Associations between alcohol use and accelerated biological ageing

Harmful alcohol use is a leading cause of premature death and is associated with age-related disease. Biological ageing is highly variable between individuals and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (derived from DNA methylation or brain structural measures) may be clinically relevant. Here, we investigated the relationships between alcohol phenotypes and both brain and DNA methylation age estimates. First, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (Alcohol Use Disorders Identification Test [AUDIT] scores) and accelerated brain and epigenetic ageing in 20,258 and 8051 individuals, respectively. Second, we used Mendelian randomisation (MR) to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing. Alcohol use showed a consistent positive association with higher predicted brain age (AUDIT-C: β = 0.053, p = 3.16 × 10−13; AUDIT-P: β = 0.052, p = 1.6 × 10−13; total AUDIT score: β = 0.062, p = 5.52 × 10−16; units/week: β = 0.078, p = 2.20 × 10−16), and two DNA methylation-based estimates of ageing, GrimAge (units/week: β = 0.053, p = 1.48 × 10−7) and PhenoAge (units/week: β = 0.077, p = 2.18x10−10). MR analyses revealed limited evidence for a causal effect of AUD on accelerated brain ageing (β = 0.118, p = 0.044). However, this result should be interpreted cautiously as the significant effect was driven by a single genetic variant. We found no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted

Mental Health as a Mediator of the Association Between Educational Inequality and Cardiovascular Disease: A Mendelian Randomization Study.

Background Education is inversely associated with cardiovascular disease (CVD). Several mediators of this have been established; however, a proportion of the protective effect remains unaccounted for. Mental health is a proposed mediator, but current evidence is mixed and subject to bias from confounding factors and reverse causation. Mendelian randomization is an instrumental variable technique that uses genetic proxies for exposures and mediators to reduce such bias. Methods and Results We performed logistic regression and 2-step Mendelian randomization analyses using UK Biobank data and genetic summary statistics to investigate whether educational attainment affects risk of mental health disorders. We then performed mediation analyses to explore whether mental health disorders mediate the association between educational attainment and cardiovascular risk. Higher levels of educational attainment were associated with reduced depression, anxiety, and CVD in observational analyses (odds ratio [OR], 0.79 [95% CI, 0.77-0.81], 0.76 [95% CI, 0.73-0.79], and 0.75 [95% CI, 0.74-0.76], respectively), and Mendelian randomization analyses provided evidence of causality (OR, 0.72 [95% CI, 0.67-0.77], 0.50 [95% CI, 0.42-0.59], and 0.62 [95% CI, 0.58-0.66], respectively). Both anxiety and depression were associated with CVD in observational analyses (OR, 1.63 [95% CI, 1.49-1.79] and 1.70 [95% CI, 1.59-1.82], respectively) but only depression showed evidence of causality in the Mendelian randomization analyses (OR, 1.09; 95% CI, 1.03-1.15). An estimated 2% of the total protective effect of education on CVD was mediated by depression. Conclusions Higher levels of educational attainment protect against mental health disorders, and reduced depression accounts for a small proportion of the total protective effect of education on CVD

Use of complementary and alternative medicine by cancer patients at the University of Nigeria Teaching Hospital, Enugu, Nigeria

<p>Abstract</p> <p>Background</p> <p>The use of Complementary and Alternative Medicine (CAM) by cancer patients is very common and varies between populations. The referenced English literature has no local study from Africa on this subject. This study was conducted to define the prevalence, pattern of use, and factors influencing the use of CAM by cancer patients at the University of Nigeria Teaching Hospital Enugu (UNTH-E), Nigeria</p> <p>Method</p> <p>Face-to-face interviews using semi-structured questionnaire were used to determine the use of CAM by cancer patients. All consenting cancer patients were interviewed as they presented at the core surgical units of the UNTH- E, from June 2003 to September 2005.</p> <p>Results</p> <p>160 patients were interviewed; 68 (42.5%) were males and 94 (57.5%) were females. Ages ranged from 13–86 years. Breast, urogenital system, gastrointestinal system, and soft tissue cancers predominated. One hundred and four patients (65.0%) have used CAM at some time during their current cancer illness; 56 (35.0%) patients have not used any form of CAM. There were more females than males among the non-CAM users. The use of CAM was not affected by age, marital status, level of education, religious affiliation, or socioeconomic status. The most frequently used CAMs were herbs (51.9%), faith/prayer healing (49.4%), aloe vera (23.1%), Forever Living Products (16.3%), medicinal tea (14.4%), and Blackstone (12.5%). Over 23% of those who used CAM were satisfied, but 68.3% were disappointed. Most users (67.3%) did not see any benefit from the CAM, but 25% could describe some specific benefits. More than 21% of users reported various unwanted effects. While 86.5% of CAM users will use orthodox medicine instead of CAM in the future, 9.6% will use the two together to help each other. Most users (79.8%) will not repeat CAM or recommend its use for cancer. The majority of patients (55.8%) did not mention their use of CAM to their doctors – mostly because the doctor did not ask.</p> <p>Conclusion</p> <p>CAM use is common among cancer patients in Nigeria. Most users do not obtain the expected benefits, and adverse events are not uncommon. Every clinician in the field of oncology should ask his/her patients about the use of CAM; this knowledge will enable them to better counsel the patients.</p

Comparative morphology of the forewing base articulationin Sternorrhyncha compared with a representative of Fulgoromorpha (Insecta, Hemiptera)

