Background Future trends in disease burden and drivers of health are of great interest to policy ... more Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the allcause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2•5th and 97•5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. Funding Bill & Melinda Gates Foundation.
Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. The... more Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.
Predicting the mechanism of action of antituberculosis agents using chemical global positioning s... more Predicting the mechanism of action of antituberculosis agents using chemical global positioning system - natural product
Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million y... more Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million years ago. They are prolific producers of bioactive secondary metabolites. Over millions of years, natural selection has optimized their metabolites to possess activities impacting various biological targets. This paper discusses the historical and existential records of cyanobacteria, and their role in understanding the evolution of marine cyanobacteria through the ages. Recent advancements have focused on isolating and screening bioactive compounds and their respective medicinal properties, and we also discuss chemical property space and clinical trials, where compounds with potential pharmacological effects, such as cytotoxicity, anticancer, and antiparasitic properties, are highlighted. The data have shown that about 43% of the compounds investigated have cytotoxic effects, and around 8% have anti-trypanosome activity. We discussed the role of different marine cyanobacteria groups in ...
Objective: The objective of the present study is to formulate and evaluate a topical gel containi... more Objective: The objective of the present study is to formulate and evaluate a topical gel containing Minoxidil and Tofacitinib citrate for alopecia areata. Methods: Six gels were formulated using the direct-dispersion method by using polymers in the ratio of Carbopol 934: HPMC and Carbopol 934: HPC in three different concentrations each. All the prepared gels were then characterized for its drug content, pH, Rheologic al measurement, Spreadibility, skin adhesion study, In vitro drug release, Ex-vivo skin permeation study and stability studies. Results: All the six formulations were evaluated for various parameters such as pH, viscosity, spreadibility, and drug content and in vitro drug release. The pH of all the formulations was in the range of 6.3-6.8 which was optimum for the skin. As the concentration of the polymer increased the viscosity also increased, F6 had the highest viscosity among all of 1082 cps. F5 had the highest spreadibility of 4.3 ±0.15 cm and the drug content of all ranged between 88-96% of Minoxidil and 86-97% for Tofacitinib citrate with F5 giving the best result drug release across a cellulose membrane for a period 8 h of 94.22±0.19% for Minoxidil and 93.62±0.49% for Tofacitinib citrate. Formulation F2 and F5 were subjected to skin adhesion studies by the use of wistar rat skin with F5 giving the highest bioadhesion of 108 g/cm2. Formulation F5 was selected as an optimized formulation among the six as it gave the best results for all the parameters. Then the optimized formulation was subjected to an ex-vivo permeation study for a period of 8 h and by using wistar rat skin as a permeation barrier and the drug release for Minoxidil and Tofacitinib citrate was found to be 71.94±0.78% and 69.49±0.47%. The stability study was carried out for two months at accelerated condition i.e., 40 °C±2 °C/75±5% RH proved that the formulated gel was Stable. Conclusion: The formulated topical gel containing Minoxidil and Tofacitinib citrate were found to be a promising approach for the treatme nt of alopecia areata.
Background Future trends in disease burden and drivers of health are of great interest to policy ... more Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the allcause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2•5th and 97•5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. Funding Bill & Melinda Gates Foundation.
Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. The... more Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.
Predicting the mechanism of action of antituberculosis agents using chemical global positioning s... more Predicting the mechanism of action of antituberculosis agents using chemical global positioning system - natural product
Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million y... more Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million years ago. They are prolific producers of bioactive secondary metabolites. Over millions of years, natural selection has optimized their metabolites to possess activities impacting various biological targets. This paper discusses the historical and existential records of cyanobacteria, and their role in understanding the evolution of marine cyanobacteria through the ages. Recent advancements have focused on isolating and screening bioactive compounds and their respective medicinal properties, and we also discuss chemical property space and clinical trials, where compounds with potential pharmacological effects, such as cytotoxicity, anticancer, and antiparasitic properties, are highlighted. The data have shown that about 43% of the compounds investigated have cytotoxic effects, and around 8% have anti-trypanosome activity. We discussed the role of different marine cyanobacteria groups in ...
Objective: The objective of the present study is to formulate and evaluate a topical gel containi... more Objective: The objective of the present study is to formulate and evaluate a topical gel containing Minoxidil and Tofacitinib citrate for alopecia areata. Methods: Six gels were formulated using the direct-dispersion method by using polymers in the ratio of Carbopol 934: HPMC and Carbopol 934: HPC in three different concentrations each. All the prepared gels were then characterized for its drug content, pH, Rheologic al measurement, Spreadibility, skin adhesion study, In vitro drug release, Ex-vivo skin permeation study and stability studies. Results: All the six formulations were evaluated for various parameters such as pH, viscosity, spreadibility, and drug content and in vitro drug release. The pH of all the formulations was in the range of 6.3-6.8 which was optimum for the skin. As the concentration of the polymer increased the viscosity also increased, F6 had the highest viscosity among all of 1082 cps. F5 had the highest spreadibility of 4.3 ±0.15 cm and the drug content of all ranged between 88-96% of Minoxidil and 86-97% for Tofacitinib citrate with F5 giving the best result drug release across a cellulose membrane for a period 8 h of 94.22±0.19% for Minoxidil and 93.62±0.49% for Tofacitinib citrate. Formulation F2 and F5 were subjected to skin adhesion studies by the use of wistar rat skin with F5 giving the highest bioadhesion of 108 g/cm2. Formulation F5 was selected as an optimized formulation among the six as it gave the best results for all the parameters. Then the optimized formulation was subjected to an ex-vivo permeation study for a period of 8 h and by using wistar rat skin as a permeation barrier and the drug release for Minoxidil and Tofacitinib citrate was found to be 71.94±0.78% and 69.49±0.47%. The stability study was carried out for two months at accelerated condition i.e., 40 °C±2 °C/75±5% RH proved that the formulated gel was Stable. Conclusion: The formulated topical gel containing Minoxidil and Tofacitinib citrate were found to be a promising approach for the treatme nt of alopecia areata.
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