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In this study, both microbial inactivation and growth of Listeria spp. inoculated in commercial free-starter fresh cheese was evaluated after high-pressure processing (HPP). HPP conditions (300, 400, 500 and 600 MPa at 6 °C for 5 min) and inoculum level (3–4 or 6–7 log CFU/g of cheese), as well as differences among strains inoculated (Listeria innocua, L. monocytogenes CECT 4031 and L. monocytogenes Scott A) were investigated. Inactivation and generation of sublethal injury were determined after HPP using ALOA (Agar Listeria according to Ottaviani and Agosti) and TAL (Thin Agar Layer) plating methods, respectively. Listeria inactivation increased with the pressure applied, presenting some statistical differences between the employed strains, inoculum level and sublethal injury. The highest lethality values were obtained at 600 MPa for the three strains tested, although the 500 MPa treatment presented high lethality for L. innocua and L. monocytogenes CECT 4031. After treatment, L. innocua and L. monocytogenes CECT 4031 counts in fresh cheese increased gradually during cold storage. By contrast, counts in cheeses inoculated with L. monocytogenes Scott A did not change significantly (p ≥ 0.05), being this strain the most pressure resistant and with the slowest growth rate. The manuscript present information supporting that, strains with high-level resistance should be employed during inactivation studies, instead of surrogate microorganisms. Application of HPP treatments of 500 MPa and especially 600 MPa on fresh cheeses would be effective to eliminate the most resistant microorganism to a level that should not present a public health risk under normal conditions of distribution and storage.

Vascular anomalies are very rare, but can occur in children and adults in almost every region of the body. Due to the complexity of this disease, the path to a definitive diagnosis is often difficult. It requires interdisciplinary teamwork with close exchange of information between the individual treatment partners to reach the correct diagnosis and then to start the best therapy. This article provides an overview of the main types of vascular malformations from a clinical, imaging, and histological point of view, following the current classification of the International Society for the Study of Vascular Anomalies (ISSVA).

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

Adenosquamous carcinoma (ASqC) is an exceedingly rare subtype of colorectal cancer without any known special guidelines for treatment. The biological behaviour and molecular background are widely unknown, although a few case studies report a worse prognosis compared to ordinary colorectal adenocarcinoma. We herein report for the first time the successful immune checkpoint inhibitor therapy in a 40-year-old patient suffering from metastasized right-sided colonic ASqC with unique molecular features, after having previously progressed under standard chemotherapy.

Purpose Atrial fibrillation (AF) has been associated with increased volumes of epicardial fat and atrial adipocyte accumulation. Underlying mechanisms are not well understood. This study aims to identify rapid atrial pacing (RAP)/AF-dependent changes in atrial adipocyte/adipositas-related gene expression (AARE). Methods Right atrial (RA) and adjacent epicardial adipose tissue (EAT) samples were obtained from 26 patients; 13 with AF, 13 in sinus rhythm (SR). Left atrial (LA) samples were obtained from 9 pigs (5 RAP, 4 sham-operated controls). AARE was analyzed using microarrays and RT-qPCR. The impact of diabetes/obesity on gene expression was additionally determined in RA samples (RAP ex vivo and controls) from 3 vs. 6months old ZDF rats. Results RAP in vivo of pigs resulted in substantial changes of AARE, with 66 genes being up- and 53 down-regulated on the mRNA level. Differential expression during adipocyte differentiation was confirmed using 3T3-L1 cells. In patients with AF (compared to SR), a comparable change in RA mRNA levels concerned a fraction of genes only ( RETN , IGF1 , HK2 , PYGM , LOX , and NR4A3 ). RA and EAT were affected by AF to a different extent. In patients, concomitant disease contributes to AARE changes. Conclusions RAP, and to lesser extent AF, provoke significant changes in atrial AARE. In chronic AF, activation of this gene panel is very likely mediated by AF itself, AF risk factors and concomitant diseases. This may facilitate the development of an AF substrate by increasing atrial ectopic fat and fat infiltration of the atrial myocardium.

Different non-thermal technologies have been proposed to extend the shelf-life of solid food products, high-pressure processing (HPP) being one of the emerging technologies which has been most extensively studied. In this study, one of the first commercial industrial-scale applications of HPP on a starter-free fresh cheese, with the aim of increasing its shelf-life, is presented. The effect of 500 MPa (5 min, 16 °C) on physico-chemical, microbial, colour, microstructure, texture and sensorial characteristics of starter-free fresh cheeses during cold storage of 21 days was studied. The results showed that pressurised cheeses presented a shelf-life of about 19–21 days when stored at 4 °C, whereas control cheese became unsuitable for consumption on day 7–8. On the other hand, cheese treated at 500 MPa was firmer and more yellow than the untreated one. However, these changes, which were detected by instrumental and sensory analysis, did not affect the preference for pressurised cheese. These results may lead to practical applications of HPP in the food industry to produce microbiologically safe cheese with extended shelf-life and sensory quality.

The volatile profile of free-starter fresh cheeses was analysed by gas chromatography–mass spectrometry (GC–MS) after the application of high pressure processing (HPP; 500 MPa, 5 min). High pressure treatments were performed in an industrial HPP unit, using commercial cheeses; unpressurised cheeses were used as control. Volatile compound analyses were performed during shelf life (7 days for control cheeses and 21 days for pressurised cheeses). Forty nine compounds were identified in the volatile fraction of fresh cheeses, including ketones, acids, sulphur compounds, terpenes, aldehydes, alcohols, lactones, and miscellaneous compounds. In general, no significant changes in the volatile compound profile of treated cheeses were observed during their shelf life. Only a few volatile compounds were significantly influenced (p Industrial relevance High pressure processing (HPP) is an efficient method to improve cheese quality and achieve microbial safety of food. It has already successfully been proven on an industrial scale of several food products. The data presented in this study further indicate that volatile compound profile of a commercial free-starter fresh cheese was not significantly modified under pressure considering that the shelf life of pressurised cheese was threefold that of the control cheese. This research provides evidence that HPP is able to maintain aroma characteristics of cheese while extending its shelf life.

Magnetic resonance imaging (MRI) with small surface coils is a well established method for the diagnostic evaluation of finger masses. Until now, histological examination has been required to reliably assess tumor extent and infiltration of surrounding structures. Ultra-high-field MR microscopy (MRM) allows evaluation of anatomical structures and pathologies with submillimeter resolution. This study describes the diagnostic prospects and potential of MRM based on the ex-vivo examination of different finger pathologies. Ten human digits were examined by ex-vivo MRM at 7.1 Tesla (ClinScan, Bruker BioScan) using a T2-weighted turbo spin echo (TSE) sequence. Imaging parameters were: TE 48 ms; TR 8370 ms; slice thickness 700 µm; matrix size 1024 × 1024 pixels; FOV 37 × 37 mm; in-plane resolution 36 × 36 µm/voxel. Afterwards specimens were examined histologically. Histology and MRM were correlated. MRM allowed evaluation of the anatomy of the nail, the tendon insertions, the distal interphalangeal joint, and the neurovascular bundles. Finger abnormalities evaluated by MRM included osteomyelitis and metastatic disease. Subsequent histological examination confirmed MRM findings regarding origin, internal makeup, and extent of the structures visualized. This study demonstrates the potential of MRM for imaging small anatomical structures and pathologies of the human finger. Our ex-vivo findings correlate strongly with histology, suggesting that MRM may gain a central role in assessing anatomical structures and pathology in terms of morphology, extent, and infiltration of surrounding structures. Therefore, with increasing availability, MRM is expected to become an essential tool not only in experimental studies but also for daily routine.

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

The effect of high pressure (HP; 300 and 400 MPa for 5 min at 6 °C) on physico-chemical, microbial, color, texture and sensorial characteristics of starter-free fresh cheeses stored at 4 and 8 °C was studied. Physico-chemical parameters considered were total solids, fat, total protein, pH, whey loss and water activity. The microbiological quality was studied, on cheeses stored at 4 and 8 °C, by enumerating aerobic mesophilic bacteria, lactococci, psychrotrophic bacteria, Enterobacteriaceae , Escherichia coli , molds and yeasts. Cheeses treated at 300 and 400 MPa, stored at 4 °C, presented a shelf - life of 14 and 21 days, respectively, compared to untreated control cheese, which presented a shelf life of 7 days. On the other hand, HP treatments modified the texture (more firm) and color (more yellow) compared to control cheeses. These changes were detected by instrumental and sensory analysis.

Mounting epidemiological evidence supports a role for insulin-signaling deregulation and diabetes mellitus in human hepatocarcinogenesis. However, the underlying molecular mechanisms remain unknown. To study the oncogenic effect of chronically elevated insulin on hepatocytes in the presence of mild hyperglycemia, we developed a model of pancreatic islet transplantation into the liver. In this model, islets of a donor rat are transplanted into the liver of a recipient diabetic rat, with resulting local hyperinsulinism that leads to the development of preneoplastic lesions and hepatocellular carcinoma (HCC). Here, we investigated the metabolic and growth properties of the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (AKT/mTOR) pathway, a major downstream effector of insulin signaling, in this model of insulin-induced hepatocarcinogenesis. We found that activation of insulin signaling triggers a strong induction of the AKT/mTOR cascade that is paralleled by increased synthesis of fatty acids, cholesterol, and triglycerides, induction of glycolysis, and decrease of fatty acid oxidation and gluconeogenesis in rat preneoplastic and neoplastic liver lesions, when compared with the healthy liver. AKT/mTOR metabolic effects on hepatocytes, after insulin stimulation, were found to be mTORC1 dependent and independent in human HCC cell lines. In these cells, suppression of lipogenesis, glycolysis, and the pentose phosphate pathway triggered a strong growth restraint, despite insulin administration. Noticeably, metabolic abnormalities and proliferation driven by insulin were effectively reverted using the dual PI3K/mTOR inhibitor, NVP-BEZ235, both in vitro and in vivo. Conclusions: The present results indicate that activation of the AKT/mTOR cascade by unconstrained insulin signaling induces a defined module of metabolic alterations in hepatocytes contributing to aberrant cell growth. Thus, inhibition of AKT/mTOR and related metabolic changes might represent a novel preventive and therapeutic approach to effectively inhibit insulin-induced hepatocarcinogenesis. (Hepatology 2012;)

Patients with chronic pancreatitis are burdened with an increased risk of developing pancreatic cancer. Strategies or guidelines for the surveillance and early detection of pancreatic adenocarcinoma in patients with chronic pancreatitis are not established, because available clinical, serologic or imaging techniques are still of limited sensitivity and specificity. Despite these limitations do patients with chronic pancreatitis and suspected pancreatic cancer need a careful and sometimes repeated diagnostic work-up. A clear benefit of surveillance programs outside of clinical trials for the early detection of pancreatic cancer has not been demonstrated. A 51-year-old patient with chronic pancreatitis is reported who developed cancer of the pancreatic head while undergoing repeated imaging studies.

Einleitung: Die Entwicklung von neuartigen Antiinfektiva sollte bei steigenden Antibiotikaresistenzen ein zentraler Forschungsschwerpunkt sein. Eine Innovation stellt die Behandlung mit Tissue Tolerable Plasma (TTP) dar. Hierbei handelt es sich um den 4. Aggregatzustand. TTP ist ein elektrisch neutrales Medium, welches aus positiv und negativ geladenen Ionen, freien Radikalen, angeregten und nicht angeregten Molekulen und Photonen besteht. Die antimikrobiellen Eigenschaften wurden bereits bewiesen, chronische Wunden konnten schneller zur Ausheilung gebracht werden. TTP wirkt durch die Entstehung von Radikalen, einem lokalen Temperaturanstieg und einer Hyperamie in dem betroffenen Gewebe. Es kann zur vermehrten Angiogenesis kommen, welche in chronischen Wunden zur Heilung gewunscht ist. Die Anwendung von TTP erzeugt einen dosisabhangigen Schaden und muss daher abhangig von der Vulnerabiliat des Gewebes adaquat eingesetzt werden. Ziele: Ziel dieser Studie war es die Dosis-abhangige Vertraglichkeit des TTP auf den Darm der Maus zu uberprufen, um TTP zukunftig als ein potenzielles Medizinprodukt zur intraperitonealen Behandlung von Krankheiten bspw. zur Dekontamination nach Anastomoseninsuffizinz einsetzen zu konnen. Methodik: Die Wirksamkeit von TTP auf die Beschaffenheit von murinem Dunndarm wurde untersucht. Es wurden weibliche 10 – 12 Wochen alte C57Bl/6 Mause verwendet. Die Plasmaquelle (kINPen Med) wurde im gepulsten Modus genutzt. Argon stellte das verwendete Tragergas dar. Nach einer Laparotomie wurde ein definierter Darmabschnitt in einer Plottervorrichtung standardisiert mit unterschiedlicher Dauer und Flussgeschwindigkeit bestrahlt. Zur Kontrolle diente der reine Gasfluss bzw. die alleinige Laparotomie. Zu verschiedenen Zeitpunkten (1h, 24h und 7 Tage) wurden die Abschnitte makroskopisch untersucht und histologisch aufgearbeitet. Ergebnisse: In der vorgelegten Arbeit konnte gezeigt werden, dass die Anwendung von TTP am murinen Darm zu keinen Zelluntergangen im Darm selbst fuhrt. Es kommt zu einer Entzundungsreaktion im Sinne einer Peritonitis, welche ebenfalls in den Kontrollmausen detektierbar war. Schlussfolgerung: TTP ist zur intraperitonealen Anwendung am Darm geeignet und stellt ein vielversprechendes Antimikrobiotikum der Zukunft dar.

Magnetic resonance imaging (MRI) with small surface coils is a well established method for the diagnostic evaluation of finger masses. Until now, histological examination has been required to reliably assess tumor extent and infiltration of surrounding structures. Ultra-high-field MR microscopy (MRM) allows evaluation of anatomical structures and pathologies with submillimeter resolution. This study describes the diagnostic prospects and potential of MRM based on the ex-vivo examination of different finger pathologies. Ten human digits were examined by ex-vivo MRM at 7.1 Tesla (ClinScan, Bruker BioScan) using a T2-weighted turbo spin echo (TSE) sequence. Imaging parameters were: TE 48 ms; TR 8370 ms; slice thickness 700 µm; matrix size 1024 × 1024 pixels; FOV 37 × 37 mm; in-plane resolution 36 × 36 µm/voxel. Afterwards specimens were examined histologically. Histology and MRM were correlated. MRM allowed evaluation of the anatomy of the nail, the tendon insertions, the distal interphalangeal joint, and the neurovascular bundles. Finger abnormalities evaluated by MRM included osteomyelitis and metastatic disease. Subsequent histological examination confirmed MRM findings regarding origin, internal makeup, and extent of the structures visualized. This study demonstrates the potential of MRM for imaging small anatomical structures and pathologies of the human finger. Our ex-vivo findings correlate strongly with histology, suggesting that MRM may gain a central role in assessing anatomical structures and pathology in terms of morphology, extent, and infiltration of surrounding structures. Therefore, with increasing availability, MRM is expected to become an essential tool not only in experimental studies but also for daily routine.