The Impact of Social Disparity on Prefrontal Function in Childhood

The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

A primary care database study of asthma among patients with and without opioid use disorders

Substance misuse is associated with poor asthma outcome and death. People with opioid use disorder (OUD) may be at particular risk, however, there have been no case-control studies of asthma care and outcomes in this patient group. A primary care database study of patients with asthma aged 16–65 years was conducted using a matched case-control methodology. The dataset comprised 275,151 adults with asthma, of whom 459 had a clinical code indicating a lifetime history of OUD. Cases with a history of OUD were matched to controls 1:3 by age, gender, smoking status and deprivation index decile. Attendance at annual review (30%) and for immunisation (25%) was poor amongst the overall matched study population (N = 1832). Compared to matched controls, cases were less likely to have attended for asthma review during the previous 12 months (OR = 0.60, 95% CI 0.45–0.80) but had similar immunisation rates. Higher rates of ICS (OR = 1.50, 1.13–1.98) and oral prednisolone use (OR = 1.71, 1.25–2.40) were seen amongst those with a history of OUD and 7.2% had a concurrent diagnosis of COPD (OR = 1.86, 1.12–2.40). We found that people with asthma and a history of OUD have worse outcomes on several commonly measured metrics of asthma care. Further research is required to identify reasons for these findings, the most effective strategies to help this vulnerable group access basic asthma care, and to better understand long-term respiratory outcomes

Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis

<p>Abstract</p> <p>Background</p> <p>Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on <it>TLR2, TLR3</it>, and <it>TLR4 </it>participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of <it>TLR1 to 9 </it>in colonic mucosa of UC patients, according to disease activity.</p> <p>Methods</p> <p>Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of <it>TLR1 to 9, Tollip</it>, inflammatory cytokines <it>IL6 </it>and <it>TNF </it>were assessed by RT-qPCR with hydrolysis probes. Characterization of <it>TLR9 </it>protein expression was performed by Immunohistochemistry.</p> <p>Results</p> <p>Toll-like receptors <it>TLR8, TLR9</it>, and <it>IL6 </it>mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the <it>TLR2, TLR4, TLR8 </it>and <it>TLR9 </it>mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas <it>TLR5 </it>showed a trend (p = 0.06). <it>IL6 </it>and <it>TNF </it>mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, <it>IL6 </it>and <it>TNF </it>mRNA positively correlate with TLRs mRNA with the exception for <it>TLR3</it>, with stronger correlations for <it>TLR5, TLR8</it>, and <it>TLR9 </it>(p < 0.0001). <it>TLR9 </it>protein expression was mainly in the lamina propria infiltrate.</p> <p>Conclusions</p> <p>This study demonstrates that <it>TLR2, TLR4, TLR8</it>, and <it>TLR9 </it>expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.</p

Developing inclusive pedagogies in HE through an understanding of the learner-consumer : promiscuity, hybridisation, and innovation

Abstract: This article contributes to debates about how to respond to the changing profile of Higher Education (HE) students, and the marketisation of HE, by challenging prevailing views about student engagement, in order to develop learner-centric and inclusive pedagogies which are relevant to the twenty-first century. The concepts of ‘participatory culture’ and ‘co-creativity’ are often associated with the digital world in which the current generation of students have grown up. But it is a mistake to assume that some learning styles are inherently more participatory than others: participation is not an effect of the medium or form, (analog vs digital), or the space (actual vs virtual), or the mode of interaction a (face-to-face vs networked) through which the learner participates – it is an effect of the practices involved. Students engage with a complex network of both digital and analog texts and spaces, and it is this postdigital hybrid setting within which student engagement takes place. Marketisation provides an opportunity to actively demonstrate our commitments to student-centredness and inclusive practice, by transcending the binary opposition between ‘Student as Partner’ and ‘Student as Consumer’ and recognizing that students are learner-consumers, and allowing students’ diversity to drive innovation, rather than continuing to disempower students by bolstering practices which privilege some learning styles above others, informed by the assumption that innovation is technology-led

The Active for Life Year 5 (AFLY5) school based cluster randomised controlled trial: study protocol for a randomized controlled trial

