ROLE OF COMBINATION DRUG THERAPY FOR MANAGEMENT OF HYPERTENSION WITH INCREASING AGE

Objective: In South Asia, hypertension is the third highest factor contributing in public health burden of disease and major risk factor for coronary artery disease especially in women and old age people. The study was aimed to determine the role of gender and age (20–80 years) on severity of hypertension to design an effective schedule for management of hypertension. Methods: The levels of serum cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoproteins (LDL), and blood pressure (BP) of 240 hypertensive patients were monitored. Cholesterol, TG, and HDL levels were detected using ERBA Reagent kit of Transasia Bio-medicals LTD by CHOD-PAP, glycerol phosphate oxidase trinder End point, and polyvinyl sulfonic and polyethyleneglycol-methyl ether based methods, respectively. Results: The BP and levels of serum cholesterol, TG and LDL were increased in both the genders after 40 years of age. However, the rise in levels of these parameters was more in females in comparison to males. A hypertension management schedule involving (BP)/Cholesterol lowering drugs and lifestyle changes for period of 60 days showed that combination drug therapy was more effective than monotherapies of same drugs used at higher dosages. Conclusion: Hypertensive patients strictly followed the prescribed healthy food and exercise schedule showed improvement in their BP and lipid profile even with limited drug intervention

Self-tuning and the cosmological constant problem

The cosmological constant problem is one of the biggest theoretical hurdles of the modern age. It comes out of two great theories in physics: General Relativity (GR) and Quantum Field Theory (QFT). QFT predicts the existence of vacuum energy and GR predicts that it will gravitate like a cosmological constant, Λ_{vac}. Through observations we find that the Universe is undergoing an accelerated expansion which can be sourced by a constant term, Λ_{obs}, whose value is set by observations. Therefore it would be tempting to compare Λobs with Λ_{vac}, but through this we find that the predicted value of the vacuum energy is far, far greater than that of observation. In fact, at a lower estimate it represents a fine-tuning of∼ 10^{36} orders of magnitude. However, this is not the full extent of the problem. Even if we accept a fine-tuning in Λ_{vac}, its value is unstable to higher order perturbations, leading to repeated fine-tunings and re-tunings. This is known as radiative instability of the vacuum, and it is the true source of the cosmological constant problem. This thesis chooses to focus on self-tuning as a method for alleviating this problem. Self-tuning refers to the practice of modifying GR by adding extra fields which act to force Λ_{vac} ∼ Λ_{obs}, removing the need for fine-tuning. In this thesis we review a variety of self-tuning mechanisms to allow the reader to get a basic idea of the different approaches adopted. The bulk of the thesis focuses on self-tuning with a massive scalar-tensor theory on an Anti-de Sitter (AdS) background, the idea for which originated by examining a range of allowed modifications to GR and placing some self-tuning conditions upon them. Here, we construct an explicit model and analyse the resultant field equations to check whether it can or cannot self-tune. We then perform a numerical analysis on the resultant cosmological equations to understand the dynamics of the system; focusing specifically on whether our model can self-tune regardless of initial conditions. Finally, we conduct a rudimentary analysis on the stability of this model to further understand whether we can consistently self-tune without fine-tuning. Overall this work serves as an initial point of exploration in self-tuning on an AdS background. As we later discuss, there are many exciting future directions this model can take beyond this thesis

Correlation of Glycated Hemoglobin with Oxidative Stress in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) has a heavy disease burden and is one of the leading causes of death worldwide. It is considered to be evolving from a complex and multifactorial metabolic disorder to an inflammatory condition. The strong link between hyperglycemia and oxidative stress has long been established. Oxidative stress leads to the generation of inflammatory mediators and reactive oxygen species, which results in an inflammatory state, which plays a key role in the pathogenesis of diabetic complications. We aimed to correlate the levels of Glycated Hemoglobin with Oxidative Stress.This cross-sectional study included 200 subjects, 100 were type 2 diabetic patients and 100 were healthy non-diabetic individuals. The data were analyzed using a t test. The results showed that as the Glycated Hb increased, the levels of FBS, MDA increased and Serum SOD, Glutathione and Catalase levels decreased. The results showed a positive correlation between HbA1c and fasting blood glucose (r = 0.417, p= 0.000) and MDA (r= 0.340, p=0.000). Whereas negative correlation was observed between HbA1c and other antioxidant parameters, SOD (r= 0.025, p=0.803) Catalase (r= 0.096, p= 0.342), Glutathione (r= -0.164, p= 0.103). It is hereby concluded for the present study that when glycated Hb increases the natural antioxidants that is SOD, catalase and glutathione decrease to combact the increased formation of ROS. Serum MDA, a marker of lipid peroxidation, increased with increased glycated Hb, and shows a positive correlation, indicating that lipid peroxidation increased, when glycation of Hb increased, thus depicting an increased chance of macrovascular complication in type 2 diabetics

