Improved prediction of mortality by combinations of inflammatory markers and standard clinical scores in patients with acute-on-chronic liver failure and acute decompensation

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) as a sinister prognosis and there is a need for accurate biomarkers and scoring systems to better characterize ACLF patients and predict prognosis. Systemic inflammation and renal failure are hallmarks in ACLF disease development and progression. We hypothesized that the combination of specific inflammatory markers in combination with clinical scores are better predictors of survival than the originally developed CLIF-C acute decompensation (AD) and CLIF-C ACLF scores. METHODS: We re-evaluated all previously measured inflammatory markers in 522 patients from the CANONIC study, 342 without and 180 with ACLF. We used the Harrell's C-index to determine the best marker alone or in combination with the original scores and calculated new scores for prediction of mortality in the original CANONIC cohort. RESULTS: The best markers to predict 90-day mortality in patients without ACLF were the plasma macrophage activation markers soluble (s)CD163 and mannose receptor (sMR). Urinary neutrophil gelatinase associated lipocalin (UNGAL) and sCD163 were predictors for 28-day mortality in patients with ACLF. The new developed CLIF-C AD+sMR score in patients without ACLF improved 90-days mortality prediction compared to the original CLIF-C AD score (C-index 0.82(0.78-0.86) vs. 0.74(0.70-0.78, P=0.004). Further, the new CLIF-C ACLF+sCD163+UNGAL improved the original CLIF-C ACLF score for 28-days mortality (0.85(0.79-0.91) vs. 0.75(0.70-0.80), P=0.039). CONCLUSIONS: The capability of these inflammatory markers to improve the original prognostic scores in cirrhosis patients without and with ACLF points to a key role of macrophage activation and inflammation in the development and progression of AD and ACLF

The Lyman Alpha Forest in the Spectra of QSOs

Observations of redshifted Lyman alpha forest absorption in the spectra of quasistellar objects (QSOs) provide a highly sensitive probe of the distribution of gaseous matter in the universe. Over the past two decades optical spectroscopy with large ground-based telescopes, and more recently ultraviolet spectroscopy from space have yielded a wealth of information on what appears to be a gaseous, photoionized intergalactic medium, partly enriched by the products of stellar nucleosynthesis, residing in coherent structures over many hundreds of kiloparsecs. Recent progress with cosmological hydro-simulations based on hierarchical structure formation models has led to important insights into the physical structures giving rise to the forest. If these ideas are correct, a truely inter- and proto-galactic medium [at high redshift (z ~ 3), the main repository of baryons] collapses under the influence of dark matter gravity into flattened or filamentary structures, which are seen in absorption against background QSOs. With decreasing redshift, galaxies forming in the denser regions, may contribute an increasing part of the Lyman alpha absorption cross-section. Comparisons between large data samples from the new generation of telescopes and artificial Lyman alpha forest spectra from cosmological simulations promise to become a useful cosmological tool.Comment: latex plus three postscript figures, uses psfig,sty; Annual Review of Astronomy and Astrophysics 1998, vol. 36 (in press

Uptake of genetic testing by the children of Lynch syndrome variant carriers across three generations

Many Lynch syndrome (LS) carriers remain unidentified, thus missing early cancer detection and prevention opportunities. Tested probands should inform their relatives about cancer risk and options for genetic counselling and predictive gene testing, but many fail to undergo testing. To assess predictive testing uptake and demographic factors influencing this decision in LS families, a cross-sectional registry-based cohort study utilizing the Finnish Lynch syndrome registry was undertaken. Tested LS variant probands (1184) had 2068 children divided among three generations: 660 parents and 1324 children (first), 445 and 667 (second), and 79 and 77 (third). Of children aged 418 years, 801 (67.4%), 146 (43.2%), and 5 (23.8%), respectively, were genetically tested. Together, 539 first-generation LS variant carriers had 2068 children and grandchildren (3.84 per carrier). Of the 1548 (2.87 per carrier) eligible children, 952 (61.5%) were tested (1.77 per carrier). In multivariate models, age (OR 1.08 per year; 95% CI 1.06-1.10), family gene (OR 2.83; 1.75-4.57 for MLH1 and 2.59; 1.47-4.56 for MSH2 compared with MSH6), one or more tested siblings (OR 6.60; 4.82-9.03), no siblings (OR 4.63; 2.64-8.10), and parent under endoscopic surveillance (OR 5.22; 2.41-11.31) were independent predictors of having genetic testing. Examples of parental adherence to regular surveillance and genetically tested siblings strongly influenced children at 50% risk of LS to undergo predictive gene testing. High numbers of untested, adult at-risk individuals exist even among well-established cohorts of known LS families with good adherence to endoscopic surveillance.Peer reviewe

