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Therapy failure and metastasis-associated mortality are stumbling blocks in the management of PDAC in patients. Failure of therapy is associated to intense hypoxic conditions of tumors. To develop effective therapies, a complete understanding of hypoxia-associated changes in genetic landscape of tumors during disease progression is needed. Because artificially immortalized cell lines do not rightly represent the disease progression, studying genetics of tumors in spontaneous models is warranted. In the current study, we generated a spectrum of spontaneous human (UM-PDC1; UM-PDC2) and murine (HI-PanL, HI-PancI, HI-PanM) models representing localized, invasive, and metastatic PDAC from a patient and transgenic mice (K-rasG12D/Pdxcre/Ink4a/p16-/). These spontaneous models grow vigorously under hypoxia and exhibit activated K-ras signaling, progressive loss of PTEN, and tumorigenicity in vivo. Whereas UM-PDC1 form localized tumors, the UM-PDC2 metastasize to lungs in mice. In an order of progression, these models exhibit genomic instability marked by gross chromosomal rearrangements, centrosome-number variations, Aurora-kinase/H2AX colocalization, loss of primary cilia, and α-tubulin acetylation. The RNA sequencing of hypoxic models followed by qRT-PCR validation and gene-set enrichment identified Intestine-Specific Homeobox factor (ISX)–driven molecular pathway as an indicator PDAC aggressivness. TCGA-PAAD clinical data analysis showed high ISX expression correlation to poor survival of PDAC patients, particularly women. The functional studies showed ISX as a regulator of i) invasiveness and migratory potential and ii) VEGF, MMP2, and NFκB activation in PDAC cells. We suggest that ISX is a potential druggable target and newly developed spontaneous cell models are valuable tools for studying mechanism and testing therapies for PDAC.

The aim of the present study was to evaluate the sensory acceptability limit of refrigerated fish through a multivariate approach, involving classic physicochemical and bacteriological indicators and considering different consumer profiles. The results of the survival analysis demonstrated that, in general, consumers still considered the fish to be suitable for purchase (4.128 days of storage), despite being microbiologically unsuitable for consumption. However, the subsequent division of consumers into clusters indicated that women and individuals with high income and education levels tend to reject fish with few days of storage (3.650 days), mainly due to discoloration, despite still being microbiologically suitable for consumption. Thus, these segments present a safer behavior regarding the purchase of fresh fish. The influence of different frequencies of fish consumption and age of consumers on the assessment of fish freshness was not clarified. The responsibility for ensuring safe and healthy products at the point of sale must lie with the producers and distributors. However, improving consumers’ ability to make good choices when buying fresh fish would bring social and economic benefits related to public health and to the seafood industry, because it would enable them to make relevant claims and demand their rights.

OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p

Abstract Background Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma. The possibility to act on DLL1 expression levels by using microRNAs (miRNAs) was assessed. Methods DLL1 mRNA and protein expression levels were measured in three different neuroblastoma cell lines using quantitative real-time PCR and Western Blot analysis, respectively. Activation of the Notch pathway as a result of increased levels of DLL1 was analyzed by Immunofluorescence and Western Blot methods. In silico tools revealed the possibility to act on DLL1 expression levels with miRNAs, in particular with the miRNA-34 family. Neuroblastoma cells were transfected with miRNA-34 family members, and the effect of miRNAs transfection on DLL1 mRNA expression levels, on cell differentiation, proliferation and apoptosis was measured. Results In this study, the DLL1 ligand was identified as the Notch pathway component highly expressed in neuroblastoma cells with MYCN amplification. In silico analysis demonstrated that DLL1 is one of the targets of miRNA-34 family members that maps on chromosome regions that are frequently deregulated or deleted in neuroblastoma. We studied the possibility to use miRNAs to target DLL1. Among all miRNA-34 family members, miRNA-34b is able to significantly downregulate DLL1 mRNA expression levels, to arrest cell proliferation and to induce neuronal differentiation in malignant neuroblastoma cells. Conclusions Targeted therapies have emerged as new strategies for cancer treatment. This study identified the Notch ligand DLL1 as a novel and attractive molecular target in childhood neuroblastoma and its results could help to devise a targeted therapy using miRNAs.

Patellar tendinopathy, or Jumper’s knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper’s knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper’s knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.

