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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
We identified and characterized a new cosmocercid nematode species, Cosmocercoides wuyiensis n. sp., through microscopic examination and sequencing of the partial small ribosomal RNA gene (18S rDNA), internal transcribed spacer (ITS) and mitochondrial cytochrome c oxidase subunit 1 (COI) genes. The new species was isolated from the intestine of the Asiatic frog Amolops wuyiensis Liu and Hu, 1975 captured from four localities of the Anhui province in south-east China. Among the 25 recorded species of the Cosmocercoides genus, the morphology of C. wuyiensis n. sp. is closest to that of C. kiliwai and C. malayensis, which were isolated from various Mexican frog and Malaysian lizard species, respectively. However, C. wuyiensis n. sp. displayed several distinguishing features, such as small size of the male body, two spicules of unequal lengths in the male, small gubernaculum, pre-, ad- and post-cloacal caudal rosette papillae in the ratio of 18–24:2:6 and simple papillae in the ratio of 14:multiple:4, circle and number of punctation in each rosette at 1:11–16, sharply conical tail-end and the presence of lateral alae and somatic papillae in both sexes. BLAST and the phylogenetic analyses of the 18S rDNA and ITS sequences indicated that C. wuyiensis n. sp. belonged to the genus Cosmocercoides, while that of the COI gene sequence of C. wuyiensis n. sp. showed 16.36% nucleotide divergence with C. pulcher and 47.99% nucleotide divergence with C. qingtianensis. The morphological and molecular characterization of C. wuyiensis n. sp. provides new taxonomic data for this genus.
Sodium and chloride are the key factors maintaining normal osmotic pressure (OSM) and volume of the extracellular fluid, and influencing the acid–base balance of body fluids. The experiment was conducted to investigate the effects of dietary Na+ and Cl− level on growth performance, excreta moisture, blood biochemical parameters, intestinal Na+–glucose transporter 1 (SGLT1) messenger RNA (mRNA), and Na+–H+ exchanger 2 (NHE2) mRNA, and to estimate the optimal dietary sodium and chlorine level for yellow-feathered chickens from 22 to 42days. A total of 900 22-day-old Lingnan yellow-feathered male chickens were randomly allotted to five treatments, each of which included six replicates of 30 chickens per floor pen. The basal control diet was based on corn and soybean meal (without added NaCl and NaHCO3). Treatments 2 to 5 consisted of the basal diet supplemented with equal weights of Na+ and Cl−, constituting 0.1%, 0.2%, 0.3% and 0.4% of the diets. Supplemental dietary Na+ and Cl− improved the growth performance (P<0.05). Average daily gain (ADG) showed a quadratic broken-line regression to increasing dietary Na+ and Cl− (R2=0.979, P<0.001), and reached a plateau at 0.1%. Supplemental Na+ and Cl− increased (P<0.05) serum Na+ and OSM in serum and showed a quadratic broken-line regression (R2=0.997, P=0.004) at 0.11%. However, supplemental Na+ and Cl− decreased (P<0.05) serum levels of K+, glucose (GLU) and triglyceride. Higher levels of Na+and Cl− decreased duodenal NHE2 transcripts (P<0.05), but had no effect on ileal SGLT1 transcripts. The activity of Na+ /K+-ATPase in the duodenum decreased (P<0.05) with higher levels of dietary Na+ and Cl−. In conclusion, the optimal dietary Na+ and Cl− requirements for yellow-feathered chickens in the grower phase, from 22 to 42 days of age, to optimize ADG, serum Na+, OSM, K+ and GLU were 0.10%, 0.11%, 0.11%,0.17% and 0.16%, respectively, by regression analysis.
Various surgical approaches have been described to remove tumours in the parapharyngeal space. This study investigated the feasibility of a transoral approach in the surgical management of parapharyngeal space benign tumours located in the medial portion of the carotid sheaths and extending toward the skull base.
