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The incidence of the most common foodborne outbreaks reported by the European Food Safety Authority and the European Centre for Disease Prevention and Control during the years 2015–2019 is described. Campylobacter spp., Salmonella spp., Listeria monocytogenes, and Yersinia enterocolitica are the investigated microorganisms, and symptomatology, food categories responsible for human disease, as well as some prevention measures are the most important information schedules supplied to the readers. Campylobacteriosis and salmonellosis are the most common zoonoses with a notification rate of 59.7 and 20.0 per 100,000 population, respectively, in the year 2019. Good hygienic practices both at farm and domestic level could prevent such infections. The highest number of deaths is reported for listeriosis, corresponding to 31 fatal events in the year 2019. Therefore, awareness of the hazards linked to L. monocytogenes is particularly recommended amongst high-risk groups. By contrast, most cases of yersiniosis are sporadic and the most important prophylactic measures include adequate sanitation in pork chain, personnel hygiene, and protection of water supplies.

The aim of the present study was to explore the prognostic role of 2- deoxy-2-[18F]fluoro-D-glucose PET (FDG PET)/CT in recurrent luminal A and luminal B breast cancer.From two institutional databases, we retrospectively retrieved data about breast cancer patients undergoing FDG PET/CT between 2011 and 2018 for the assessment of recurrency. Molecular subtypes of breast cancer were defined based on the expression of estrogen, progesterone, human epidermal growth factor receptor 2 (HER2)-b receptors and proliferation index. Overall survival (OS, intended as the time from PET/CT and the time of death) was registered for each patient, by checking the medical charts. Parametric and survival analyses were computed.Data of 179 patients were retrieved. Sixty-three patients had luminal A, 88 luminal B and 28 luminal B/He breast cancer. At the time of PET/CT scan, cancer antigen (CA) 15.3 levels was within the normal range in 119 patients, whereas it was increased in 60 patients. FDG PET/CT results were suggestive for disease recurrence in 114 (63.7%) patients. The median time lapse from the FDG PET/CT scan to the last clinical follow-up visit was 51 months (1-192 months). Patients with evidence of a PET/CT scan suggestive for disease recurrence showed a significantly shorter OS (P 0.001) compared to patients with no PET/CT evidence of recurrence, in each subset of luminal breast cancer. Moreover, PET/CT was able to stratify the prognosis of patients independently from the level of tumor marker.These data suggest that FDG PET/CT may be an attractive prognostic tool in recurrent breast cancer. Our study supports its prognostic role both in luminal A and B-type molecular subtypes, regardless of the CA 15.3 levels.

Visual Abstract, Highlights • Because autophagy and Nox2 activation were identified as possible mechanisms for preservation of vessel integrity, they could be useful biomarkers to predict risk of aneurysm rupture by detecting the presence of a subclinical aneurysm or monitoring their growth. • Biomarkers such as molecules involved in autophagic machinery or Nox2 activation may help to explain pathological processes involved in TAA development and expansion, thereby opening up novel potential therapeutic strategies, such as the use of natural activators of autophagy or molecules that inhibit Nox2 activation, in the setting of aneurysmatic pathology. • Formation of aortic aneurysmal disease is multifactorial. Among the mechanisms involved, there is endothelial damage, oxidative stress, as well as an autophagy process, that seem to play a key role in TAA. Therefore, to identify the molecular mechanisms of these processes in TAA patients could lay the groundwork for defining strategies for preventing and slowing the progression of TAA., Summary Thoracic aortic aneurysms (TAA) pathogenesis and progression include many mechanisms. The authors investigated the role of autophagy, oxidative stress, and endothelial dysfunction in 36 TAA patients and 23 control patients. Univariable and multivariable analyses were performed. TAA patients displayed higher oxidative stress and endothelial dysfunction then control patients. Autophagy in the TAA group was reduced. The association of oxidative stress and autophagy with aortic disease supports the role of these processes in TAA. The authors demonstrate a putative role of Nox2 and autophagy dysregulation in human TAA. These findings could pinpoint novel treatment targets to prevent or limit TAA progression.

Background The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. Patients and methods This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. Results From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. Conclusions The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. EudraCT number 2012-003505-10., Highlights • Eribulin plus gemcitabine showed a remarkable best ORR of 37.3% and a clinical benefit rate of 48.8%. • The most common grade 3/4 toxicities were liver toxicity and neutropenia without febrile neutropenia. • The study regimen partially lost its efficacy in patients harboring BRCA1/2 pathogenic variants. • SNPs in CYP3A4 and FGD4 genes were associated with increased risk of liver toxicity. • Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS.

Background: Acute type A aortic dissection (AAD) is a life-threatening emergency in cardiac surgery, with high in-hospital (22%) and long-term morbidity and mortality rates. Methods: Data from 134 patients were collected from anamnesis and computed tomography before and after aortic surgery. Data were analyzed using IBM SPSS v23. Results: We found that male patients had better survival than the female (p 0.05).Among survived patients, we found that an increased pre-operative ascending aorta diameter is associated with the establishment of a chronic partial thrombosis (54.2 ± 4.6 vs 50.5 ± 7.0 mm, p 0,05). Entre los pacientes supervivientes, el diámetro de la aorta ascendente preoperatoria se asocia con la trombosis parcial crónica (54,2 ± 4,6 frente a 50,5 ± 7,0 mm, p < 0,05). Además, el diámetro de la aorta descendente preoperatoria se asocia con un tiempo de trombosis completa más prolongado (29,2 ± 6,1 frente a 37,2 ± 6,9 mm, p < 0,05). Conclusiones: En nuestra experiencia, no existe una diferencia significativa entre los procedimientos quirúrgicos más utilizados. Sin embargo, encontramos que la edad, el sexo, el estado de shock, la permeabilidad de la falsa luz preoperatoria y el tiempo de CEC son importantes predictores de supervivencia. Además, los diámetros aórticos preoperatorios son relevantes para determinar el tiempo para llegar a una trombosis completa de la falsa luz.

The process of mitochondrial dynamics is emerging as a core player in cardiovascular homeostasis. This process refers to the co-ordinated cycles of biogenesis, fusion, fission and degradation to which mitochondria constantly undergo to maintain their integrity, distribution and size. These mechanisms represent an early response to mitochondrial stress, confining organelle portions that are irreversibly damaged and preserving mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to myocardial damage and cardiac disease progression in a variety of disease models, including pressure overload, ischaemia/reperfusion and metabolic disturbance. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in cardiovascular diseases. In this review, we discuss the current evidence about the role of mitochondrial dynamics in cardiac pathophysiology, with a particular focus on the mechanisms underlying the development of cardiac hypertrophy and heart failure, metabolic and genetic cardiomyopathies, ischaemia/reperfusion injury, atherosclerosis and ischaemic stroke. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.

Background NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. Methods In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. Results Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65–0.50 for no CINV events on cycles 3 and 4). Conclusion The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle. Trial registration This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

The aim of the present study was to evaluate the microbial contamination of domestic swine carcasses over an 8-year period in a slaughterhouse located in the Marche region, Central Italy. The hygiene of the slaughter process was assessed by microbiological criteria involving aerobic colony count (ACC), Enterobacteriaceae and Salmonella spp. [Regulation (EC) No 2073/2005 and amendments]. Five carcasses were tested during five sampling sessions each year (four different sites from each carcass were pooled before the analysis) for a total of 200 samples. The results of the study showed low levels of ACC and Enterobacteriaceae and the absence of Salmonella spp., except for one sample. The values of ACC were consistently satisfactory (

Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Cerebrovascular disease, a frequent complication of hypertension, is a major public health issue for which novel therapeutic and preventive approaches are needed. Autophagy activation is emerging as a potential therapeutic and preventive strategy toward stroke. Among usual activators of autophagy, the natural disaccharide trehalose (TRE) has been reported to be beneficial in preclinical models of neurodegenerative diseases, atherosclerosis and myocardial infarction. In this study, we tested for the first time the effects of TRE in the stroke-prone spontaneously hypertensive rat (SHRSP) fed with a high-salt stroke permissive diet (JD). We found that TRE reduced stroke occurrence and renal damage in high salt-fed SHRSP. TRE was also able to decrease systolic blood pressure. Through ex-vivo studies, we assessed the beneficial effect of TRE on the vascular function of high salt-fed SHRSP. At the molecular level, TRE restored brain autophagy and reduced mitochondrial mass, along with the improvement of mitochondrial function. The beneficial effects of TRE were associated with increased nuclear translocation of TFEB, a transcriptional activator of autophagy. Our results suggest that TRE may be considered as a natural compound efficacious for the prevention of hypertension-related target organ damage, with particular regard to stroke and renal damage.

Background: The diagnosis of brucellosis by serological tests is based on antigen suspensions derived from smooth lipopolysaccharide extracts, which can give false positive results linked to cross-reactivity with other Gram-negative microorganisms, especially Yersinia enterocolitica O:9 and Escherichia coli O157:H7. Objective: The objective of the present study was the characterization by proteomic analysis of specific immunogenic proteins not associated with smooth lipopolysaccharide to improve the diagnostic tests used in the ovine brucellosis eradication programs. Methods: The serum from a sheep positive to Brucella melitensis was treated to eliminate all antibodies against such lipopolysaccharide and highlight the reaction towards the immunoreactive proteins in Western Blotting. Results: The immunoreactive bands were identified by nLC-MS/MS and through bioinformatic tools, it was possible to select 12 potential candidates as protein antigens specific for Brucella melitensis. Conclusion: The detection of new antigens not subjected to cross-reactivity with other Gram-negative microorganisms can offer an additional tool for the serological diagnosis of such disease.

Chronic cardiac muscle inflammation and fibrosis are key features of Duchenne Muscular Dystrophy (DMD). Around 90% of 18-year-old patients already show signs of DMD-related cardiomyopathy, and cardiac failure is rising as the main cause of death among DMD patients. The evaluation of novel therapies for the treatment of dystrophic heart problems depends on the availability of animal models that closely mirror the human pathology. The widely used DMD animal model, the mdx mouse, presents a milder cardiac pathology compared to humans, with a late onset, which precludes large-scale and reliable studies. In this study, we used an exercise protocol to accelerate and worsen the cardiac pathology in mdx mice. The mice were subjected to a 1 h-long running session on a treadmill, at moderate speed, twice a week for 8 weeks. We demonstrate that subjecting young mdx mice (4-week-old) to “endurance” exercise accelerates heart pathology progression, as shown by early fibrosis deposition, increases necrosis and inflammation, and reduces heart function compared to controls. We believe that our exercised mdx model represents an easily reproducible and useful tool to study the molecular and cellular networks involved in dystrophic heart alterations, as well as to evaluate novel therapeutic strategies aimed at ameliorating dystrophic heart pathology.

Hazelnut shells represent a waste material (about 42% of the total biomass) deriving from hazelnut harvest. These are mainly used as a heating source, however, they represent an interesting source of polyphenols useful in health field. The impact on phenolic profile and concentrations of hazelnut shell extracts obtained by three extraction methods (maceration, ultrasonic bath, and high-power ultrasonic), as well as temperature, extraction time, and preventive maceration, was studied. The prepared extracts were characterized in terms of chemical composition, antioxidant and antimicrobial activities. Eighteen different phenolic compounds were identified and quantified by chemical analysis and gallic acid was the most abundant in all the extracts analyzed. Other relevant compounds were chlorogenic acid, protocatechuic acid and catechin. Preventive maceration had a positive effect on the extraction of different types of compounds regardless of the method performed. Application of the high-power ultrasonic method had different effects, either positive or negative, depending on the type of compound and extraction time. All the prepared extracts showed antioxidant activity especially those prepared by maceration, and many of them were able to inhibit the growth of both B. subtilis and B. cereus.

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

BACKGROUND: The present analysis focuses on real-world data of Everolimus- Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS: Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and [greater than or equal to] 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel- Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS: From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged [greater than or equal to] 65 years, of whom 87 were [greater than or equal to] 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged [greater than or equal to] 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (> 7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged [greater than or equal to] 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS: EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

Lessons LearnedThe androgen receptor (AR) is present in most breast cancers (BC), but its exploitation as a therapeutic target has been limited. This study explored the activity of dehydroepiandrosterone (DHEA), a precursor being transformed into androgens within BC cells, in combination with an aromatase inhibitor (to block DHEA conversion into estrogens), in a two-stage phase II study in patients with AR-positive/estrogen receptor-positive/human epidermal growth receptor 2-negative metastatic BC. Although well tolerated, only 1 of 12 patients obtained a prolonged clinical benefit, and the study was closed after its first stage for poor activity.BackgroundAndrogen receptors (AR) are expressed in most breast cancers, and AR-agonists have some activity in these neoplasms. We investigated the safety and activity of the androgen precursor dehydroepiandrosterone (DHEA) in combination with an aromatase inhibitor (AI) in patients with AR-positive metastatic breast cancer (MBC).MethodsA two-stage phase II study was conducted in two patient cohorts, one with estrogen receptor (ER)-positive (resistant to AIs) and the other with triple-negative MBC. DHEA 100 mg/day was administered orally. The combination with an AI aimed to prevent the conversion of DHEA into estrogens. The main endpoint was the clinical benefit rate. The triple-negative cohort was closed early.ResultsTwelve patients with ER-positive MBC were enrolled. DHEA-related adverse events, reported in four patients, included grade 2 fatigue, erythema, and transaminitis, and grade 1 drowsiness and musculoskeletal pain. Clinical benefit was observed in one patient with ER-positive disease whose tumor had AR gene amplification. There was wide inter- and intra-patient variation in serum levels of DHEA and its metabolites.ConclusionDHEA showed excellent safety but poor activity in MBC. Although dose and patient selection could be improved, high serum level variability may hamper further DHEA development in this setting.

Background: Mentalizing, the mental capacity to understand oneself and others in terms of mental states, has been found to be reduced in several mental disorders. Some studies have suggested that eating disorders (EDs) may also be associated with impairments in mentalizing. The aim of this work is to investigate the possible presence of mentalizing subtypes in a sample of patients with EDs.Method: A sample of patients with eating disorders (N = 157) completed a battery of measures assessing mentalization and related variables, including the Reflective Functioning Questionnaire (RFQ), the Difficulties in Emotion Regulation Strategies (DERS), the Interpersonal Reactivity Index (IRI). Clinicians rated patients in relation to imbalances in different dimensions of mentalization to prementalizing modes and attachment style by using the Mentalization Imbalances Scale, the Modes of Mentalization Scale (MMS), and the Adult Attachment Questionnaire. A latent profile analysis was conducted to test the possible presence of different subgroups. MANOVA was used to test the possible differences between the four mentalizing profiles in relation to emotion dysregulation (DERS), empathy (IRI), and adequate and impairments in mentalizing (MMS and RFQ).Results: The latent profile analysis suggested the presence of four different profiles in relation to impairments in the dimensions of mentalization: (1) affective/self/automatic imbalances, (2) external imbalance, (3) cognitive/self/automatic imbalances, and (4) cognitive/other/automatic imbalances. Patients belonging to profile 1 are characterized by the prevalence of affective mentalization that overwhelms the capacity to reflect on mental states with an imbalance on the self-dimension; profile 2 patients are excessively focused on the external cues of mentalization; profile 3 patients are characterized by an over-involvement on the cognitive and self-facets of mentalization, with an impairment in adopting the other mind perspective; and profile 4 patients have similar impairments compared to profile 3 patients but with an excessive focus on others and deficits in self-reflection. These profiles were heterogeneous in terms of EDs represented in each group and presented significant differences on various variables such as attachment style, emotion dysregulation, empathy, interpersonal reactivity, and reflective function. This study represents, so far, the first work that confirms the presence of different mentalizing patterns in ED patients.Conclusions: ED patients can be classified in relation to impairments in different dimensions of mentalization above and beyond ED diagnosis.

Background End-stage renal disease (ESRD) is associated with a broad spectrum of morphological and functional thyroid disorders. Recent studies have shown that low free triiodothyronine (fT3) levels are related to inflammatory status and endothelial activation in ESRD patients on haemodialysis (HD). Limited data exist about a possible relationship between dialysis regimen, namely long nocturnal haemodialysis (LNHD), and thyroid function parameters. The aim of this study was to evaluate the relationship between dialysis regimen and thyroid function, and consequently with the main patient outcomes. Methods To this purpose, we performed a retrospective, single-centre cohort study including 220 incident chronic HD patients treated during an 8-year period (from January 2010 to December 2017). The main clinical and haematochemical parameters, including thyroid function, were evaluated and related to the main patient outcomes. Results Patients with low fT3 levels ( 3.05 ng/mL) (P 3.05 ng/mL was significantly higher in LNHD patients than in patients treated with diurnal dialysis. Conclusions Our data suggest that the application of alternative dialysis regimens, also reducing the frequency of low T3, could ameliorate outcomes and therefore reduce the incidence of cardiovascular events in HD patients.

In this study, thirteen batches of broiler chicken from an integrated Italian poultry company were investigated for the detection of Listeria monocytogenes. The prevalence was evaluated in faeces samples at farm level and after transport, caecal contents and carcass neck skin from 2 slaughterhouses (M1 and M2), for a total of 2080 samples, throughout a 27-month period. No positive results were recorded in faeces, while the overall prevalence of contamination in carcass neck skin was 26.7%. Then, 123 isolates out of 139 positive skin samples, with the prevalent serotypes 4b (76%) and 1/2b (94%) from slaughterhouses M1 and M2 respectively, were PFGE characterized, showing the presence of 18 different pulsotypes and 8 genetic clusters. The same pulsotypes were found in carcasses from different farms, but slaughtered in the same abattoir, highlighting the environmental origin of contamination. The persistence of the pathogen over long time seemed to be very likely, considering that undistinguishable pulsotypes were found in carcasses slaughtered in the same slaughterhouse after periods up to 18 months long. The implementation of cleaning and sanitation at slaughterhouse level could represent the main factor for the control of such pathogen in the poultry meat processing line.

Massive pulmonary embolism (PE) is a severe condition that can potentially lead to death caused by right ventricular (RV) failure and the consequent cardiogenic shock. Despite the fact thrombolysis is often administrated to critical patients to increase pulmonary perfusion and to reduce RV afterload, surgical treatment represents another valid option in case of failure or contraindications to thrombolytic therapy. Correct risk stratification and multidisciplinary proactive teams are critical factors to dramatically decrease the mortality of this global health burden. In fact, the worldwide incidence of PE is 60-70 per 100,000, with a mortality ranging from 1% for small PE to 65% for massive PE. This review provides an overview of the diagnosis and management of this highly lethal pathology, with a focus on the surgical approaches at the state of the art.

Bicuspid aortic valve (BAV) is frequently associated with the development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. For this purpose, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 ± 12.8 years) and AAA complicated or not, were included. Interestingly, patients with AAA showed a significant increase in circulating Notch1 levels and EPC number than subjects without AAA. However, circulating Notch1 levels and EPC number were significantly lower in BAV subjects than TAV patients either in the presence or absence of AAA. Finally, Notch pathway was activated to a greater extent in aortic aneurysmatic portions with respect to healthy aortic fragments in both BAV and TAV patients. However, the expression of genes encoding components and ligands of Notch pathway in aortic tissues was significantly lower in BAV than TAV subjects. Our study demonstrates that BAV subjects are characterized by a significant decrease in both tissue and circulating levels of Notch pathway, and in blood EPC number than TAV patients, either in presence or absence of AAA disease.

[This corrects the article DOI: 10.18632/oncotarget.25874.].

Scientific interest in the genus Taxus has recently increased worldwide, for both conservation and biotechnological purposes. In contrast with abundant studies on other gymnosperms, basic cytogenetic information on this genus is still very limited, likely due to difficulties in appropriate tissue handling and lack of efficient procedures for chromosome analyses. In the present study, chromosome pre-treatment protocols were established, and karyotype analyses successfully performed on meristematic tissue of root-tips derived from plant cuttings of English yew (Taxus baccata L.). Twelve homologous pairs were identified, including seven metacentric and five sub-metacentric chromosomes. No heteromorphic sex chromosomes were found. Multicolour fluorescence in situ hybridization (FISH) was successfully applied using the 18S and 5S rDNA probe sequences. Loci of both sequences turned out to be located on the same sub-metacentric chromosome pair. Microsatellite (simple sequence repeat) sequences were also ...

Purpose Combination of anthracyclines with trastuzumab is hampered by cardiotoxicity. Pegylated liposomal doxorubicin and lapatinib could represent a safer alternative to combination therapy. Methods In this phase Ib study with 3 + 3 dose escalation design, patients with HER2-positive advanced breast cancer received pegylated liposomal doxorubicin 30 mg/m2 intravenously on day 1 plus lapatinib 1250 (level 1) or 1500 (level 2) mg/day orally on days 1–21 of each 21-day cycle. The aims were to establish the maximum tolerated dose at first cycle, and the activity and safety of multiple cycles. Results Nine patients out of 11 enrolled were evaluable: 3 at level 1 and 6 at level 2. No dose-limiting toxicities occurred at dose level 1, while 1 (grade 3 diarrhea) occurred at dose level 2, leading to the expansion of this cohort to 6 patients, with no further dose-limiting toxicities. Main grade 1–2 toxicities at first cycle were leucopenia, diarrhea, elevated transaminases, mucositis. Three patients had grade 3 toxicities at subsequent cycles, including colitis, anorexia, stomatitis plus hand-foot syndrome. One partial response, 5 disease stabilizations, and 3 disease progressions were reported. Conclusions Combination of pegylated liposomal doxorubicin and lapatinib is feasible and potentially active in pretreated HER2-positive advanced breast cancer patients. Trial registration NCT02131506 (ClinicalTrials.gov identifier).

Background: Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is a hallmark of hormone receptor-positive (HR+) breast cancer (BC) resistant to endocrine therapy (ET). Preclinical and clinical data suggest that adding a PI3K inhibitor (PI3Ki) to ET may overcome resistance. In BELLE-2, a Phase III randomized study, buparlisib (BUP; BKM120; pan-PI3Ki) + fulvestrant (FULV) demonstrated clinical activity and manageable safety in patients (pts) with HR+, human epidermal growth factor receptor 2-negative advanced BC, with the greatest treatment effect in pts with PIK3CA mutation in circulating tumor DNA (ctDNA). Here, we report results from the final progression-free survival (PFS) analysis of the BELLE-3 study. Methods: Pts (N=432) were randomized 2:1 to BUP (100mg/day) or placebo (PBO) + FULV (500mg per standard of care) and stratified by visceral disease status. Key inclusion criteria: prior aromatase inhibitor therapy; disease progression ≤30 days from combination therapy of ET + mTOR inhibitor as last regimen. Key exclusion criteria: >1 chemotherapy regimen for advanced BC; prior PI3Ki, AKT inhibitor, or FULV; history of/active mood disorders. Primary and key secondary endpoints were PFS (local assessment; Response Evaluation Criteria In Solid Tumors v1.1) and overall survival (OS), respectively. Other secondary endpoints included: overall response rate (ORR); clinical benefit rate (CBR); efficacy by PIK3CA status in ctDNA (BEAMing technology); safety. Results: BELLE-3 met its primary endpoint with a statistically significant improvement in PFS per investigator assessment in favor of BUP + FULV (BUP arm) vs PBO + FULV (PBO arm; hazard ratio [HR] 0.67; 95% confidence interval [CI]: 0.53–0.84; p10%; BUP vs PBO arm) Grade 3/4 AEs were increased alanine aminotransferase (21.9% vs 2.9%), increased aspartate aminotransferase (17.7% vs 2.9%), and hyperglycemia (12.2% vs 0). Conclusions: BELLE-3 met its primary endpoint in the full population. PFS improvement in the BUP vs PBO arm was greater in pts with PIK3CA-mut than PIK3CA-wt tumors, based on ctDNA and PCR. Secondary endpoints showed improved clinical benefit with BUP + FULV vs PBO + FULV. Safety was in line with that previously seen with the combination. Keywords: Breast cancer; PI3K inhibitor; Fulvestrant; Buparlisib. Citation Format: Di Leo A, Seok Lee K, Ciruelos E, Lønning P, Janni W, O'Regan R, Mouret Reynier M-A, Kalev D, Egle D, Csoszi T, Bordonaro R, Decker T, Tjan-Heijnen VC, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. BELLE-3: A phase III study of buparlisib + fulvestrant in postmenopausal women with HR+, HER2–, aromatase inhibitor-treated, locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor-based treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S4-07.

// Roberta Maltoni 1 , Valentina Casadio 2, * , Sara Ravaioli 2, * , Flavia Foca 3 , Maria Maddalena Tumedei 2 , Samanta Salvi 2 , Filippo Martignano 2 , Daniele Calistri 2 , Andrea Rocca 1 , Alessio Schirone 1 , Dino Amadori 1 , Sara Bravaccini 2 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy * These authors contributed equally to this work Correspondence to: Sara Bravaccini, email: sara.bravaccini@irst.emr.it Keywords: CF-DNA, HER2, PI3KCA, prognosis, breast cancer subtypes Received: August 20, 2016 Accepted: January 23, 2017 Published: February 06, 2017 ABSTRACT As conventional biomarkers for defining breast cancer (BC) subtypes are not always capable of predicting prognosis, search for new biomarkers which can be easily detected by liquid biopsy is ongoing. It has long been known that cell-free DNA (CF-DNA) could be a promising diagnostic and prognostic marker in different tumor types, although its prognostic value in BC is yet to be confirmed. This retrospective study evaluated the prognostic role of CF-DNA quantity and integrity of HER2 , MYC , BCAS1 and PI3KCA , which are frequently altered in BC. We collected 79 serum samples before surgery from women at first diagnosis of BC at Forli Hospital (Italy) from 2002 to 2010. Twenty-one relapsed and 58 non-relapsed patients were matched by subtype and age. Blood samples were also collected from 10 healthy donors. All samples were analyzed by Real Time PCR for CF-DNA quantity and integrity of all oncogenes. Except for MYC , BC patients showed significantly higher median values of CF-DNA quantity (ng) than healthy controls, who had higher integrity and lower apoptotic index. A difference nearing statistical significance was observed for HER2 short CF-DNA ( p = 0.078, AUC value: 0.6305). HER2 short CF-DNA showed an odds ratio of 1.39 for disease recurrence with p = 0.056 (95% CI 0.991-1.973). Our study suggests that CF-DNA detected as liquid biopsy could have great potential in clinical practice once demonstration of its clinical validity and utility has been provided by prospective studies with robust assays.

The foodborne outbreaks occurred in last decades highlight the importance of the development and implementation of preventive measures and programs aiming at ensuring food safety on one hand and constituting a common basis for the hygienic production of food on the other hand. In particular, a farm to fork approach has been applied in all sectors of food production chain in order to improve hygiene and reduce all potential biological hazards. The food supply chain is very complex because of the differences in food composition and processing and this can result in emergence and re-emergence of foodborne pathogens. However, many factors related to an increase in foodborne illness have been reported, such as the change in eating habits and consumer preferences, increased international travels, change in food processing, production and distribution, pathogen adaptation to new environments, acquisition of virulence factors and antimicrobial drug resistance by microorganisms, advances in pathogen detection methods, inadequate sanitation and vector control measures, inadequate public health services, including consumer information (Smith and Fratamico, 2018). This Research Topic titled “Foodborne Pathogens: Hygiene and Safety” focuses on important food safety concerns such as the potential presence of pathogens in food as well as their toxins/metabolites, the resistance to antibiotics or sanitizers, and other virulence characteristics. It includes four reviews and 44 original research papers. The main foodborne pathogens studied herein are: Campylobacter jejuni, Cronobacter sakazakii, Escherichia coli, Listeria monocytogenes, Salmonella spp., and Staphyloccus aureus, but some other researches deal with Helicobacter pilori, Klebsiella pneumoniae, Vibrio parahaemolyticus, mycobacteria, and molds as well. Studies on characterization and genetic typing of foodborne pathogens, detection methods and inactivation of these microorganisms by natural preservatives derived from plant sources, essential oils and biocontrol, and influence of probiotics are also reported.

Background Deficiency of NADH dehydrogenase [ubiquinone], the mitochondrial complex I, represents an emerging mechanism of cardiovascular diseases. Ndufc2, a subunit of mitochondrial complex I, is involved in stroke development. We aimed to gain some insights on the role of Ndufc2 into acute coronary syndrome (ACS) through the assessment of its gene expression, along with that of anti-oxidant proteins and of mitochondrial function parameters, in circulating mononuclear cells (PBMCs) of ACS versus stable angina (SA) patients. The impact of NDUFC2 silencing in human endothelial and vascular smooth muscle cells was assessed in vitro. Methods and results One hundred twenty-three patients presenting with SA (n = 41) or ACS (n = 82) were enrolled. PBMCs were used to assess the gene expression level of: NDUFC2, uncoupling protein 2 (UCP2), superoxide dysmutases 1 and 2 (SOD1, SOD2), levels of ROS and ATP. The mitochondrial dysfunction was assessed by cytofluorimetry; the structural damage by transmission electron microscopy. Cell viability, angiogenesis, markers of atherogenesis were evaluated in NDUFC2-silenced vascular cells. NDUFC2 mRNA level was significantly downregulated, along with UCP2, SOD1, SOD2 expression, in ACS patients. We found significant increases of ROS levels, reduced ATP levels, higher degree of mitochondrial structural damage and dysfunction in ACS patients. In vitro, NDUFC2 silencing favored mechanisms involved in atherogenesis and plaque vulnerability. Conclusions A significant reduction of NDUFC2 expression is detected in ACS. In vitro, NDUFC2 silencing affects vascular cell viability and angiogenesis while stimulating the expression of markers of plaque rupture. Our observations suggest that these mechanisms may contribute to ACS development.

