Cytokines from Bench to Bedside: A Retrospective Study Identifies a Definite Panel of Biomarkers to Early Assess the Risk of Negative Outcome in COVID-19 Patients

The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 ± 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-γ, interleukin 6 (IL-6), IL-1β, IL-8, IL-10, soluble IL2-receptor-α (sIL2Rα), IP10 and TNFα. Extensive statistical analyses were performed (correlations, t-tests, ranking tests and tree modeling). The mortality rate was 65/415 (15.7%) and a negative outcome (death and/or orotracheal intubation) affected 98/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2Rα, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2Rα and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention.     

Magnetic Force Microscopy in Liquids

In this work, the use of magnetic force microscopy (MFM) to acquire images of magnetic nanostructures in liquid environments is presented. Optimization of the MFM signal acquisition in liquid media is performed and it is applied to characterize the magnetic signal of magnetite nanoparticles. The ability for detecting magnetic nanostructures along with the well‐known capabilities of atomic force microscopy in liquids suggests potential applications in fields such as nanomedicine, nanobiotechnology, or nanocatalysis.     

Degradation Kinetics of Anthocyanin of Traditional and Low-Sugar Blackberry Jam

The objective of this study was to monitor the stability of anthocyanin and phenolic compounds contained in two formulations of blackberry jam (traditional and low-sugar) during storage. For that purpose, jams were prepared with varying amounts of hydrocolloids and investigated as to pH, total soluble solids, water activity, total acidity, total anthocyanins and total polyphenols. In order to accompany and assess the levels of phenolic compounds and colour (L*, a* and b*) changes, the samples were stored for 180 days at two different temperatures (10 and 25 °C). The Arrhenius model was used to determine the relationship between the reaction rate (k) at the different storage temperatures, yielding activation energy values of 19 and 12 kcal/mol and Q ₁₀ values of 3.0 and 2.0 for traditional and low-sugar jams, respectively. The results show that by the end of the storage time investigated, the anthocyanin compounds had been partially degraded, with the greatest loss being observed in traditional jam stored at 25 °C. Colour stability was also lower in traditional jam as compared to the low-sugar product.     

TIGUKAT: A uniform behavioral objectbase management system

We describe the TIGUKAT objectbase management system, which is under development at the Laboratory for Database Systems Research at the University of Alberta. TIGUKAT has a novel object model, whose identifying characteristics include a purely behavioral semantics and a uniform approach to objects. Everything in the system, including types, classes, collections, behaviors, and functions, as well as meta-information, is a first-class object with well-defined behavior. In this way, the model abstracts everything, including traditional structural notions such as instance variables, method implementation, and schema definition, into a uniform semantics of behaviors on objects. Our emphasis in this article is on the object model, its implementation, the persistence model, and the query language. We also (briefly) present other database management functions that are under development such as the query optimizer, the version control system, and the transaction manager.Bell Northem Research     

Nonlinear dynamic study of a bistable MEMS: model and experiment

In the Journal of Microelectromechanical Systems (see vol. 11, pp. 574-583, Oct. 2002), we presented an actuation scheme for toggling a bistable MEMS, a buckled beam, from one stable state to the other using radiation pressure of light. The experiments revealed some anomalous behavior of the beam. While long duration laser pulses at a power level slightly above the toggle threshold reliably toggled the beam every time, short duration pulses of the same power toggled the beam only about two-thirds of the time. In addition, when excessively high power levels (far above the toggle threshold) were used, the beam would not reliably toggle regardless of the pulse duration. This paper resolves the anomaly. It presents a nonlinear dynamical analysis of the bistable beam device which explains the anomaly as follows: a slightly higher than threshold force, applied for sufficient time, toggles the beam. If the force duration is longer than the time of decay of the oscillation of the beam about the toggled state, then the beam remains in that state after the force is removed. Otherwise, the beam may return to the original state. On the other hand, if the beam is toggled by a force far above the threshold, then after removal of the force, the beam may oscillate spanning both the states until the motion decays and the beam settles down to one of the states, not necessarily the toggled state, which may appear to be an anomalous behavior. The theoretical model is validated by a series of toggling experiments.     

Resistance of Vigna unguiculata (cowpea) seeds to Callosobruchus maculatus is restricted to cotyledonary tissues

We have investigated the survival of Callosobruchus maculatus larvae when reared on resistant IT81D 1045 Vigna unguiculata seeds, whose resistance has been associated with variant forms of vicilins. Here, we present data which show that larvae of C. maculatus feeding on embryonic axis of resistant cowpea reach a mass of around 28 times higher than those feeding on cotyledonary tissues. Additionally, incorporation of 5–10% of embryonic axis flour on artificial seeds made of resistant flour restores toxicity of seeds to the bruchid. Vicilins purified from both susceptible and resistant embryonic axis had no deleterious effects either on insect development or on insect survival until a level of 4% of incorporation. In contrast, vicilins from resistant cotyledons show an LD₅₀ (50% lethal dose) and WD₅₀ (half weight dose) of 2%. Total vicilin contents of embryonic axes were around two times lower than in cotyledonary tissues, while proteolytic activities of all four proteinase classes were always higher in the former tissues. By 2D‐PAGE we visualized eight protein spots, which seem to be exclusively found on resistant cotyledons. Copyright © 2006 Society of Chemical Industry     

Cytological criteria for assessing the evolution of herpetic keratitis

There were studied 33 patients admitted with clinical diagnosis of superficial herpetic keratitis, typical form of dendritic ulcer. In all these cases there were performed smears from the level of cornea and conjunctiva, that were stained with rapid blue polycrome tanin Dragan staining method. Smears were performed before and during the evolution of the disease, in patients specifically treated with antiviral drugs and also in cases treated unspecifically. There are described some cytological particularities which have a relative specificity for the diagnosis: a high number of lymphocytes with cytoplasmic blebs, giant multinucleated cells, and epithelial cells with degenerative lesions (nucleocytoplasmic inclusions, vacuoles, chromophobe halo around nucleus). Such lesions were not observed in patients with non herpetic keratitis. Modifications noticed in epithelial corneal cells could suggest the diagnosis, which can be associated with clinical examination, in order to administer a specific therapy. Dynamic cytological evolution shows early regression of specific cellular modifications in patients treated by Acyclovir.     

Chlorogenic acids and related compounds in medicinal plants and infusions

The consumption of plant infusions for prevention and treatment of health disorders is a worldwide practise. Various pharmacological activities inherent to medicinal plants have been attributed to their phenolic composition, including chlorogenic acids (CGA). Studies have shown potential beneficial properties of CGA to humans such as antioxidant, hepatoprotective, hypoglycaemic. In the present study, the CGA composition of 14 dried medicinal plants was determined by HPLC-UV and LC-DAD–ESI-MS. The plants with the highest CGA contents were Ilex paraguariensis, Bacharis genistelloides, Pimpinella anisum, Achyrochine satureioides, Camellia sinensis, Melissa officinalis and Cymbopogon citratus, with 84.7 mg/100 g–9.7 g/100 g, dry weight. Plant infusions were prepared (at 0.5%) in order to evaluate the actual consumption of CGA through these beverages. Total CGA contents in the infusions were similar to those in the methanolic extracts and indicated that a satisfactory extraction occurs during the preparation of infusions. These CGA-rich plants deserve attention regarding the pharmacological properties attributed to CGA.     

Involvement of residues 296-299 in the enzymatic activity of tissue-type plasminogen activator

The tetra-alanine substitution variant KHRR 296–299 AAAAof tissue-type plasminogen activator (t-PA) was previously shownto have enhanced fibrin specificity and enhanced activity inthe presence of fibrin compared with the wild-type form of themolecule. The structural requirements for these alterationsin enzymatic activity were investigated by constructing severalamino acid substitution variants at each of the positions from296 to 299 and evaluating their activities under a variety ofconditions. Effects on plasminogen activator activity were commonamong the point mutants at positions 296–299; nearly allhad a phenotype similar to the KHRR 296–299 AAAA variant.The greatest effects on enzymatic function were found with multiplesubstitution variants, but some single charge reversals andproline substitutions had substantial effects. The enhancedfibrin specificity of KHRR 296–299 AAAA t-PA results inless fibrinogenolysis than seen with wild-type t-PA. Approximatelyfour times greater concentration of KHRR 296–299 AAAAcompared with wild-type t-PA was required to consume 50% ofthe fibrinogen in human plasma.     

Biomass estimation in batch biotechnological processes by Bayesian Gaussian process regression

This paper proposes a biomass concentration estimator for a batch biotechnological process based on Bayesian regression with Gaussian process. On the basis of experimental data, a two-stage bootstrap technique has been developed for the estimator design. In the first stage, the biomass data set was augmented with virtual filtered measurements, and in the second stage, the biomass estimator design was completed. The method provides information on the confidence level of the estimates, and the biomass estimator performances are illustrated for the Bacillus thuringiensis δ-endotoxins production process.