Uredinorubellins and caeruleoramularin, photodynamically active anthraquinone derivatives produced by two species of the genus ramularia

Both the phytopathogenic fungus Ramularia collo-cygni and the hyperparasite R. uredinicola biosynthesize a number of red and yellow anthraquinone derivatives called rubellins. The new compounds uredinorubellins I and II, which were isolated from R. uredinicola, contribute to understanding the biosynthesis pathway that leads from simple anthraquinones to the rubellins. In addition, we isolated for the first time such simple compounds as chrysophanol and helminthsporin from both Ramularia species. A blue compound isolated from the mycelium of R. collo-cygni was revealed to be a unique 9,4-anthracenedione derivative. Structure elucidation by (1)H and (13)C NMR of the new but unstable compound caeruleoramularin was possible only by feeding the fungus different labeled (13)C acetates. The photodynamic activity of the uredinorubellins was comparable to rubellin D, whereas chrysophanol and caeruleoramularin did not display such activity.     

Weight gain in pregnancy according to maternal height and weight

Abstract Weight gain during pregnancy is of great importance for the health of mother and child. There is considerable individual variability with regard to the weight gain, with maternal height and pre-pregnancy body weight being important determinants. We aim to assess the usefulness of the maternal body mass index (BMI) and other ways of combining maternal weight and height in predicting weight gain during pregnancy. We analyzed data of more than 2.2 million pregnancies taken from the German perinatal statistics of 1995-2000. We found that BMI is not useful as a predictor of weight gain during pregnancy. We developed an alternative system of using maternal weight and height to predict weight gain by classifying pregnant women according to their weight and height. This allows an assessment of weight gain by comparing a given pregnant woman to other women with similar weights and heights.     

Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs.

When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.     

Comparing the performance of propensity score methods in healthcare database studies with rare outcomes

Nonrandomized studies of treatments from electronic healthcare databases are critical for producing the evidence necessary to making informed treatment decisions, but often rely on comparing rates of events observed in a small number of patients. In addition, studies constructed from electronic healthcare databases, for example, administrative claims data, often adjust for many, possibly hundreds, of potential confounders. Despite the importance of maximizing efficiency when there are many confounders and few observed outcome events, there has been relatively little research on the relative performance of different propensity score methods in this context. In this paper, we compare a wide variety of propensity‐based estimators of the marginal relative risk. In contrast to prior research that has focused on specific statistical methods in isolation of other analytic choices, we instead consider a method to be defined by the complete multistep process from propensity score modeling to final treatment effect estimation. Propensity score model estimation methods considered include ordinary logistic regression, Bayesian logistic regression, lasso, and boosted regression trees. Methods for utilizing the propensity score include pair matching, full matching, decile strata, fine strata, regression adjustment using one or two nonlinear splines, inverse propensity weighting, and matching weights. We evaluate methods via a ‘plasmode’ simulation study, which creates simulated datasets on the basis of a real cohort study of two treatments constructed from administrative claims data. Our results suggest that regression adjustment and matching weights, regardless of the propensity score model estimation method, provide lower bias and mean squared error in the context of rare binary outcomes. Copyright © 2017 John Wiley & Sons, Ltd.     

Improved prediction of medical expenditures and health care utilization using an updated chronic disease score and claims data

ObjectiveTo predict future medical expenditures, health care utilization, and mortality in Switzerland using an updated chronic disease score (CDS), a chronic morbidity measure based on pharmacy data.Study Design and SettingWe performed a cohort study using medical claims data from insured persons enrolled in 2009 and 2010. Patient's characteristics, chronic conditions, and health care costs from baseline were used to calculate each patient's disease score. Two-part regression models were fit to predict health care expenditures, utilization, and mortality during the following year using the score's baseline values. We calculated the proportion of explained variation for each regression model to assess their performance.ResultsThe CDS model, controlled for sociodemographics and health insurance plan, showed a significant improvement in explained variance of health care costs, outpatient costs, and outpatient visits in 2010. Future outpatient visits were predicted best with an R² of 29.2% (age group: 18–65 years) and 22.9% (>65 years), and models predicted future mortality with a c-statistic of 0.8.ConclusionThe CDS showed reasonable predictive validity of future health care utilization and medical expenditure based on pharmacy dispensing data, which may support health care decision makers in the planning delivery systems and resource allocation.     

Decision heuristic or preference? Attribute non‐attendance in discrete choice problems

This paper investigates if respondents' choice to not consider all characteristics of a multiattribute health service may represent preferences. Over the last decade, an increasing number of studies account for attribute non‐attendance (ANA) when using discrete choice experiments to elicit individuals' preferences. Most studies assume such behaviour is a heuristic and therefore uninformative. This assumption may result in misleading welfare estimates if ANA reflects preferences. This is the first paper to assess if ANA is a heuristic or genuine preference without relying on respondents' self‐stated motivation and the first study to explore this question within a health context. Based on findings from cognitive psychology, we expect that familiar respondents are less likely to use a decision heuristic to simplify choices than unfamiliar respondents. We employ a latent class model of discrete choice experiment data concerned with National Health Service managers' preferences for support services that assist with performance concerns. We present quantitative and qualitative evidence that in our study ANA mostly represents preferences. We also show that wrong assumptions about ANA result in inadequate welfare measures that can result in suboptimal policy advice. Future research should proceed with caution when assuming that ANA is a heuristic.     

Integration of Hot Isostatic Pressing and Heat Treatment for Advanced Modified γ-TiAl TNM Alloys

The conventional processing route of TNM (Ti-Nb-Mo) alloys combines casting and Hot Isostatic Pressing (HIP) followed by forging and multiple heat treatments to establish optimum properties. This is a time-consuming and costly process. In this study we present an advanced alternative TNM alloy processing route combining HIP and heat treatments into a single process, which we refer to as IHT (integrated HIP heat treatment), applied to a modified TNM alloy with 1.5B. A Quintus HIP lab unit with a quenching module was used, achieving fast and controlled cooling, which differs from the slow cooling rates of conventional HIP units. A Ti-42.5Al-3.5Nb-1Mo-1.5B (at.%) was subjected to an integrated two HIP steps at 200 MPa, one at 1250 °C for 3 h and another at 1260 °C for 1 h, both under a protective Ar atmosphere and followed by cooling at 30 K/min down to room temperature. The results were compared against the Ti-43.5Al-3.5Nb-1Mo-0.8B (at.%) thermomechanically processed in a conventional way. Applying IHT processing to the 1.5B alloy does indeed achieve good creep strength, and the secondary creep rate of the IHT processed materials is similar to that of conventionally forged TNM alloys. Thus, the proposed advanced IHT processing route could manufacture more cost-effective TiAl components.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Biocompatible fluorocarbon liquid underlays for in situ extraction of isoprenoids from microbial cultures

Microbial production of heterologous metabolites is now a mature technology in many host organisms, opening new avenues for green production processes of specialty chemicals. At lab scale, petroleum-based hydrophobic bio-compatible solvents like dodecane can be used as a second phase on top of microbial cultures to act as a physical sink for heterologous hydrocarbon products like isoprenoids. However, this approach has significant drawbacks at scale due to the difficulty of handling solvents and their potential contamination with unwanted byproducts of their manufacture. We discovered that synthetic perfluorocarbon liquids (FCs), commonly used for heat transfer, can also act as physical sinks for microbially produced isoprenoid compounds. FCs are stable, inert, and are amenable to direct liquid–liquid extraction with alcohols for rapid product isolation. These liquids are more dense than water and form a lower phase to microbial cultures rather than an upper phase as with other solvents. Their ability to form an under-layer or ‘underlay’ also enables the cultivation of microbes directly at the FC–culture medium interface via gravity settling, which could open their application for filamentous or mat-forming organisms. We present comparisons of the isoprenoid extraction potential of three commercial FCs: FC-3283, FC-40, and FC-770 with engineered green microalga cultures producing patchoulol, taxadiene, casbene, or 13R(+) manoyl oxide. We demonstrate that FCs are promising alternatives to traditional solvents and open new avenues in bio-process design for microbial heterologous metabolite milking.

A novel bioprocess to capture and purify terpenoids produced by engineered microbes using 2-phase cultivation of the algae with liquid perfluorocarbons followed by liquid–liquid extraction of the terpenoids with ethanol.