Self-tuning and the cosmological constant problem

The cosmological constant problem is one of the biggest theoretical hurdles of the modern age. It comes out of two great theories in physics: General Relativity (GR) and Quantum Field Theory (QFT). QFT predicts the existence of vacuum energy and GR predicts that it will gravitate like a cosmological constant, Λ_{vac}. Through observations we find that the Universe is undergoing an accelerated expansion which can be sourced by a constant term, Λ_{obs}, whose value is set by observations. Therefore it would be tempting to compare Λobs with Λ_{vac}, but through this we find that the predicted value of the vacuum energy is far, far greater than that of observation. In fact, at a lower estimate it represents a fine-tuning of∼ 10^{36} orders of magnitude. However, this is not the full extent of the problem. Even if we accept a fine-tuning in Λ_{vac}, its value is unstable to higher order perturbations, leading to repeated fine-tunings and re-tunings. This is known as radiative instability of the vacuum, and it is the true source of the cosmological constant problem. This thesis chooses to focus on self-tuning as a method for alleviating this problem. Self-tuning refers to the practice of modifying GR by adding extra fields which act to force Λ_{vac} ∼ Λ_{obs}, removing the need for fine-tuning. In this thesis we review a variety of self-tuning mechanisms to allow the reader to get a basic idea of the different approaches adopted. The bulk of the thesis focuses on self-tuning with a massive scalar-tensor theory on an Anti-de Sitter (AdS) background, the idea for which originated by examining a range of allowed modifications to GR and placing some self-tuning conditions upon them. Here, we construct an explicit model and analyse the resultant field equations to check whether it can or cannot self-tune. We then perform a numerical analysis on the resultant cosmological equations to understand the dynamics of the system; focusing specifically on whether our model can self-tune regardless of initial conditions. Finally, we conduct a rudimentary analysis on the stability of this model to further understand whether we can consistently self-tune without fine-tuning. Overall this work serves as an initial point of exploration in self-tuning on an AdS background. As we later discuss, there are many exciting future directions this model can take beyond this thesis

Classification of spatial functional data: application on COVID-19 incidence in Italy

non

Tidal friction of the earth-moon system

Abstract not availabl

Intro to Ecology Study on Hair Colour correlation with Shoe Size

<div>Methods: </div><div>Primarily, personal group data was collected, subsequently peer group data was obtained by verbal account. Data was collected in an indoor controlled laboratory setting.    </div><div>In order to assess patterns in hair colour, 20 subjects were surveyed. </div><div><br></div>Hypothesis: There is no correlation between shoe and hair colour because they are coded for by different genes. <div><br></div><div>Prediction: </div><div>1) As shoe size increases, hair colour will increase. </div><div><br></div

Identifying novel drug therapies for acute myeloid leukaemia by targeting the interactions between leukaemia cells and bone marrow microenvironment

Acute myeloid leukaemia (AML) is a malignancy caused by a block in differentiation in which aberrant leukemic stem cells drive the production of undifferentiated or partially differentiated leukemic blast cell clones. Between 10-40% of patients, however, have refractory disease or undergo relapse. The impact of the bone marrow microenvironment (BMM) is increasingly recognised as a reason for this. Hence, this thesis is aimed at understanding the interactions between leukemic cells and the BMM and to devise a therapeutic strategy to target these interactions. We have developed a functional, drug testing system that can incorporate the impact of BMM while rapidly and faithfully predicting the clinical response of the patient to cytarabine+daunorubicin (AraC+Dnr) therapy. We have developed and characterised a layered co-culture system consisting of primary AML blasts with immortalised bone marrow stromal cells (BMSCs). This BMSC-AML co-culture can predict the clinical response of AraC+Dnr therapy with very high accuracy [area under the curve (AUC=0.94)]. The advantage of this model over more complex pre-clinical AML models is its suitability to be developed into a laboratory diagnostic tool, which could greatly advance the clinical decision on treatment choice. Having established the model that mimics the BMM, we have studied its role in protecting the AML cells against cytotoxic agents such as BH3-mimetics, cytarabine and daunorubicin. We found that BMSCs induce Mcl-1 expression over Bcl-2 and/or Bcl-XL in AML cells and that inhibition of Mcl-1 with a small-molecule inhibitor, A1210477, or through repression of its expression with the cell division cycle-7 kinase/ cyclin dependent kinase 9 (CDC7/CDK9) dual-inhibitor, PHA-767491, restores sensitivity to chemotherapeutics. Importantly, the CD34+/CD38− leukemic stem cell-encompassing population was equally sensitive to this combination. These results highlight the potential of Mcl-1-repression to revert BMM-mediated drug resistance thus preventing disease relapse and ultimately improving patient survival. Next, we investigated the mechanism through which the BMM protects the FLT3-ITD mutated AML cells against tyrosine kinase inhibitors (TKIs). We found that FLT3- ITD cells do not depend on intrinsic, FLT3-driven survival signalling pathways in BMM. We also observed that exposure of BMSCs to a mild, proteostatic stress revert its ability to protect AML cells against chemotherapeutics. Importantly, we also found that proteostatic stressconditioned BMSCs themselves trigger an anti-leukemic effect, which is mediated through secreted lipids or non-protein moieties. In summary, the results presented in this thesis illustrate the role of microenvironment interactions in providing chemoresistance to malignantly transformed cells. We have also presented strategies to target these interactions for effective and novel therapies that could improve patient outcome.2023-10-2