Background: Low levels of physical activity, high levels of sedentary behaviour and low levels of fruit and vegetable consumption are common in children and are associated with adverse health outcomes. The aim of this paper is to describe the protocol for a cluster randomised controlled trial (RCT) designed to evaluate a school-based intervention that aims to increase levels of physical activity, decrease sedentary behaviour and increase consumption of fruit and vegetables in school children. Methods/design: The Active for Life Year 5 (AFLY5) study is a school-based, cluster RCT that targets school children in Year 5 (age 9-10 years). All state junior/primary schools in the area covered by Bristol City and North Somerset Council are invited to participate; special schools are excluded. Eligible schools are randomised to one of two arms: intervention arm (receive the intervention 2011-2012) and control arm (receive the intervention after the final follow-up assessment, 2013-2014). The primary outcomes of the trial are levels of accelerometer assessed physical activity and sedentary behaviour and questionnaire assessed fruit and vegetable consumption. A number of secondary outcomes will also be measured, including body mass index, waist circumference and overweight/obesity. Outcomes will be assessed at baseline (prior to intervention when the children are in Year 4), at the end of intervention ‘immediate follow-up’ and ‘12 months long-term’ follow-up. We will use random effects linear and logistic regression models to compare outcomes by randomised arm. The economic evaluation from a societal perspective will take the form of a cost consequence analysis. Data from focus groups and interviews with pupils, parents and teachers will be used to increase understanding of how the intervention has any effect and is integrated into normal school activity. Discussion: The results of the trial will provide information about the public health effectiveness of a school-based intervention aimed at improving levels of physical activity, sedentary behaviour and diet in children.Debbie A Lawlor, Russell Jago, Sian M Noble, Catherine R Chittleborough, Rona Campbell, Julie Mytton, Laura D Howe, Tim J Peters and Ruth R Kippin

Transfer of Neuroplasticity from Nucleus Accumbens Core to Shell Is Required for Cocaine Reward

It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell

Rapidly measured indicators of recreational water quality and swimming-associated illness at marine beaches: a prospective cohort study

<p>Abstract</p> <p>Introduction</p> <p>In the United States and elsewhere, recreational water quality is monitored for fecal indicator bacteria to help prevent swimming-associated illnesses. Standard methods to measure these bacteria take at least 24 hours to obtain results. Molecular approaches such as quantitative polymerase chain reaction (qPCR) can estimate these bacteria faster, in under 3 hours. Previously, we demonstrated that measurements of the fecal indicator bacteria <it>Enterococcus </it>using qPCR were associated with gastrointestinal (GI) illness among swimmers at freshwater beaches. In this paper, we report on results from three marine beach sites.</p> <p>Methods</p> <p>We interviewed beach-goers and collected water samples at marine beaches affected by treated sewage discharges in Mississippi in 2005, and Rhode Island and Alabama in 2007. Ten to twelve days later, we obtained information about gastrointestinal, respiratory, eye, ear and skin symptoms by telephone. We tested water samples for fecal indicator organisms using qPCR and other methods.</p> <p>Results</p> <p>We enrolled 6,350 beach-goers. The occurrence of GI illness among swimmers was associated with a log₁₀-increase in exposure to qPCR-determined estimates of fecal indicator organisms in the genus <it>Enterococcus </it>(AOR = 2.6, 95% CI 1.3-5.1) and order <it>Bacteroidales </it>(AOR = 1.9, 95% CI 1.3-2.9). Estimates of organisms related to <it>Clostridium perfringens </it>and a subgroup of organisms in the genus <it>Bacteroides </it>were also determined by qPCR in 2007, as was F+ coliphage, but relationships between these indicators and illness were not statistically significant.</p> <p>Conclusions</p> <p>This study provides the first evidence of a relationship between gastrointestinal illness and estimates of fecal indicator organisms determined by qPCR at marine beaches.</p

Systems Genetics of Hepatic Metabolome Reveals Octopamine as a Target for Non-Alcoholic Fatty Liver Disease Treatment.

Non-alcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. To disentangle etiological relationships between these conditions and identify genetically-determined metabolites involved in NAFLD processes, we mapped 1H nuclear magnetic resonance (NMR) metabolomic and disease-related phenotypes in a mouse F2 cross derived from strains showing resistance (BALB/c) and increased susceptibility (129S6) to these diseases. Quantitative trait locus (QTL) analysis based on single nucleotide polymorphism (SNP) genotypes identified diet responsive QTLs in F2 mice fed control or high fat diet (HFD). In HFD fed F2 mice we mapped on chromosome 18 a QTL regulating liver micro- and macrovesicular steatosis and inflammation, independently from glucose intolerance and adiposity, which was linked to chromosome 4. Linkage analysis of liver metabolomic profiling data identified a QTL for octopamine, which co-localised with the QTL for liver histopathology in the cross. Functional relationship between these two QTLs was validated in vivo in mice chronically treated with octopamine, which exhibited reduction in liver histopathology and metabolic benefits, underlining its role as a mechanistic biomarker of fatty liver with potential therapeutic applications