The uronic acid content of coccolith-associated polysaccharides provides insight into coccolithogenesis and past climate

Unicellular phytoplanktonic algae (coccolithophores) are among the most prolific producers of calcium carbonate on the planet, with a production of ∼1026 coccoliths per year. During their lith formation, coccolithophores mainly employ coccolith-associated polysaccharides (CAPs) for the regulation of crystal nucleation and growth. These macromolecules interact with the intracellular calcifying compartment (coccolith vesicle) through the charged carboxyl groups of their uronic acid residues. Here we report the isolation of CAPs from modern day coccolithophores and their prehistoric predecessors and we demonstrate that their uronic acid content (UAC) offers a species-specific signature. We also show that there is a correlation between the UAC of CAPs and the internal saturation state of the coccolith vesicle that, for most geologically abundant species, is inextricably linked to carbon availability. These findings suggest that the UAC of CAPs reports on the adaptation of coccolithogenesis to environmental changes and can be used for the estimation of past CO2 concentrations

Tryptophan and Non-Tryptophan Fluorescence of the Eye Lens Proteins Provides Diagnostics of Cataract at the Molecular Level

The chemical nature of the non-tryptophan (non-Trp) fluorescence of porcine and human eye lens proteins was identified by Mass Spectrometry (MS) and Fluorescence Steady-State and Lifetime spectroscopy as post-translational modifications (PTM) of Trp and Arg amino acid residues. Fluorescence intensity profiles measured along the optical axis of human eye lenses with age-related nuclear cataract showed increasing concentration of fluorescent PTM towards the lens centre in accord with the increased optical density in the lens nucleolus. Significant differences between fluorescence lifetimes of “free” Trp derivatives hydroxytryptophan (OH-Trp), N-formylkynurenine (NFK), kynurenine (Kyn), hydroxykynurenine (OH-Kyn) and their residues were observed. Notably, the lifetime constants of these residues in a model peptide were considerably greater than those of their “free” counterparts. Fluorescence of Trp, its derivatives and argpyrimidine (ArgP) can be excited at the red edge of the Trp absorption band which allows normalisation of the emission spectra of these PTMs to the fluorescence intensity of Trp, to determine semi-quantitatively their concentration. We show that the cumulative fraction of OH-Trp, NFK and ArgP emission dominates the total fluorescence spectrum in both emulsified post-surgical human cataract protein samples, as well as in whole lenses and that this correlates strongly with cataract grade and age

Female preference for blue in Japan blue guppies (Poecilia reticulata)

Guppies (Poecilia reticulata) are widely used as a model species in mate choice studies. Although native to South America, guppies have been introduced to natural water bodies in disparate regions of the globe. Here, for the first time, we examine guppies from one such introduced population in Japan where males have evolved a predominantly blue color pattern. Previous studies of wild-type guppies have shown blue to play a relatively minor role in the mate choice decisions of females compared to other traits, such as orange, and the importance of blue is not universally supported by all studies. The Japanese population therefore presents an ideal opportunity to re-examine the potential significance of blue as a mate choice cue in guppies. Mate choice experiments, in which female Japan blue guppies were given a choice between pairs of males that differed in their area of blue coloration but were matched for other traits, revealed that females prefer males with proportionately larger amounts of blue in their color patterns. We discuss possible factors, including sexual and ecological selection, which may have led to the evolution of unusually large areas of blue at the expense of other colors in Japan blue guppies. However, further studies are needed to distinguish between these scenarios.Web of Scienc