Four lots of sea bream were fed with different ration levels (R100, R75, R50, and R25, corresponding to 100, 75, 50 and 25%, respectively, of the standard ration fed in the fish farm), in order to ...assess the effects of a 30-day pre-slaughtering period of feed restriction on the textural characteristics of the edible muscle of farmed sea bream (
Sparus aurata). Results showed that food restriction over 50% influenced negatively total body and individual organ weights. Fish in a good nutritional condition presented lower muscle pH and poorer muscle characteristics, showing soft texture and decreased water holding capacity (WHC). When the intake was moderately restricted (R75), a positive influence on pH and WHC of muscle was found. A 50% reduction of the ration size also delayed muscle softening during cold storage; whereas, a more severe restriction (R25) did not improve this parameter. Electrophoretic studies showed minor changes in the relative optical density of sarcoplasmic and myofibrillar protein fractions attributable to the different ration sizes assayed. These results suggest that the main contributing factor to the observed enhancement in muscle texture due to feed restriction is likely the decrease of lipid deposits in the structural components of the muscle.
Background
CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined ...CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6.
Methods
Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3‐month follow‐up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia.
Results
Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj: 19.702 1.815–213.918, P = 0.014) and mortality after 3 months (ORadj: 21.47 3.434–134.221, P = 0.001).
In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia.
Conclusions
Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.
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Abstract Background and aims Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous ...studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. Methods and results The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval CI = 0.33–0.91; P -trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23–0.72; P -trend = 0.003), lignans (HR = 0.51; CI 0.30–0.86; P -trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26–0.86; P -trend 0.02). Conclusion Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations. Clinical trial registry : International Standard Randomized Controlled Trial Number (ISRCTN of London, England) 35739639.
Background
Aging-related traits, including gradual loss of skeletal muscle mass and chronic inflammation, are linked to altered body composition and impaired physical functionality, which are ...important contributing factors to the disabling process. We sought to explore the potential relationship between lower-body muscle strength decline and inflammatory mediators in older adults.
Methods
We performed a cross-sectional analysis in 38 older adults admitted to an acute care of the elderly unit (57.9% women, mean age=87.9±4.9 years; mean body mass index BMI=26.5±4.7 kg/m
2
). Clinical and functional outcomes including weight, height, BMI, dependence, physical and cognitive performance, and muscle strength measured by one-repetition maximum (1RM) for leg-extension, leg-press, chest-press and handgrip strength, were assessed. Blood serum content of 59 cytokines, chemokines and growth factors was assessed by protein arrays. Multivariate linear regression analyses were used to examine the relationship between cytokine concentrations and muscle strength parameters.
Results
After controlling for confounding factors (age, sex, BMI, cumulative illness rating score and physical performance score), 1RM leg-press had a significant negative relationship with GRO (CXCL2) (β= −18.13, p=0.049), MIG (CXCL9) (β= −13.94, p=0.004), IGF-1 (β= −19.63, p=0.003), CK-BETA 8 (CCL23) (β= −28.31, p=0.018) and GCP-2 (CXCL6) (β= −25.78, p=0.004). Likewise, 1RM leg-extension had a significant negative relationship with IGFBP-1 (β= −11.49, p=0.023).
Conclusions
Thus, several serum cytokines/chemokines and growth factors are negatively associated with lower muscle strength in older patients. Further investigation is required to elucidate the mechanism of elevated inflammatory mediators leading to lower muscle strength.
The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with ...(i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status.
Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status.
HER2DX pCR score was significantly associated with pCR in all patients odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75, with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk.
HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.
•Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (n = 765).•HER2DX pCR score was found to be significantly associated with pCR in all patients.•HER2DX identify patients who benefit more from dual HER2 blockade.•HER2DX identify patients who benefit more from multi-agent chemotherapy over single taxane.•HER2DX risk score identify patients with lower risk of recurrence irrespective of pCR status.
Objectives
Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe ...the clinical experience with lacosamide in neuro‐oncological patients.
Materials and methods
Multicenter retrospective study in patients with cancer‐related seizures, who received lacosamide as an add‐on therapy.
Results
Forty‐eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug‐resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio‐/chemotherapy. Lacosamide‐related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug‐related adverse events.
Conclusion
Lacosamide is an AED to consider in cases of cancer‐related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio‐/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.
Summary Background and aims Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A ...comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. Methods and results The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55–80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day−1 (443 ± 218 mg day−1 of flavonoids and 304 ± 156 mg day−1 of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. Conclusion In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil. Clinical trial registry International Standard Randomised Controlled Trial Number (ISRCTN of London, England) 35739639.
Escherichia coli is one of the most-studied microorganisms worldwide but its characteristics are continually changing. Extraintestinal E. coli infections, such as urinary tract infections and ...neonatal sepsis, represent a huge public health problem. They are caused mainly by specialized extraintestinal pathogenic E. coli (ExPEC) strains that can innocuously colonize human hosts but can also cause disease upon entering a normally sterile body site. The virulence capability of such strains is determined by a combination of distinctive accessory traits, called virulence factors, in conjunction with their distinctive phylogenetic background. It is conceivable that by developing interventions against the most successful ExPEC lineages or their key virulence/colonization factors the associated burden of disease and health care costs could foreseeably be reduced in the future. On the other hand, one important problem worldwide is the increase of antimicrobial resistance shown by bacteria. As underscored in the last WHO global report, within a wide range of infectious agents including E. coli, antimicrobial resistance has reached an extremely worrisome situation that ‘threatens the achievements of modern medicine’. In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.
New knowledgements about pathogenesis, antimicrobial resistance and clinical aspects of Escherichia coli.
Graphical Abstract Figure.
New knowledgements about pathogenesis, antimicrobial resistance and clinical aspects of Escherichia coli.