Obstetric and perinatal factors as predictors of child behaviour at 5 years

Objective To identify whether obstetric and perinatal factors are independent predictors of child behaviour at 5 years. Methodology The Mater University Study of Pregnancy (MUSP) is a prospective cohort study of 8556 mothers enrolled in early pregnancy. The relationship of obstetric and perinatal factors, maternal lifestyle, age and gender of the child, and social disadvantage were examined as predictors of child behaviour in 5005 children completing a modified child behaviour checklist at 5 years. This checklist contained three independent groups of behaviour: externalizng, internalizing and SAT (social, attentional and thought problems). Results In the initial analysis a limited number of associations were present. After adjusting for measures of social disadvantage, only number of antenatal admissions was associated with child behaviour in all three scales, while maternal cigarette smoking in pregnancy and male gender were associated with externalising and SAT behaviours. Conclusions Most common epidemiologic obstetric and perinatal risk factors were not independent predictors of behaviour problems in children at 5 years

The association between levels of alcohol consumption and mental health problems and academic performance among young university students

Purpose: Mental health problems and harmful alcohol consumption have been found to be high among young university students compared to the general population in Australia. This research aimed to investigate the association between levels of drinking and mental health problems and academic performance among university students aged 18 to 24 years. Methods: This study used a quantitative cross-sectional design using data that were collected in 2014 as part of the Youth Alcohol Project (YAP). Participants were randomly drawn from a cross sectional sample of 6000 undergraduate students. Included in the study were only students who were within the age of 18-24, undergraduate, and internally enrolled at the main campus. A total of 2518 undergraduate students aged 18 to 24 years who were enrolled internally at Curtin University Bentley campus were randomly recruited. Data were collected through an online survey. Students were invited to participate in the study through their student email address. The email invitations coincided with the release of semester results to increase the likelihood of students accessing their emails. A further 628 students were randomly recruited through face to face intercept survey during the campus market days. Data were collected by trained research assistants. Validated instruments were used to collected data on levels of alcohol consumption, mental health, and academic performance. Results: A considerable proportion of participants (44%) reported consuming alcohol at hazardous or harmful levels. Multiple logistic regression analysis showed that students who were consuming alcohol at hazardous levels were 1.2 times more likely to report psychological distress than those with lower levels of alcohol consumption (aOR 1.2, 95% CI: 1.1-1.5). In addition, being late for class (aOR 1.7, 95% CI:1.1-2.4), missing classes (aOR = 2.6, 95% CI: 1.9-2.6), inability to concentrate in class (aOR = 2.6, 95% CI: 1.9-3.4), and inability to complete assignments (aOR = 3.5, 95% CI 2.0-6.0) independently predicted for moderate or hazardous alcohol consumption. Conclusion: The study shows that a considerable proportion of undergraduate students at university consume alcohol at hazardous or harmful levels. In addition, high levels of alcohol consumption are associated with poor academic performance and mental health outcomes among students. The results of the study warrant multi-strategy interventions that focus on policy, organisational, educational, environmental and economic strategies that will help to reduce alcohol related harms among university students

Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time.</p> <p>Methods</p> <p>Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (<it>MAOA</it>), lipoprotein lipase (<it>LPL</it>), paraoxonase 1 and 2 (<it>PON1 </it>and <it>PON2</it>), leptin receptor (<it>LEPR</it>), tumor necrosis factor-α (<it>TNFα</it>), and peroxisome proliferative activated receptor-γ and -δ (<it>PPARG </it>and <it>PPARD</it>). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes.</p> <p>Results</p> <p>The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between <it>PPARG </it>rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93) and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90) and <it>TNFα </it>rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28). Additional analyses showed significant associations between SNPs in <it>LEPR </it>with BMI (rs1137101) and change in BMI over time (rs1045895 and rs1137101).</p> <p>Conclusion</p> <p>Findings from this cohort study suggest that the selected SNPs are not associated with overall or cause-specific death, although several <it>LEPR </it>SNPs may be related to BMI and BMI change over time.</p

Zinc Finger Nuclease mediated knockout of ADP dependent Glucokinase in Cancer cell lines: Effects on cell survival and Mitochondrial Oxidative Metabolism

<div><p>Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of <i>ADPGK</i>, which encodes an ADP-dependent glucokinase (ADPGK), in human tumour cell lines. The hypothesis we tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two lines (H460 and HCT116). All four clones had frameshift mutations in all alleles at the target site in exon 1 of <i>ADPGK,</i> and were ADPGK-null by immunoblotting. <i>ADPGK</i> knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 21±3% for the parental line to 6.4±0.8% (p = 0.002) and 4.3±0.8% (p = 0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when <i>ADPGK</i> was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of <i>ADPGK</i> in HCT116 cells caused few changes in global gene expression, knockout of <i>ADPGK</i> in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no consistent effect on glycolysis as measured by glucose consumption or lactate formation under anoxia, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the <i>ADPGK</i> knockouts, in some cases markedly so. Collectively, the results demonstrate that <i>ADPGK</i> can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of <i>ADPGK</i> is cell line dependent and appears to be unrelated to priming of glycolysis in these lines.</p></div

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

PurposeWe have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves V˙O2V˙O2 max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT.MethodsIn Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m−2, V˙O2V˙O2 max: 51 ± 11 ml kg−1 min−1) performed a single 10-min REHIT cycling session (60 W and two 20-s ‘all-out’ sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4. In Study 2, eight men (21 ± 2 year; 25 ± 4 kg·m−2; 39 ± 10 ml kg−1 min−1) performed three trials (REHIT, 30-min cycling at 50 % of V˙O2V˙O2 max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise.ResultsAcutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1α. When compared to aerobic exercise, changes in V˙O2V˙O2 , RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected.ConclusionsCollectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise

Do inattention and hyperactivity symptoms equal scholastic impairment? evidence from three European cohorts

Background Attention Deficit/Hyperactivity Disorder (ADHD) affects many children, adolescents, and adults and is associated with a number of impairments. Poor academic performance is related to ADHD in clinical samples. However, it is unclear to what extent core ADHD symptoms and scholastic impairment are related in non-referred school-aged children. Methods Data come from three population-based cohorts from Sweden, Denmark, and Finland, which are part of the Nordic Network on ADHD. The combined sample size was 13,087 children who were studied at ages 7–8 or 10–12 years. Teachers rated children on inattention and hyperactivity symptoms and reported children's scholastic performance on basic skills. Results There was a significant association in all cohorts between core ADHD symptoms and scholastic impairment in reading, writing, and mathematics. Particularly, inattention was related to a two to tenfold increase in scholastic impairment. Prevalence of hyperactivity symptoms was similar across the three cohorts, but inattention was lowest among children from the Finnish cohort, after stratification on living conditions. Conclusion These results extend previous reports of scholastic impairment among children with clinically diagnosed ADHD to non-referred population samples from three European countries. Surveillance policies should be implemented in school systems to catch children in need of behavioral or scholastic support early

Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth