as well as formycin A resistant and toyocamycin resistant cells (Toyʳ), the drug resistant phenotype of Fomᴿ mutants behaved codominantly as indicated by the degree of resistance of the hybrid cells to formycin B. However, extracts from these hybrid cells contained either≈50% (Fomᴿ x Fomˢ) or Since formycin A under the normal cell culture condition is rapidly deaminated to the inosine analog, formycin B, cellular toxicity and resistance of formycin B was also investigated. Mutants of CHO cells selected for resistance to formycin B (Fomʳ mutants) were found to be 5- to 8-fold resistant to this drug. Cross-resistance studies with these mutants revealed that they exhibit increased resistance to all adenosine analogs (N- and C-nucleosides); as well as reduced cellular uptake and phosphorylation. However, unlike the Fomᴿ and Toyʳ mutants, which contained no AK activity in their cell extracts, the Fomʳ mutants were found to contain between 60 - 110% of WT activity in their cell extracts. The AK activity present in both Fomʳ mutant cell extracts differed from the WT AK activity in terms of its specific activity as well as in its ability to phosphorylate adenosine analogs. The AK activity from the Fomʳ mutants was found to have less affinity for phosphorylation of the formycin A derivative, Bbb-85. Like Toyʳ mutants, Fomʳ mutants were found to show recessive-behaviour in cell hybrids. Biochemical studies on the metabolism of formycin B indicated that upon incubation with CHO cells, [³H]formycin B is metabolized into formycin B-5'-monophosphate, formycin A-5'-monophosphate and higher phosphorylated derivatives of formycin A which are incorporated into RNA. All three different classes of mutants affected In AK exhibit appreciable cross-resistance as well as reduced cellular uptake and phosphorylation of formycin B. These observations strongly indicate that in CHO cells, formycin B is phosphorylated via AK and like other nucleoside analogs, its phosphorylation is essential for the cellular toxicity. Formycin B-5'-monophosphate and formycin A-5'-monophosphate have been found to inhibit the purine nucleotide biosynthetic enzyme adenylosuccinate synthetase. To gain further insight into the nature of genetic and biochemical alterations in different types of mutants affected in adenosine kinase, this enzyme from CHO cells was purified to homogeneity. Antibodies which specifically cross-react with adenosine kinase have been raised. Immunoblot analyses using these antibodies showed that all three classes of mutants i.e., Toyʳ, Fomᴿ and Fomʳ contained nearly similar amounts of cross-reacting material that had a similar electrophoretic mobility to the enzyme in the WT cells. These results indicate that the lesion in these mutants does not involve a deletion or regulatory type of genetic alteration in the AK gene nor a nonsense type of mutation which may cause premature chain termination. Instead, these mutants may contain a missense type of alteration in the structural gene of AK. Using these antibodies, regions (or spots) on two-dimensional gels that correspond to the AK protein have been identified. Comparison of the 2-D gel electrophoretic patterns of total cellular proteins from different-mutant lines indicates that some of the mutants show a specific alteration in this region. This supports the inference that these mutants may contain a missense type of mutation in the structural gene of AK. The results presented in this thesis have been presented or submitted in the following publications. 1. Mehta, K.D. and Gupta, R.S. (1983) Formycin B-Resistant Mutants of Chinese Hamster Ovary Cells: Novel Genetic and Biochemical Phenotype Affecting Adenosine Kinase. Mol. Cell. Biol. 3, 1468. 2. Gupta, R.S. and Mehta, K.D. (1984) Genetic and Biochemical Studies on Mutants of CHO Cells Resistant to 7-Deazapurine Nucleosides: Differences in the Mechanisms of Action of Toyocamycin and Tubercidin. Biochem. Biophys. Res. Commun. 120, 88. 3. Mehta, K.D. and Gupta, R.S. Novel Mutants of Adenosine Kinase Specifically Affected in the Phosphorylation of C-Nucleosides. Manuscript submitted to FEBS Lett. 4. Mehta, K.D. and Gupta, R.S. Metabolism and the Mechanism of Action of Formycin B in Chinese Hamster Ovary Cells: Involvement of Adenosine Kinase in Drug Phosphorylation. Manuscript submitted to J. BioI. Chem.Doctor of Philosophy (PhD
Applying Atomicity and Model Decomposition to a Space Craft System in Event-B
No full textEvent-B is a formal method for modeling and verifying consistency of systems. In formal methods such as Event-B, refinement is the process of enriching or modifying an abstract model in a step-wise manner in order to manage the development of complex and large systems. To further alleviate the complexity of developing large systems, Event-B refinement can be augmented with two techniques, namely atomicity decomposition and model decomposition. Our main objective in this paper is to investigate and evaluate the application of these techniques when used in a refinement based development. These techniques have been applied to the formal development of a space craft system. The outcomes of this experimental work are presented as assessment results. The experience and assessment can form the basis for some guidelines in applying these techniques in future cases
A systematic approach to atomicity decomposition in Event-B
