In this study we analyzed the exudate of beef to evaluate its potential as non invasive sampling for nuclear magnetic resonance (NMR) based metabolomic analysis of meat samples. Exudate, as the ...natural juice from raw meat, is an easy to obtain matrix that it is usually collected in small amounts in commercial meat packages. Although meat exudate could provide complete and homogeneous metabolic information about the whole meat piece, this sample has been poorly studied. Exudates from 48 beef samples of different breeds, cattle and storage times have been studied by 1H NMR spectroscopy. The liquid exudate spectra were compared with those obtained by High Resolution Magic Angle Spinning (HRMAS) of the original meat pieces. The close correlation found between both spectra (>95% of coincident peaks in both registers; Spearman correlation coefficient = 0.945) lead us to propose the exudate as an excellent alternative analytical matrix with a view to apply meat metabolomics. 60 metabolites could be identified through the analysis of mono and bidimensional exudate spectra, 23 of them for the first time in NMR meat studies. The application of chemometric tools to analyze exudate dataset has revealed significant metabolite variations associated with meat aging. Hence, NMR based metabolomics have made it possible both to classify meat samples according to their storage time through Principal Component Analysis (PCA), and to predict that storage time through Partial Least Squares (PLS) regression.
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•NMR spectra from beef samples and their exudates are very strongly correlated.•23 metabolites not reported in previous NMR meat studies have been identified.•Meat exudate NMR spectra allow monitoring of biochemical changes related to aging.•PCA of exudate NMR spectra classified meat samples by their storage time.•The aging of a meat sample can be predicted by PLS analysis of its exudate.
Studies using the Global Leadership Initiative on Malnutrition (GLIM) criteria for patients with liver cirrhosis are limited. This study aimed to assess the impact of malnutrition according to the ...GLIM criteria on the outcomes of patients awaiting a liver transplant (LTx) and compare these criteria with Subjective Global Assessment (SGA).
This retrospective observational study included adult patients awaiting LTx. Patient clinical data, nutritional status according to various tools including SGA, and resting energy expenditure were assessed. The distinct phenotypic and etiologic criteria provided 36 different GLIM combinations. The GLIM criteria and SGA were compared using the kappa coefficient. The variables associated with mortality before and after the LTx and with a longer length of stay (LOS) after LTx (≥18 days) were assessed by Cox regression and logistic regression analyses, respectively.
A total of 152 patients were included median age 52.0 (interquartile range: 46.5–59.5) years; 66.4% men; 63.2% malnourished according to SGA. The prevalence of malnutrition according to the GLIM criteria ranged from 0.7% to 30.9%. The majority of the GLIM combinations exhibited poor agreement with SGA. Independent predictors of mortality before and after LTx were presence of ascites or edema (p = 0.011; HR:2.58; CI95%:1.24–5.36), GLIM 32 (PA-phase angle + MELD) (p = 0.026; HR:2.08; CI95%:1.09–3.97), GLIM 33 (PA + MELD-Na≥12) (p = 0.018; HR:2.17; CI95%:1.14–4.13), and GLIM 34 (PA + Child–Pugh) (p = 0.043; HR:1.96; CI95%:1.02–3.77). Malnutrition according to GLIM 28 (handgrip strength + Child-Pugh) was independently associated with a longer LOS (p = 0.029; OR:7.21; CI95%:1.22–42.50).
The majority of GLIM combinations had poor agreement with SGA, and 4 of the 36 GLIM combinations were independently associated with adverse outcomes.
Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused ...our efforts on the search of allosteric modulators. Based on the crystal structure of the PDE10A GAF-B domain, a virtual screening study allowed the discovery of new hits that were also tested experimentally, showing inhibitory activities in the micromolar range. Moreover, these new PDE10A inhibitors were able to decrease the nitrite production in LPS-stimulated cells, thus demonstrating their potential as anti-inflammatory agents.
Metabolomics has become an invaluable tool for both studying metabolism and biomarker discovery. The great technical advances in analytical chemistry and bioinformatics have considerably increased ...the number of measurable metabolites, yet an important part of the human metabolome remains uncovered. Among the various MS hyphenated techniques available, LC-MS stands out as the most used. Here, we aimed to show the capabilities of LC-MS to uncover part of the metabolome and how to best proceed with sample preparation and LC to maximise metabolite detection. The analyses of various open metabolite databases served us to estimate the size of the already detected human metabolome, the expected metabolite composition of most used human biospecimens and which part of the metabolome can be detected when LC-MS is used. Based on an extensive review and on our experience, we have outlined standard procedures for LC-MS analysis of urine, cells, serum/plasma, tissues and faeces, to guide in the selection of the sample preparation method that best matches with one or more LC techniques in order to get the widest metabolome coverage. These standard procedures may be a useful tool to explore, at a glance, the wide spectrum of possibilities available, which can be a good starting point for most of the LC-MS metabolomic studies.