Thirty-two patients were selected and underwent a transoral or an endoscope-assisted transoral approach in the surgical management of parapharyngeal space benign tumours located in the medial portion of the carotid sheaths. Medical photographs were used.
All patients underwent complete resection of their lesions via a transoral or endoscope-assisted transoral approach. None of the patients demonstrated residual or recurrent neoplasms, either clinically or radiographically, during their follow up.
Based on our studies, we assert that transoral and endoscope-assisted transoral approaches are suitable in managing parapharyngeal space benign tumours located in the medial portion of the carotid sheaths and extending toward the skull base.
Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers’ routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.
It was reported that high blood cholesterol levels increased the susceptibility to mitochondrial dysfunction. This study hypothesized that the gestational hypercholesterolemia (HC) could induce the mitochondrial dysfunction in term human placenta. The eligible pregnant women were recruited from Xuanwu Hospital in Beijing during their first prenatal visit (before their 10th week of pregnancy). In total, 19 pregnant women whose serum total cholesterol levels were higher than 7.25 mm at third trimester (measured at 36–38 weeks) were selected as gestational HC. Other 19 pregnant women with normal cholesterol level matched with age, pre-gestational body mass index, and the neonatal gender were included as the control group. Full-term placenta samples were collected. The mitochondrial DNA (mtDNA) copy number, messenger RNA (mRNA) expression of cytochrome c oxidase subunit I, adenosine triphosphate monophosphatase 6 (ATP6ase), citrate synthase, peroxisome proliferator-activated receptor-γ (PPARγ) co-activator 1α, PPARγ co-activator 1β and estrogen-related receptor-α, and the activity of mitochondrial respiratory chain enzyme complex were measured. Pregnancy outcomes were obtained by extraction from medical records and the labor ward register. The results showed that only placental mtDNA copy number and mRNA expression of ATP6ase were significantly decreased in HC group. No significant differences were detected of other measurements between the two groups. These findings indicated that gestational HC might not induce the damage of placental function seriously.
In ovo feeding (IOF) of l-arginine (Arg) can affect growth performance of broilers, but the response of IOF of Arg on breast muscle growth is unclear, and the mechanism involved in protein deposition remains unknown. Hense, this experiment was conducted to evaluate the effects of IOF of Arg on breast muscle growth and protein-deposited signalling in post-hatch broilers. A total of 720 fertile eggs were collected from 34-week-old Arbor Acres breeder hens and distributed to three treatments: (1) non-injected control group; (2) 7.5 g/l (w/v) NaCl diluent-injected control group; (3) 0.6 mg Arg/egg solution-injected group. At 17.5 days of incubation, fertile eggs were injected 0.6 ml solutions into the amnion of the injected groups. Upon hatching, 80 male chicks were randomly assigned to eight replicates of 10 birds each and fed ad libitum for 21 days. The results indicated that IOF of Arg increased relative breast muscle weight compared with those of control groups at hatch, 3-, 7- and 21-day post-hatch (P<0.05). In the Arg-injected group, the plasma total protein and albumen concentrations were higher at 7- and 21-day post-hatch than those of control groups (P<0.05). The alanine aminotransferase activity in Arg group was higher at hatch than that of control groups (P<0.05). The levels of triiodothyronine at four time points and thyroxine hormones at hatch, 7- and 21-day post-hatch in Arg group were higher than those of control groups (P<0.05). In addition, IOF of Arg increased the amino acid concentrations of breast muscle at hatch, 7- and 21-day post-hatch (P<0.05). In ovo feeding of Arg also enhanced mammalian target of rapamycin, ribosomal protein S6 kinase-1 and eIF4E-bindingprotein-1 messenger RNA expression levels at hatch compared with those of control groups (P<0.05). It was concluded that IOF of Arg treatment improved breast muscle growth, which might be associated with the enhancement of protein deposition.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
To investigate lung function in Chinese patients suffering from chronic rhinosinusitis with nasal polyps and examine its association with histopathological features.
