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Purpose: Quadrivalent influenza vaccine (QIV) includes the same strains as trivalent influenza vaccine (TIV) plus an additional B strain of the other B lineage. The aim of the study was to analyse the public health and economic impact of replacing TIV with QIV in different scenarios in Spain., Methods: A dynamic transmission model was developed to estimate the number of influenza B cases prevented under TIV and QIV strategies (<65 years (high risk) and ≥65 years). This model considers cross-protective immunity induced by different lineages of influenza B. The output of the transmission model was used as input for a decision tree model that estimated the economic impact of switching TIV to QIV. The models were populated with Spanish data whenever possible. Deterministic univariate and probabilistic multivariate sensitivity analyses were performed., Results: Replacing TIV with QIV in all eligible patients with current vaccine coverage in Spain may have prevented 138,707 influenza B cases per season and, therefore avoided 10,748 outpatient visits, 3,179 hospitalizations and 192 deaths. The replacement could save €532,768 in outpatient visit costs, €13 million in hospitalization costs, and €3 million in costs of influenza-related deaths per year. An additional €5 million costs associated with productivity loss could be saved per year, from the societal perspective. The budget impact from societal perspective would be €6.5 million, and the incremental cost-effectiveness ratio (ICER) €1,527 per quality-adjusted life year (QALY). Sensitivity analyses showed robust results. In additional scenarios, QIV also showed an impact at public health level reducing influenza B related cases, outpatient visits, hospitalizations and deaths., Conclusions: Our results show public health and economic benefits for influenza prevention with QIV. It would be an efficient intervention for the Spanish National Health Service with major health benefits especially in the population ≥65-year., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PC has received scientific consultancy from Sanofi Pasteur. ER has received funding for scientific consultancy and speaker fees, as well as congress attendance grants from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme and Pfizer. JD has received funding for scientific consultancy and speaker fees from Sanofi Pasteur and Seqirus. RO has received funding for scientific consultancy and speaker fees from Sanofi Pasteur, GlaxoSmithKline and Seqirus. FM and his institution have received funding for consultancy and research and speaker fees from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme, Pfizer, Astrazeneca, Janssen, Seqirus and Ablynx. AG has received funding for scientific consultancy and speaker fees from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme y Pfizer. JLLB, FPA and HB are employed by the commercial Sanofi Pasteur. MS is employed by the commercial IQVIA and works in consultancy projects with Sanofi Pasteur and other Pharmaceutical Companies. JLLB, FPA, HB and MS were involved in the design of the study, data collection and the decision to publish the results. The manuscript was reviewed by the study sponsor prior to submission. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Background: Endoscopic ultrasound (EUS) is useful in the diagnostic workup of idiopathic acute pancreatitis but its role as a predictor of recurrence has not been thoroughly assessed. Our aim was to study the performance of EUS in idiopathic acute pancreatitis, its impact on the natural history of the disease, and the factors related to recurrence., Methods: Patients with idiopathic acute pancreatitis referred to our endoscopy unit were enrolled and followed, with assessment of the performance of endoscopic retrograde cholangiopancreatography (ERCP), cholecystectomy, and the incidence of recurrence. EUS findings and recurrence rates were compared between patients with a first episode or recurrent attacks and in patients with previous cholecystectomy versus those with gallbladder in situ., Results: One hundred six patients were included (mean follow up: 53.59±27.79 months). Biliary disease related to stones was the most common finding on EUS (49.1%), and patients referred for recurrent attacks showed the highest recurrence rate during follow up (57.1%). ERCP or cholecystectomy reduced recurrences to 14.3% in patients with biliary disease. Age under 65 (odds ratio [OR] 3.56, 95% confidence interval [CI] 1.21-10.44; P=0.02), previous cholecystectomy (OR 3.19, 95%CI 1.11-9.17; P=0.03), and no lithiasis on EUS (OR 2.87, 95%CI 1.04-7.87; P=0.04) were independent risks factors for recurrence., Conclusions: EUS-directed ERCP/cholecystectomy was associated with lower relapse rates in idiopathic acute pancreatitis. Along with age and gallbladder status, it provides predictive information about recurrence likelihood., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background and Aims: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models., Methods: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies., Results: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets., Conclusions: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

ZBTB7A is frequently mutated in acute myeloid leukemia (AML) with t(8;21) translocation. However, the oncogenic collaboration between mutated ZBTB7A and the RUNX1-RUNX1T1 fusion gene in AML t(8;21) remains unclear. Here, we investigate the role of ZBTB7A and its mutations in the context of normal and malignant hematopoiesis. We demonstrate that clinically relevant ZBTB7A mutations in AML t(8;21) lead to loss of function and result in perturbed myeloid differentiation with block of the granulocytic lineage in favor of monocytic commitment. In addition, loss of ZBTB7A increases glycolysis and hence sensitizes leukemic blasts to metabolic inhibition with 2-deoxy-D-glucose. We observed that ectopic expression of wild-type ZBTB7A prevents RUNX1-RUNX1T1-mediated clonal expansion of human CD34+ cells, whereas the outgrowth of progenitors is enabled by ZBTB7A mutation. Finally, ZBTB7A expression in t(8;21) cells lead to a cell cycle arrest that could be mimicked by inhibition of glycolysis. Our findings suggest that loss of ZBTB7A may facilitate the onset of AML t(8;21), and that RUNX1-RUNX1T1-rearranged leukemia might be treated with glycolytic inhibitors.

