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For decades, fructose intake has been recognised as an environmental risk for metabolic syndromes and diseases. Here we comprehensively examined the effects of fructose intake on mice liver transcriptomes. Fructose-supplemented water (34 %; w/v) was fed to both male and female C57BL/6N mice at their free will for 6 weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEG) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. As a result, we identified eighty-nine down-regulated and eighty-eight up-regulated mRNA in fructose-fed mice livers. These DEG were subjected to bioinformatics analysis tools in which DEG were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes, while fructose suppresses the AhR signalling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signalling through modulating expressions of transcription factor (AhR nuclear translocator; Arnt) and upstream regulators (Ncor2, and Rb1). Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signalling pathway in C57BL/6N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on (1) other types of carcinogens and (2) inflammation-inducing agents (or even diets such as a high-fat diet), to find implications of fructose-induced AhR suppression.
This study sets out to determine the influence of age at the time of surgery as a risk factor for post-operative length of stay after bidirectional cavopulmonary anastomosis.
All patients undergoing a Glenn procedure between January 2010 and July 2015 were included in this retrospective cohort study. Demographic data were examined. Standard descriptive statistics was used. A univariable analysis was conducted using the appropriate test based on data distribution. A propensity score for balancing the group difference was included in the multi-variable analysis, which was then completed using predictors from the univariable analysis that achieved significance of p<0.1.
Over the study period, 50 patients met the inclusion criteria. Patients were separated into two cohorts of ⩾4 months (28 patients) and <4 months (22 patients). Other than height and weight, the two cohorts were indistinguishable in their pre-operative saturation, medications, catheterisation haemodynamics, atrioventricular valve regurgitation, and ventricular function. After adjusting group differences, younger age was associated with longer post-operative length of hospitalisation – adjusted mean 15 (±2.53) versus 8 (±2.15) days (p=0.03). In a multi-variable regression analysis, in addition to ventricular dysfunction (β coefficient=8.8, p=0.05), Glenn procedures performed before 4 months were independently associated with longer length of stay (β coefficient=−6.9, p=0.03).
We found that Glenn procedures performed after 4 months of age had shorter post-operative length of stay when compared to a younger cohort. These findings suggest that balancing timing of surgery to decrease the inter-stage period should take into consideration differences in post-operative recovery with earlier operations.
The purpose of this research was to understand the preferences of patients receiving integrative medicine services for return of aggregate study results.
A brief online survey (survey 1) was sent to 341 cancer patients receiving integrative medicine interventions; subsequently, a minimally revised survey (survey 2) was sent to 812 individuals with various medical conditions who had been either research participants in integrative medicine studies (n = 446) or patients (n = 346) of mind–body medicine.
Feedback to a model plain language summary was elicited from survey 1 and survey 2 respondents. Seventy-seven survey recipients (23%) responded to survey 1, and 134 survey recipients (17%) responded to survey 2. The majority of respondents to the surveys were female and 51–70 years of age. Ninety percent of responders to survey 1 and 89% of responders to survey 2 indicated that researchers should share overall results of a study with participants. In terms of the means of result distribution, 37%–47% preferred email, while 22%–27% indicated that, as long as the results are shared, it did not matter how this occurred. Of 38 survey 1 respondents who had previously participated in a clinical trial, 37% had received the results of their study. In survey 2, 63 individuals indicated that they previously participated in clinical trials, but only 16% recalled receiving results.
These results confirm that the majority (89%–90%) of integrative medicine patients are interested in receiving the results of clinical trials. The majority (82%–94%) of respondents felt the model plain language summary of results provided was helpful.
Neuroticism, a ‘Big Five’ personality trait, has been associated with sub-clinical traits of both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The objective of the current study was to examine whether causal overlap between ASD and ADHD traits can be accounted for by genetic and environmental risk factors that are shared with neuroticism. We performed twin-based structural equation modeling using self-report data from 12 items of the Neo Five-Factor Inventory Neuroticism domain, 11 Social Responsiveness Scale items, and 12 Adult ADHD Self-Report Scale items obtained from 3,170 young adult Australian individual twins (1,081 complete pairs). Univariate analysis for neuroticism, ASD, and ADHD traits suggested that the most parsimonious models were those with additive genetic and unique environmental components, without sex limitation effects. Heritability of neuroticism, ASD, and ADHD traits, as measured by these methods, was moderate (between 40% and 45% for each respective trait). In a trivariate model, we observed moderate phenotypic (between 0.45 and 0.62), genetic (between 0.56 and 0.71), and unique environmental correlations (between 0.37and 0.55) among neuroticism, ASD, and ADHD traits, with the highest value for the shared genetic influence between neuroticism and self-reported ASD traits (rg = 0.71). Together, our results suggest that in young adults, genetic, and unique environmental risk factors indexed by neuroticism overlap with those that are shared by ASD and ADHD.