The lung function of 99 patients with nasal polyps was measured. Haematoxylin and eosin and immunohistochemistry staining were performed to evaluate any inflammatory cells and epithelial tissue remodelling.
Predicted maximal expiratory flow rate at 25 per cent vital capacity was reduced (p < 0.05) in epithelial hyperplasia, and predicted maximal expiratory flow rate at 50 per cent vital capacity was reduced (p < 0.05) in goblet cell hyperplasia. Both peripheral blood eosinophilia and tissue eosinophilia nasal polyps manifested significantly reduced: forced expiratory volume in 1 second/forced vital capacity ratio, predicted maximal expiratory flow rate at 25, 50 and 75 per cent of vital capacity, and predicted maximal mid-expiratory flow. Peripheral blood eosinophils were negatively correlated with predicted maximal expiratory flow rate at 25 and 50 per cent of vital capacity, and predicted maximal mid-expiratory flow. Eosinophils in tissue were negatively correlated with all lung function parameters investigated except predicted forced vital capacity.
Clinicians should be aware of lung function decline in nasal polyps patients, especially in those with tissue eosinophilia.
To investigate the effect of microRNA let-7a on OPN expression in a mouse model of allergic rhinitis.
Thirty-two mature female C57BL/6 mice were randomly divided into four groups, with eight mice in each group: microRNA let-7a, microRNA control, OVA and phosphate-buffered saline groups. The microRNA let-7a, microRNA control and OVA groups were sensitised with OVA to establish a mouse model of allergic rhinitis. Nose-scratching events were counted. Nasal mucosa was used to evaluate histological changes of goblet cell hyperplasia. Interleukins 5 and 13 were detected. Interferon-γ levels in the nasal lavage fluid were assayed with enzyme-linked immunosorbent assay. OPN expression was estimated with polymerase chain reaction.
Compared with microRNA control mice, microRNA let-7a treated mice had a significantly increased number of nose-scratching events, nasal mucosal eosinophilia and goblet cell hyperplasia (p < 0.05), and significantly higher interleukins 5 and 13 in nasal mucosa (p < 0.05), but there was no significant difference in interferon-γ (p > 0.05). In addition, microRNA let-7a treated mice had significantly enhanced OPN expression in nasal mucosa (p < 0.05).
MicroRNA let-7a can promote allergic rhinitis development partly by regulating OPN expression.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression of target messenger RNAs (mRNAs) and miRNAs have been proven to play vital roles in skeletal muscle development. The miRNA-499-5p has been reported to be negatively related with the expression of Sox6, a critical transcription factor for the maintenance of fast-twitch skeletal muscle. In this study, we amplified a length of 2012-bp mRNA that contains a 1512-bp porcine Sox6 (pSox6) 3'UTR from skeletal muscle of a Duroc×Landrace×Yorkshire pig. By luciferase reporter assay we verified that pSox6 is a target of miR-499-5p. In extensor digitorum longus and Soleus muscles of pigs, the expression levels of miR-499-5p and pSox6 mRNA were also inversely correlated. Besides, overexpression of miR-499-5p in porcine satellite cells promoted the expression of MyHC I and MyHC IIa mRNA, along with a reduction of pSox6 mRNA. Taken together, these results indicate that miR-499-5p may facilitate the oxidative myofibers formation by downregulating pSox6 expression.
This study aimed to test the expression of maspin in invasive fungal rhinosinusitis and explore its value in diagnosing invasive fungal rhinosinusitis.
Forty-two fungal rhinosinusitis cases (12 invasive and 30 non-invasive) were selected as the experimental group, and 30 chronic rhinosinusitis cases comprised the control group. Maspin expression was assessed in nasal mucous membrane specimens by immunohistochemical staining.
