Diagnostic performance of MRI for detection of intestinal fistulas in patients with complicated inflammatory bowel conditions

The diagnostic performance of magnetic resonance imaging (MRI) for detection of intestinal fistulas, other than perianal, in patients with known complicated inflammatory bowel conditions (CIBC) was investigated. Our study group consisted of 20 patients (12 women, mean age 43years) with CIBC, including Crohn's disease (n=13), colonic diverticulitis (n=3), colitis after radiotherapy (n=3) and of postoperative origin (n=1). Eleven surgically proven enteral fistulas were known in ten (50%) of these patients, being of enterovesical (n=3), enterocolic (n=2), enteroenteral (n=2), rectovaginal (n=2), rectovaginovesical (n=1) and of entercutaneous (n=1) localisation. The other ten patients (50%), used as the control group, showed MR features of CIBC, although without any fistulous tract. Multiplanar T1- and T2-weighted sequences had been performed, including gadolinium-enhanced acquisition with fat saturation (1.5T). MR findings were independently blindly and retrospectively reviewed by three radiologists for the presence and etiology of any fistula, as well as visualization and characterization of the fistulous tract. Results were compared with surgical findings (n=16) and clinical evolution (n=4). Interobserver agreement was calculated. Interobserver agreement kappa for fistula detection was 0.71. Overall sensitivity, specificity and accuracy for fistula detection were 78.6%, 75% and 77.2%, respectively. Sensitivity for fistula characterization was 80.6%, with visualization of the fistulous tract in all cases, whereby T1-weighted gadolinium-enhanced fat-saturated images were considered the most useful sequences. Gadolinium-enhanced MRI is a reliable and reproducible tool for detection of enteral fistulas secondary to inflammatory condition

CT enteroclysis: technique and clinical applications.

CT enteroclysis (CTE) has been gradually evolving with technical developments of spiral and multidetector row CT technology. It has nowadays become a well-defined imaging modality for the evaluation of various small bowel disorders. Volume challenge of 2L of enteral contrast agent administrated to the small bowel via a nasojejunal catheter ensures luminal distension, the prerequisite for the detection of mural abnormalities, also facilitating the accurate visualization of intraluminal lesions. CT acquisition is centered on small bowel loops, reconstructed in thin axial slices and completed by multiplanar views. Image analysis is essentially done in cine-mode on work-stations. CTE is of particular diagnostic value in intermediate or advanced stages of Cohn's disease, including the depiction of extraintestinal complications. It has become the imaging modality of choice for the localization and characterization of small bowel tumors. The cause and degree of low-grade small bowel obstruction is more readily analyzed with the technique of CTE than conventional CT. Limitations of CTE concern the assessment of pure intestinal motility disorders, superficial mucosal lesions and arteriovenous malformations of the small bowel, which are not consistently visualized. CTE should be selectively used to answer specific questions of the small bowel. It essentially contributes to the diagnostic quality of modern small bowel imaging, and therefore deserves an established, well-defined place among the other available techniques

Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the –161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis- regulatory elements within this –161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells

Diagnostic performance of MRI for detection of intestinal fistulas in patients with complicated inflammatory bowel conditions.

The diagnostic performance of magnetic resonance imaging (MRI) for detection of intestinal fistulas, other than perianal, in patients with known complicated inflammatory bowel conditions (CIBC) was investigated. Our study group consisted of 20 patients (12 women, mean age 43 years) with CIBC, including Crohn's disease (n=13), colonic diverticulitis (n=3), colitis after radiotherapy (n=3) and of postoperative origin (n=1). Eleven surgically proven enteral fistulas were known in ten (50%) of these patients, being of enterovesical (n=3), enterocolic (n=2), enteroenteral (n=2), rectovaginal (n=2), rectovaginovesical (n=1) and of entercutaneous (n=1) localisation. The other ten patients (50%), used as the control group, showed MR features of CIBC, although without any fistulous tract. Multiplanar T1- and T2-weighted sequences had been performed, including gadolinium-enhanced acquisition with fat saturation (1.5 T). MR findings were independently blindly and retrospectively reviewed by three radiologists for the presence and etiology of any fistula, as well as visualization and characterization of the fistulous tract. Results were compared with surgical findings (n=16) and clinical evolution (n=4). Interobserver agreement was calculated. Interobserver agreement kappa for fistula detection was 0.71. Overall sensitivity, specificity and accuracy for fistula detection were 78.6%, 75% and 77.2%, respectively. Sensitivity for fistula characterization was 80.6%, with visualization of the fistulous tract in all cases, whereby T1-weighted gadolinium-enhanced fat-saturated images were considered the most useful sequences. Gadolinium-enhanced MRI is a reliable and reproducible tool for detection of enteral fistulas secondary to inflammatory conditions

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here

Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma.

The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies

Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma

The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies

Notes on age determination, size and age structure, longevity, and growth of co-occurring macrourid fishes

ACKNOWLEDGEMENTS We are grateful to crew and colleagues who sampled and processed macrourids on the MARECO and ECOMAR cruise, to Ms Hege Ø Hansen for assistance in the otolith laboratory, and to home institutions and the Alfred P Sloan Foundation for financial support. An early version of the results was submitted in partial fulfilment of the requirements for the MSc degree of R.H. Fundings: Data for this paper were collected on cruises funded by Norway and the United Kingdom (Natural Environment Research Council). In addition to institutional funding, the work benefitted from a grant to the ecosystems of the mid-atlantic ridge (MAR-ECO) Programme from the Alfred P. Sloan Foundation, New York, USA.Peer reviewedPublisher PD

Down-regulation of protein kinase Cdelta inhibits inducible nitric oxide synthase expression through IRF1

Peer reviewe