ALBERT

Description: Background: Studies have suggested that inflammatory bowel diseases (IBD) follow a seasonal pattern with regard to their onset and exacerbations. The aim of this study is to determine if there is any seasonal pattern to the onset and exacerbation of IBD in the pediatric population and if the birth of children diagnosed with IBD follows a seasonal pattern. Methods: Patients between the ages of 1 and 21 years and with a diagnosis of IBD established between July 1992 and July 2012 were included. Their onset and exacerbations of IBD (year and season) were recorded. The birth dates of the patients were aggregated to determine whether a seasonal birth pattern existed amongst them. Results: A total of 170 children were included in this study; 34 % of patients had their onset in the fall and 19 % of them had their onset in the summer. The total number of documented exacerbations was 358 and the median number of exacerbations was two, with a range of 1–11. IBD exacerbations were generally uniformly distributed throughout the year. We did not observe any specific season where children with IBD tended to be born. Conclusions: Our data suggests that the onset of symptoms of IBD tends to have a seasonal trend with the highest incidence in the fall. However, we did not observe any association between seasonality and exacerbations in the pediatric population. Moreover, there was no specific season in which children with IBD tended to be born in greater numbers.

Description: Background: Celiac disease (CD) and eosinophilic esophagitis (EoE) are distinct diseases of the gastrointestinal tract with specific clinico-pathological characteristics. Recent studies have found higher rates of EoE in patients with CD than in the general population. Our aim was to estimate the incidence of EoE among children who were diagnosed with CD over a 42-month period. Methods: The study included patients diagnosed with CD based on endoscopy and histopathological findings between January 2010 and June 2013. Histopathology reports of esophageal biopsies were reviewed to identify all cases of EoE. The patients’ presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, treatments, and follow-ups were analysed. Results: Fifty-six patients with CD were identified, of whom six (10.7%) were diagnosed with both CD and EoE. Four of these patients presented with abdominal pain and diarrhea, two presented with failure to thrive, and three presented with food allergies. Endoscopic and histopathological changes typical of EoE were observed in all six patients. During follow-up, two patients showed significant improvement with the gluten-free diet and a proton-pump inhibitor (PPI). Two patients improved with the elimination diet and two patients were treated with topical corticosteroid therapy. Endoscopic appearance was normal in all children on follow-up endoscopy after treatment. Biopsy samples also showed resolution of the histologic features of EoE in all of the children. Conclusion: The incidence of EoE in our cohort of children with CD was 10.7%, which is higher than what has been reported for the general population. In all children undergoing upper gastrointestinal endoscopy for suspected CD, coexistence of EoE should be considered.

Description: Endophytes are microbes that inhabit internal plant tissues without causing disease. Plant microbial communities consist of large numbers of endophyte species. Understanding the functions of these endophytes i...

Description: Background: A UK Register of people with Multiple Sclerosis has been developed to address the need foran increased knowledge-base about MS. The Register is being populated via: a web-basedportal; NHS neurology clinical systems; and administrative data sources. The data are deidentifiedand linked at the individual level. At the outset, it was not known whether peoplewith MS would wish to participate in the UK MS Register by personally contributing theirdata to the Register via a web-based system. Therefore, the research aim of this work was tobuild an internet-mounted recruitment and consenting technology for people with MultipleSclerosis, and to assess its feasibility as a questionnaire delivery platform to contribute datato the UK MS Register, by determining whether the information provided could be used todescribe a cohort of people with MS. Methods: The web portal was developed using VB.net and JQuery with a Microsoft SQL 2008database. UK adults with MS can self-register and enter data about themselves by completingvalidated questionnaires. Descriptive statistics were used to characterise the respondents. Results: The web portal was launched in May 2011, and in first three months 7,279 individualsregistered on the portal. The ratio of men to women was 1:2.4 (n = 5,899), the mean selfreportedage at first symptoms was 33.8 (SD 10.5) years, and at diagnosis 39.6 (SD 10.3)years (n = 4,401). The reported types of MS were: 15% primary progressive, 63% relapsingremitting,8% secondary progressive, and 14% unknown (n = 5,400). These characteristics aresimilar to those of the prevalent MS population. Employment rates, sickness/disability rates,ethnicity and educational qualifications were compared with the general UK population.Information about the respondents' experience of early symptoms and the process ofdiagnosis, plus living arrangements are also reported. Conclusions: These initial findings from the MS Register portal demonstrate the feasibility of collectingdata about people with MS via a web platform, and show that sufficient information can begathered to characterise a cohort of people with MS. The innovative design of the UK MSregister, bringing together three disparate sources of data, is creating a rich resource forresearch into this condition.