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•The LC-MS detectable human metabolome is estimated.•The metabolite composition of the most widespread human biospecimens in metabolomics is estimated.•The most suitable sample preparation methods for LC-MS are described.•The metabolome coverage of LC techniques in MS-based metabolomics is discussed.•A guide to best select sample preparation and LC configuration based on the chosen biospecimen is proposed.
Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate ...information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.
The International Multiple Sclerosis Genetics Consortium and MultipleMS Consortium recently reported a genetic variant associated with multiple sclerosis (MS) severity. However, it remains unclear if ...these variants remain associated with more robust, longitudinal measures of disease severity.
We examined the top variant, rs10191329, from Harroud et al.'s study in 1813 relapse-onset MS patients from the MSBase Registry to assess association with longitudinal disease severity.
Our analysis revealed no significant association between rs10191329 genotype and longitudinal binary disease severity (
> 0.05).
These findings highlight the complexity of genetic factors mediating long-term MS outcomes and the need for further research.
This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with β-hydroxy-β-methylbutyrate (HMB) on ...nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6-3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (
= 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. -0.36 (0.4), and 2.98 (0.5) vs. -0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.
Purpose
– The purpose of this paper is to analyze empirically the fundamental role that information asymmetry plays in the functioning of an efficient capital market as mediator in the relation ...between corporate disclosures and cost of capital.
Design/methodology/approach
– By using a sample of 1,260 international non-financial listed companies in the period 2007-2014.
Findings
– The findings suggest that high-quality financial and social disclosures quality reduce the cost of capital, by decreasing information asymmetry. In other words, the authors find evidence of the mediator role of information asymmetry in the relation between corporate disclosures and the cost of capital. These results are also controlled for differences on accounting standards and other institutional factors.
Originality/value
– The central assumption is that the demand for corporate disclosures that reduces the information advantages of some investors (who are more informed) arises from agency conflicts and these information differences in turn, determine the cost of capital. This paper is the first attempt to study, jointly, the effects of decreasing information asymmetries by corporate disclosures on the cost of capital in an international setting. In addition, the authors focussed on both financial and social disclosures, creating empirical proxies whose validity for the analysis has been evidenced.
Cancer-related malnutrition is still unrecognized and undertreated in clinical practice. The morphofunctional assessment of disease-related malnutrition (DRM) is a new approach that focuses on ...evaluating changes in body composition and function. The aim of this study is to evaluate the prognostic value of classic and emerging assessment of malnutrition at 12-months survival in cancer patients.
We conducted a prospective study on cancer outpatients. Bioelectrical impedance with phase angle (PhA), nutritional ultrasound by rectus femoris cross-sectional area (RFCSA), hand grip strength, and "Timed Up and Go Test" (TUG) were evaluated as predictors of mortality.
Fifty-seven patients were included. The non-survivors had lower PhA values than the survivors (4.7° vs. 5.4°;
< 0.001), and we had the same results with RFCSA 2.98 cm
/m
vs. 4.27 cm
/m
(
= 0.03). Cut-off points were identified using the ROC (receiver operating characteristic) curves for PhA (≤5.6° cancer patients, ≤5.9° men, ≤5.3° women), RFCSA (≤4.47 cm
/m
cancer patients, ≤4.47° men, ≤2.73° women) and rectus femoris-Y-axis (RF-Y-axis; ≤1.3 cm cancer patients, ≤1.06 men, ≤1 women). In multivariate logistic regression analysis, we found that high PhA was significantly associated with a lower mortality hazard ratio (HR: 0.42 95% CI: 0.21-0.84,
= 0.014). Likewise, high RFCSA was associated with a decrease in mortality risk in the crude model (HR: 0.61 95% CI: 0.39-0.96,
= 0.031). This trend was also maintained in the adjusted models by the confounding variables.
Low PhA and RFCSA values are significant independent predictors of mortality in cancer patients. These cut-off points are clinical data that can be used for nutritional assessment and the prediction of clinical outcomes.
Abstract Eco‐innovation strategies are essential elements for companies developing core competencies in the circular economy model. The academic world has begun to study the knowledge of these ...business decisions, and there is incipient literature on the subject. In this context, this paper aims to contribute to the current knowledge on the impact of eco‐innovation strategies on corporate performance by exposing and synthesizing the distinct positions found in the literature. For this purpose, a systematic and bibliometric review of 81 articles related to the economic impact of eco‐innovation on firm performance, as well as the barriers and drivers of these strategies, was carried out. After analyzing the several types of eco‐innovation, our results show that although previous empirical evidence suggests the existence of a positive effect, it is not generalizable due to the existence of several factors that may condition the impact of eco‐innovation on corporate performance and its implementation. This study delves into the current academic literature on eco‐innovation and firm performance, determining that both size and the environment in which a company is framed constitute a series of conditioning factors that may clarify why there is no consensus in the academic literature in this regard. In addition, this work encourages future lines of research with the aim of shedding light on this field of knowledge.
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