Validation of an Analytical Method for Determination of Benzoapyrene Bread using QuEChERS Method by GC-MS

A fast and simple modified QuEChERS (quick, easy, cheap, rugged and safe) extraction method based on spiked calibration curves and direct sample introduction was developed for determination of Benzo[a]pyrene (BaP) in bread by gas chromatography-mass spectrometry single quadrupole selected ion monitoring (GC/MS-SQ-SIM). Sample preparation includes: extraction of BaP into acetone followed by cleanup with dispersive solid phase extraction. The use of spiked samples for constructing the calibration curve substantially reduced adverse matrix-related effects. The average recovery of BaP at 6 concentration levels was in range of 95-120%. The method was proved to be reproducible with relative standard deviation less than 14.5% for all of the concentration levels. The limit of detection and limit of quantification were 0.3 ng/g and 0.5 ng/g, respectively. Correlation coefficient of 0.997 was obtained for spiked calibration standards over the concentration range of 0.5-20 ng/g. To the best of our knowledge, this is the first time that a QuEChERS method is used for the analysis of BaP in breads. The developed method was used for determination of BaP in 29 traditional (Sangak) and industrial (Senan) bread samples collected from Tehran in 2014. These results showed that two Sangak samples were contaminated with BaP. Therefore, a comprehensive survey for monitoring of BaP in Sangak bread samples seems to be needed. This is the first report concerning contamination of bread samples with BaP in Iran. © 2016 by School of Pharmacy

Determination of benzoapyrene in traditional, industrial and semi-industrial breads using a modified QuEChERS extraction, dispersive SPE and GC-MS and estimation of its dietary intake

A fast and simple modified QuEChERS extraction method was developed for determination of Benzo[a]pyrene (BaP) in 137 traditional (Sangak), semi-industrial (Sangak) and industrial bread samples using spiked calibration curves by GC/MS. Sample preparation includes extraction of BaP into acetone followed by cleanup with dispersive solid phase extraction. The limit of detection and limit of quantification were 0.3 ng/g and 0.5 ng/g, respectively. The values for recoveries and RSD were calculated as 110.5-119.85% and 1 ng/g. BaP content in all industrial samples was lower than LOQ. Assuming the consumption of bread in Tehran and Shiraz is limited to these kinds of breads, the daily intake of BaP in Tehran and Shiraz population through bread consumption was estimated to be 170.6 and 168.7 ng/day, respectively. This is the first report concerning contamination of bread samples with BaP in Iran

Mendelian randomization analyses implicate biogenesis of translation machinery in human aging

Reduced provision of protein translation machinery promotes healthy aging in a number of animal models. In humans, however, inborn impairments in translation machinery are a known cause of several developmental disorders, collectively termed ribosomopathies. Here, we use casual inference approaches in genetic epidemiology to investigate whether adult, tissue-specific biogenesis of translation machinery drives human aging. We assess naturally occurring variation in the expression of genes encoding subunits specific to the two RNA polymerases (Pols) that transcribe ribosomal and transfer RNAs, namely Pol I and III, and the variation in expression of ribosomal protein (RP) genes, using Mendelian randomization. We find each causally associated with human longevity (β = −0.15 ± 0.047, P = 9.6 × 10−4, q = 0.015; β = −0.13 ± 0.040, P = 1.4 × 10−3, q = 0.023; β = −0.048 ± 0.016, P = 3.5 × 10−3, q = 0.056, respectively), and this does not appear to be mediated by altered susceptibility to a single disease. We find that reduced expression of Pol III, RPs, or Pol I promotes longevity from different organs, namely visceral adipose, liver, and skeletal muscle, echoing the tissue specificity of ribosomopathies. Our study shows the utility of leveraging genetic variation in expression to elucidate how essential cellular processes impact human aging. The findings extend the evolutionary conservation of protein synthesis as a critical process that drives animal aging to include humans

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Biogenesis of translation machinery and longevity

The extension of health and life spans can be achieved by changes in gene expression. Partial inhibition of PoI III has recently been shown to produce an evolutionarily conserved lifespan extension in yeast, worms, and flies. In this research, using Drosophila melanogaster the effect on lifespan of partial inhibition of transcription factors (TFs) required for Pol III transcription was investigated to determine which of the hundreds of Pol III targets are the most relevant to its effects on lifespan. The significant role of tRNA genes in lifespan extension downstream of Pol III is demonstrated by the discovery that the TFIIIC mutant (dGTF3C5KG04199/+) is considerably long-lived. Additionally, TFIIIC mutant (dGTF3C5KG04199/+) flies exhibit improved health in terms of intestinal permeability and muscle activity, which even outweighs the benefits achieved by Pol III loss of function. Further experiments indicate that TFIIIC and Pol III likely drive ageing through the same mechanism, as expected. In humans, we use Mendelian Randomization(MR) to examine whether human ageing is influenced by adult, tissue-specific biogenesis of translation machinery. We use MR to evaluate naturally occurring variation in the expression of genes encoding specific subunits for Pol I and III, as well as ribosomal protein (RP) genes. We find each causally associated with human longevity (ß=-0.15±0.047, p=9.6x10-4; ß=-0.13±0.040, p=1.4x10-3; ß=-0.048±0.016, p=3.5x10-3, respectively). These correlations don't seem to be caused by a different sensitivity to a particular disease. Intriguingly, we discover that reduced expression of Pol III, RPs, or Pol I promotes longevity from various organs, including visceral adipose, liver, and skeletal muscle. This finding supports the tissue-specificity of ribosomopathies and provides evidence that Pol I and RPs may act from organs where their expression is restricted. Our findings expand on the evolutionary conservation of protein synthesis as a process of animal ageing that also applies to humans

Validation of an Analytical Method for Determination of benzo[a]pyrene in bread using QuEChERS method by

Abstract A fast and simple modified QuEChERS (quick, easy, cheap, rugged and safe) extraction method based on spiked calibration curves and direct sample introduction was developed for determination of Benzo[a]pyrene (BaP) in bread by gas chromatography-mass spectrometry single quadrupole selected ion monitoring (GC/MS-SQ-SIM). Sample preparation includes: extraction of BaP into acetone followed by cleanup with dispersive solid phase extraction. The use of spiked samples for constructing the calibration curve substantially reduced adverse matrix-related effects. The average recovery of BaP at 6 concentration levels was in range of 95-120%. The method was proved to be reproducible with relative standard deviation less than 14.5% for all of the concentration levels. The limit of detection and limit of quantification were 0.3 ng/g and 0.5 ng/g, respectively. Correlation coefficient of 0.997 was obtained for spiked calibration standards over the concentration range of 0.5-20 ng/g. To the best of our knowledge, this is the first time that a QuEChERS method is used for the analysis of BaP in breads. The developed method was used for determination of BaP in 29 traditional (Sangak) and industrial (Senan) bread samples collected from Tehran in 2014. These results showed that two Sangak samples were contaminated with BaP. Therefore, a comprehensive survey for monitoring of BaP in Sangak bread samples seems to be needed. This is the first report concerning contamination of bread samples with BaP in Iran