Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility

<p>Abstract</p> <p>Background</p> <p>Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors) or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated.</p> <p>Methods</p> <p>The association of polymorphic variants of <it>GRIA1</it>-<it>GRIA4 </it>genes which encode for the four subunits (GluR1-GluR4) of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor for glutamate was tested in migraineurs with and without aura (MA and MO) and healthy controls.</p> <p>Results</p> <p>Two variants in the regulative regions of <it>GRIA1 </it>(rs2195450) and <it>GRIA3 </it>(rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in <it>GRIA1 </it>gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of <it>GRIA1 </it>and <it>GRIA3 </it>genes in different conditions.</p> <p>Conclusions</p> <p>This study represents the first genetic evidence of a link between glutamate receptors and migraine.</p

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

The concentration of potentially hazardous elements (PHEs) in the muscle of blue crabs (Callinectes sapidus) and associated health risk

In this study, the concentration of potentially hazardous elements (PHEs) in the muscle of Blue crabs (Callinectes sapidus) from the Strait of Hormuz was analyzed and following the health risk in the consumers by uncertainty and sensitivity analysis in the Monte Carlo simulation (MCS) technique was estimated. Fifty-eight blue card samples (male blue crabs = 33 samples; female blue crabs = 25 samples) were collected in the Strait of Hormuz from May to September 2020 for analysis of Nickel (Ni), Lead (Pb), Cadmium (Cd), and Iron (Fe) using Flame Absorption Spectrometer (FAAS). The order of PHEs in the in muscle male blue crabs was Fe (414.37 ± 288.07 μg/kg.ww) > Pb (238.78 ± 87.83 μg/kg.ww) > Ni (92.57 ± 39.72 μg/kg.ww) > Cd (52.73 ± 18.39 μg/kg.ww) and in female blue crabs Fe (461.16 ± 320.56 μg/kg.ww) > Pb (230.79 ± 125.59 μg/kg.ww) > Ni (84.13 ± 46.07 μg/kg.ww) > Cd (67.412 ± 43.93 μg/kg.ww). The concentration of PHEs muscle of male blue crabs and female blue crabs was not significantly different (P-value > 0.05). Uncertainty of non-carcinogenic risk revealed that P95 of total target hazard quotient (TTHQ) in the adult and children consumers due to ingestion male blue crabs was 5.30E-3 and 1.08E-3, respectively, and P95 of TTHQ in the adult and children due to ingestion female blue crabs was 7.05E-3 and 1.20E-3, respectively. P95 of TTHQ in both adult and children consumers was lower than one value. Therefore, consumers are at the acceptable range of the non-carcinogenic risk due to ingestion muscle of male and female blue crabs in Bandar Abbas. Although the non-carcinogenic risk of blue crab was in the safe range, due to the increase in its consumption and the increase of pollution sources in the Persian Gulf, it is recommended to monitor PHEs in Blue's muscle crabs. © 2021 Elsevier Lt

Microplastics captured by snowfall: A study in Northern Iran.

Samples of fresh snow (n = 34) have been collected from 29 locations in various urban and remote regions of northern Iran following a period of sustained snowfall and the thawed contents examined for microplastics (MPs) according to established techniques. MP concentrations ranged from undetected to 86 MP L-1 (mean and median concentrations ~20 MP and 12 MP L-1, respectively) and there was no significant difference in MP concentration between sample location type or between different depths of snow (or time of deposition) sampled at selected sites. Fibres were the dominant shape of MP and μ-Raman spectroscopy of selected samples revealed a variety of polymer types, with nylon most abundant. Scanning electron microscopy coupled with energy-dispersive X-ray analysis showed that some MPs were smooth and unweathered while others were more irregular and exhibited significant photo-oxidative and mechanical weathering as well as contamination by extraneous geogenic particles. These characteristics reflect the importance of both local and distal sources to the heterogeneous pool of MPs in precipitated snow. The mean and median concentrations of MPs in the snow samples were not dissimilar to the published mean and median concentrations for MPs in rainfall collected from an elevated location in southwest Iran. However, compared with rainfall, MPs in snow appear to be larger and more diverse in their shape and composition (and include rubber particulates), possibly because of the greater size but lower terminal velocities of snowflakes relative to raindrops. Snowfall represents a significant means by which MPs are scavenged from the atmosphere and transferred to soil and surface waters that warrants further attention