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The effects of pre-processing decreasing temperature (19, 15 and 10 °C) of olive fruit (cv. Leccino) harvested at three developmental stages (semi-ripe, ripe, advanced ripening) have been evaluated on oil in terms of basic quality parameters, composition, organoleptic traits, and aroma profiles. A total of 40 metabolites (volatiles and non-volatiles) were identified by 1 H NMR and GC/MS analyses. Multivariate statistical analysis showed that samples obtained from ripe and advanced ripe olives cooled at 10 and 15 °C better correlated with C6 aldehydes, mainly associated with herbal/green olfactory traits. Compounds responsible for sweet/fruity traits were more abundantly present in oil extracted from 19 °C olive samples. Decreasing pulp temperature before crushing also resulted in reduced presence of 1-penten-3-ol, 1-penten-3-one, acetic acid and ethyl alcohol, associated with specific defects of the oil. Results indicate that slightly lowering fruit temperature just before crushing modulates oil composition by reducing oil off flavours while enhancing green and fresh attributes in particular when ripe olives are processed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Few studies are available on metabolic changes in liver injuries and this is the first metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using 1 H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors. The investigation clearly shows differences in the metabolomic profile of HCV patients before and after effective DAA treatment. Significant changes in metabolites levels in patients undergoing therapy suggest alterations in several metabolic pathways. It has been shown that 1 H-NMR fingerprinting approach is an optimal technique in predicting the specific infection and the healthy status of studied subjects (Monte-Carlo cross validated accuracies: 86% in the HCV vs HBV model, 98.7% in the HCV vs HC model). Metabolite data collected support the hypothesis that the HCV virus induces glycolysis over oxidative phosphorylation in a similar manner to the Warburg effect in cancer, moreover our results have demonstrated a different action of the two viruses on cellular metabolism, corroborating the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection. This metabolomic study has revealed some alteration in metabolites for the first time (2-oxoglutarate and 3-hydroxybutrate) concerning the HCV-infection model that could explain several extrahepatic manifestations associated with such an infection.

Metabolomics deals with the whole ensemble of metabolites (the metabolome). As one of the -omic sciences, it relates to biology, physiology, pathology and medicine; but metabolites are chemical entities, small organic molecules or inorganic ions. Therefore, their proper identification and quantitation in complex biological matrices requires a solid chemical ground. With respect to for example, DNA, metabolites are much more prone to oxidation or enzymatic degradation: we can reconstruct large parts of a mammoth's genome from a small specimen, but we are unable to do the same with its metabolome, which was probably largely degraded a few hours after the animal's death. Thus, we need standard operating procedures, good chemical skills in sample preparation for storage and subsequent analysis, accurate analytical procedures, a broad knowledge of chemometrics and advanced statistical tools, and a good knowledge of at least one of the two metabolomic techniques, MS or NMR. All these skills are traditionally cultivated by chemists. Here we focus on metabolomics from the chemical standpoint and restrict ourselves to NMR. From the analytical point of view, NMR has pros and cons but does provide a peculiar holistic perspective that may speak for its future adoption as a population-wide health screening technique., (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Objective: Metabolomic analysis of saliva proved its accuracy in discriminating patients with generalized chronic periodontitis (GCP) from healthy subjects by identifying specific molecular signatures of the disease. There is lack of investigations concerning the effect of periodontal treatment on individual metabolic fingerprints. Therefore, the aim of this study was to determine whether non-surgical periodontal therapy could change salivary metabolomic profile in GCP to one more similar to periodontal health., Design: Unstimulated whole saliva of 32 controls and 19 GCP patients were obtained prior to and 3 months after conventional staged non-surgical periodontal therapy. Metabolic profiling was performed using Nuclear Magnetic Resonance (NMR) spectroscopy, followed by univariate and multivariate paired approaches to assess the changes introduced by the therapy., Results: In GCP group, periodontal treatment led to an improvement in all clinical parameters (p < 0.001). The accuracy of the multivariate model in discriminating the metabolomic profile of each GCP patient at two time points was 92.5%. Despite the almost perfect separation of the spectra in the metabolic space, the univariate analysis failed to identify significant variations in single metabolite content. The post-treatment metabolic profile of GCP patients could not be assimilated to that of healthy controls who exhibited different levels of lactate, pyruvate, valine, proline, tyrosine, and formate., Conclusions: Based on these data, NMR-spectroscopic analysis revealed that, despite significant changes in the overall metabolomic fingerprint after non-surgical therapy, GCP patients maintained a distinctive metabolic profile compared to healthy individuals., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Recent findings about the differential gene expression signature of periodontal lesions have raised the hypothesis of distinctive biological phenotypes expressed by generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients. Therefore, this cross-sectional investigation was planned, primarily, to determine the ability of nuclear magnetic resonance (NMR) spectroscopic analysis of unstimulated whole saliva to discriminate GCP and GAgP disease-specific metabolomic fingerprint and, secondarily, to assess potential metabolites discriminating periodontitis patients from periodontally healthy individuals (HI)., Methods: NMR-metabolomics spectra were acquired from salivary samples of patients with a clinical diagnosis of GCP (n = 33) or GAgP (n = 28) and from HI (n = 39). The clustering of HI, GCP, and GAgP patients was achieved by using a combination of the Principal Component Analysis and Canonical Correlation Analysis on the NMR profiles., Results: These analyses revealed a significant predictive accuracy discriminating HI from GCP, and discriminating HI from GAgP patients (both 81%). In contrast, the GAgP and GCP saliva samples seem to belong to the same metabolic space (60% predictive accuracy). Significantly lower levels (P < 0.05) of pyruvate, N-acetyl groups and lactate and higher levels (P < 0.05) of proline, phenylalanine, and tyrosine were found in GCP and GAgP patients compared with HI., Conclusions: Within the limitations of this study, CGP and GAgP metabolomic profiles were not unequivocally discriminated through a NMR-based spectroscopic analysis of saliva., (© 2018 American Academy of Periodontology.)