Description: Background: SPARCLE is a study across nine European regions which examines the predictors of participation and quality of life of children with cerebral palsy. Children and their families were initially interviewed in 2004/2005 when the children were aged 8-12 years (SPARCLE1); they were approached again in 2009/2010 at age 13-17 years (SPARCLE2). The objective of this report is to assess potential for bias due to family non-response in SPARCLE2. Logistic regression was used to assess whether socio-demographic factors, parental stress and child impairment were related to non-response, both overall and by category (failure to trace families, death of child, traced families declining to participate). Results: Of the 818 families who participated in SPARCLE1, 224/818 (27%) did not participate in SPARCLE2. 51/818 (6%) were not traced. Among the 767 traced families, 32/767 (4%) children with cerebral palsy had died, seven children had been incorrectly diagnosed as having cerebral palsy, thirteen families had moved out of the region and one family had language problems. Of the remaining 714 families, 120/714 (17%) declined to participate. Drop-out between SPARCLE1 and SPARCLE2 varied significantly between regions; families were more difficult to trace and more likely to decline to participate if the parents' educational qualifications, as recorded in SPARCLE1, were lower; they were also more likely to decline to participate if SPARCLE1 recorded that they were more stressed or if they had not completed a SPARCLE1 stress questionnaire. Conclusions: To reduce the risk of bias, all SPARCLE2 analyses should allow for factors (region and walking ability) which determined the sampling strategy, either by adjusting for these factors or by using sampling weights. Further analyses should be performed, adjusting for additional factors that were associated with non-response: parents' educational qualifications, family structure and parental stress. To allow for differential non-response in studies which sample from population registers, such registers should routinely record socio-demographic information.

Description: Background: The behaviour of tumour cells depends on factors such as genetics and the tumourmicroenvironment. The latter plays a crucial role in normal mammary gland development andalso in breast cancer initiation and progression. Breast cancer tissues tend to be highlydesmoplastic and dense matrix as a pre-existing condition poses one of the highest riskfactors for cancer development. However, matrix influence on tumour cell gene expressionand behaviour such as cell migration is not fully elucidated. Results: We generated high-density (HD) matrices that mimicked tumour collagen content of 20mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cellimaging showed breast cancer cells utilizing cytoplasmic streaming and cell bodycontractility for migration within HD matrix. Cell migration was blocked in the presence ofboth the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugsindividually. This suggests roles for ROCK1 and MMP in cell migration are complicated bycompensatory mechanisms. ROCK1 expression and protein activity, were significantlyupregulated in HD matrix but these were blocked by treatment with a histone deacetylase(HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirectand relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA orDAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion: Increased matrix density elevates ROCK1 activity, which aids in cell migration via cellcontractility. The upregulation of ROCK1 is epigenetically regulated in an indirect mannerinvolving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1expression.