Additive manufacturing (also known as three-dimensional (3D) printing) is being extensively utilized in many areas of electrochemistry to produce electrodes and devices, as this technique allows for fast prototyping and is relatively low cost. Furthermore, there is a variety of 3D-printing technologies available, which include fused deposition modeling (FDM), inkjet printing, select laser melting (SLM), and stereolithography (SLA), making additive manufacturing a highly desirable technique for electrochemical purposes. In particular, over the last number of years, a significant amount of research into using 3D printing to create electrodes/devices for electrochemical energy conversion and storage has emerged. Strides have been made in this area; however, there are still a number of challenges and drawbacks that need to be overcome in order to 3D print active and stable electrodes/devices for electrochemical energy conversion and storage to rival that of the state-of-the-art. In this Review, we will give an overview of the reasoning behind using 3D printing for these electrochemical applications. We will then discuss how the electrochemical performance of the electrodes/devices are affected by the various 3D-printing technologies and by manipulating the 3D-printed electrodes by post modification techniques. Finally, we will give our insights into the future perspectives of this exciting field based on our discussion through this Review.

Background: Calcineurin inhibitors are associated with the development of de novo tumors and increased recurrence of hepatocellular carcinoma after liver transplant. It has been suggested that mammalian target of rapamycin inhibitors (everolimus [EVR]) may improve prognosis. We analyzed our experience on the use of EVR in malignant neoplasms in liver transplantation., Methods: We performed a retrospective descriptive analysis of 477 transplants performed between 2002 and 2019 at Virgen de las Nieves Hospital. A total of 100 patients received EVR; 23 transplants were because of tumor disease (23%), with de novo tumor in 12 patients and hepatocarcinoma in 11. The statistical study was carried out using the statistical program SPSS 17.0 software., Results: The study included 18 male patients (78.3%) and 5 female patients (21.7%) with an average age of 59.67 years. The most common indications of liver transplant have been alcoholic cirrhosis in 39% and hepatitis C virus cirrhosis in 21.7%. De novo tumors were lung neoplasm in 4 patients (33.3%), lymphoma in 2 patients(16.7%), oropharynx in 2 patients (16.7%), skin tumors in 2 patients (16.7%), and a kidney tumor (8.3%) in 1 patient. As for hepatocellular carcinoma, 8 patients met Milan criteria on the explant (61.5%). Tacrolimus was discontinued in all cases. The average onset time of post-transplant EVR was 2231.42 days in the de novo neoplasms and 307.45 days in those receiving transplants because of hepatocellular carcinoma (P = .05). We observed 5 deaths (21.7%)., Conclusion: Although the beneficial long-term role of EVR in liver transplant recipients with tumor disease is not demonstrated, it is used by most transplant units, both in de novo neoplasms and those receiving transplants because of hepatocellular carcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Calcineurin inhibitors have been implicated in acute and chronic kidney disease after liver transplant (LT). Everolimus (EVR) is a mammalian target of rapamycin inhibitor efficacious in preventing acute cellular rejection while preserving renal function among LT recipients. We evaluated the benefits on renal function of EVR immunosuppression in LT recipients., Methods: We performed a retrospective and observational study in 477 LT recipients in Virgen de las Nieves Hospital from 2002 to 2019 on the use of EVR with tacrolimus minimization or withdrawal in LT recipients with renal dysfunction. The study included 100 patients starting EVR (20.96%); in 66 (66%) the indication was renal dysfunction. The change in renal function was assessed by estimated glomerular filtration rate. Statistical analyses were performed using SPSS 17.0 software (IBM, Munich, Germany)., Results: Fifty 8 patients received mycophenolate mofetil (87.8%), and tacrolimus therapy was stopped in 27 patients (40.9%). Induction therapy with basiliximab was administered in 41 patients (62.12%). There was significant difference between estimated glomerular filtration rate at the time of starting EVR and the first month at last follow-up (49.42 mL/min/1.73 m 2 vs 75.27 mL/min/1.73 m 2 ; P < .001) and at end of follow-up (24 months) (49.42 mL/min/1.73 m 2 vs 64.32 mL/min/1.73 m 2 ; P = .001). The rate of incidence of adverse events was 48.48% (32/66). Seven patients died during follow-up (10.6%), but there were no EVR-related deaths. Eleven patients (16.6%) developed biopsy-proven acute rejection., Conclusion: This study showed that EVR is associated with a beneficial effect on glomerular filtration rate in both the short and long term in LT recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients' data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.

Background and Aim: Risk stratification for upper gastrointestinal bleeding (UGIB) is recommended. However, scoring system accuracy is suboptimal, and score calculation can be complex. Our aim was to develop a new score, the MAP(ASH) score, with information available in the emergency room and to validate it., Methods: The score was built from a prospective database of patients with UGIB and validated in an international database of 3012 patients from six hospitals. Outcomes were 30-day mortality, endoscopic intervention, any intervention (red blood transfusion, endoscopic treatment, interventional radiology, surgery, or death), and rebleeding. Accuracy to predict outcomes was assessed by the area under the receiver operating characteristic curve (AUROC)., Results: Five hundred forty-seven patients were included in the development cohort. Impaired mental status, albumin < 2.5 g/dL, pulse > 100, American Society of Anesthesiologists score > 2, systolic blood pressure < 90 mmHg, and hemoglobin < 10 g/dL were included in the score. The model had a good predictive accuracy for intervention (AUROC = 0.83; 95% confidence interval [CI]: 0.79-0.88) and fair for mortality (AUROC = 0.74; 95% CI: 0.68-0.81). Regarding endoscopic intervention, AUROC was 0.61 (95% CI: 0.56-0.66) in the original cohort and 0.69 (95% CI: 0.66-0.71) in the validation cohort, showing a poor performance, similar to other scores. For rebleeding, the MAP(ASH) (AUROC 0.73; 95% CI: 0.69-0.77) was similar to Glasgow Blatchford score (AUROC = 0.72; 95% CI: 0.67-0.76) but superior to AIMS65 (AUROC = 0.64; 95% CI: 0.59-0.68)., Conclusion: MAP(ASH) is a simple pre-endoscopy risk score to predict intervention after UGIB, with fair discrimination at predicting mortality. Because of its applicability, it could be an option in clinical practice., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The histomorphological changes occurring in the Dama dama reticulum during prenatal development have been investigated. Twenty-five Dama dama embryos were used, from the first stages of prenatal life until birth. Differentiation of the reticulum was observed at 23% gestation. By 25% gestation the reticular wall comprised three layers: an internal epithelial layer, a middle layer of pluripotential blastemic tissue and an external layer or serosa. Primary reticular crests were visible at 38% gestation. Secondary reticular crests were observed at 61% gestation. Neuroendocrine cells were detected by synaptophysin (SYP) at 35% gestation, in the lamina propria-submucosa, tunica muscularis, and serosa. Epithelial Cytokeratin-18 (CK-18) cells were observed at 35% gestation extended throughout the epithelial layers. The glial cells (vimentin -VIM- and glial fibrillary acidic protein-GFAP-markers) were discerned at 25% and 43% gestation, respectively, in myenteric and submucosal plexuses, lamina propria, muscularis mucosae, tunica muscularis, and perivascular connective tissue. The neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) markers were immunodetected at 75% and 80 gestation, respectively, in the lamina propria-submucosa, muscularis mucosae, tunica muscularis, serosa, and myenteric plexuses. The prenatal development of the fallow deer reticular mucosa evidenced a considerable precocity similar to that previously reported in goat and red deer., (© 2020 Japanese Society of Animal Science.)

The GATA family of transcription factors are zinc finger (ZF) DNA-binding proteins that regulate transcription during development and cell differentiation. GATA2 plays an essential role in the regulation of hematopoiesis. As a result, mutations in this gene or alterations in its expression level or function have been linked to a variety of human hematologic disorders. In this review, we summarize the findings and developments over the recent years regarding the clinical correlations and functional properties of distinct GATA2 mutations in hematopoietic malignancies, with particular focus on the mutational hotspots in the ZF domains., (© 2019 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.)

Inflammation plays a central role in the pathophysiology of acute pancreatitis (AP). We hypothesized that changes in the function of key components of the inflammatory cascade, caused by genetic polymorphisms, could determine the development and/or severity of AP. We studied the following polymorphisms in 269 patients: IL23R rs11209026, TNF rs1800629, RIPK2 rs42490, NOD2 rs9302752, MCP1 rs1024611 and NFKB1 rs28362491. The rs11209026 A allele was related to the presence of AP (p = 0.007261; OR = 1 .523). Epistasis analysis revealed that AP susceptibility was increased by interaction between IL23R rs11209026 and TNF rs1800629 (p = 1.205 × 10 -5 ; OR interaction  = 4.031). The rs42490-G allele was associated with an increased risk of severe pancreatitis (p = 0.01583; OR = 2.736), severe or moderately severe pancreatitis (p = 0.04206; OR = 1.609), and death (p = 0.03226; OR = 3.010). In conclusion, these results point to a plausible role for genetic polymorphisms in IL23R and RIPK2 in the development and severity of AP.

