Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis

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Dynamic flow synthesis of porous organic cages

The dynamic covalent synthesis of two imine-based porous organic cages was successfully transferred from batch to continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures. Preparative HPLC purification of one of these mixtures allowed rapid access to a desymmetrised cage molecule.We thank the Engineering and Physical Sciences Research Council (EPSRC) for financial support under the Grants EP/H000925/1 (AIC), EP/K009494/1 (SVL) and EP/M004120/1 (SVL), and Pfizer Worldwide Research & Development (CB). The authors would like to thank EPSRC Dial-a-Molecule Grand Challenge Network (EP/K004840/1) for funding a placement with SVL via the Interdisciplinary Mobility Funding scheme (AGS).This is the author accepted manuscript. The final version is available from RSC via http://dx.doi.org/10.1039/C5CC07447

Assessing hippocampal functional reserve in temporal lobe epilepsy:A multi-voxel pattern analysis of fMRI data

Assessing the functional reserve of key memory structures in the medial temporal lobes (MTL) of pre-surgical patients with intractable temporal lobe epilepsy (TLE) remains a challenge. Conventional functional MRI (fMRI) memory paradigms have yet to fully convince of their ability to confidently assess the risk of a post-surgical amnesia. An alternative fMRI analysis method, multi-voxel pattern analysis (MVPA), focuses on the patterns of activity across voxels in specific brain regions that are associated with individual memory traces. This method makes it possible to investigate whether the hippocampus and related structures contralateral to any proposed surgery are capable of laying down and representing specific memories. Here we used MVPA-fMRI to assess the functional integrity of the hippocampi and MTL in patients with long-standing medically refractory TLE associated with unilateral hippocampal sclerosis (HS). Patients were exposed to movie clips of everyday events prior to scanning, which they subsequently recalled during high-resolution fMRI. MTL structures were delineated and pattern classifiers were trained to learn the patterns of brain activity across voxels associated with each memory. Predictable patterns of activity across voxels associated with specific memories could be detected in MTL structures, including the hippocampus, on the side contralateral to the HS, indicating their functional viability. By contrast, no discernible memory representations were apparent in the sclerotic hippocampus, but adjacent MTL regions contained detectable information about the memories. These findings suggest that MVPA in fMRI memory studies of TLE can indicate hippocampal functional reserve and may be useful to predict the effects of hippocampal resection in individual patients

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

High-resolution targeted bisulfite sequencing reveals blood cell type-specific DNA methylation patterns in IL13 and ORMDL3

Background Methylation of DNA at CpG sites is an epigenetic modification and a potential modifier of disease risk, possibly mediating environmental effects. Currently, DNA methylation is commonly assessed using specific microarrays that sample methylation at a few % of all methylated sites. Methods To understand if significant information on methylation can be added by a more comprehensive analysis of methylation, we set up a quantitative method, bisulfite oligonucleotide-selective sequencing (Bs-OS-seq), and compared the data with microarray-derived methylation data. We assessed methylation at two asthma-associated genes, IL13 and ORMDL3, in blood samples collected from children with and without asthma and fractionated white blood cell types from healthy adult controls. Results Our results show that Bs-OS-seq can uncover vast amounts of methylation variation not detected by commonly used array methods. We found that high-density methylation information from even one gene can delineate the main white blood cell lineages. Conclusions We conclude that high-resolution methylation studies can yield clinically important information at selected specific loci missed by array-based methods, with potential implications for future studies of methylation-disease associations.Peer reviewe