Description: Background: We have used the genomic data in the Integrated Microbial Genomes system of the Department of Energy's Joint Genome Institute to make predictions about rhizobial open reading frames that play a role in nodulation of host plants. The genomic data was screened by searching for ORFs conserved in alpha-proteobacterial rhizobia, but not conserved in closely-related non-nitrogen-fixing alpha-proteobacteria. Results: Using this approach, we identified many genes known to be involved in nodulation or nitrogen fixation, as well as several new candidate genes. We knocked out selected new genes and assayed for the presence of nodulation phenotypes and/or nodule-specific expression. One of these genes, SMc00911, is strongly expressed by bacterial cells within host plant nodules, but is expressed minimally by free-living bacterial cells. A strain carrying an insertion mutation in SMc00911 is not defective in the symbiosis with host plants, but in contrast to expectations, this mutant strain is able to out-compete the S. meliloti 1021 wild type strain for nodule occupancy in co-inoculation experiments. The Smc00911 ORF is predicted to encode a "SodM-like" (superoxide dismutase-like) protein containing a rhodanese sulfurtransferase domain at the N-terminus and a chromate-resistance superfamily domain at the C-terminus. Several other ORFs (SMb20360, SMc01562, SMc01266, SMc03964, and the SMc01424-22 operon) identified in the screen are expressed at a moderate level by bacteria within nodules, but not by free-living bacteria. Conclusions: Based on the analysis of ORFs identified in this study, we conclude that this comparative genomics approach can identify rhizobial genes involved in the nitrogen-fixing symbiosis with host plants, although none of the newly identified genes were found to be essential for this process.

Description: Background: Polyethylene Glycol 3350 (Miralax(R)) without electrolytes is commonly used for 3-4 days as bowel preparation for colonoscopy in children. One-day preparation has been anecdotally reported to be effective but there are few published prospective studies comparing the safety and efficacy of one-day preparation with that of three-day preparation. This study was conducted to compare the efficacy and safety of a one-day bowel preparation with Miralax(R) with that of a three-day preparation for colonoscopy in children. Methods: We conducted a prospective, randomized controlled trial with children age 2-21 yrs. undergoing elective colonoscopy. Patients were randomly assigned to receive Miralax(R) for either one or three days. Children with known electrolyte disturbances, dehydration, fecal impaction, metabolic or renal disease were excluded. A metabolic panel was monitored before and after bowel preparation. Subjects reported the tolerability and side effects of Miralax(R) via a survey. Effectiveness of the bowel preparation was assessed using a stool diary and a bowel cleansing scale during colonoscopy. Results: 32 subjects were enrolled; 18 received one-day bowel preparation and 14 received 3-day preparation. There were no differences between the groups in efficacy of bowel preparation based on colonoscopic grading or the safety of the preparation. One-day preparation was as well tolerated as three-day preparation. Conclusion: Miralax(R) used one day as bowel preparation for elective colonoscopy in children is safe, effective and well tolerated. Physicians should consider offering a one-day option for bowel preparation, which would allow children to miss fewer days of school prior to colonoscopy.Trial registration: Trial Registration Number: NCT02174497. Date of Registration: 02 May, 2014 URL of register: clinicaltrials.gov.

Description: Background: Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties of microarray data using diverse biological samples. Most microarray experiments seek to identify subtle differences between samples with variable background noise, a scenario poorly represented by constructed datasets. Thus, microarray users lack important information regarding the complexities introduced in real-world experimental settings. The recent development of a multiplexed, digital technology for nucleic acid measurement enables counting of individual RNA molecules without amplification and, for the first time, permits such a study. Results: Using a set of human leukocyte subset RNA samples, we compared previously acquired microarray expression values with RNA molecule counts determined by the nCounter Analysis System (NanoString Technologies) in selected genes. We found that gene measurements across samples correlated well between the two platforms, particularly for high-variance genes, while genes deemed unexpressed by the nCounter generally had both low expression and low variance on the microarray. Confirming previous findings from spike-in and dilution datasets, this "gold-standard" comparison demonstrated signal compression that varied dramatically by expression level and, to a lesser extent, by dataset. Most importantly, examination of three different cell types revealed that noise levels differed across tissues. Conclusions: Microarray measurements generally correlate with relative RNA molecule counts within optimal ranges but suffer from expression-dependent accuracy bias and precision that varies across datasets. We urge microarray users to consider expression-level effects in signal interpretation and to evaluate noise properties in each dataset independently.

Description: The robustness of epidemiological research using routinely collected primary care electronic data to support policy and practice for common mental disorders (CMD) anxiety and depression would be greatly enhanc...