16 research outputs found
mTORC1 inhibitors rapamycin and metformin affect cardiovascular markers differentially in ZDF rats
Get PDFMammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. Here we investigated the differential effects of rapamycin (1.2mg/kg/day delivered subcutaneously for six weeks) and metformin (300mg/kg/day delivered orally for 11 weeks) treatments on male Zucker diabetic fatty (ZDF) rats that mimic the cardio-renal pathology of T2DM patients and progress to insulin insufficiency. Rapamycin and metformin improved proteinuria, and rapamycin also reduced urinary gamma glutamyl transferase (GGT) indicating improvement of tubular health. Metformin reduced food and water intake, and urinary sodium and potassium, whereas rapamycin increased urinary sodium. Metformin reduced plasma alkaline phosphatase, but induced transaminitis as evidenced by significant increases in plasma AST and ALT. Metformin also induced hyperinsulinemia, but did not suppress fasting plasma glucose after ZDF rats reached 17-weeks of age, and worsened lipid profile. Rapamycin also induced mild transaminitis. Additionally, both rapamycin and metformin increased plasma uric acid and creatinine, biomarkers for cardiovascular and renal disease. These observations define how rapamycin and metformin differentially modulate metabolic profiles that regulate cardio-renal pathology in conditions of severe T2DM.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Hardy’s Wessex: An Imaginary-Literary-Topography
Get PDFGeo - (topo) graphically Hardy’s Wessex is located on the West Country of England and lying south of the Thames and the Bristol Channel. The invention of “Wessex” is described by hardy in his preface to Far from the Madding Crowd in which, he first re- introduced the old word to give territorial definition. Travelling into Hardy, I wish to argue that place ought to receive special attention. Most of the writers have written their works with deep concerned with their native special attention. Place needs to be understood as something local, regional and real, despite the complexities and difficulties involved in the use of such terms. Generally, places themselves could have the sort of centrality in literary studies that has more frequently been given to notions such as author, character, text, historical context and narration etc. This paper wants to Geo - (topo) graphically appreciates the correspondence between Wessex and Hardy’s relationship in an imaginary and cartographical mode
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Technological impact on the art of moviemaking: deploying new and convergent media to redefine a model for Pakistan’s cinema
No full textThis thesis examines the decline in Pakistani cinema during the last two decades. It examines the history of the cinema and exposes some possible, previously ignored, causes for that decline. This research led the author to ask “Can new and convergent media be helpful in reviving the Pakistani cinema?” The thesis introduces the ideas of established and emergent cinema, building on the work of Williams (1977) in discussing the ideas of dominant, residual and emergent culture. The exploration reveals two gaps in the film industry: first, the lack of training in the making of films; and, second, the change in possible production methods allowed by new and emergent technologies. The thesis addresses both of these gaps by suggesting new production paradigms which incorporate the new technology and by examining two scripts to develop methodologies for teaching. The scripts are produced into films as the practice section of the research. The first film, creative element 1, is developed using some of the new tehnologies, students as crew and the available resources of an educational establishment to test the methodologies that have been derived. The outcomes of the creative element 1 laid the foundation of the second film, creative element 2. It is shot on mobile phones and distributed from Pakistan through Vimeo with a negligible budget. The social networks helped to arrange equipment and locations and allowed extreme freedom to the filmmaker
BIOCONTROL POTENTIAL OF ENTOMOPATHOGENIC FUNGUS BEAUVERIA BASSIANA (BALSAMO) AGAINST PERICALLIA RICINI (FAB.) (LEPIDOPTERA: ARCTIIDAE) LARVAE
No full textABSTRACT
In the recent study, the entomopathogenic fungus, Beauveria bassiana (Balsamo) used to evaluate its pathogenecity against Pericallia ricini Fab. (Lepidoptera: Arctiidae) third, fourth and fifth instars larvae. B. bassiana found effective at all concentrations i.e., 2x04, 2x105 and 2x106 spores ml-1 on the P. ricini, but the uppermost concentration (2.0 x106 spores ml-1) provided maximum control within short period of time (P<0.002) than the other spore concentrations. Mortality of P. ricini was observed maximum on highest concentration of 2.0x106 spores ml-1. The value of LC50 lies between 2.32x102 and 13.89x107 spores ml-1. P.ricini body weight was increased at 2.0x105 (452.7±7.8 mg) spores ml-1 followed by 2.0x106 (450.9±18.9) and 2.0x104 spores ml-1 (443.8±6.2) by testing the field efficacy of B. bassiana against P. ricini, this insect pathogenic fungus can be used as potential biocontrol agent for the management of P. ricini. Results revealed that B. bassiana caused infection and caused death.
Key words : Beauveria bassiana, Pericallia ricini, insecticidal activity, biological control potential.
