Ibsenholt9249
Diagnostic delay in IBD is a major problem and diagnosis is frequently arrived when irreversible damage has already occurred. This study evaluated accuracy of faecal calprotectin (fCAL) integrated with diagnostic criteria for early diagnosis of IBD in a primary care setting.
General practitioners (GPs) were trained to recognize alarm symptoms for IBD classified as major and minor criteria. Fulfilment of one major or at least two minor criteria was followed by free fCAL testing and a visit by an IBD specialist and follow-up over 12months. All patients with positive fCAL testing, i.e., ≥70 μg/g underwent colonoscopy. The diagnostic accuracy of fCAL was estimated after adjusting for differential-verification bias following a Bayesian approach.
Thirty-four GPs participated in the study and 133 patients were tested for fCAL between July 2016 and August 2017. Positivity of fCAL was seen in 45/133 patients (34%) and a final IBD diagnosis was made in 10/45 (22%). According to the threshold of 70 μg/g, fCAL achieved a sensitivity of 74.8% (95%CI 39.10-96.01%), a specificity of 70.4% (95%CI 61.76-78.16%) and an overall diagnostic accuracy of 70.6% (95%CI 61.04-78.37%). As for prognostic accuracy, despite positive predictive value being low, 21.9% (95%CI 11.74-35.18%), the negative predictive value was definitely higher 96.2% (95%CI 84.96-99.51%).
fCAL with a threshold set at 70 μg/g seems to represent a potentially reliable negative test to be used in primary care settings for patients with symptoms suggestive of IBD.
fCAL with a threshold set at 70 μg/g seems to represent a potentially reliable negative test to be used in primary care settings for patients with symptoms suggestive of IBD.
The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type-specific regulation of gene expression are not yet clear.
Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how gene expression varied according to the effect of pioneer factors using RNA-seq and RT-qPCR.
Our RNA-seq results identified 19 and 63 genes regulated by GR that are ARPE-19-specific and A549-specific, respectively, suggesting that GR induces the expression of different sets of genes in a cell type-specific manner. RT-qPCR confirmed that the epithelial sodium channel (
) gene is an ARPE-19 cell-specific GR target gene, whereas the FK506 binding protein 5 (
) gene was A549 cell-specific. There was a significant decrease in
expression in FOXA1-deficient ARPE-19 cells, suggesting that FOXA1 might function as a pioneer factor enabling the selective expression of
in ARPE-19 cells but not in A549 cells.
These findings indicate that
expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type-specific expression of GR-regulated genes.
These findings indicate that ENACα expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type-specific expression of GR-regulated genes.The aim of this study was to determine the relationship between pilot workload, performance, subjective fatigue, sleep duration, number of sectors and flight duration during short-haul operations. Ninety pilots completed a NASA Task Load Index, Psychomotor Vigilance Task and a Samn-Perelli fatigue scale on top-of-descent of each flight and wore an activity monitor throughout the study. Weak, but significant, correlations were revealed between workload and all factors. Subjective fatigue, number of sectors and lapses were significant predictors of workload. Pilots reported higher workload when fatigue increased, the number of sectors were higher, and objective performance was worse.The RAS and RHO family comprise two major branches of the RAS superfamily of small GTPases. These proteins function as regulated molecular switches and control cytoplasmic signaling networks that regulate a diversity of cellular processes, including cell proliferation and cell migration. In the early 1980s, mutationally activated RAS genes encoding KRAS, HRAS and NRAS were discovered in human cancer and now comprise the most frequently mutated oncogene family in cancer. Only recently, exome sequencing studies identified cancer-associated alterations in two RHO family GTPases, RAC1 and RHOA. RAS and RHO proteins share significant identity in their amino acid sequences, protein structure and biochemistry. Cancer-associated RAS mutant proteins harbor missense mutations that are found primarily at one of three mutational hotspots (G12, G13 and Q61) and have been identified as gain-of-function oncogenic alterations. Although these residues are conserved in RHO family proteins, the gain-of-function mutations found in RAC1 are found primarily at a distinct hotspot. Gefitinib Unexpectedly, the cancer-associated mutations found with RHOA are located at different hotspots than those found with RAS. Furthermore, since the RHOA mutations suggested a loss-of-function phenotype, it has been unclear whether RHOA functions as an oncogene or tumor suppressor in cancer development. Finally, whereas RAS mutations are found in a broad spectrum of cancer types, RHOA and RAC1 mutations occur in a highly restricted range of cancer types. In this review, we focus on RHOA missense mutations found in cancer and their role in driving tumorigenesis, with comparisons to cancer-associated mutations in RAC1 and RAS GTPases.
To compare the analgesic efficacy and tolerability of tramadol/dexketoprofen 75/25 mg (TRAM/DKP) versus diclofenac/thiocolchicoside 75/4 mg (DIC/THIO) in patients with moderate-to-severe acute low back pain (LBP).
Single-centre, observational study in 82 adult outpatients with LBP due to disc herniation (≥4 Numerical Rating scale, NRS) who received either oral TRAM/DKP (
= 44) or intramuscular DIC/THIO (
= 38), both given every 12 h for 5 days. The primary endpoint was the change from baseline in pain intensity (PI) at pre-specified post-dose time points (t day1, t day3, t day7) and compared between the two treatments. Additional endpoints, all evaluated at day 7, included the sum of PI difference (SPID), percentage of responders in terms of PI reduction versus baseline and change from baseline in Douleur Neuropathique (DN4) score. Tolerability and safety were also assessed.
Both treatment groups were comparable for demographic characteristics and comorbidities. Over the 5-day treatment period and up to day 7, compared to DIC/THIO, TRAM/DKP provided a significantly greater and sustained analgesia at day 3 and day 7 (
< .