Choosing the right cross-sectional imaging technique: Trading image quality for radiation risk

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83765/1/21536_ftp.pd

College adjustment in University of Michigan students with Crohn's and colitis

Background: Adjustment to college is critical for academic success. Poor college adjustment correlates with poor academic performance, low graduation rates, and poor success later in life. Limited data are available on the effects of inflammatory bowel disease (IBD) on college adjustment. We hypothesize that disease activity negatively impacts on QOL, and adversely affects college adjustment. Methods: Undergraduate students (6 Crohn's disease [CD], 12 ulcerative colitis [UC], 19 healthy controls) completed a standardized college adjustment survey (SACQ) and QOL instrument (SF-12). Where appropriate, disease specific activity and QOL indices were obtained (HBI, SCCAI, SIBDQ). Results: There was an inverse correlation between disease activity and college adjustment in CD and UC (R = −0.6554, p = 0.0032). IBD students had lower physical QOL (SF-12) than controls (p = 0.0009). Emotional domain of college adjustment correlated best with SIBDQ (R = 0.8228, p < 0.0001), and correlated better in CD (R = 0.8619) than UC (R = 0.7946). Mental QOL (SF-12) was worse in CD than UC (p = 0.0211), but neither differed from controls (p = 0.4, p = 0.6). Conclusions: Students with active Crohn's and colitis adjust less well to college life. Physical and emotional factors likely contribute. More aggressive medical therapy and better emotional support before and during college may result in happier and healthier college students, leading to higher graduation rates and future success. Interventions resulting in better disease control and support systems may improve college performance and provide long-term benefits to young adults with IBD. (Inflamm Bowel Dis 2008)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60909/1/20484_ftp.pd

Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease

Background: CT enterography yields striking findings in the bowel wall in Crohn's disease. These images may help to evaluate whether small bowel narrowing results from active disease requiring anti-inflammatory therapy. However, the clinical relevance of these images is unknown. It is also not known if these radiologic findings correlate with objective biomarkers of inflammation. Methods: In a blinded and independent evaluation, IBD subspecialty gastroenterologists reviewed clinical data, and CT radiologists reviewed CT enterography scans of 67 consecutive patients with Crohn's disease and suspicion of either small bowel inflammation or stricture. Comparisons were made between (1) clinical and radiologic assessments of inflammation and stricture, (2) clinical assessments before and after computed tomographic enterography (CTE) reports were revealed, and (3) radiologic findings and objective biomarkers of inflammation. Results: (1) Individual CTE findings correlated poorly (Spearman's rho < 0.30) with clinical assessment; (2) clinicians did not suspect 16% of radiologic strictures, and more than half the cases of clinically suspected strictures did not have them on CTE; (3) CTE data changed clinicians' perceptions of the likelihood of steroid benefit in 41 of 67 cases; (4) specific CTE findings correlated with CRP, and a distinct set of CTE findings correlated with ESR in the subset of patients who had these biomarkers measured. Conclusions: CTE seems to add unique information to clinical assessment, both in detecting additional strictures and in changing clinicians' perceptions of the likelihood of steroids benefiting patients. The biomarker correlations suggest that CTE is measuring real biologic phenomena that correlate with inflammation, providing information distinct from that in a standard clinical assessment. (Inflamm Bowel Dis 2006)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55965/1/20013_ftp.pd

Identification of symptom domains in ulcerative colitis that occur frequently during flares and are responsive to changes in disease activity

<p>Abstract</p> <p>Background</p> <p>Ulcerative colitis disease activity is determined by measuring symptoms and signs. Our aim was to determine which symptom domains are frequent and responsive to change in the evaluation of disease activity, which are those defined by three criteria: 1) they occur frequently during flares; 2) they improve during effective therapy for ulcerative colitis; and 3) they resolve during remission.</p> <p>Methods</p> <p>Twenty-eight symptom domains, 16 from standard indices and 12 novel domains identified by ulcerative colitis patient focus groups, were evaluated. Sixty subjects with ulcerative colitis were surveyed, rating each symptom on the three criteria with a 100 mm Visual Analogue Scale. Frequent and responsive symptoms were defined <it>a priori </it>as those whose median Visual Analogue Scale rating for all 3 criteria was significantly greater than 50.</p> <p>Results</p> <p>Thirteen of the 28 symptom domains were identified as both frequent in ulcerative colitis flares and responsive to changes in disease activity. Seven of these 13 symptom domains were novel symptoms derived from ulcerative colitis patient focus groups including stool mucus, tenesmus, fatigue, rapid postprandial bowel movements, and inability to differentiate liquid or gas from solid stool when rectal urgency occurs. Ten of the 16 symptom domains from standard indices were either infrequent or unresponsive to changes in disease activity.</p> <p>Conclusion</p> <p>Only some of the symptoms of ulcerative colitis that are important to patients are included in standard indices, and several symptoms currently measured are not frequent or responsive to change in ulcerative colitis patients. Development of survey measures of these symptom domains could significantly improve the assessment of disease activity in ulcerative colitis.</p

Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan‐polysaccharide rat model of Crohn's disease

