Gene polymorphisms in association with emerging cardiovascular risk markers in adult women

<p>Abstract</p> <p>Background</p> <p>Evidence on the associations of emerging cardiovascular disease risk factors/markers with genes may help identify intermediate pathways of disease susceptibility in the general population. This population-based study is aimed to determine the presence of associations between a wide array of genetic variants and emerging cardiovascular risk markers among adult US women.</p> <p>Methods</p> <p>The current analysis was performed among the National Health and Nutrition Examination Survey (NHANES) III phase 2 samples of adult women aged 17 years and older (sample size n = 3409). Fourteen candidate genes within <it>ADRB2, ADRB3, CAT, CRP, F2, F5, FGB, ITGB3, MTHFR, NOS3, PON1, PPARG, TLR4</it>, and <it>TNF </it>were examined for associations with emerging cardiovascular risk markers such as serum C-reactive protein, homocysteine, uric acid, and plasma fibrinogen. Linear regression models were performed using SAS-callable SUDAAN 9.0. The covariates included age, race/ethnicity, education, menopausal status, female hormone use, aspirin use, and lifestyle factors.</p> <p>Results</p> <p>In covariate-adjusted models, serum C-reactive protein concentrations were significantly (P value controlling for false-discovery rate ≤ 0.05) associated with polymorphisms in <it>CRP </it>(rs3093058, rs1205)<it>, MTHFR </it>(rs1801131)<it>, and ADRB3 </it>(rs4994). Serum homocysteine levels were significantly associated with <it>MTHFR </it>(rs1801133).</p> <p>Conclusion</p> <p>The significant associations between certain gene variants with concentration variations in serum C-reactive protein and homocysteine among adult women need to be confirmed in further genetic association studies.</p

Mycorrhizal feedbacks influence global forest structure and diversity

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure

Attention training for infants at familial risk of ADHD (INTERSTAARS): study protocol for a randomised controlled trial

Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can negatively impact on an individual’s quality of life. It is pathophysiologically complex and heterogeneous with different neuropsychological processes being impaired in different individuals. Executive function deficits, including those affecting attention, working memory and inhibitory control, are common. Cognitive training has been promoted as a treatment option, based on the notion that by strengthening the neurocognitive networks underlying these executive processes, ADHD symptoms will also be reduced. However, if implemented in childhood or later, when the full disorder has become well-established, cognitive training has only limited value. INTERSTAARS is a trial designed to test a novel approach to intervention, in which cognitive training is implemented early in development, before the emergence of the disorder. The aim of INTERSTAARS is to train early executive skills, thereby increasing resilience and reducing later ADHD symptoms and associated impairment. Methods/design: Fifty 10–14-month-old infants at familial risk of ADHD will participate in INTERSTAARS. Infants will be randomised to an intervention or a control group. The intervention aims to train early attention skills by using novel eye-tracking technology and gaze-contingent training paradigms. Infants view animated games on a screen and different events take place contingent on where on the screen the infant is looking. Infants allocated to the intervention will receive nine weekly home-based attention training sessions. Control group infants will also receive nine weekly home visits, but instead of viewing the training games during these visits they will view non-gaze-contingent age-appropriate videos. At baseline and post treatment, infant attention control will be assessed using a range of eye-tracking, observational, parent-report and neurophysiological measures. The primary outcome will be a composite of eye-tracking tasks used to assess infant attention skills. Follow-up data will be collected on emerging ADHD symptoms when the infants are 2 and 3 years old. Discussion: This is the first randomised controlled trial to assess the potential efficacy of cognitive training as a prevention measure for infants at familial risk of ADHD. If successful, INTERSTAARS could offer a promising new approach for developing early interventions for ADHD. Trial registration: International Standard Randomised Controlled Trial registry: ISRCTN37683928. Registered on 22 June 2015

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Maze design: size and number of choices impact fish performance in cognitive assays

While studies on fish cognition are increasing, consideration of how methodological details influence the ability to detect and measure performance is lagging. Here, in two separate experiments we compared latency to leave the start position, latency to make a decision, levels of participation and success rates (whether fish entered the rewarded chamber as first choice) across different physical designs. Experiments compared fish performance across 1) two sizes of T-mazes, large and standard, and a plus-maze, and 2) open choice arenas with either two or four doors. Fish in T-mazes with longer arms took longer to leave the start chamber and were less likely to participate in a trial than fish in T-mazes with shorter arms. The number of options, or complexity, in a maze significantly impacted success, but did not necessarily impact behavioural measures, and did not impact the number of fish that reached a chamber. Fish in the plus-maze had similar latencies to leave the start box and time to reach any chamber as fish in the same sized T-maze but exhibited lower overall success. Similarly, in an open choice arena, increasing the number of options – doors to potential reward chambers- resulted in lower probability of success. There was an influence of reward position in the choice arena, with rewarded chambers closest to the sides of the arena resulting in lower latencies to enter and higher probability of decision success. Together our results allow us to offer practical suggestions towards optimal maze design for studies of fish cognition