Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Structure–Activity Relationship Study of <i>N</i>⁶-(2-(4-(1<i>H</i>-Indol-5-yl)piperazin-1-yl)ethyl)-<i>N</i>⁶-propyl-4,5,6,7-tetrahydrobenzo[<i>d</i>]thiazole-2,6-diamine Analogues: Development of Highly Selective D3 Dopamine Receptor Agonists along with a Highly Potent D2/D3 Agonist and Their Pharmacological Characterization

In our effort to develop multifunctional drugs against Parkinson’s disease, a structure–activity-relationship study was carried out based on our hybrid molecular template targeting D2/D3 receptors. Competitive binding with [³H]­spiroperidol was used to evaluate affinity (<i>K</i>_i) of test compounds. Functional activity of selected compounds in stimulating [³⁵S]­GTPγS binding was assessed in CHO cells expressing either human D2 or D3 receptors. Our results demonstrated development of highly selective compounds for D3 receptor (for (−)-<b>40</b> <i>K</i>_i, D3 = 1.84 nM, D2/D3 = 583.2; for (−)-<b>45</b> <i>K</i>_i, D3 = 1.09 nM, D2/D3 = 827.5). Functional data identified (−)-<b>40</b> (EC₅₀, D2 = 114 nM, D3 = 0.26 nM, D2/D3 = 438) as one of the highest D3 selective agonists known to date. In addition, high affinity, nonselective D3 agonist (−)-<b>19</b> (EC₅₀, D2 = 2.96 nM and D3 = 1.26 nM) was also developed. Lead compounds with antioxidant activity were evaluated using an in vivo PD animal model