Compared with the control group, maspin expression was down-regulated in the fungal rhinosinusitis group (p < 0.05). Furthermore, the staining score for maspin was lowest in the invasive fungal rhinosinusitis group, as compared with both the non-invasive fungal rhinosinusitis group and the control group (p < 0.05). A maspin staining score of 5.70 was the critical value for diagnosis of invasive fungal rhinosinusitis, with sensitivity and specificity of 91.7 per cent and 88.3 per cent, respectively.
The results of this study suggest that the maspin staining score may be a biomarker for effective and rapid diagnosis of invasive fungal rhinosinusitis.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
EVA foams, like all other polymers, also exhibit strain-rate effects and hysteresis. However, currently available approaches for predicting the mechanical response of polymeric foam subjected to an arbitrarily imposed loading history and strain-rate effect are highly limited. Especially, the strain rates in the intermediate rate domain (between 100 and 102 s–1) are extremely difficult to study. The use of data generated through the drop tower technique for implementation in constitutive equations or numerical models has not been considered in past studies. In this study, an experiment including a quasi-static compression test and drop impact tests with a high speed camera was conducted. An inverse analysis technique combined with a finite element model for material parameter identification was developed to determine the stress–strain behavior of foam at different specific strain rates. It was used in this study to simulate multiple loading and unloading cycles on foam specimens, and the results were compared with experimental measurements.
The natural boundary integral equation (NBIE) is developed to calculate potential derivatives for potential problems with anisotropic media. Firstly, the governing equation of the two-dimensional anisotropic potential problem is transformed into standard Laplace equation by a coordinate transformation method. Then a potential derivative boundary integral equation named as NBIE is extended to solve the anisotropic potential problem. The most important virtue of the NBIE is that the singularity of the integral kernel function is reduced by one order in comparison with the conventional potential derivative boundary integral equation(CDBIE). Therefore the new potential derivative boundary integral equation only contains strongly singular integrals rather than hyper-singular integrals. Thus the NBIE can calculate more accurate potential derivative results for both boundary nodes and interior points. Moreover, in combination with the analytical integral regularization algorithm of nearly singular integrals, the NBIE can obtain more accurate potential derivatives of interior points very close to the boundary than the CDBIE. Numerical examples on heat conduction in anisotropic media demonstrate the accuracy and efficiency of the NBIE.
Interest in minor planets and comets continued to grow during the triennium, sparked in part by the highly successful 1983 mission of the Infrared Astronomy Satellite (IRAS) as well as by activities associated with the return of P/Halley and the first spacecraft missions to comets. A trial of the Astrometry Network of the International Halley Watch (IHW) on P/Crommelin was quite successful. Yet with an increasing need for precise ephemerides, there continued to be concern for acquisition and timely reporting of astrometric observations of even the best known comets.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Despite the potential of declared serving size to encourage appropriate portion size consumption, most countries including Australia have not developed clear reference guidelines for serving size. The present study evaluated variability in manufacturer-declared serving size of discretionary food and beverage products in Australia, and how declared serving size compared with the 2013 Australian Dietary Guideline (ADG) standard serve (600 kJ). Serving sizes were obtained from the Nutrition Information Panel for 4466 packaged, discretionary products in 2013 at four large supermarkets in Sydney, Australia, and categorised into fifteen categories in line with the 2013 ADG. For unique products that were sold in multiple package sizes, the percentage difference between the minimum and the maximum serving size across different package sizes was calculated. A high variation in serving size was found within the majority of food and beverage categories – for example, among 347 non-alcoholic beverages (e.g. soft drinks), the median for serving size was 250 (interquartile range (IQR) 250, 355) ml (range 100–750 ml). Declared serving size for unique products that are available in multiple package sizes also showed high variation, particularly for chocolate-based confectionery, with median percentage difference between minimum and maximum serving size of 183 (IQR 150) %. Categories with a high proportion of products that exceeded the 600 kJ ADG standard serve included cakes and muffins, pastries and desserts (≥74 % for each). High variability in declared serving size may confound interpretation and understanding of consumers interested in standardising and controlling their portion selection. Future research is needed to assess if and how standardising declared serving size might affect consumer behaviour.