The use of pig rennet is very ancient and in Italy is only applied in the manufacture of Pecorino di Farindola cheese. In order to evaluate the key role of this rennet in the establishment of peculiar features of Pecorino di Farindola, cheeses made from raw ewes’ milk using calf (A) and kid (B) rennets were compared to those produced with pig (C) rennet. The use of pig rennet for Pecorino di Farindola cheese making confers physico-chemical and proteolytic characteristics that differentiate it from cheeses produced with other coagulants. However, no microbiological differences were observed. Chesses made with pig and kid rennets were characterised by higher proteolysis after 7 days of ripening. The content of isovaleric and propionic acids at the end of ripening was correlated with the presence of propionibacteria.

BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The Oncologist 2017;22:1-8Implications for Practice: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.

NADPH oxidases (NOXs) represent one of the major sources of reactive oxygen species in the vascular district. Reactive oxygen species are responsible for vascular damage that leads to several cardiovascular pathological conditions. Among NOX isoforms, NOX2 is widely expressed in many cells types, such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells, confirming its pivotal role in vascular pathophysiology. Studies in mice models with systemic deletion of NOX2, as well as in transgenic mice overexpressing NOX2, have demonstrated the undeniable involvement of NOX2 in the development of hypertension, atherosclerosis, diabetes mellitus, cardiac hypertrophy, platelet aggregation, and aging. Of note, the inhibition of NOX2 has been found to be protective for cardiovascular homeostasis. Here, we review the evidence demonstrating that the modulation of NOX2 activity is able to improve vascular physiology, suggesting that NOX2 may be a potential target for therapeutic applications.

Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated. Among breast cancers, those with functioning cyclin D-CDK4/6-Rb-E2F are mainly hormone-receptor (HR) positive, with some HER2-positive and rare triple-negative cases. Deregulation results from genetic or otherwise occurring hyperactivation of molecules subtending cell cycle progression, or inactivation of cell cycle inhibitors. Based on results of randomized clinical trials, palbociclib was granted accelerated approval by the US Food and Drug Administration (FDA) for use in combination with letrozole as initial endocrine-based therapy for metastatic disease in postmenopausal women with HR-positive, HER2-negative breast cancer, and was approved for use in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. This review provides an update of the available knowledge on the cell cycle and its regulation, on the alterations in cyclin D-CDK4/6-Rb-E2F axis in breast cancer and their roles in endocrine resistance, on the preclinical activity of CDK4/6 inhibitors in breast cancer, both as monotherapy and as partners of combinatorial synergic treatments, and on the clinical development of palbociclib in breast cancer.

Background. Evidence on the management and treatment of male breast cancer is scant. We report the analysis of a multicenter Italian series of patients with male breast cancer treated with eribulin. To our knowledge, this is the first report on the use or eribulin in this setting. Patients and Methods. Patients were retrospectively identified in 19 reference centers. All patients received eribulin treatment, according to the standard practice of each center. Data on the identified patients were collected using a standardized form and were then centrally reviewed by two experienced oncologists. Results. A total of 23 patients (median age, 64 years; range, 42–80) were considered. The median age at the time of diagnosis of breast cancer was 57 years (range, 42–74). HER2 status was negative in 14 patients (61%), and 2 patients (9%) had triple-negative disease. The most common metastatic sites were the lung (n = 14; 61%) and bone (n = 13; 56%). Eribulin was administered for a median of 6 cycles (range, 3–15). All patients reported at least stable disease; two complete responses (9%) were documented. Eribulin was well-tolerated, with only four patients (17%) reporting grade 3 adverse events and two (9%) with treatment interruptions because of toxicity. Eight subjects (35%) did not report any adverse event during treatment. For patients with a reported fatal event, the median overall survival from the diagnosis of metastatic disease was 65 months (range, 22–228). Conclusion. Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer.

Food safety represents a central issue for the global food chain and a daily concern for all people. Contaminated food by physical, biological or chemical hazards can harm consumers, increasing demand for health services, government expenditure on public health and other social costs. The quality assurance programs are based on the continuous monitoring of raw matter, production process, storage and distribution of the end products, including the purpose for which they are intended. Such programs represent an important objective for food producers, not only for the potential risk to human health, but also for the economic losses to which they can be subjected. The development and use of rapid analytical methods able to identify the main failures in food production can benefit food companies by saving time and costs for the good and fast control of products through the entire food chain.

BACKGROUND: Trehalose is a natural, non-reducing disaccharide synthesized by lower organisms. Trehalose exhibits an extraordinary ability to protect cells against different kinds of stresses through activation of autophagy. However, the effect of trehalose on the heart during stress has never been tested. OBJECTIVES: We evaluated the effect of trehalose administration in a mouse model of chronic ischemic remodeling. METHODS: Wild type (WT) or beclin 1+/− mice were subjected to permanent ligation of the left anterior descending artery (LAD) and then treated with either placebo or trehalose (1 mg/g/day i.p. for 48 hours, then 2% in the drinking water). After 4 weeks, echocardiographic, hemodynamic, gravimetric, histological and biochemical analyses were conducted. RESULTS: Trehalose reduced left ventricular (LV) dilation and increased ventricular function in mice with LAD ligation, as compared to placebo. Sucrose, another non-reducing disaccharide, did not exert protective effects during post-infarction LV remodeling. Trehalose administration to mice overexpressing GFP-tagged LC3 significantly increased the number of GFP-LC3 dots, both in the presence and absence of chloroquine administration. Trehalose also increased cardiac LC3-II levels after 4 weeks of myocardial infarction (MI), indicating that it induces autophagy in the heart in vivo. In order to evaluate whether trehalose exerts beneficial effects through the activation of autophagy, trehalose was administered to beclin 1+/− mice. The improvement of LV function, lung congestion, cardiac remodeling, apoptosis and fibrosis following trehalose treatment observed in WT mice were all significantly blunted in beclin 1+/− mice. CONCLUSIONS: Trehalose reduces MI-induced cardiac remodeling and dysfunction through activation of autophagy.

Lipophilic marine biotoxins include okadaic acid, pectenotoxin, yessotoxin and azaspiracid groups. The consumption of contaminated molluscs can lead to acute food poisoning syndromes depending on the exposure level. Regulatory limits have been set by Regulation (European Community, 2004a) No 853/2004 and LC-MS/MS is used as the official analytical method according to Regulation (European Community, 2011) No 15/2011. In this study specimens of mussels (Mytilus galloprovincialis) were collected along the coasts of the central Adriatic Sea during the years 2015-2017 and analyzed by the European harmonized Standard Operating Procedure. The method was validated for linearity, specificity, repeatability and reproducibility and it revealed able to be used for the detection of the lipophilic marine biotoxins. Levels of okadaic acid, pectenotoxin, yessotoxin and its analogs were detected at different concentrations in 148 (37%) out of a total of 400 samples, always below the maximum limits, except for 11 (4.3%) of them that were non-compliant because they exceeded the regulatory limit. Moreover, some samples were exposed to a multi-toxin mixture with regards to okadaic acid, yessotoxin and 1-Homo yessotoxin. Following these results, the aquaculture farms from which the non-compliant samples derived were closed until the analytical data of two consecutive samplings returned favorable. Besides the potential risk of consumption of mussels contaminated by lipophilic marine biotoxins, these marine organisms can be considered as bio-indicators of the contamination status of the marine ecosystem.

Intensive physical exercise may cause increase oxidative stress and muscular injury in elite football athletes. The aim of this study was to exploit the effect of cocoa polyphenols on oxidative stress and muscular injuries induced by intensive physical exercise in elite football players. Oxidant/antioxidant status and markers of muscle damage were evaluated in 24 elite football players and 15 controls. Furthermore, the 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n=12) or a control group (n=12) for 30 days in a randomized controlled trial. Oxidative stress, antioxidant status, and muscle damage were assessed at baseline and after 30 days of chocolate intake. Compared to controls, elite football players showed lower antioxidant power and higher oxidative stress paralleled by an increase in muscle damage markers. After 30 days of dark chocolate intake, an increased antioxidant power was found in elite athletes assuming dark chocolate. Moreover, a significant reduction in muscle damage markers (CK and LDH, p<0.001) was observed. In the control group, no changes were observed with the exception of an increase of sNox2-dp, H2O2, and myoglobin. A simple linear regression analysis showed that sNox2-dp was associated with a significant increase in muscle damage biomarker release (p=0.001). An in vitro study also confirmed that polyphenol extracts significantly decreased oxidative stress in murine myoblast cell line C2C12-derived. These results indicate that polyphenol-rich nutrient supplementation by means of dark chocolate positively modulates redox status and reduced exercise-induced muscular injury biomarkers in elite football athletes. This trial is registered with NCT03288623.

In this study, a new and alternative method based on monoclonal antibodies (MAbs) for the rapid detection of Yersinia enterocolitica O:8 was developed. This microorganism is an emerging foodborne pathogen causing gastrointestinal disease in humans. The transmission can occur through contaminated food such as raw or undercooked meat, milk and dairy products, water and fresh vegetables. Nine MAbs (46F7, 54B11, 54C11, 62D10, 64C7, 64C10, 72E8, 72E10, 72G6) were characterized and selected versus Y. enterocolitica O:8, and only 2 of them showed also a weak cross-reaction with Campylobacter jejuni. The MAb 54B11 was used for the development of Y. enterocolitica capture-ELISA in food matrices, i.e. meat and dairy products (n = 132). The method was validated by ISO 16140:2003 and compared with the official method for the detection of presumptive pathogenic Y. enterocolitica (ISO 10273:2003). Relative accuracy, sensitivity and specificity corresponded to 100%. The selectivity was evaluated on other food samples (n = 126) showing a lower confidence limit of 90.3% and an upper confidence limit of 100%. The results from this study demonstrated that the developed method was rapid and cheap, specific and sensitive for the screening of the pathogen in food.