We developed a flare prediction model based on the supervised machine learning of solar observation data for 2010-2015. We used vector magnetograms, lower chromospheric brightening, and soft-X-ray data taken by Solar Dynamics Observatory and Geostationary Operational Environmental Satellite. We detected active regions and extracted 60 solar features such as magnetic neutral lines, current helicity, chromospheric brightening, and flare history. We fully shuffled the database and randomly divided it into two for training and testing. To predict the maximum size of flares occurring in the following 24 hours, we used three machine-learning algorithms independently: the support vector machine, the k nearest neighbors (kNN), and the extremely randomized trees. We achieved a skill score (TSS) of greater than 0.9 for kNN. Furthermore, we compared the prediction results in a more operational setting by shuffling and dividing the database with a week unit. It was found that the prediction score depends on the way the database is prepared.
Fluid residence time is a key concept in the understanding and design of chemically reacting flows. In order to investigate how turbulent mixing affects the residence time distribution within a flow, this study examines statistics of fluid residence time from a direct numerical simulation (DNS) of a statistically stationary turbulent round jet with a jet Reynolds number of 7290. The residence time distribution in the flow is characterised by solving transport equations for the residence time of the jet fluid and for the jet fluid mass fraction. The product of the jet fluid residence time and the jet fluid mass fraction, referred to as the mass-weighted stream age, gives a quantity that has stationary statistics in the turbulent jet. Based on the observation that the statistics of the mass fraction and velocity are self-similar downstream of an initial development region, the transport equation for the jet fluid residence time is used to derive a model describing a self-similar profile for the mean of the mass-weighted stream age. The self-similar profile predicted is dependent on, but different from, the self-similar profiles for the mass fraction and the axial velocity. The DNS data confirm that the first four moments and the shape of the one-point probability density function of mass-weighted stream age are indeed self-similar, and that the model derived for the mean mass-weighted stream-age profile provides a useful approximation. Using the self-similar form of the moments and probability density functions presented it is therefore possible to estimate the local residence time distribution in a wide range of practical situations in which fluid is introduced by a high-Reynolds-number jet of fluid.
Substance misuse and associated health-risking behaviors are prevalent in emerging adulthood. There is a knowledge gap concerning the post-high school effects of community-based delivery systems for universal preventive interventions implemented during young adolescence. This study reports effects of the PROSPER delivery system through age 19, 7.5 years past baseline.
A cohort sequential design included 28 public school districts randomly assigned to the PROSPER partnership delivery system or usual-programming conditions. PROSPER community teams implemented a family-focused intervention in 6th grade and a school-based intervention in 7th grade. Outcomes for the age 19, post-high school report included lifetime, current, and frequency of substance misuse, as well as antisocial and health-risking sexual behaviors. Intent-to-treat, multi-level analyses of covariance of point-in-time outcomes were conducted, along with analyses of risk-related moderation of intervention effects.
Results showed emerging adults from PROSPER communities reported significantly lower substance misuse across a range of types of substances, with relative reduction rates of up to 41.0%. No significant findings were observed for associated antisocial and health-risking sexual behavior indices; or for lifetime rates of sexually transmitted infections. Risk-related moderation effects were non-significant, suggesting generally comparable outcomes across higher- and lower-risk subgroups of emerging adults.
The PROSPER delivery system for brief universal preventive interventions has potential for public health impact by reducing long-term substance misuse, with positive results extending beyond high school.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Antipsychotic agents have limited efficacy for Behavioral and Psychological Symptoms of Dementia (BPSD) and there are concerns about their safety. Despite this, they are frequently used for the management of BPSD. This study aimed to assess the use of antipsychotics among people on anti-dementia medicines in Australian residential aged care facilities.
Data were obtained from an individual patient unit dose packaging database covering 40 residential aged care facilities in New South Wales, Australia. Residents supplied an anti-dementia medicine between July 2008 and June 2013 were included. Prevalence of concurrent antipsychotic use was established. Incident antipsychotic users between January 2009 and December 2011 were identified. We examined initial antipsychotic dose, maximum titrated doses, type and duration of antipsychotic use, and compared use with Australian guidelines.
There were 291 residents treated with anti-dementia medicines, 129 (44%) of whom received antipsychotics concomitantly with an anti-dementia medicine. Among the 59 incident antipsychotic users, risperidone (73%) was the most commonly used antipsychotic agent. Amongst the risperidone initiators, 43% of patients had initial doses greater than 0.5 mg/day and 6% of patients exceeded 2.0 mg/day for their maximum dose. 53% of concomitant users received daily treatment for greater than six months.
Our study using records of individual patient unit dose supply, which represents the intended medication consumption schedule, shows high rates of concurrent use of antipsychotics and anti-dementia medicines and long durations of use. The use of antipsychotics in patients with dementia needs to be carefully monitored to improve patient outcomes.
Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.
Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory Emax model we developed previously.
The inhibitory Emax model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), −5.67 (dorsal raphe nucleus)].
This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Impairment on inhibitory tasks has been well documented in bipolar disorder (BD). Differences in cerebral blood flow (CBF) between BD patients and healthy comparison (HC) participants have also been reported. Few studies have examined the relationship between cognitive performance and regional CBF in this patient population. We hypothesized that group differences on an inhibitory task (the Delis-Kaplan Executive Function Scale’s Color-Word Inhibition task) would be associated with differential CBF in bilateral anterior cingulate cortex (ACC), inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants. Total gray matter (GM) CBF was measured, and regional CBF values were extracted for each region of interest (ROI) using Freesurfer-based individual parcellations. Group, CBF, and group-by-CBF interaction were examined as predictors of inhibition performance. Groups did not differ in age, gender or education. BD patients performed significantly worse on Color-Word inhibition. There were no significant group differences in CBF in either total GM or in any ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and right DLPFC such that better inhibitory performance was generally associated with higher resting state CBF in BD subjects, but not HC participants. Although CBF was not abnormal in this euthymic BD sample, results confirm previous reports of inter-episode inhibitory deficits and indicate that the perfusion-cognition relationship is different in BD compared to HC individuals. (JINS, 2015, 21, 105–115)
Substantial empirical evidence has indicated impairment in the cognitive functioning of patients with obsessive-compulsive disorder (OCD) despite inconsistencies. Although several confounding factors have been investigated to explain the conflicting results, the findings remain mixed. This study aimed to investigate cognitive dysfunction in patients with OCD using a meta-analytic approach.
The PubMed database was searched between 1980 and October 2012, and reference lists of review papers were examined. A total of 221 studies were identified, of which 88 studies met inclusion criteria. Neuropsychological performance and demographic and clinical variables were extracted from each study.
Patients with OCD were significantly impaired in tasks that measured visuospatial memory, executive function, verbal memory and verbal fluency, whereas auditory attention was preserved in these individuals. The largest effect size was found in the ability to recall complex visual stimuli. Overall effect estimates were in the small to medium ranges for executive function, verbal memory and verbal fluency. The effects of potentially confounding factors including educational level, symptom severity, medication status and co-morbid disorders were not significant.
Patients with OCD appear to have wide-ranging cognitive deficits, although their impairment is not so large in general. The different test forms and methods of testing may have influenced the performance of patients with OCD, indicating the need to select carefully the test forms and methods of testing used in future research. The effects of various confounding variables on cognitive functioning need to be investigated further and to be controlled before a definite conclusion can be made.
Detailed descriptions of effective intervention protocols for Asian smokers are uncommon which makes it difficult for others to successfully implement a protocol that has been proven to be effective. This article fills a gap by detailing such a protocol, specifically a telephone counselling intervention for Asian smokers. The protocol was tested in a large randomised trial with Chinese-, Korean-, and Vietnamese-speaking smokers and was shown to significantly increase quit rates. The article describes the approach used to develop the protocol and critical components of the intervention. In addition, the paper compares data on programme participation and satisfaction among Chinese-, Korean-, and Vietnamese-speaking smokers with those for English- and Spanish-speaking smokers from two studies conducted in the US and shows that the former are no less likely to engage in counselling and no less likely to be satisfied with the process.
We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children.
In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD Rating Scale – IV (ADHD-RS) and Learning Disability Evaluation Scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways.
After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities.
Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.
Thermally activated axial intrusion of nickel silicides into the silicon nanowire (NW) from pre-patterned Ni reservoirs is used in formation of nickel silicide/silicon contacts in SiNW field effect transistors. This intrusion consists usually of different nickel silicide phases which grow simultaneously during thermal annealing (TA). The growth is often accompanied by local thickening and tapering of the NW, up to full disintegration of segments adjacent to the silicon. In the present work this process was investigated in SiNWs of 30-60 nm in diameters with pre-patterned Ni electrodes after a TA at 420-440°C and times up to 15 s. The process was analyzed in the framework of a model taking into account simultaneous formation of two silicide phases in the NW. Additional flux of atoms caused by the NW curvature gradients due to different radii of different silicides was taken into account as well. For a certain set of parameters thickening of the nickel-rich silicide intrusion and tapering of the monosilicide part of intrusion were obtained.
Silicon nanowires (NWs) are promising thermoelectric materials as they offer large reductions in thermal conductivity over bulk Si without a significant decrease in the Seebeck coefficient or electrical conductivity. In this work, interference lithography was used to pattern a square lattice photoresist template over 2 cm x 2 cm Si substrates. The resulting vertical Si NW arrays were 1 μm tall with a packing density of ~15%, and the diameter of the Si NWs were 80 - 90 nm. The Si NW arrays were then embedded in spin-on glass (SOG) to form a dense composite material with a measured thermal conductivity of 1.45 W/m-K at 300 K. Devices were fabricated for cross-plane Seebeck coefficient measurements and the Si NW/SOG composite was found to have a Seebeck coefficient of roughly -284 μV/K, which is similar to bulk Si with the same doping. We also report a combined power generation of 29.3 μW from both the Si NW array and Si substrate with a temperature difference of 56 K and 50 μm x 50 μm device area.