Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents

<p>Abstract</p> <p>Background</p> <p>Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management of nursing home residents.</p> <p>Methods</p> <p>Nineteen subjects (8M, 11F; mean age 77.1 ± 10.1) suffering with chronic constipation were assigned to receive LAB (3.0 × 10¹¹CFU/g) twice (to be taken 30 minutes after breakfast and dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on defecation habits (frequency of defecation, amount and state of stool), and we collected fecal samples from the subjects both before entering and after ending the trial, to investigate LAB levels and inhibition of harmful enzyme activities. Results were tested with SAS and Student's t-test.</p> <p>Results</p> <p>Analysis of questionnaire showed that there was an increase in the frequency of defecation and amount of stool excreted in defecation habit after LAB treatment, but there were no significant changes. And it also affects the intestinal environment, through significantly increase (<it>p </it>< 0.05) fecal LAB levels. In addition, tryptophanase and urease among harmful enzyme activities of intestinal microflora were significantly decreased (<it>p </it>< 0.05) after LAB treatment.</p> <p>Conclusion</p> <p>LAB, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased defecation habit such as frequency of defecation, amount and state of stool. So, it may be used as functional probiotics to improve human health by helping to prevent constipation.</p

Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

BackgroundChildhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated.MethodsCross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated.ResultsOverweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null.ConclusionsOur data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders

Association between neighborhood safety and overweight status among urban adolescents

<p>Abstract</p> <p>Background</p> <p>Neighborhood safety may be an important social environmental determinant of overweight. We examined the relationship between perceived neighborhood safety and overweight status, and assessed the validity of reported neighborhood safety among a representative community sample of urban adolescents (who were racially and ethnically diverse).</p> <p>Methods</p> <p>Data come from the 2006 Boston Youth Survey, a cross-sectional study in which public high school students in Boston, MA completed a pencil-and-paper survey. The study used a two-stage, stratified sampling design whereby schools and then 9^th–12^thgrade classrooms within schools were selected (the analytic sample included 1,140 students). Students reported their perceptions of neighborhood safety and several associated dimensions. With self-reported height and weight data, we computed body mass index (BMI, kg/m²) for the adolescents based on CDC growth charts. Chi-square statistics and corresponding <it>p</it>-values were computed to compare perceived neighborhood safety by the several associated dimensions. Prevalence ratios (PRs) and 95% confidence intervals (CI) were calculated to examine the association between perceived neighborhood safety and the prevalence of overweight status controlling for relevant covariates and school site.</p> <p>Results</p> <p>More than one-third (35.6%) of students said they always felt safe in their neighborhood, 43.9% said they sometimes felt safe, 11.6% rarely felt safe, and 8.9% never felt safe. Those students who reported that they rarely or never feel safe in their neighborhoods were more likely than those who said they always or sometimes feel safe to believe that gang violence was a serious problem in their neighborhood or school (68.0% vs. 44.1%, <it>p </it>< 0.001), and to have seen someone in their neighborhood assaulted with a weapon (other than a firearm) in the past 12 months (17.8% vs. 11.3%, <it>p </it>= 0.025). In the fully adjusted model (including grade and school) stratified by race/ethnicity, we found a statistically significant association between feeling unsafe in one's own neighborhood and overweight status among those in the Other race/ethnicity group [(PR = 1.56, (95% CI: 1.02, 2.40)].</p> <p>Conclusion</p> <p>Data suggest that perception of neighborhood safety may be associated with overweight status among urban adolescents in certain racial/ethnic groups. Policies and programs to address neighborhood safety may also be preventive for adolescent overweight.</p

The Detectability of Earth's Biosignatures Across Time

Over the past two decades, enormous advances in the detection of exoplanets have taken place. Currently, we have discovered hundreds of earth-sized planets, several of them within the habitable zone of their star. In the coming years, the efforts will concentrate in the characterization of these planets and their atmospheres to try to detect the presence of biosignatures. However, even if we discovered a second Earth, it is very unlikely that it would present a stage of evolution similar to the present-day Earth. Our planet has been far from static since its formation about 4.5 Ga ago; on the contrary, during this time, it has undergone multiple changes in it's atmospheric composition, it's temperature structure, it's continental distribution, and even changes in the forms of life that inhabit it. All these changes have affected the global properties of Earth as seen from an astronomical distance. Thus, it is of interest not only to characterize the observables of the Earth as it is today, but also at different epochs. Here we review the detectability of the Earth's globally-averaged properties over time. This includes atmospheric composition and biosignatures, and surface properties that can be interpreted as sings of habitability (bioclues). The resulting picture is that truly unambiguous biosignatures are only detectable for about 1/4 of the Earth's history. The rest of the time we rely on detectable bioclues that can only establish an statistical likelihood for the presence of life on a given planet.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018). arXiv admin note: text overlap with arXiv:astro-ph/0609398 by other author

A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci

Recent advances of metabolomics in plant biotechnology

Biotechnology, including genetic modification, is a very important approach to regulate the production of particular metabolites in plants to improve their adaptation to environmental stress, to improve food quality, and to increase crop yield. Unfortunately, these approaches do not necessarily lead to the expected results due to the highly complex mechanisms underlying metabolic regulation in plants. In this context, metabolomics plays a key role in plant molecular biotechnology, where plant cells are modified by the expression of engineered genes, because we can obtain information on the metabolic status of cells via a snapshot of their metabolome. Although metabolome analysis could be used to evaluate the effect of foreign genes and understand the metabolic state of cells, there is no single analytical method for metabolomics because of the wide range of chemicals synthesized in plants. Here, we describe the basic analytical advancements in plant metabolomics and bioinformatics and the application of metabolomics to the biological study of plants

The PLATO 2.0 mission

PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4-16 mag). It focusses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk