The quantum foundations of utility and value.

This work presents a generalization of game theory and new perspectives on utility and value. Using quantum formalism, we prove that classical game theory is a special case of quantum game theory. We show that the von Neumann entropy and von Neumann-Morgenstern utility are equivalent and that the Hamiltonian operator represents value. This article is part of the theme issue 'Thermodynamics 2.0: Bridging the natural and social sciences (Part 1)'.

The anti-ageing effects of a natural peptide discovered by artificial intelligence.

OBJECTIVE: As skin ages, impaired extracellular matrix (ECM) protein synthesis and increased action of degradative enzymes manifest as atrophy, wrinkling and laxity. There is mounting evidence for the functional role of exogenous peptides across many areas, including in offsetting the effects of cutaneous ageing. Here, using an artificial intelligence (AI) approach, we identified peptide RTE62G (pep_RTE62G), a naturally occurring, unmodified peptide with ECM stimulatory properties. The AI-predicted anti-ageing properties of pep_RTE62G were then validated through in vitro, ex vivo and proof of concept clinical testing. METHODS: A deep learning approach was applied to unlock pep_RTE62G from a plant source, Pisum sativum (pea). Cell culture assays of human dermal fibroblasts (HDFs) and keratinocytes (HaCaTs) were subsequently used to evaluate the in vitro effect of pep_RTE62G. Distinct activities such as cell proliferation and ECM protein production properties were determined by ELISA assays. Cell migration was assessed using a wound healing assay, while ECM protein synthesis and gene expression were analysed, respectively, by immunofluorescence microscopy and PCR. Immunohistochemistry of human skin explants was employed to further investigate the induction of ECM proteins by pep_RTE62G ex vivo. Finally, the clinical effect of pep_RTE626 was evaluated in a proof of concept 28-day pilot study. RESULTS: In vitro testing confirmed that pep_RTE62G is an effective multi-functional anti-ageing ingredient. In HaCaTs, pep_RTE62G treatment significantly increases both cellular proliferation and migration. Similarly, in HDFs, pep_RTE62G consistently induced the neosynthesis of ECM protein elastin and collagen, effects that are upheld in human skin explants. Lastly, in our proof of concept clinical study, application of pep_RTE626 over 28 days demonstrated anti-wrinkle and collagen stimulatory potential. CONCLUSION: pep_RTE62G represents a natural, unmodified peptide with AI-predicted and experimentally validated anti-ageing properties. Our results affirm the utility of AI in the discovery of novel, functional topical ingredients.

OBJECTIF: À mesure que la peau vieillit, une altération de la synthèse des protéines de la matrice extracellulaire (ECM) et une action accrue des enzymes dégradantes se manifestent par une atrophie, des rides et un laxisme. Il existe de plus en plus de preuves du rôle fonctionnel des peptides exogènes dans de nombreux domaines, y compris pour compenser les effets du vieillissement cutané. Ici, en utilisant une approche d'intelligence artificielle (AI), nous avons identifié le peptide RTE62G (pep_RTE62G), un peptide naturel non modifié avec des propriétés de stimulation ECM. Les propriétés anti-âge prédites par l'IA de pep_RTE62G ont ensuite été validées par des tests cliniques in vitro, ex vivo et de validation de principe. LES MÉTHODES: Une approche d'apprentissage en profondeur a été appliquée pour déverrouiller pep_RTE62G à partir d'une source végétale, Pisum sativum (pois). Des tests de culture cellulaire de fibroblastes dermiques humains (HDF) et de kératinocytes (HaCaTs) ont ensuite été utilisés pour évaluer l'effet in vitro de pep_RTE62G. Des activités distinctes telles que la prolifération cellulaire et les propriétés de production de protéines ECM ont été déterminées par des tests ELISA. La migration cellulaire a été évaluée à l'aide d'un test de cicatrisation des plaies, tandis que la synthèse des protéines ECM et l'expression des gènes ont été analysées, respectivement, par microscopie à immunofluorescence et PCR. L'immunohistochimie des explants de peau humaine a été utilisée pour approfondir l'induction des protéines ECM par pep_RTE62G ex vivo. Enfin, l'effet clinique de pep_RTE626 a été évalué dans une étude pilote de 28 jours de validation de principe. RÉSULTATS: Les tests in vitro ont confirmé que pep_RTE62G est un ingrédient anti-âge multifonctionnel efficace. Dans HaCaTs, le traitement pep_RTE62G augmente de manière significative à la fois la prolifération et la migration cellulaire. De même, dans les HDF, pep_RTE62G a induit de manière cohérente la néosynthèse de la protéine ECM élastine et collagène, effets qui sont maintenus dans les explants de peau humaine. Enfin, dans notre étude clinique de preuve de concept, l'application de pep_RTE626 sur 28 jours a démontré un potentiel stimulant anti-rides et collagène. CONCLUSION: pep_RTE62G représente un peptide naturel, non modifié avec des propriétés anti-âge prédites par l'IA et validées expérimentalement. Nos résultats confirment l'utilité de l'IA dans la découverte de nouveaux ingrédients topiques fonctionnels.

Effect of triploidy on digestive enzyme activity of early stages of turbot (Scophthalmus maximus).

In the present work, growth and digestive enzyme activities of total acid and alkaline proteases, pepsin, trypsin, lipase, and α-amylase, as well as partial characterization of enzyme activity, were studied in diploid and triploid turbot. Growth was similar between both groups. Acid protease activity increased consistently during the experiment, for both diploid (2n) and triploid (3n) fish. The alkaline protease activity was always higher for triploids throughout the experiment. Proteolytic acid activity (pH 2) was generally higher for diploids, at all temperatures tested. Higher activity was at pH 2 and 3 for 2n and 3n fish, respectively. Regarding temperature, acid and alkaline protease activity was higher at 37 °C and 60 °C, respectively, for both groups. The general increase in pancreatic enzymes (trypsin and amylase) before 35 days after hatching (DAH) and posterior decrease until 60 DAH. There was a marked effect on enzyme activity when changing from live prey to pellets (35 DAH), especially on triploids.

Molecular cloning and characterization of the matricellular protein Sparc/osteonectin in flatfish, Scophthalmus maximus, and its developmental stage-dependent transcriptional regulation during metamorphosis.

SPARC/osteonectin is a multifunctional matricellular glycoprotein, which is expressed in embryonic and adult tissues that undergo active proliferation and dynamic morphogenesis. Recent studies indicate that Sparc expression appears early in development, although its function and regulation during development are largely unknown. In this report, we describe the isolation, characterization, post-embryonic developmental expression and environmental thermal regulation of sparc in turbot. The full-length turbot sparc cDNA contains 930 bp and encodes a protein of 310 amino acids, which shares 77, 75 and 80% identity with human, frog and zebrafish, respectively. Results of whole-mount in situ hybridization reveal a dynamic expression profile during post-embryonic turbot development. Sparc is expressed differentially in the cranioencephalic region; mainly in jaws, branchial arches, fin folds and rays of caudal, dorsal and anal fins. Furthermore, ontogenetic studies demonstrated that Sparc gene expression is dynamically regulated during post-embryonic turbot development, with high expression during stage-specific post-embryonic remodeling. Additionally, the effect of thermal environmental conditions on turbot development and on ontogenetic sparc expression was evaluated.

Lipopolysaccharide downregulates CD91/low-density lipoprotein receptor-related protein 1 expression through SREBP-1 overexpression in human macrophages.

Sterol regulatory element-binding proteins (SREBPs) negatively modulate the expression of the CD91/low-density lipoprotein receptor-related protein (LRP1), a carrier and signaling receptor that mediates the endocytosis of more than 40 structurally and functionally distinct ligands. The aim of this work was to analyze whether lipopolysaccharide (LPS) can regulate LRP1 expression through SREBPs in human monocyte-derived macrophages (HMDM). LPS led to LRP1 mRNA and protein inhibition in a dose- and time-dependent manner. Concomitantly, a strong upregulation of SREBP-1 mRNA and SREBP-1 nuclear protein levels was observed in LPS-treated HMDM. The specific silencing of SREBP-1 efficiently prevented LRP1 reduction caused by LPS. SREBP-1 mRNA and nuclear protein levels remained high in HMDM treated with LPS unexposed or exposed to LDL. Native (nLDL) or aggregated LDL (agLDL) per se downregulated SREBP-2 expression levels and increased LRP1 expression. However, lipoproteins did not significantly alter the effect of LPS on SREBP-1 and LRP1 expression. Collectively, these data support that lipoproteins and LPS exert their modulatory effect on LRP1 expression through different SREBP isoforms, SREBP-2 and SREBP-1, respectively. These results highlight a crucial role of SREBP-1 as a mediator of the downregulatory effects of LPS on LRP1 expression in human macrophages, independently of the absence or presence of modified lipoproteins.

Comparison of air-kerma strength determinations for HDR (192)Ir sources.

PURPOSE: To perform a comparison of the interim air-kerma strength standard for high dose rate (HDR) (192)Ir brachytherapy sources maintained by the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) with measurements of the various source models using modified techniques from the literature. The current interim standard was established by Goetsch et al. in 1991 and has remained unchanged to date. METHODS: The improved, laser-aligned seven-distance apparatus of the University of Wisconsin Medical Radiation Research Center (UWMRRC) was used to perform air-kerma strength measurements of five different HDR (192)Ir source models. The results of these measurements were compared with those from well chambers traceable to the original standard. Alternative methodologies for interpolating the (192)Ir air-kerma calibration coefficient from the NIST air-kerma standards at (137)Cs and 250 kVp x rays (M250) were investigated and intercompared. As part of the interpolation method comparison, the Monte Carlo code EGSnrc was used to calculate updated values of A(wall) for the Exradin A3 chamber used for air-kerma strength measurements. The effects of air attenuation and scatter, room scatter, as well as the solution method were investigated in detail. RESULTS: The average measurements when using the inverse N(K) interpolation method for the Classic Nucletron, Nucletron microSelectron, VariSource VS2000, GammaMed Plus, and Flexisource were found to be 0.47%, -0.10%, -1.13%, -0.20%, and 0.89% different than the existing standard, respectively. A further investigation of the differences observed between the sources was performed using MCNP5 Monte Carlo simulations of each source model inside a full model of an HDR 1000 Plus well chamber. CONCLUSIONS: Although the differences between the source models were found to be statistically significant, the equally weighted average difference between the seven-distance measurements and the well chambers was 0.01%, confirming that it is not necessary to update the current standard maintained at the UWADCL.

Effect of several variables in the polymer toys additive migration to saliva.

Capacity to migrate of a representative group of polymeric additives, dyes, antioxidants, hindered amine light stabilizers (HALS) or antistatics, from plastic toys to saliva was analyzed to protect children in their habits of sucking and biting. Most of target additives appear no-regulated in toys normative but adverse effects on human health of some of them have been demonstrated and their presence in others commercial articles normative has been included. In order to offer an effective and easy tool to perform these controls, migration tests by dynamic and static contact, followed by a preconcentration step by liquid-liquid extraction (LLE) and ultra performance liquid chromatographic analysis with ultraviolet-visible and evaporative light scattering detections (UPLC-UV/Vis-ELSD) have been optimized to evaluate the migrated amounts of the additives in saliva simulant. The detection limits of the migration methodologies were ranged from 8.68 × 10(-2) to 1.30 × 10(-3)mg migrated (L simulant)(-1). Influence of several variables on this mass transport, as time, temperature and friction, was also analyzed to achieve the most aggressive methodology to protect consumers. Migration of several studied additives, whose presence has been demonstrated in several purchased commercial toys, has been observed.

Double-lumen central venous catheters impregnated with chlorhexidine and silver sulfadiazine to prevent catheter colonisation in the intensive care unit setting: a prospective randomised study.

Antimicrobial- and antiseptic-impregnated catheters are strategies recommended to prevent central venous catheter (CVC) colonisation. Few data regarding chlorhexidine/silver sulfadiazine-impregnated catheters in intensive care unit (ICU) patients have been reported. We performed a prospective, randomised study comparing the colonisation rates of chlorhexidine/silver sulfadiazine-impregnated CVCs (group 1) against standard CVCs (group 2). In order to assess catheter colonisation rates, a 4cm segment from the tips of aseptically removed catheters was cultured by the roll-plate method. In all, 109 patients were enrolled with successful catheter insertion, 51 of them in group 1 and 58 in group 2. There were no statistically significant differences between the two groups with regards to age, Sequential Organ Failure Assessment (SOFA) score, ICU admission diagnosis, infection risk, catheter insertion sites or catheter length of stay. The colonisation rates were 29.4% (15 catheters) for group 1 and 34.5% (20 catheters) for group 2 (P=0.50). Double-lumen CVCs impregnated with chlorhexidine and silver sulfadiazine were not effective in reducing the incidence of catheter colonisation in ICU patients.

High-performance liquid chromatography analysis of ten dyes for control of safety of commercial articles.

Two high-performance liquid chromatographic methods, with ultraviolet-visible spectrophotometry detection (HPLC-UV/Vis) and with tandem mass spectrometry triple quadrupole interfaced with positive ion mode electrospray ionization detection (HPLC-ESI+-QqQ-MS/MS), for determination and quantification of ten commercial dyes are proposed for control in commercial products. Multiple peaks observed for some of the studied dyes in HPLC-UV/Vis chromatograms forced to obtain structural information by HPLC-ESI-MS/MS method with scan mode. The quality parameters of the two proposed chromatographic methods were evaluated for different requirements of normative, showing detection (LODs) and quantification (LOQs) limits around 60-890 and 200-2990 microg L(-1) for HPLC-UV/Vis, and 4.54-14.3 and 15.0-47.6 microg L(-1) for HPLC-ESI+-QqQ-MS/MS.

Health and economic outcomes of the detection of Klebsiella pneumoniae-produced extended-spectrum beta-lactamase (ESBL) in a hospital with high prevalence of this infection.

INTRODUCTION: Klebsiella pneumoniae is of high prevalence in hospital infections, mainly in bloodstream infections (BSI), and some produce extended-spectrum beta-lactamase (ESBL). For hospitals with a high prevalence of strains producing this enzyme, there is no reference material to show whether the use of the E-test method for their detection, which can be quite expensive, is actually required. OBJECTIVE: To evaluate the cost-benefit of the disk diffusion and E-test methods for the detection of ESBL-producing K. pneumoniae strains in hospitals where a high prevalence of this resistance mechanism in BSI is found. METHODS: One hundred and eight patients with K. pneumoniae BSI were evaluated retrospectively. ESBL-producing strains were identified by the disk diffusion method and by the E-test method. We estimated the costs of both diagnostic methods based on antimicrobial therapy adequacy. RESULTS: Fifty-two percent of K. pneumoniae infections were due to ESBL-producing strains. The disk diffusion method yielded a positive predictive value (PPV) of 94.7% (95% CI: 88.9-100%) and a negative predictive value (NPV) of 96.1% (CI 95%: 90.8-101.4%) in relation to the E-test. We evaluated cost-effectiveness, i.e., we analyzed the cost of both E-test and disk diffusion methods with carbapenem and cephalosporins, and found that the use of the disk diffusion method accounts for approximately US$3300. CONCLUSIONS: In hospitals with a high prevalence of ESBL-producing strains, the disk diffusion method can be used to detect ESBL-producing K. pneumoniae without compromising the clinical progression of patients with BSI. The E-test showed higher accuracy but this method was more expensive than the disk diffusion method. However, the use of the E-test method was demonstrated to be more cost-effective, as we evaluated cost based on antimicrobial therapy adequacy.

Effect of triploidy on turbot haematology.

