Dietary iron intakes based on food composition data may underestimate the contribution of potentially exchangeable contaminant iron from soil

Iron intakes calculated from one-day weighed records were compared with those from same day analyzed duplicate diet composites collected from 120 Malawian women living in two rural districts with contrasting soil mineralogy and where threshing may contaminate cereals with soil iron. Soils and diet composites from the two districts were then subjected to a simulated gastrointestinal digestion and iron availability in the digests measured using a Caco-2 cell model. Median analyzed iron intakes (mg/d) were higher (p < 0.001) than calculated intakes in both Zombwe (16.6 vs. 10.1 mg/d) and Mikalango (29.6 vs. 19.1 mg/d), attributed to some soil contaminant iron based on high Al and Ti concentrations in diet composites. A small portion of iron in acidic soil from Zombwe, but not Mikalango calcareous soil, was bioavailable, as it induced ferritin expression in the cells, and may have contributed to higher plasma ferritin and total body iron for the Zombwe women reported earlier, despite lower iron intakes. In conclusion, iron intakes calculated from food composition data were underestimated, highlighting the importance of analyzing duplicate diet composites where extraneous contaminant iron from soil is likely. Acidic contaminant soil may make a small but useful contribution to iron nutrition

Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS)

An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120–160 Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology

Copy number deletion burden is associated with cognitive, structural, and resting-state network differences in patients with schizophrenia

Total burden of copy number deletions has been implicated in schizophrenia risk and has been associated with reduced cognitive functioning. The current study aims to replicate the cognitive findings and investigate regional grey and white matter volumes. Moreover, it will explore resting-state networks for correlations between functional connectivity and total deletion burden. All imaging differences will be investigated for correlations with cognitive differences. Seventy-eight patients with chronic schizophrenia, who formed a subset of a large genome-wide association study (GWAS), were assessed for intelligence, 34 had structural magnetic resonance imaging, 33 had resting-state functional magnetic resonance imaging, and 32 had diffusion tensor imaging (DTI). Total deletion burden was negatively associated with IQ performance and positively associated with regional volumes in the striatum bilaterally and in the right superior temporal gyrus and white-matter in the corpus callosum. Correlations were identified between deletion burden and both hyper and hypoconnectivity within the default-mode network and hypoconnectivity within the cognitive control network. The functional connectivity correlations with deletion burden were also correlated with the IQ differences identified. Total deletion burden affects regional volumes and resting-state functional connectivity in key brain networks in patients with schizophrenia. Moreover, effects of deletions on cognitive functioning in may be due to inefficiency of key brain networks as identified by dysconnectivity in resting-state networks

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies

The presence and severity of cognitive symptoms, including working memory, executive dysfunction and attentional impairment, contributes materially to functional impairment in schizophrenia. Cognitive symptoms have proven resistant to both first- and second-generation antipsychotic drugs. Efforts to develop a consensus set of cognitive domains that are both disrupted in schizophrenia and are amenable to cross-species validation (e.g. the NIMH CNTRICS and RDoC initiatives) are an important step towards standardisation of outcome measures that can used in preclinical testing of new drugs. While causative genetic mutations have not been identified, new technologies have identified novel genes as well as hitherto candidate genes previously implicated in the pathophysiology of schizophrenia and/or mechanisms of antipsychotic efficacy. This review comprises a selective summary of these developments, particularly phenotypic data arising from preclinical genetic models for cognitive dysfunction in schizophrenia, with the aim of indicating potential new directions for pro-cognitive therapeutics

Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working Memory

BACKGROUND: Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans. METHODS: Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable. RESULTS: ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons. CONCLUSIONS: Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators

Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM

<p>Abstract</p> <p>Background</p> <p>Structural changes have been found predominantly in the frontal cortex and in the striatum in children and adolescents with Gilles de la Tourette syndrome (GTS). The influence of comorbid symptomatology is unclear. Here we sought to address the question of gray matter abnormalities in GTS patients <it>with </it>co-morbid obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD) using voxel-based morphometry (VBM) in twenty-nine adult actually unmedicated GTS patients and twenty-five healthy control subjects.</p> <p>Results</p> <p>In GTS we detected a cluster of decreased gray matter volume in the left inferior frontal gyrus (IFG), but no regions demonstrating volume increases. By comparing subgroups of GTS with comorbid ADHD to the subgroup with comorbid OCD, we found a left-sided amygdalar volume increase.</p> <p>Conclusions</p> <p>From our results it is suggested that the left IFG may constitute a common underlying structural correlate of GTS with co-morbid OCD/ADHD. A volume reduction in this brain region that has been previously identified as a key region in OCD and was associated with the active inhibition of attentional processes may reflect the failure to control behavior. Amygdala volume increase is discussed on the background of a linkage of this structure with ADHD symptomatology. Correlations with clinical data revealed gray matter volume changes in specific brain areas that have been described in these conditions each.</p

No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis

OBJECTIVE: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects. METHODS: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1. RESULTS: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. CONCLUSIONS: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia