A Mineral Extract from red Algae Ameliorates Chronic Spontaneous Colitis in IL‐10 Deficient Mice in a Mouse Strain Dependent Manner

Inflammatory bowel disease is an urgent public health problem with a high incidence in developed countries. Alterations of lifestyle or dietary interventions may attenuate the disease progression and increase the efficacy of current therapies. Here we tested the effect of chronic supplementation with a mineral extract from red marine algae – rich in calcium (34%), magnesium, phosphorus, selenium and other trace minerals – in a clinically relevant model of spontaneous enterocolitis, interleukin (IL)‐10^‐/‐ mice. The mineral extract was administered in the drinking water of Il10^‐/‐ mice on C57BL/6 J and BALB/c strain backgrounds for 25 weeks commencing from 3 to 4 weeks of age. The mineral extract ameliorated the spontaneous development of colitis and severity of disease in Il10^‐/‐ mice on a C57BL/6 J background. Mineral extract‐treated Il10^‐/‐ C57BL/6 J strain mice had significantly reduced mortality, circulating levels of serum Amyloid A and reduced colonic tissue damage. In contrast, comparable treatment of Il10^‐/‐ mice on a BALB/c background with the mineral extract did not alter the course of colitis. These data demonstrate that chronic supplementation with a natural mineral extract selectively ameliorates spontaneous mild–moderate colitis in Il10^‐/‐ mice on a C57BL/6 J, but does not attenuate more moderate–severe colitis in BALB/c strain animals. Copyright © 2013 John Wiley & Sons, Ltd.     

Novel approaches in colorectal endoscopy: What do we need biopsies for?

Magnification chromoendoscopy, narrow band imaging (NBI) and confocal endomicroscopy can all provide accurate assessment of small and diminutive colonic lesions for neoplastic change that approaches the accuracy of standard histopathology. It is likely that there will be a move to use these techniques in clinical practice for small and particularly diminutive, non-depressed lesions in the near future. Non-neoplastic lesions would be left in situ, and neoplastic lesions resected and disposed of without histopathological assessment. Histopathology would be reserved for larger lesions, indeterminate lesions or lesions where invasion was suspected. There are potentially significant cost savings and patient benefits, with a focussing of histopathological expertise on higher risk lesions, particularly in the era of bowel cancer screening. These techniques may also help target biopsies in colitis surveillance, removing the need for large numbers of random samples. However, in order to convince patients, histopathologists and those funding healthcare of the validity of this approach, further trial data will be needed, with an accreditation process for endoscopists wishing to take on this responsibility.     

Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing

A piezoelectric actuated, drop-on-demand inkjet printing system has been used to deliver suspensions of human fibroblast cells from a well-characterized cell line (HT 1080) in order to investigate the behaviour of cells exposed to the mechanical and fluid stresses associated with the printing process. By varying the amplitude and rise time of the electrical pulse used to excite the piezoelectric actuator, it is possible to alter the stresses experienced by the cells. It is shown that the amplitude of the pulse has a small influence on cell survivability with regression analysis showing cell survival rates falling from 98% with a 40 V pulse (indistinguishable from control measurements) to approximately 94% with a 80 V pulse. The rise time of the pulse was found to have no influence on cell survival. Cell viability post-printing was also assessed using the Alamar Blue metabolic assay and the cells that survived were unaffected by the printing process, with neither pulse amplitude nor rise time showing any significant influence on cell viability (using the standard 5% probability threshold). However, inkjet printing requires cell suspensions to be stable over several minutes during the printing process and it was found that after about 20 min printing, some cell agglomeration or sedimentation affected the printing performance.     

A mathematical model platform for optimizing a multiprojection breast imaging system

Multiprojection imaging is a technique in which a plurality of digital radiographic images of the same patient are acquired within a short interval of time from slightly different angles. Information from each image is combined to determine the final diagnosis. Projection data are either reconstructed into slices as in the case of tomosynthesis or analyzed directly as in the case of multiprojection correlation imaging technique, thereby avoiding reconstruction artifacts. In this study, the authors investigated the optimum geometry of acquisitions of a multiprojection breast correlation imaging system in terms of the number of projections and their total angular span that yield maximum performance in a task that models clinical decision. Twenty-five angular projections of each breast from 82 human subjects in our breast tomosynthesis database were each supplemented with a simulated 3 mm mass. An approach based on Laguerre-Gauss channelized Hotelling observer was developed to assess the detectability of the mass in terms of receiver operating characteristic (ROC) curves. Two methodologies were developed to integrate results from individual projections into one combined ROC curve as the overall figure of merit. To optimize the acquisition geometry, different components of acquisitions were changed to investigate which one of the many possible configurations maximized the area under the combined ROC curve. Optimization was investigated under two acquisition dose conditions corresponding to a fixed total dose delivered to the patient and a variable dose condition, based on the number of projections used. In either case, the detectability was dependent on the number of projections used, the total angular span of those projections, and the acquisition dose level. In the first case, the detectability approximately followed a bell curve as a function of the number of projections with the maximum between 8 and 16 projections spanning angular arcs of about 23 degrees-45 degrees, respectively. In the second case, the detectability increased with the number of projections approaching an asymptote at 11-17 projections for an angular span of about 45 degrees. These results indicate the inherent information content of the multi-projection image data reflecting the relative role of quantum and anatomical noise in multiprojection breast imaging. The optimization scheme presented here may be applied to any multiprojection imaging modalities and may be extended by including reconstruction in the case of digital breast tomosynthesis and breast computed tomography.     

Association of race, socioeconomic status, and health care access with pressure ulcers after spinal cord injury

Saunders LL, Krause JS, Acuna J. Association of race, socioeconomic status, and health care access with pressure ulcers after spinal cord injury.ObjectiveTo assess the associations of race and socioeconomic status (SES) with pressure ulcers (PUs) after accounting for health care access among persons with spinal cord injury (SCI).DesignCross-sectional.SettingLarge specialty hospital in the southeastern United States.ParticipantsPersons with traumatic SCI who (1) had residual effects from their injury, (2) were 18 years or older at the time of the survey, and (3) were a year or more postinjury at the time of survey (N=2549).InterventionsNone.Main Outcome MeasuresOutcomes were measured by a mail-in survey: having a current PU (yes vs no), having a PU in the past year with or without reduced sitting time (no PU, no reduced sitting time, month or less, ≥5wk), and having at least 1 PU surgery since SCI onset (yes vs no).ResultsOf participants, 39.3% reported a PU in the past year, 19.9% had a current PU, and 21.9% reported having had surgery for a PU since their SCI onset. While race was preliminarily associated with each PU outcome, it became nonsignificant after controlling for SES and health care access. In each analysis, household income was significantly associated with PU outcomes after controlling for demographic and injury factors and remained significant after accounting for the health care access factors. Persons with lower income had higher odds of each PU outcome. Health care access was not consistently related to PU outcomes.ConclusionsEven after accounting for health care access, household income, a measure of SES, remained significantly associated with PU outcomes after SCI; however, race became nonsignificant.     

Evidence of linkage to chromosomes 10p15.3-p15.1, 14q24.3-q31.1 and 9q33.3-q34.3 in non-syndromic colorectal cancer families

Up to 25% of colorectal cancer (CRC) may be caused by inherited genetic variants that have yet to be identified. Previous genome-wide linkage studies (GWLSs) have identified a new loci postulated to contain novel CRC risk genes amongst affected families carrying no identifiable mutations in any of the known susceptibility genes for familial CRC syndromes. To undertake a new GWLS, we recruited members from 54 non-syndromic families from Australia and Spain where at least two first-degree relatives were affected by CRC. We used single-nucleotide polymorphism arrays to genotype 98 concordant affected relative pairs that were informative for linkage analyses. We tested for genome-wide significance (GWS) for linkage to CRC using a quantile statistic method, and we found that GWS was achieved at the 5% level. Independently, using the PSEUDO gene-dropping algorithm, we also found that GWS for linkage to CRC was achieved (P=0.02). Merlin non-parametric linkage analysis revealed significant linkage to CRC for chromosomal region 10p15.3-p15.1 and suggestive linkage to CRC for regions on 14q and 9q. The 10p15.3-p15.1 has not been reported to be linked to hereditary CRC in previous linkage studies, but this region does harbour the Kruppel-like factor 6 (KLF6) gene that is known to be altered in common CRC. Further studies aimed at localising the responsible genes, and characterising their function will give insight into the factors responsible for susceptibility in such families, and perhaps shed further light on the mechanisms of CRC development.     

Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.     

Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy

The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.