International multicenter study comparing demographics, therapy and outcomes in bleeding from Mallory Weiss tears and peptic ulcers.

Background and study aims Mallory Weiss tears (MWTs) are relatively uncommon causes of upper gastrointestinal bleeding (UGIB), and patients are generally considered at low risk of poor outcome, although data are limited. There is uncertainty about use of endoscopic therapy. We aimed to describe and compare an international cohort of patients presenting with UGIB secondary to MWT and peptic ulcer bleeding (PUB). Patients and methods From an international dataset of patients undergoing endoscopy for acute UGIB at seven hospitals, we assessed patients with MWT bleeding, including the endoscopic stigmata and endoscopic therapy applied. We compared baseline parameters, rebleeding rate, and 30-day mortality between patients with MWT and PUB. Results A total of 3648 patients presented with UGIB, 125 of whom (3.4 %) had bleeding from a MWT. Those patients were younger (61 vs 69 years, P  < 0.0001) and more likely to be men (66 % vs 53 %, P  = 0.006) compared to the patients PUB. The most common endoscopic stigmata seen in MWTs were oozing blood (26 %) or clean base (26 %). Of the patients with MWT, 53 (42 %) received endoscopic therapy. Forty-eight of them (90 %) had epinephrine injections and 25 (48 %) had through-the-scope clips. The rebleeding rate was lower in MWT patients compared with PUB patients (4.9 % vs 12 %, P  = 0.016), but mortality was similar (5.7 vs 7.0 %, P  = 0.71). Conclusions Although patients presenting with MWT were younger, with a lower rebleeding rate, their mortality was similar to that of patients with PUB. Endoscopic therapy was applied to 42 % MWT patients, with epinephrine injection as the most common modality.

Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial.

Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.

Residential Segregation of European and Non-European Migrants in Sweden: 1990-2012.

In this paper, we analyse how a migrant population that is both expanding and changing in composition has affected the composition of Swedish neighbourhoods at different scales. The analysis is based on Swedish geocoded individual-level register data for the years 1990, 1997, 2005, and 2012. This allows us to compute and analyse the demographic composition of neighbourhoods that range in size from encompassing the nearest 100 individuals to the nearest 409,600 individuals. First, the results confirm earlier findings that migrants, especially those from non-European countries, face high levels of segregation in Sweden. Second, large increases in the non-European populations in combination with high levels of segregation have increased the proportion of non-European migrants living in neighbourhoods that already have high proportions of non-European migrants. Third, in contrast to what has been the established image of segregation trends in Sweden, and in an apparent contrast to the finding that non-European migrants increasingly live in migrant-dense neighbourhoods, our results show that segregation, when defined as an uneven distribution of different populations across residential contexts, is not increasing. On the contrary, for both European migrants from 1990 and non-European migrants from 1997, there is a downward trend in unevenness as measured by the dissimilarity index at all scale levels. However, if segregation is measured as differences in the neighbourhood concentration of migrants, segregation has increased.

The Arabidopsis thaliana NAC transcription factor family: structure-function relationships and determinants of ANAC019 stress signalling.

TFs (transcription factors) are modular proteins minimally containing a DBD (DNA-binding domain) and a TRD (transcription regulatory domain). NAC [for NAM (no apical meristem), ATAF, CUC (cup-shaped cotyledon)] proteins comprise one of the largest plant TF families. They are key regulators of stress perception and developmental programmes, and most share an N-terminal NAC domain. On the basis of analyses of gene expression data and the phylogeny of Arabidopsis thaliana NAC TFs we systematically decipher structural and functional specificities of the conserved NAC domains and the divergent C-termini. Nine of the ten NAC domains analysed bind a previously identified conserved DNA target sequence with a CGT[GA] core, although with different affinities. Likewise, all but one of the NAC proteins analysed is dependent on the C-terminal region for transactivational activity. In silico analyses show that the NAC TRDs contain group-specific sequence motifs and are characterized by a high degree of intrinsic disorder. Furthermore, ANAC019 was identified as a new positive regulator of ABA (abscisic acid) signalling, conferring ABA hypersensitivity when ectopically expressed in plants. Interestingly, ectopic expression of the ANAC019 DBD or TRD alone also resulted in ABA hypersensitivity. Expression of stress-responsive marker genes [COR47 (cold-responsive 47), RD29b (responsive-to-desiccation 29b) and ERD11 (early-responsive-to-dehydration 11)] were also induced by full-length and truncated ANAC019. Domain-swapping experiments were used to analyse the specificity of this function. Chimaeric proteins, where the NAC domain of ANAC019 was replaced with the analogous regions from other NAC TFs, also have the ability to positively regulate ABA signalling. In contrast, replacing the ANAC019 TRD with other TRDs abolished ANAC019-mediated ABA hypersensitivity. In conclusion, our results demonstrate that the biochemical and functional specificity of NAC TFs is associated with both the DBDs and the TRDs.