The forewing articulation of single species from each of the four subgroups of Sternorrhyncha (Aleyrodomorpha, Aphidomorpha, Coccomorpha, Psyllomorpha) was examined by optical and scanning electron microscopy. The species were compared with a species of Cixiidae (Fulgoromorpha), as an outgroup of Sternorrhyncha. We present the results of a comparative analysis of the forewing articulation in these five groups, propose a standardized terminology and compare our findings with those previously reported. The wing base of all examined species is composed of the following structures: anterior and posterior notal wing process, first, second, and third axillary sclerites, tegula, and axillary cord. The number of elements included in the wing base and the surrounding area is the greatest in Cacopsylla mali, the most complicated species from Sternorrhyncha. Based on the shape of axillary sclerites and the number of elements forming the wing base environment, Orthezia urticae (Coccomorpha) and Cixius nervosus (Fulgoromorpha) are the most similar. Among Sternorrhyncha, the most similar axillaries are those of Aphis fabae and Orthezia urticae, which is congruent with existing classifications. In this paper we show that the four groups from Sternorrhyncha exhibit their own distinct wing base morphology

EPGD: a comprehensive web resource for integrating and displaying eukaryotic paralog/paralogon information

Gene duplication is common in all three domains of life, especially in eukaryotic genomes. The duplicates provide new material for the action of evolutionary forces such as selection or genetic drift. Here we describe a sophisticated procedure to extract duplicated genes (paralogs) from 26 available eukaryotic genomes, to pre-calculate several evolutionary indexes (evolutionary rate, synonymous distance/clock, transition redundant exchange clock, etc.) based on the paralog family, and to identify block or segmental duplications (paralogons). We also constructed an internet-accessible Eukaryotic Paralog Group Database (EPGD; http://epgd.biosino.org/EPGD/). The database is gene-centered and organized by paralog family. It focuses on paralogs and evolutionary duplication events. The paralog families and paralogons can be searched by text or sequence, and are downloadable from the website as plain text files. The database will be very useful for both experimentalists and bioinformaticians interested in the study of duplication events or paralog families

Rapid Environmental Change over the Past Decade Revealed by Isotopic Analysis of the California Mussel in the Northeast Pacific

The anthropogenic input of fossil fuel carbon into the atmosphere results in increased carbon dioxide (CO2) into the oceans, a process that lowers seawater pH, decreases alkalinity and can inhibit the production of shell material. Corrosive water has recently been documented in the northeast Pacific, along with a rapid decline in seawater pH over the past decade. A lack of instrumentation prior to the 1990s means that we have no indication whether these carbon cycle changes have precedence or are a response to recent anthropogenic CO2 inputs. We analyzed stable carbon and oxygen isotopes (δ13C, δ18O) of decade-old California mussel shells (Mytilus californianus) in the context of an instrumental seawater record of the same length. We further compared modern shells to shells from 1000 to 1340 years BP and from the 1960s to the present and show declines in the δ13C of modern shells that have no historical precedent. Our finding of decline in another shelled mollusk (limpet) and our extensive environmental data show that these δ13C declines are unexplained by changes to the coastal food web, upwelling regime, or local circulation. Our observed decline in shell δ13C parallels other signs of rapid changes to the nearshore carbon cycle in the Pacific, including a decline in pH that is an order of magnitude greater than predicted by an equilibrium response to rising atmospheric CO2, the presence of low pH water throughout the region, and a record of a similarly steep decline in δ13C in algae in the Gulf of Alaska. These unprecedented changes and the lack of a clear causal variable underscores the need for better quantifying carbon dynamics in nearshore environments

Polymorphism Data Can Reveal the Origin of Species Abundance Statistics

What is the underlying mechanism behind the fat-tailed statistics observed for species abundance distributions? The two main hypotheses in the field are the adaptive (niche) theories, where species abundance reflects its fitness, and the neutral theory that assumes demographic stochasticity as the main factor determining community structure. Both explanations suggest quite similar species-abundance distributions, but very different histories: niche scenarios assume that a species population in the past was similar to the observed one, while neutral scenarios are characterized by strongly fluctuating populations. Since the genetic variations within a population depend on its abundance in the past, we present here a way to discriminate between the theories using the genetic diversity of noncoding DNA. A statistical test, based on the Fu-Li method, has been developed and enables such a differentiation. We have analyzed the results gathered from individual-based simulation of both types of histories and obtained clear distinction between the Fu-Li statistics of the neutral scenario and that of the niche scenario. Our results suggest that data for 10–50 species, with approximately 30 sequenced individuals for each species, may allow one to distinguish between these two theories

Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study

OBJECTIVES: To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. DESIGN: Mendelian randomisation study. SETTING: UK Biobank and international genome-wide association study data. PARTICIPANTS: Predominantly participants of European ancestry. EXPOSURE: Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. MAIN OUTCOMES MEASURE: The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. RESULTS: Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. CONCLUSIONS: BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation

Neutrality and the Response of Rare Species to Environmental Variance

Neutral models and differential responses of species to environmental heterogeneity offer complementary explanations of species abundance distribution and dynamics. Under what circumstances one model prevails over the other is still a matter of debate. We show that the decay of similarity over time in rocky seashore assemblages of algae and invertebrates sampled over a period of 16 years was consistent with the predictions of a stochastic model of ecological drift at time scales larger than 2 years, but not at time scales between 3 and 24 months when similarity was quantified with an index that reflected changes in abundance of rare species. A field experiment was performed to examine whether assemblages responded neutrally or non-neutrally to changes in temporal variance of disturbance. The experimental results did not reject neutrality, but identified a positive effect of intermediate levels of environmental heterogeneity on the abundance of rare species. This effect translated into a marked decrease in the characteristic time scale of species turnover, highlighting the role of rare species in driving assemblage dynamics in fluctuating environments