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Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV
Get PDFStudies on standardization and purification processes of VEERAM
Get PDFIn Siddha system of medicine Veeram is one of the toxins among the sixty four known toxins. Geologically it is called Calomel. It is a very toxic material therapeutically, these arsenic based medicines are used in Siddha system. Natural substances of milk, tender coconut water, bitter guard and lemon juice are used to purify the veeram. This research work analyzed the raw veeram and products obtained after purification. Geochemical, physico-chemical analysis, instrumentation techniques of XRF, TG-DTA, FE-SEM, EDAX and particle size analyzer. Among physicochemical parameters total ash value was low. Loss on drying increased in the products in the various intermediate stages which due to the impact of plant agents used in the process. XRF results revealed mercury is present in major concentration. Raw veeram showed 77.14% of mercury. In the raw veeram particles observed were distributed within the range of 0.0920 µm–0.948 µm. FE-SEM analysis suggested that the bitter gourd treated veeram consisted of individual particles with a size ranging from 94 nm to 144 nm. Milk treated samples when subjected to analysis revealed increased particle size which may be attributed to aggregation. Lemon juice treated samples showed particle size in the range of 82 nm to 96 nm and in tender coconut range was 78 nm to 91 nm. In the EDAX raw and other samples showed peak for mercury and chloride. TG-DTA analysis showed that the raw veeram sample had a sublimation temperature of 220°C where as in other treated samples sublimation temperature was reduced compared to raw veeram. The from the stydy depict that these purification processes forms new organic substances and transformation of the starting toxic metal. These processes have an important role in the formation of complexes and in altering toxic state to non-toxic state.
Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019
Get PDFGlobally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10-24 years during the past three decades
Global, regional, and national progress towards the 2030 global nutrition targets and forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021
Get PDFBackground: The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories. Methods: The prevalence and attributable burden of each target indicator were estimated by age group, sex, and year in 204 countries and territories from 2012 to 2021 in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, the most comprehensive assessment of causes of death, disability, and risk factors to date. Country-specific relative performance to date was evaluated with a Bayesian meta-regression model that compares prevalence to expected values based on Socio-demographic Index (SDI), a composite indicator of societal development status. Target progress was forecasted from 2021 up to 2050 by modelling past trends with meta-regression using a combination of key quantities and then extrapolating future projections of those quantities. Findings: In 2021, a few countries had already met some of the GNTs: five for exclusive breastfeeding, four for stunting, 96 for child wasting, and three for child overweight, and none met the target for low birthweight or anaemia in females of reproductive age. Since 2012, the annualised rates of change (ARC) in the prevalence of child overweight increased in 201 countries and territories and ARC in the prevalence of anaemia in females of reproductive age decreased considerably in 26 countries. Between 2012 and 2021, SDI was strongly associated with indicator prevalence, apart from exclusive breastfeeding (|r-|=0·46-0·86). Many countries in sub-Saharan Africa had a decrease in the prevalence of multiple indicators that was more rapid than expected on the basis of SDI (the differences between observed and expected ARCs for child stunting and wasting were -0·5% and -1·3%, respectively). The ARC in the attributable burden of low birthweight, child stunting, and child wasting decreased faster than the ARC of the prevalence for each in most low-income and middle-income countries. In 2030, we project that 94 countries will meet one of the six targets, 21 countries will meet two targets, and 89 countries will not meet any targets. We project that seven countries will meet the target for exclusive breastfeeding, 28 for child stunting, and 101 for child wasting, and no countries will meet the targets for low birthweight, child overweight, and anaemia. In 2050, we project that seven additional countries will meet the target for exclusive breastfeeding, five for low birthweight, 96 for child stunting, nine for child wasting, and one for child overweight, and no countries are projected to meet the anaemia target. Interpretation: Based on current levels and past trends, few GNTs will be met by 2030. Major reductions in attributable burden for exclusive breastfeeding and anthropometric indicators should be recognised as huge scientific and policy successes, but the comparative lack of progress in reducing the prevalence of each, along with stagnant anaemia in women of reproductive age and widespread increases in child overweight, suggests a tenuous status quo. Continued investment in preventive and treatment efforts for acute childhood illness is crucial to prevent backsliding. Parallel development of effective treatments, along with commitment to multisectoral, long-term policies to address the determinants and causes of suboptimal nutrition, are sorely needed to gain ground. Funding: Bill & Melinda Gates Foundation
The global, regional, and national burden of cancer, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023
No full textBackground: Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Methods: Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. Findings: In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Interpretation: Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Funding: Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation
Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021
Get PDFBackgroundOverweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050. MethodsLeveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends. FindingsRates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989–1·01) adult males and 1·11 billion (1·10–1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397–407] individuals), followed by India (180 million [167–194]) and the USA (172 million [169–174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8–160·3) in males and 104·9% (95% UI 100·9–108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39–4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4–269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121–162) by 2050, making it the country with the fourth-largest population with overweight and obesity. InterpretationNo country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels. FundingBill & Melinda Gates Foundation.This study was funded by the Bill & Melinda Gates Foundation (OPP1152504)
