Longitudinal relationships of the neighbourhood built environment with cardio-metabolic health

Neighbourhood built environments may have the potential to impact residents’ cardiometabolic health through physical activity. This Thesis aims to advance the understanding of such potential impacts. This Thesis consists of three published peer-reviewed studies. Study One, a systematic review and meta-analyses of longitudinal studies, found strong evidence for longitudinal relationships of built environment attributes with cardiometabolic health among adults. In particular, it found strong evidence for relationships of higher walkability with reduced risks of obesity, type 2 diabetes and hypertension. This systematic review has been published in Obesity Reviews. Two empirical studies were designed to address the gaps identified in the systematic review. These studies were conducted using the Australian Diabetes, Obesity and Lifestyle (AusDiab) study data, which were collected from a national cohort at three time points between 1999 and 2012. The outcomes examined in the empirical studies were 12-year changes in eight cardio-metabolic risk markers: waist circumference; weight; systolic and diastolic blood pressure; fasting and 2-hr postload plasma glucose; high-density lipoprotein cholesterol; and triglycerides. Built environmental attributes for AusDiab study participants were calculated using geographic information systems as an original work of this Thesis. The analytical sample consisted of participants who provided 12-year followup data and did not change their residence during the study period. One gap identified in the systematic review was that most longitudinal studies examined environmental attributes (typically composite measures such as walkability) assessed at one time point, disregarding environmental changes. To address this gap, Study Two examined the relationships of neighbourhood population density increases (densification) on changes in cardio-metabolic risk markers. Densification was calculated using the population density values measured within a 1-km straight-line buffer at three time points in concordance with the AusDiab data collection points. Analysing data from 2,354 eligible participants, higher densification was found related to smaller increases in obesity markers, but it was adversely related to blood pressure and lipid changes. This study has been published in the Journal of the American Heart Association. Study Three investigated the potential mediating role of physical activity (baseline and change) in the relationships between walkability and changes in cardio-metabolic risk markers, as a lack of studies rigorously examining underlying mechanisms of these relationships was another gap identified. For physical activity, self-reported time spent in moderate-to-vigorous physical activity (including walking) was used. A walkability index (consisting of residential density, intersection density, and destinations density) was calculated, within a 1-km street-network buffer using geospatial data sourced around the second follow-up of AusDiab. Analyses of data from 2,023 participants found that higher walkability was related to higher baseline physical activity, which, in turn, was related to smaller increases in obesity markers. There was no evidence for a relationship of higher walkability with a change in physical activity. This study has been published in the International Journal of Behavioral Nutrition and Physical Activity. Collectively, this Thesis adds evidence for potential long-term impacts of the neighbourhood built environment on adult residents’ cardio-metabolic health. In particular, higher walkability and higher densification may have protective effects against obesity risk over time. This Thesis also found evidence suggesting that physical activity may partly explain the potential long-term protective effect of higher walkability against obesity risk. However, there were also some unexpected findings, for instance, potential adverse impacts of higher densification on blood pressure and lipid, which warrants further investigation. The Thesis findings support the potential utility of environmental initiatives to reduce the burden of obesity at the population level through enhancing physical activity. To further advance understanding of the impacts of the built environment on cardio-metabolic health, future research needs to examine diverse built environmental attributes, investigate a broader range of cardio-metabolic health outcomes, and examine multiple pathways between the built environment and cardio-metabolic health

Docking-based virtual screening of known drugs against murE of Mycobacterium tuberculosis towards repurposing for TB.

Repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. Several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (DR-TB). Though TB can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of Mycobacterium tuberculosis and the huge death toll globally, together necessitate urgently newer and effective drugs for TB. Therefore, we performed virtual screening of 1554 FDA approved drugs against murE, which is essential for peptidoglycan biosynthesis of M. tuberculosis. We used Glide and AutoDock Vina for virtual screening and applied rigid docking algorithm followed by induced fit docking algorithm in order to enhance the quality of the docking prediction and to prioritize drugs for repurposing. We found 17 drugs binding strongly with murE and three of them, namely, lymecycline, acarbose and desmopressin were consistently present within top 10 ranks by both Glide and AutoDock Vina in the induced fit docking algorithm, which strongly indicates that these three drugs are potential candidates for further studies towards repurposing for TB

Heterostructured Metaloxide Photocatalytic (Copper Oxide and Titanium Oxide) for Degradation and Removal of Water Organic Pollutants

