Mechanisms of metabolic dysfunction in cancer-associated cachexia.

Metabolic dysfunction contributes to the clinical deterioration observed in advanced cancer patients and is characterized by weight loss, skeletal muscle wasting, and atrophy of the adipose tissue. This systemic syndrome, termed cancer-associated cachexia (CAC), is a major cause of morbidity and mortality. While once attributed solely to decreased food intake, the present description of cancer cachexia is a disorder of multiorgan energy imbalance. Here we review the molecules and pathways responsible for metabolic dysfunction in CAC and the ideas that led to the current understanding.EFW is supported by a grant from the Spanish Ministry of Economy (BFU2012-40230) and a European Research Council Advanced Grant (ERC FCK/2008/37).This is the author accepted manuscript. It is currently embargoed pending publication

Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone

Building an outward-oriented social family legacy: rhetorical history in family business foundations

Scholars have recently paid growing attention to the transfer of family legacies across generations, but existing work has been mainly focused on an inward-oriented, intra-family, perspective. In this article, we seek to understand how family firms engage in rhetorical history to transfer their social family legacy to external stakeholders, what we call “outward-oriented social legacy.” By carrying out a 12-months field study in three Italian family business foundations, our findings unveil three distinctive narrative practices—founder foreshadowing, emplacing the legacy within the broader community, and weaving family history with macro—history—that contribute to transferring outward-oriented social legacies

Implementing a Digital Strategy:Learning from the Experience of Three Digital Transformation Projects

The rapid growth of digital technologies and the extraordinary amount of data that devices and applications collect each day are increasingly driving companies to radically transform the business architecture through which they create and appropriate value. However, companies may fail to extract value from digital transformation due to the disconnection between strategy formulation and strategy implementation. Through the analysis of three case studies of firms that digitally transformed their business - namely ABB, CNH Industrial, and Vodafone -, this article presents a framework than can help companies implement their digital transformation strategy and thereby renovate their business model

Iron entry route in horse spleen apoferritin Involvement of the three-fold channels as probed by selective reaction of cysteine-126 with the spin label 4-maleimido-tempo

AbstractApoferritin has been selectively labeled with a maleimide nitroxide derivative at Cys-126, located in the hydrophilic 3-fold channels. Titration of this derivative with Fe(II), which gives rise to the initial Fe(III)-apoferritin complex, produces, at low metal-to-protein ratios, a decrease of the intensity of the label EPR signal due to the occurrence of a magnetic dipolar interaction. A label-metal distance ranging between 8–12 Å can be estimated from titrations performed with VO(IV), which is known to bind in the 3-fold channels, and likewise produces a decrease in the label EPR signal. The present findings indicate that iron binds in the hydrophilic channels in its higher oxidation slate and that these channels represent the metal entry route at least at low metal-to-protein ratios

Glucose Metabolism, Thyroid Function, and Prolactin Level in Adolescent Patients With First Episode of Schizophrenia and Affective Disorders

Schizophrenia and affective spectrum disorders (ASD) typically begin in adolescence or early adulthood. The pathophysiological mechanisms underlying these disorders are still not fully understood, and recent studies have suggested an involvement of dysfunctions in cardiometabolic and neuroendocrine systems at the onset of both disorders. In this context, we aimed to assess thyroid function, prolactin level, glucose metabolism, and lipid profile in drug naive adolescents, comparing patients with first episode of schizophrenia spectrum disorders (SSD) and patients with ASD. We performed a retrospective chart review from inpatients aged from ten to eighteen years, referred to Child and Adolescent Psychiatric Unit of University of Bari “Aldo Moro” over a period of 4 years, with diagnosis of SSD (n=30) or ASD (n=22), according to Diagnostic and Statistical Manual for Mental Disorders-fifth edition (DSM-5) criteria. Data on serum prolactin, glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, thyroid stimulating hormone, free triiodothyronin, and free thyroxin were collected, and the insulin resistance (IR) indexes “HOMA1-IR“ and “HOMA2-IR” were calculated. The multivariable linear regression models, adjusting for potential confounding factors (age, sex, and BMI), showed HOMA1-IR (p=0.001), HOMA2-IR (p=0.002), glucose (p=0.004), insulin (p=0.004) and free thyroxin (p&lt;0.001) values higher in the SSD group than in ASD. No others significant differences were found. Our findings suggest the need for a metabolic and endocrine screening at the onset of SSD and ASD, particularly for indexes of IR, that is a testable and treatable risk factor for cardiometabolic diseases. Further studies are required to better understand the role of endocrinological and metabolic dysfunctions at the onset of severe mental illness also considering influencing factors as age, gender, and BMI

IDENTIFICATION OF E. COLI O157 IN A BOVINE MILK FARM BY MULTIPLEX REAL-TIME PCR

Law provisions about direct sell of raw bovine milk require VTEC O157 monitoring in bovine milk farms (milk and faeces). It has been showed that culture-based methods used for this scope, besides being cumbersome and time-consuming, may be also less sensitive, compared to molecular approaches. In this study, a multiplex Real-Time PCR, able to identify VTEC O157, Salmonella spp and Listeria monocytogenes, has been used to analyse milk, filter, sewage and stool samples from a milk farm, in comparison with standard OIE methods. The performances of the molecular protocol have been preliminary assessed with lyophilized samples from proficiency testing VLA, showing 100% accordance. Results from field samples indicated the absence of the pathogen in milk, and the higher sensitivity of Real-Time PCR with other matrices, suggesting its potential use for fast VTEC O157 identification

Respiratory inhibition of isolated mammalian mitochondria by salivary antifungal peptide histatin-5

Histatin-5 is a peptide secreted in the human saliva, which possesses powerful antifungal activity. Previous studies have shown that this peptide exerts its candidacidal activity, through the inhibition of both mitochondrial respiration and the formation of reactive oxygen species. The purpose of the present study was to investigate the biological consequences of histatin-5 action on mammalian mitochondria to verify if the toxic mechanism exerted on mitochondria from Candida albicans is an exclusive for fungal cells. Moreover, hypothesising that the damage exerted on mitochondria may induce programmed cellular death pathways, we evaluated two main markers of apoptosis: the mitochondrial membrane potential (DeltaPsi) and the release of cytochrome c. The results obtained show that exposure of isolated mammalian mitochondria to histatin-5 determines: (i) a large inhibition of the respiratory chain at the level of complex 1, (ii) a slight decrease in the mitochondrial membrane potential, and (iii) no release of cytochrome c. (C) 2003 Elsevier Inc. All rights reserved

MOLECULAR IDENTIFICATION AND GENOTYPING OF CIAUSCOLO AUTOCHTHONOUS MICROFLORA: PRELIMINARY STUDY

The present study reports the results of a preliminary characterization of the bacterial population of Ciauscolo, a typical Italian fermented sausage, traditionally manufactured in Marche region. The bacterial community involved in Ciauscolo fermentation was investigated using both molecular and culturebased methods. The estimation of genotypic intra-species variation of the autochthonous bacteria isolated was also evaluated by using randomly amplified polymorphic DNA (RAPD) analysis and unweighted pairgroup method with arithmetic averages (UPGMA) cluster analysis. Our findings revealed an high diversity of the autochthonous bacterial population investigated, both at species and strain level

Vitamin D Deficiency in Autism Spectrum Disorder: A Cross-Sectional Study

Vitamin D plays a role in central nervous system (CNS) development. Recent literature focused on Vitamin D status in children and adolescents with autism spectrum disorder (ASD), but with inconsistent results. Our case-control study is aimed at evaluating serum 25-hydroxyl-Vitamin D (25(OH)D) concentration in children with ASD (ASD group, n=54) compared to children affected by other neurological and psychiatric disorders (non-ASD group, n=36). All patients were admitted at the Complex Operative Unit of Child Neuropsychiatry, Polyclinic of Bari, Italy. 25(OH)D was quantified by chemiluminescence immunoassay and level defined as: Deficiency (&lt;20 ng/mL); insufficiency (20-30); normality (30-100); toxicity (&gt;100). Statistical analysis was performed using SPSS20 (significance&lt;0.05). The ASD group showed 25(OH)D a mean level significantly lower than control (p=0.014). Multivariable logistic regression analysis showed an association between ASD and Vitamin D deficiency (p=0.006). The nature of such association is unclear. Vitamin D deficiency may probably act as a risk factor for the development of ASD. Further studies are needed to unravel the role of Vitamin D in ASD etiology and investigate its therapeutic potential