No full textEvent-B is a state-based formal method that supports a refinement process in which an abstract model is elaborated towards an implementation in a step-wise manner. One weakness of Event-B is that control flow between events is typically modelled implicitly via variables and event guards. While this fits well with Event-B refinement, it can make models involving sequencing of events more difficult to specify and understand than if control flow was explicitly specified. New events may be introduced in Event-B refinement and these are often used to decompose the atomicity of an abstract event into a series of steps. A second weakness of Event-B is that there is no explicit link between such new events that represent a step in the decomposition of atomicity and the abstract event to which they contribute. To address these weaknesses, atomicity decomposition diagrams support the explicit modelling of control flow and refinement relationships for new events. In previous work, the atomicity decomposition approach has been evaluated manually in the development of two large case studies, a multi media protocol and a spacecraft sub-system. The evaluation results helped us to develop a systematic definition of the atomicity decomposition approach, and to develop a tool supporting the approach. In this paper we outline this systematic definition of the approach, the tool that supports it and evaluate the contribution that the tool makes
Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF Cohort Study
No full textAbstract not availableRajeev K. Pathak, Melissa E. Middeldorp, Dennis H. Lau, Abhinav B. Mehta, Rajiv Mahajan, Darragh Twomey, Muayad Alasady, Lorraine Hanley, Nicholas A. Antic, R. Doug McEvoy, Jonathan M. Kalman, Walter P. Abhayaratna, Prashanthan Sander
Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up
No full textPatients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV) showed promising early efficacy in patients with R/R PMBL in the phase 1/2 open-label, multicenter CheckMate 436 study; we report safety and efficacy findings from the 3-year follow-up. Patients who were eligible were aged ≥15 years with R/R PMBL previously treated with either high-dose chemotherapy plus autologous hematopoietic cell transplantation (HCT) or ≥2 prior multiagent chemotherapies, and had Eastern Cooperative Oncology Group performance status scores of 0 to 1 and CD30 expression of ≥1%. Patients were treated with nivolumab 240 mg and BV 1.8 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points included complete response rate, duration of response, progression-free survival (PFS), and overall survival (OS). Safety was monitored throughout. At final database lock (30 March 2022), 29 patients had received nivolumab plus BV; median follow-up was 39.6 months. Investigator-assessed ORR was 73.3%; median time to response was 1.3 months (range, 1.1-4.8). Median PFS was 26.0 months; median OS was not reached. PFS and OS rates at 24 months were 55.5% (95% confidence interval [CI], 32.0-73.8) and 75.5% (95% CI, 55.4-87.5), respectively. The most frequently occurring grade 3/4 treatment-related adverse event was neutropenia. Consolidative HCT was received by 12 patients, with a 100-day complete response rate of 100.0%. This 3-year follow-up showed long-term efficacy for nivolumab plus BV in R/R PMBL, with no new safety signals. This trial was registered at www.clinicaltrials.gov as #NCT02581631
Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells
No full textCopyright @ 2011 Mehta et al.; licensee BioMed Central Ltd. This article has been made available through the Brunel Open Access Publishing Fund.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a premature ageing syndrome that affects children leading to premature death, usually from heart infarction or strokes, making this syndrome similar to normative ageing. HGPS is commonly caused by a mutation in the A-type lamin gene, LMNA (G608G). This leads to the expression of an aberrant truncated lamin A protein, progerin. Progerin cannot be processed as wild-type pre-lamin A and remains farnesylated, leading to its aberrant behavior during interphase and mitosis. Farnesyltransferase inhibitors prevent the accumulation of farnesylated progerin, producing a less toxic protein. RESULTS: We have found that in proliferating fibroblasts derived from HGPS patients the nuclear location of interphase chromosomes differs from control proliferating cells and mimics that of control quiescent fibroblasts, with smaller chromosomes toward the nuclear interior and larger chromosomes toward the nuclear periphery. For this study we have treated HGPS fibroblasts with farnesyltransferase inhibitors and analyzed the nuclear location of individual chromosome territories. We have found that after exposure to farnesyltransferase inhibitors mis-localized chromosome territories were restored to a nuclear position akin to chromosomes in proliferating control cells. Furthermore, not only has this treatment afforded chromosomes to be repositioned but has also restored the machinery that controls their rapid movement upon serum removal. This machinery contains nuclear myosin 1β, whose distribution is also restored after farnesyltransferase inhibitor treatment of HGPS cells. CONCLUSIONS: This study not only progresses the understanding of genome behavior in HGPS cells but demonstrates that interphase chromosome movement requires processed lamin A.This work was funded by an ORSAS award and the Brunel Progeria Research Fund
Respiratory muscle aids to avert respiratory failure and tracheostomy: a new patient management paradigm
No full textAn April 2010 consensus of clinicians from 22 centers in 18 countries reported 1,623 spinal muscular atrophy type 1, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis noninvasive intermittent positive pressure ventilatory support users, of whom 760 developed continuous dependence that prolonged their survival by more than 3,000 patient-years without tracheostomies. Four of the centers routinely extubated unweanable patients with Duchenne muscular dystrophy, so that none of their more than 250 such patients has undergone tracheotomy. This article describes the manner in which this is accomplished; that is, the use of noninvasive inspiratory and expiratory muscle aids to prevent ventilatory failure and to permit the extubation and tracheostomy tube decannulation of patients with no autonomous ability to breathe (ie, who are “unweanable” from ventilator support). Noninvasive airway pressure aids can provide up to continuous ventilatory support for patients with little or no vital capacity and can provide for effective cough flows for patients with severely dysfunctional expiratory muscles.Peer reviewe
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