A fast and reproducible protocol for milk Nuclear Magnetic Resonance (NMR) metabolomic fingerprinting was developed, allowing for an accurate discrimination among milk samples from large-scale distribution, as well as among milk sample from different farms located in the same restricted geographical area. Seasonal variations in milk composition and correlations with cows' nutritional patterns are also assessed, underlining relationships between feeding and metabolites. The most important difference was related to the use of silage feeding. This finding is relevant to assess the suitability of milk for different dairy products. A prominent example is parmesan cheese, the preparation protocol of which excludes milk from silage-fed cows., (Copyright © 2018. Published by Elsevier Ltd.)

The aim of this first study was to reveal the new potential biomarkers by a metabolomics approach in severe septic calves. Sepsis is a common cause of morbidity and mortality in newborn dairy calves. The main challenges with the use of biomarkers of sepsis in domestic animals are their availability, cost, and time required to obtain a result. Metabolomics may offer the potential to identify biomarkers that define calf sepsis in terms of combined clinical, physiological, and pathobiological abnormalities. To our knowledge, this is the first study presenting an NMR- (nuclear magnetic resonance-) based plasma metabolomics at set intervals in neonatal septic calves. Twenty neonatal dairy calves with severe sepsis and ten healthy calves were used. Hematological and biochemical health profiles were gathered in plasma samples at set intervals. Similarly, NMR spectra were acquired. All diseased animals (except one) died after 72 hours. Clinical and laboratory results were in accordance with those of severe septic animals. Multivariate analysis on NMR plasma spectra proved to be an excellent tool for faster identification of calves with severe sepsis from healthy animals. The NMR-based metabolomic profile may contribute to the better understanding of severe sepsis in newborn calves.

Non-small-cell lung cancer is a term that encompasses a number of subtypes of lung cancer. In recent years, several intracellular pathways have been studied in order to discover a potential target for novel anticancer therapies such as anaplastic lymphoma kinase (ALK) and reactive oxygen species 1 (ROS1). Increased interest in oncologic treatment research has resulted from the observation that ALK- and ROS1-associated tyrosine kinases show molecular analogies in some of their domains. This discovery led to the hypothesis that target therapy against ALK translocation could have efficacy also in ROS1-positive tumors. Crizotinib is an oral tyrosine kinase inhibitor that binds the ALK tyrosine kinase domain, blocking its function. We report the case of a woman with heavily pretreated metastatic lung adenocarcinoma harboring ROS1 positivity who experienced a prolonged and dramatic clinical benefit from crizotinib therapy.

Introduction: The multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome characterized by the onset of hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary lesions., Presentation of Case: This appears to be the first described case of a massive intrathoracic lipoma in MEN1. The patient was affected with primary hyperparathyroidism treated with a total parathyroidectomy followed by a distal pancreatectomy for insulinoma. At follow-up, the computed tomography showed a massive lesion on the left emithorax suggestive of a lipoma. At the onset of a mild dyspnea we decided to perform the surgical excision of the mass obtaining a complete relief of the symptoms., Discussion: This case is evidence of the importance of a strict follow-up of such patients., Conclusion: Lipomas are the most frequent benign soft tissue tumors. They are usually sporadic but are sometimes related to hereditary syndromes. Intrathoracic localizations are rare and can arise mainly in the mediastinum, bronchus or lung. The diagnosis is often incidental; despite preoperative imaging will accurately show the features of the lesions, it is impossible obtain an accurate diagnosis-hence, the treatment of choice remains the surgical excision., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gallbladder neuroendocrine neoplasms (GB-NENs) are rare. The majority of GB-NENs are poorly differentiated, with increased mitotic activity and clinically aggressive course. Surgery is the only curative approach and the optimal medical treatment is uncertain. In this report we describe the case of a woman affected by metastatic well differentiated GB-NEN with increased Ki 67. The patient underwent surgical removal of the gallbladder neoplasm and showed disease recurrence with pulmonary and liver metastases. After achieving a partial chemotherapy response, the patient rapidly died due to progressive disease. This case raises important issues. Well differentiated NENs with a high proliferative index are not included as a specific entity in any of the most widely used nomenclature systems. Moreover considering the proliferative index of the disease, it is reasonable to consider the patient a candidate for chemotherapy. Nevertheless, recently published papers raise the possibility that well differentiated NENs and specific proliferative index cutoff can predict low chemosensitivity in patients with highly proliferative neuroendocrine carcinoma.

Objectives: Customized chemotherapy has several advantages: patients are more likely to be treated with the most effective agents and can be spared the toxicity of ineffective drugs. Based on the literature, excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) genes represent predictive biomarkers of response to platinum compound and gemcitabine, in NSCLC., Materials and Methods: We had planned a phase II trial (Simon design) to evaluate combination chemotherapy according to single nucleotide polymorphisms (SNPs) of ERCC1 (118T/C and 8092C/A) and RRM1 (-37C/A and -524T/C) in naïve patients affected by advanced NSCLC. ERCC1 and RRM1 SNPs assessment was performed in peripheral blood lymphocytes (PBLs). Combination chemotherapy was selected based on ERCC1 and RRM1 SNPs: we assume that patients with one or two C alleles at position 118 and with one or two A alleles at position 8092 in ERCC1 gene would correspond to Cisplatin non-responder and than with two A alleles at -37 and two C alleles at -524 in RRM1 gene to gemcitabine non-responder. Four schedules were provided: cisplatin+gemcitabine, cisplatin+docetaxel, gemcitabine+docetaxel; docetaxel+vinorelbine. Primary endpoint was overall response (ORR) in the intention-to-treat population., Results: 42 patients were enrolled from January 2010 to November 2011; 40 patients received at least 1 cycle of chemotherapy; median age was 66 years (range: 47-72); 36(90%) had stage IV, 4(10%) IIIB; 23(58%) had adenocarcinoma, 14(35%) squamous carcinoma. Twenty-five (62%) patients received treatment A, 3(8%) treatment B, 11(28%) treatment C, 1(23%) treatment D. ORR was 55%, analysis in squamous patients subgroups showed 71.4% ORR. The median follow-up was 19.7 months, PFS was 23 weeks (95% CI = 15-26) and OS was 40.4 weeks (95% CI = 32-55). Treatment was well tolerated., Conclusion: We observed an increase of ORR in NSCLC patients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Lung cancer is the leading cause of cancer related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all cases. Half of the patients at diagnosis of NSCLC are over seventy years old; therefore, the elderly represent a large subgroup of patients affected by advanced NSCLC in our clinical practice. Nevertheless, the elderly are under-represented in clinical trials. Given the fact that old age is frequently associated with several comorbidities, poor general conditions and physiologic reduction in organ function, clinicians must carefully choose the best treatment option for elderly patients with advanced NSCLC, always taking into account the expected risks and benefits. In this paper we perform a review of literature evidence regarding the medical treatment of elderly patients affected by advanced NSCLC, encompassing single-agent chemotherapy, doublet chemotherapy and targeted agents. We conclude that single-agent chemotherapy with a third generation agent (vinorelbine, taxanes, gemcitabine) represents a valid treatment option for elderly patients who are not eligible for a combination chemotherapy due to clinical features such as comorbidities, poor performance status and inadequate organ function. Platinum-based doublet chemotherapy shows similar efficacy in elderly patients as compared to their younger counterpart, despite greater treatment related toxicity and it is indicated in elderly patients with ECOG PS: 0-2, adequate organ function and no major comorbidities. Elderly patients affected by epidermal growth factor receptor (EGFR) mutated NSCLC benefit mostly from a tyrosine kinase inhibitor of EGFR (erlotinib, gefitinib) which is associated with a good toxicity profile. Currently there are no available data to strongly support the use of bevacizumab in combination with first line chemotherapy in the treatment of older adults. Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment with an oral inhibitor of such a rearrangement (crizotinib)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

► We report the case of a heavily pretreated woman affected by metastatic endometrial carcinoma. ► Patient received Trabectedin as 10th line of treatment with an impressive clinical response. ► We evaluated BRCA1 and ERCC1 gene status which could be involved in Trabectedin sensitivity.