This study was carried out to compare key haematological features of diploid (2n) and triploid (3n) turbot as a first step towards the assessment of the ability of 3n turbot to withstand sub-optimal culture conditions. Morphometric indices of erythrocytes were determined on blood smears by light microscopy. Triploidy significantly (P<0.001) increased all morphometric indices measured in the erythrocytes, including size, surface, and volume, except for the size of minor nuclear axis. The increase in cell size was larger for the major (31.0%) than for the minor (8.3%) axis, thus rendering erythrocytes of 3n turbot more ellipsoidal. The increase in erythrocyte volume (45.9%) was close to the theoretical expected 50% increase as a result of one extra chromosome set. Haematological indices were measured automatically by a haematological Coulter Counter. Triploid turbot had lower numbers of red blood cells (RBC: 1.84 cells pL(-1) in 2n vs. 1.27 cells pL(-1) in 3n; P<0.001) but they were of a larger size (Mean corpuscular volume [MCV]: 145.51 fL in 2n vs. 181.78 fL in 3n; P<0.001). However, the decrease in RBC was not compensated by the increase in MCV, and thus, triploidy decreased the haematocrit (Hct: 26.80% in 2n vs. 23.11% in 3n; P<0.001) and total blood haemoglobin concentration (Hb: 73.74 g l(-1) in 2n vs. 67.54 g l(-1) in 3n; P<0.05). In contrast, mean corpuscular hemoglobin (MCH: 40.27 pg in 2n vs. 53.28 pg in 3n; P<0.001) was higher for 3n turbot as a result of their larger erythrocytes although MCH concentration (MCHC: 0.28 pg fL(-1) in 2n vs. 0.29 pg fL(-1) in 3n did not significantly differ. RBC, Hct and MCV were also determined manually using light microscopy. In general, discrepancies between the two methods were small (overall approximately 7%) but the Coulter Counter tended to overestimate RBC and Hct (and thus to underestimate MCV). Nevertheless, relative differences between ploidies were very similar, thus verifying triploidy-associated changes in hematological features. These changes, as determined in the present study, are essential when evaluating the feasibility of triploid turbot for intensive aquaculture systems in which unfavorable situations may occur.

Gynogenesis assessment using microsatellite genetic markers in turbot ( Scophthalmus maximus).

Gynogenesis was assessed by different methods in 2 families of gynogenetic offspring in turbot ( Scophthalmus maximus). Karyotype analysis in embryos and larvae demonstrated high accuracy in estimation of ploidy level, but performance was uneven given the low quality and number of plates obtained. The use of silver staining to estimate the number of nucleoli per nucleus resulted in a straightforward and easy method to evaluate the ploidy of the samples studied. However, the existence of a nucleolus organizer region polymorphism in turbot determined a small error in ploidy estimation, important when checking ploidy in specific individuals. The use of a set of 11 highly variable microsatellite loci proved to be a powerful method to confirm the exclusive maternal inheritance to gynogenetic offspring in turbot, with probabilities of detection of putative paternal genetic contribution above 99.99%.

[The relationship of brainstem auditory evoked potential to cerebral blood flow volume in with vertebrobasilar transient ischemic vertigo].

This study was aimed at the relationship of brain-stem auditory evoked potential(BAEP) with cerebral blood flow(CBF) volume and vascular pathological changes in patients with vertebro-basilar transient ischemic vertigo (VBTIV). 65 patients were examined by magnetic resonance angiography(MRA), transcranial Dopplar(TCD) and BAEP; 26 controls were examined by MRA and TCD. In the patient group, MRA showed that vascular pathological changes were obvious in 50 patients, and obscure or absent in 15 patients. The CBF volume [112.3-278.9 ml/min (2s)] of control group was higher than that (48.0-262.0 ml/min) of the patients group (t = 2.43, P < 0.01) in which 15 patients had low CBF volume and 50 patients had normal CBF volume. The BAEP of 47(72.3%) patients was abnormal. Out of 15 patients with low CBF volume, 14(93.3%) had abnormal BAEP, but out of 50 patients with normal CBF volume, only 33(66%) patients had abnormal BAED (chi 2 = 4.34, P < 0.05). In the 50 patients with obscure obvious vascular pathological changes, 40(80%) patients had abnormal BAEP, but in the 15 patients with obscure or without the changes, only 7(43.3%) patients had abnormal BAEP (chi 2 = 4.86, P < 0.05). These results suggested that there might be a close relationship of BAEP with CBF volume and vascular pathological changes.