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Additional file 1. Appendix 1. National survey.

Background Severe and prolonged asphyxia can result in either intrauterine fetal death and stillbirth or multiorgan failure in surviving neonates. Establishing effective ventilation is the primary aim of resuscitation in newborns with asphyxia. The objective of this study was to compare the outcome of resuscitation by applying an endotracheal tube (ETT) with less, an ETT with moderate, and an ETT with high leakage during mechanical ventilation in swine neonates after prolonged perinatal asphyxia. Materials and methods A prospective, randomized controlled laboratory study was performed. Thirty Landrace/large white pigs, aged one to four days and weighted 1.754 +/- 218 gr, were randomly allocated into three groups depending on the ETT size: Group C (less leak: ETT no 4.0, n=10); Group A (high leak: ETT no 3.0, n=10); and Group B (moderate leak: ETT no 3.5, n=10). Mechanical asphyxia was performed until their heart rate was less than 60 bpm or their mean arterial pressure was below 15 mmHg. All animals with return of spontaneous circulation (ROSC) were monitored for four hours for their hemodynamic parameters, arterial oxygen saturation, and lactate acid levels. Results We demonstrate that 70% of the surviving animals were ventilated with an ETT with a leak (no. 3.5 and 3). A statistically significant difference was noted in PO2 (p=0.032) between Group B (126.4 +/- 53.4 mmHg) compared to Group A (72.28 +/- 29.18 mmHg) and Group C (94.28 +/- 20.46 mmHg) as well as in the right atrial pressure (p

Additional file 3. Appendix 3. Post-conference questionnaire.

Additional file 4. Appendix 4. Ethical approval.

Additional file 5. Supplementary Tables.

Background: Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The “no-reflow” phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell delivery in areas of microvascular obstruction (MVO). We hypothesized that CDC-induced cardioprotection would be enhanced by cell administration prior to reperfusion, when microvasculature is still relatively intact, to facilitate widespread cell delivery within the ischemic area. Methods and Results: We studied 81 farm pigs; 55 completed the specified protocols. A dose-optimization study in infarcted pigs demonstrated that the doses of 5 million and 10 million CDCs are the maximum safe doses that can be administered intracoronarily at 5 minutes prior to and at 5 minutes post-reperfusion, respectively, without aggravating MVO. Quantification of acute cell retention by polymerase chain reaction demonstrated that cell delivery prior to reperfusion resulted in higher cardiac cell retention compared to delivery post-reperfusion. We then performed a randomized, placebo-controlled study to assess the long-term efficacy of intracoronary infusion of 5 million allogeneic CDCs, delivered at 5 minutes prior to reperfusion, in a porcine model of AMI. The CDC therapy resulted in decreased scar size, improved regional systolic function, and attenuation of adverse cardiac remodeling (manifested as preserved global systolic function, preserved end-systolic volume, and decreased interstitial fibrosis) compared to placebo at 30 days post-MI. Conclusions: Dose-optimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers long-term benefits.

Additional file 2. Appendix 2. Pre-conference questionnaire.

Introduction: Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury. Material and methods: ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression. Results: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P

Hara Afaloniati,1 Katerina Angelopoulou,1 Alexander Giakoustidis,2 Alexandros Hardas,3 Athanasios Pseftogas,4 Kali Makedou,5 Athanasios Gargavanis,2 Thomas Goulopoulos,2 Stavros Iliadis,5 Vasileios Papadopoulos,2 Apostolos Papalois,6 George Mosialos,4 Theofilos Poutahidis,3 Dimitrios Giakoustidis2 1Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece; 3Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Experimental, Educational and Research Center, ELPEN, Pikermi, Attica, GreeceCorrespondence: Dimitrios GiakoustidisFirst Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, GreeceTel +30 6932306133Email dgiak@auth.grBackground: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC.Materials and Methods: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR.Results: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC.Conclusion: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.Keywords: diethylnitrosamine, DEN, histone deacetylases, HDAC, HDAC inhibitors, HDACi, hepatocellular carcinoma, HCC, Romidepsin

Supplemental Material, CDC_no_reflow_paper_Online_Supplement_revision_clean for Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs With Acute Myocardial Infarction Reduces Infarct Size and Attenuates Adverse Cardiac Remodeling by Vasileios Sousonis, Titika Sfakianaki, Argirios Ntalianis, Ioannis Nanas, Christos Kontogiannis, Dionysios Aravantinos, Chris Kapelios, Lampros Katsaros, Maria Nana, Dimitrios Sampaziotis, Despina Sanoudou, Apostolos Papalois and Konstantinos Malliaras in Journal of Cardiovascular Pharmacology and Therapeutics