The care and management of deer in captivity is challenging, especially in the case of red brocket deer (Mazama americana), whose routine management using physical restraint is difficult. Our study evaluated the effects of azaperone and xylazine combination for immobilizing red brocket deer and allow for the standard capture and handling protocols (e.g., biological material, horn cutting, and trimming) to be conducted safely. Six adult, captive, red brocket deer received an intramuscular injection of either 1 mg/kg azaperone and 0.5 mg/kg xylazine (AX0.5) or 1 mg/kg azaperone and 1 mg/kg xylazine (AX1.0). Sedation latency, sternal recumbency, safe handling, and quality of the sedation were evaluated to provide an overview of how the immobilizing drugs affected managing the species in captivity. Additionally, heart rate, respiratory rate, mean arterial pressure, rectal temperature, pH, PaO2, PaCO2, SaO2, HCO3-, BE, Na+, K+ and serum lactate were also measured. The latency period of the animals in the AX0.5 group was greater than that of the animals in the AX1.0 group (7 ± 6.6 min vs. 5 ± 2.0 min), as was the time for them to assume sternal recumbency (12 ± 9.7 min vs. 6 ± 3.1 min). However, the time after the initial dose at which the animals could safely be handled (14 ± 4.5 min vs. 12 ± 5.2 min), and the time until the end of the safe handling period (75 ± 12.3 min vs. 85 ± 6.8 min) were similar for both groups. Animals in both groups showed physiological stability during all evaluations, but hypoxemia was observed in one animal in each group. We conclude that both drug combinations are safe and effective at sedating red brocket deer in captivity and suggest that the procedure be performed with oxygen supplementation to reduce the potential for hypoxia.

Antimicrobial resistance is a major public health problem and is mainly due to the indiscriminate use of antimicrobials in human and veterinary medicine. The consumption of animal-based foods can contribute to the transfer of these genes between animal and human bacteria. Resistant and multi-resistant bacteria such as Salmonella spp. and Campylobacter spp. have been detected both in animal-based foods and in production environments such as farms, industries and slaughterhouses. This review aims to compile the techniques for detecting antimicrobial resistance using traditional and molecular methods, highlighting their advantages and disadvantages as well as the effectiveness and confidence of their results.

L’infezione da papillomavirus umano (HPV), in particolare HPV 16, è un riconosciuto fattore causale delle neoplasie orofaringee. L’incidenza delle neoplasie orofaringee è in aumento in diversi paesi europei, inclusa l’Italia, e negli Stai Uniti dove accurati modelli matematici hanno stimato che supererà quella del cancro alla cervice nella prossima decade. Recenti evidenze scientifiche supportano la potenziale efficacia del vaccino anti-HPV nel controllare quella che è stata definita “l’epidemia di neoplasie HPV-correlate”. In questo contesto, i medici otorinolaringoiatri assumono un ruolo cruciale, non solo nella diagnosi e trattamento di questa patologia, ma anche – come è stato sottolineato dall’American Head and Neck Society – nella prevenzione. Abbiamo condotto un’indagine sulle conoscenze e le attitudini dei medici otorinolaringoiatri italiani in tema di infezione HPV, patologie correlate e prevenzione vaccinale. Si tratta della prima indagine conoscitiva in Italia e in Europa sull’argomento. 262 medici otorinolaringoiatri italiani sono stati reclutati durante il 101° Congresso Nazionale della Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, tenutosi in maggio 2014. È stato utilizzato un questionario semi-strutturato sviluppato sulla base delle evidenze disponibili in letteratura e del parere di esperti. Le conoscenze e le attitudini sono state descritte e valutate con tecniche di analisi univariata. È stato inoltre costruito uno score composito di conoscenza. I dati dimostrano come i medici otorinolaringoiatri italiani abbiano, in media, un grado di conoscenza buono dell’infezione HPV e un’attitudine positiva nei confronti della prevenzione, in particolare della vaccinazione. I nostri risultati possono essere una utile base per pianificare, implementare e valutare programmi di educazione continua specifici sul tema della prevenzione dell’infezione da HPV. Come dimostriamo nel nostro studio, programmi di educazione continua specifici sono efficaci nell’aumentare il grado di conoscenza dei medici e l’attitudine positiva nei confronti dei programmi di prevenzione; il che contribuisce a promuovere l’adesione alla vaccinazione nei pazienti e nella popolazione generale. Con l’obiettivo generale di controllare l’epidemia di neoplasie HPV-correlate, maggiori risorse ed energie devono essere dedicate alla formazione e alla diffusione della cultura della prevenzione tra i medici otorinolaringoiatri e la comunità medica in generale. In questo contesto, identifichiamo grande potenziale nella collaborazione tra le comunità e le società scientifiche dell’otorinolaringoiatria e la sanità pubblica.