Metal oxides with favourable light absorption properties and charge transport characteristics play wide application as a photocatalyst. Titanium oxide and Copper oxide are the two major earth abundant metal oxides, and this dissertation is aimed to synthesize the heterostructured copper oxide and titanium oxide for the application of water treatment by enhancing their photocatalytic activity. Metal oxides are treated with atmospheric pressure plasma or by altering the structural level in nano size region to enhance the photocatalytic activity. Cupric oxide (CuO) thin film has found widespread application as a low-cost material for photo catalytic applications. High surface wettability is a key factor to achieve enhanced efficiency in these catalytic applications. Here, we report a fast and environment friendly route to fabricate super hydrophilic CuO thin films using a low power (5–10 W) atmospheric pressure plasma jet (APPJ). With APPJ treatment for 5 min, the CuO surface transforms from hydrophobic to super-hydrophilic with increase in catalytic activity. APPJ introduces anisotropy in the crystal structure and creates unique three-dimensional surface morphology with distinct surface chemical and electronic features. The treated films exhibited a higher rate of photo degradation of Methylene Blue and phenol indicating efficient charge separation. An environment friendly alternative to epitaxially grown process of copper oxide nanowires (NWs) on copper substrates using single step atmospheric pressure plasma jet assisted oxidation is used. NWs of average length 300 nm are grown rapidly in 5 minutes along with transforming the surface to superhydrophilic. This method introduces defects in the nanowire structure which is otherwise difficult to achieve due to the highly isotropic nature of nanowire growth. High resolution transmission electron microscopy reveals vacancies and structural defects such as lattice twinning and kinks. Copper oxide NWs have an excellent degradation activity towards organic pollutants Methylene Blue. Two-dimensional (2D) Molybdenum disulfide (MoS2) has become one of the most exciting areas of research for adsorbents due to its high surface area and abundant active sites. Mainly, 2D MoS2 show promising removal of textile dye pollutants by adsorption process, but it shows high affinity for anionic type of dyes, that limits its performance in mixed dye pollutants treatment. Herein, we demonstrate an integrated approach to remove mixed dye pollutants (anionic and cationic) concurrently by combining adsorption and photocatalysis process. We synthesize MoS2/TiO2 nanocomposites for different weight percentages 2.5, 5, 10, 20, 30 and 50 wt% of pre-synthesized flower-like MoS2 nanoparticle by a two-step hydrothermal method. We demonstrate a new process of two-stage adsorption / photocatalysis using high wt% of MoS2 (Stage-I) and low wt% of MoS2 (Stage-II) nanocomposites. The proposed two-stage integrated adsorption and photocatalysis process using 50% and 2.5% of MoS2 coated TiO2, respectively showed complete removal of methylene blue dye ~5 times faster than conventional single-stage (adsorption or photocatalysis) water treatment process. Furthermore, the feasibility of the proposed two stage method in mixed dye pollutants removal (anionic and cationic) showed excellent performance even in doubling the dye pollutant concentration. This work brings a deeper insight into understanding the morphology and concentration of 2-D MoS2 in MoS2/TiO2 nanocomposite in tackling mixed dye pollutants and the possibilities of applying in textile dyeing industries wastewater treatment plants

Molecular docking of azole drugs and their analogs on CYP121 of Mycobacterium tuberculosis

The Mycobacterium tuberculosis genome codes for 20 different cytochromes. These cytochromes are involved in the breakdown of recalcitrant pollutants and the synthesis of polyketide antibiotics and other complex macromolecules. It has been demonstrated that CYP121 is essential for viability of the bacterium by gene knock-out and complementation studies. CYP121 could therefore be a probable target for the development of new drugs for TB. It has been widely reported that orthologs of CYP121 in fungi are inhibited by azole drugs. We evaluated whether these azole drugs or their structural analogs could bind to and inhibit CYP121 of M. tuberculosis using molecular docking. Six molecules with known anti-CYP121 activity were selected from literature and PubChem database was searched to identify structural analogs for these inhibitors. Three hundred and fifty seven molecules were identified as structural analogs and used in docking studies. Fifty three molecules were found to be scored better than the azole drugs and five of them were ranked among the top 12 molecules by two different scoring functions. These molecules may be further tested by in vitro experimentation for their activity against CYP121 of M. tuberculosis

Determination of salmeterol xinafoate and its degradation products according to ICH guidelines with use of UPLC technique

The objective of reducing analysis time and maintaining good efficiency, there has been substantial focus on high-speed chromatographic separations. Recently, commercially available ultra performance liquid chromatography (UPLC) has proven to be one of the most promising developments in the area of fast chromatographic separations. In this work, a new isocratic reverse phase chromatographic stability indicating assay method was developed using UPLC for salmeterol xinafoate bulk drug. A novel stability-indicating UPLC assay method was developed and validated for salmeterol xinafoate and its degradation products. An isocratic UPLC method was developed to separate the drug from the degradation products, using an Acquity UPLC BEH C18 (50 mm x 2.1 mm column). Mixture of methanol: 0.06 % and pH 3.4 ammonium acetate (65:35) was used as mobile phase. The flow rate was kept 0.6 mL/min and the detection was carried out at 228 nm. The linearity of the proposed method was investigated in the range of 10-50 μg/mL (r2 = 0.999) for salmeterol xinafoate. The method detection limit was 0.5 μg/mL and the method quantification limit was 1 μg/mL. The percentage recovery of salmeterol xinafoate was ranged from 97.2 to 99.5 %. The %RSD values for intra-day precision study were <1.0 % and for inter-day study were < 2.0 %, confirming that the method was sufficiently precise. The validation studies were carried out fulfilling International Conference on Harmonisation (ICH) requirements. The procedure was found to be specific, linear, precise (including intra and inter day precision), accurate and robust.Colegio de Farmacéuticos de la Provincia de Buenos Aire