There is a lack of a national organized screening program for colorectal cancer in Greece, and asymptomatic detection is usually the result of individual decisions. The collection of epidemiologic endoscopic data from a population of interest would therefore provide valuable information for future treatment guidance, especially during periods of economic austerity. The current cross-sectional study included 380 asymptomatic, average risk individuals undergoing screening colonoscopy for the first time, during the period of one year in a tertiary public hospital in Athens. Descriptive and analytic epidemiologic data were analyzed. The prevalence of adenomas and advanced lesions were compared between the younger and older cohort, and a regression model was applied for risk evaluation. The mean age of participants was 63 years, and 53% were male. A significant proportion of patients presented with polyps (51.5%) and 25% of them had lesions in the proximal colon. The prevalence of adenomas and advanced adenomas was 29.5 and 11.8%, respectively. Similar high prevalence rates of lesions were identified in the cohort of individuals 50 years of age). Regression models identified age, number and size of polyps as the major risk factors for the detection of adenomas. The increase of advanced lesions in the older and younger cohort requires confirmation by larger studies. Overall, the results of the present study indicate the requirement for a well-organized screening colonoscopy program starting from as early as 40 years of age. This program may confer an additional endoscopic burden with socioeconomic consequences in a country with limited health resources.

Introduction and objectives Bacterial translocation (BT) is the passage of viable bacteria or endotoxins from the gastrointestinal lumen to extra-luminal tissues and is usually observed after intestinal ischaemia-reperfusion injury. The aim of this study was to investigate post-resuscitation BT after cardiac arrest and resuscitation in a swine anaesthetized with propofol-based total intravenous anaesthesia. Materials and methods Eighteen female Landrace/Large White piglets were randomly divided into control (CON), cardiac arrest (CA) and cardiac arrest-cardiopulmonary resuscitation (CA-CPR) groups. In the CON group, the animals were only monitored for two hours. In the CA group, the animals were not resuscitated and underwent necropsy immediately after cardiac arrest. In the CA-CPR group, the animals were resuscitated until the return of spontaneous circulation (ROSC) and were monitored for two hours. The animals of the CON and CA-CPR groups underwent necropsy 24 hours later. Bacterial translocation was assessed by blood and tissue cultures and endotoxin measurement in the portal and systemic circulation. Malondialdehyde content calculation and histological analysis of the intestine were performed in order to estimate ischemia and reperfusion (I/R) tissue damage. Results Malondialdehyde content, an indicator of oxidative stress, was significantly higher in the CA-CPR group compared to the CA in homogenized ileum (p=0.016). Malondialdehyde content in homogenized colon revealed significantly higher levels in the CA-CPR group compared to the CON (p=0.004) and the CA group (p=0.016). We found significantly higher levels of portal endotoxin in the CA-CPR group compared to the CON (p=0.026) and the CA group (p=0.026). The number of positive mesenteric lymph nodes cultures for E. coli was greater in the CA-CPR group, followed by the CA and CON groups, although the difference was not significant (67%, 33%, and 33%, respectively; p=0.407). Conclusions Malondialdehyde content and portal endotoxin levels do not increase during the cardiac arrest interval, but only after CPR and ROSC. Although the number of positive MLNs cultures was greater in the CA-CPR animals, no statistically significant differences were observed between the three groups due to the short monitoring period.

Endoscopy is currently the gold standard for the diagnosis of inflammatory bowel disease (IBD). The presence of macroscopic lesions along with the microscopic detection of inflammatory infiltration in the terminal ileum often leads the gastroenterologist to the diagnosis of Crohn’s disease (CD). However, some of these cases could be, in fact, an infection caused by Yersinia spp., accompanied or not with CD, which could be easily diagnosed with the identification of serum antibodies against Yersinia outer protein antigens (YOP antigens). Since Yersiniosis is considered to be an uncommon situation, food and water are not usually checked for the possibility of contamination by Yersinia. Therefore, it is reasonable to assume that the true prevalence of Yersinia infection in patients with terminal ileitis is probably underestimated. In this article, we review the most important data regarding the various aspects of Yersinia infection with special focus on its pathophysiology and diagnosis. We recommend testing for serum antibodies against YOP antigens in all patients with an endoscopic and histological image of terminal ileitis in order to identify Yersiniosis in conjunction or not with terminal ileum CD.