Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension

BACKGROUND: Patients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH. METHODS: In this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis. RESULTS: From 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001). CONCLUSION: This is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings

Hepatocyte specific expression of an oncogenic variant of β-catenin results in cholestatic liver disease

[Background] The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. [Results] Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice. The primary bile acid synthesis enzyme Cyp7a1 was increased whereas Cyp27 and Cyp8b1 were reduced in Ctnnb1CA hep mice. Expression of compensatory bile acid transporters including Abcb1, Abcb4, Abcc2 and Abcc4 were significantly increased in Ctnnb1CA hep mice while Ntcp was reduced. Accompanying changes of bile acid transporters favoring excretion of bile acids were observed in intestine and kidneys of Ctnnb1CA hep mice. Additionally, disturbed bile acid regulation through the FXR-FGF15-FGFR4 pathway was observed in mice with activated β-catenin. [Materials and Methods] Mice with a loxP-flanked exon 3 of the Ctnnb1 gene were crossed to Albumin-Cre mice to obtain mice with hepatocyte-specific expression of a dominant stable form of β-catenin (Ctnnb1CA hep mice). Ctnnb1CA hep mice were analyzed by histology, serum biochemistry and mRNA profiling. [Conclusion] Expression of a dominant stable form of β-catenin in hepatocytes results in severe cholestasis and biliary type fibrosis

The genomic basis of parasitism in the Strongyloides clade of nematodes.

Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism

Hnanice/Gnadlersdorf in southern Moravia: Three villages in a lustrum 1945–1950

The border village Gnadlersdorf/Hnanice is an example for a lifeworld that is dominated by politics. In 1938 the few Czech villagers were expelled from the mainly German-speaking village. In 1945 and 1946 the German population flew, was expelled or deported. Within the traditional structure of the village a new Czech peasant-village was established including the traditional social structure of peasants and servants, the ways of socialisation and social hierarchies. However, the political structure of the first three years after World War II was dominated by a kind of ‘controlled democracy’ with strong bureaucratic elements. A massive way of invention was the repeated verification of the political reliability of the new settlers. The loudspeaker that was erected in the center of the village in 1947 became a symbol for the political penetration of the village by the state who ubiquitously announced its dispositions by that. The ‘Coup de Prague’ in February 1948 met a dramatically divided village in which a new communistic elite had been established by deportation of the political counterparts. But on closer examination the political power struggles were a result of traditional local struggles for influence and local hostility, as an abuse of political competence of organisation in the sphere of the lifeworld. Violence was in a certain way permitted. ‘Who fought against whom’ was negotiated on the local level, not by the superior communist authorities. The formation of the local communist elites and their influence was dominating, not the penetration of the village by the communist party. But as a result, the village society disintegrated. So the collectivisation of the village could be implemented, against initial opposition by the villagers. A new lifeworld with new structures had to be established, off the strong orientation of the village on itself to the point of a concentration on few economic and political institutions.The border village Gnadlersdorf/Hnanice is an example for a lifeworld that is dominated by politics. In 1938 the few Czech villagers were expelled from the mainly German-speaking village. In 1945 and 1946 the German population flew, was expelled or deported. Within the traditional structure of the village a new Czech peasant-village was established including the traditional social structure of peasants and servants, the ways of socialisation and social hierarchies. However, the political structure of the first three years after World War II was dominated by a kind of ‘controlled democracy’ with strong bureaucratic elements. A massive way of invention was the repeated verification of the political reliability of the new settlers. The loudspeaker that was erected in the center of the village in 1947 became a symbol for the political penetration of the village by the state who ubiquitously announced its dispositions by that. The ‘Coup de Prague’ in February 1948 met a dramatically divided village in which a new communistic elite had been established by deportation of the political counterparts. But on closer examination the political power struggles were a result of traditional local struggles for influence and local hostility, as an abuse of political competence of organisation in the sphere of the lifeworld. Violence was in a certain way permitted. ‘Who fought against whom’ was negotiated on the local level, not by the superior communist authorities. The formation of the local communist elites and their influence was dominating, not the penetration of the village by the communist party. But as a result, the village society disintegrated. So the collectivisation of the village could be implemented, against initial opposition by the villagers. A new lifeworld with new structures had to be established, off the strong orientation of the village on itself to the point of a concentration on few economic and political institutions