Background: Resveratrol has antiinflammatory and antifibrotic effects. Resveratrol decreases proliferation and collagen synthesis by intestinal smooth muscle cells. We hypothesized that resveratrol would decrease inflammation and fibrosis in an animal model of Crohn's disease. Methods: Peptidoglycan‐polysaccharide (PG‐PS) or human serum albumin (HSA) was injected into the bowel wall of Lewis rats at laparotomy. Resveratrol or vehicle was administered daily by gavage 1–27 days postinjection. On day 28, gross abdominal and histologic findings were scored. Cecal collagen content was measured by colorimetric analysis of digital images of trichrome‐stained sections. Cecal levels of procollagen, cytokine, and growth factor mRNAs were determined. Results: PG‐PS‐injected rats (vehicle‐treated) developed more fibrosis than HSA‐injected rats by all measurements: gross abdominal score ( P < 0.001), cecal collagen content ( P = 0.04), and procollagen I and III mRNAs ( P ≤ 0.0007). PG‐PS‐injected rats treated with 40 mg/kg resveratrol showed a trend toward decreased gross abdominal score, inflammatory cytokine mRNAs, and procollagen mRNAs. PG‐PS‐injected rats treated with 100 mg/kg resveratrol had lower inflammatory cytokine mRNAs (IL‐1β [3.50 ± 1.08 vs. 10.79 ± 1.88, P = 0.005], IL‐6 [17.11 ± 9.22 vs. 45.64 ± 8.83, P = 0.03], tumor necrosis factor alpha (TNF‐α) [0.80 ± 0.14 vs. 1.89 ± 0.22, P = 0.002]), transforming growth factor beta 1 (TGF‐β1) mRNA (2.24 ± 0.37 vs. 4.06 ± 0.58, P = 0.01), and histologic fibrosis score (6.4 ± 1.1 vs. 9.8 ± 1.0; P = 0.035) than those treated with vehicle. There were trends toward decreased gross abdominal score and decreased cecal collagen content. Procollagen I, procollagen III, and IGF‐I mRNAs also trended downward. Conclusions: Resveratrol decreases inflammatory cytokines and TGF‐β1 in the PG‐PS model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. These findings may have therapeutic applications in inflammatory bowel disease. (Inflamm Bowel Dis 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90530/1/21843_ftp.pd

Interannual Variability in Methane and Nitrous Oxide Concentrations and Sea-Air Fluxes Across the North American Arctic Ocean (2015–2019)

Between 2015 and 2018, we collected approximately 2,000 water column measurements of methane (CH4) and nitrous oxide (N2O) concentrations in the North American Arctic Ocean during summer and early fall. We also obtained 25 measurements of CH4 and N2O concentrations in rivers along the Northwest Passage and Ellesmere Island in midsummer 2017–2019. Our results show that N2O is generated in the highly productive Bering and Chukchi Seas and transported northeastward, producing a persistent subsurface N2O peak in the Beaufort Sea. The Chukchi and Beaufort Sea sediments are a significant source of CH4 to the water column. These sedimentary sources and associated water column consumption display significant spatial gradients and interannual variability. CH4 isotope data demonstrate the importance of CH4 oxidation across the study region. We find that rivers are not a significant source of CH4 or N2O to the Arctic Ocean at the time of year sampled. The estimated annual sea-air flux across the study region (2.3 million km2) had a median (first quartile, third quartile) of 0.009 (0.002, 0.023) Tg CH4 y−1 and −0.003 (−0.013, 0.010) Tg N y−1. These results suggest that the North American Arctic Ocean currently plays a negligible role in global CH4 and N2O budgets. Our expansive data set, with observations at many repeat stations, provides a synopsis of present-day Arctic CH4 and N2O distributions and their range of variability, as well as a benchmark against which future climatedependent changes can be evaluated

Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific

Accumulation of triacylglycerol (TAG) and lipid intermediates in skeletal muscle plays an important role in the etiology of insulin resistance and type 2 diabetes mellitus. Disturbances in skeletal muscle lipid turnover and lipolysis may contribute significantly to this. So far, knowledge on the regulation of muscle lipolysis is limited. Recently the identification of a new lipase was reported: adipose triglyceride lipase (ATGL). ATGL deficient animals show significant lipid accumulation in skeletal muscle, which may indicate that ATGL plays a pivotal role in skeletal muscle lipolysis. However, until now, it is still unknown whether ATGL protein is expressed in human skeletal muscle. Therefore, the aim of the present study was to investigate whether ATGL is expressed at the protein level in human skeletal muscle, and to examine whether its expression is fiber-type specific. To accomplish this, we established an imunohistochemical and immunofluorescent staining procedure to study ATGL protein expression in relation to fiber type in human vastus lateralis muscle of eight male subjects (BMI range: 21.0–34.5 kg/m2 and age: 38–59 years). In the present paper we report for the first time that ATGL protein is indeed expressed in human skeletal muscle. Moreover, ATGL is exclusively expressed in type I (oxidative) muscle fibers, suggesting a pivotal role for ATGL in intramuscular fatty acid handling, lipid storage and breakdown

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Genome Haploidisation with Chromosome 7 Retention in Oncocytic Follicular Thyroid Carcinoma

Contains fulltext : 108012.pdf (publisher's version ) (Open Access)BACKGROUND: Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). METHODS: Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. RESULTS: All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). CONCLUSIONS: We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828)