Background: The population of stallion spermatozoa that survive thawing experience compromised mitochondrial functionality and accelerated senescence, among other changes. It is known that stallion spermatozoa show very active oxidative phosphorylation that may accelerate sperm senescence through increased production of reactive oxygen species. Rosiglitazone has been proven to enhance the glycolytic capability of stallion spermatozoa maintained at ambient temperature., Objectives: Thus, we hypothesized that thawed sperm may also benefit from rosiglitazone supplementation., Materials and Methods: Thawed sperm were washed and resuspended in Tyrodes media, and the samples were divided and supplemented with 0 or 75 μM rosiglitazone. After one and two hours of incubation, mitochondrial functionality, Akt phosphorylation and caspase 3 activity were evaluated. Additional samples were incubated in the presence of an Akt1/2 inhibitor, compound C (an AMPK inhibitor) or GW9662 (an antagonist of the PPARγ receptor)., Results: Rosiglitazone maintained Akt phosphorylation and reduced caspase 3 activation (p<0.01), both of which were prevented by incubation in the presence of the three inhibitors. Rosiglitazone also enhanced mitochondrial functionality (P<0.01)., Conclusion: We provide the first evidence that the functionality of frozen stallion spermatozoa can be potentially improved after thawing through the activation of pro survival pathways, providing new clues for improving current sperm biotechnology., Competing Interests: The authors have declared that no competing interests exist.

Oxidative stress is considered a major mechanism causing sperm damage during cryopreservation and storage, and underlies male factor infertility. Currently, oxidative stress is no longer believed to be caused only by the overproduction of reactive oxygen species, but rather by the deregulation of redox signaling and control mechanisms. With this concept in mind, here, we describe for the first time the presence of the soluble carrier family 7 member 11 (SLC7A11) antiporter, which exchanges extracellular cystine (Cyss) for intracellular glutamate, in stallion spermatozoa, as well as its impact on sperm function using the specific inhibitor sulfasalazine. Spermatozoa incubated with Cyss exhibited an increased intracellular GSH content compared with controls (P < 0.01): 50% in fresh extended stallion spermatozoa and 30% in frozen-thawed spermatozoa. This effect was prevented by the addition of sulfasalazine to the media. Cystine supplementation also reduced the oxidation-reduction potential of spermatozoa, with sulfasalazine only preventing this effect on fresh spermatozoa that were incubated for 3 h at 37°C, but not in frozen-thawed spermatozoa. While sulfasalazine reduced the motility of frozen-thawed spermatozoa, it increased motility in fresh samples. The present findings provide new and relevant data on the mechanism regulating the redox status of spermatozoa and suggest that a different redox regulatory mechanism exists in cryopreserved spermatozoa, thus providing new clues to improve current cryopreservation technologies and treat male factor infertility., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members of the IL-1 superfamily, IL-1α, IL-1β, and IL-18, in a range of conditions and cell types, including murine bone marrow-derived and peritoneal macrophages, human monocyte-derived macrophages, HeLa cells, and mouse embryonic fibroblasts. We discovered that IL-1β and IL-18 share a common secretory pathway that depends upon membrane permeability and can operate in the absence of complete cell lysis and cell death. We also found that the pathway regulating the trafficking of IL-1α is distinct from the pathway regulating IL-1β and IL-18. Although the release of IL-1α could also be dissociated from cell death, it was independent of the effects of the membrane-stabilizing agent punicalagin, which inhibited both IL-1β and IL-18 release. These results reveal that in addition to their role as danger signals released from dead cells, IL-1 family cytokines can be secreted in the absence of cell death. We propose that models used in the study of IL-1 release should be considered context-dependently., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2019 Tapia et al.)

Introduction: Information about community-acquired pneumonia (CAP) risk in primary care is limited. We assess different lifestyle and comorbid conditions as risk factors (RF) for CAP in adults in primary care., Methods: A retrospective-observational-controlled study was designed. Adult CAP cases diagnosed at primary care in Spain between 2009 and 2013 were retrieved using the National Surveillance System of Primary Care Data (BiFAP). Age-matched and sex-matched controls were selected by incidence density sampling (ratio 2:1). Associations are presented as percentages and OR. Binomial regression models were constructed to avoid bias effects., Results: 51 139 patients and 102 372 controls were compared. Mean age (SD) was 61.4 (19.9) years. RF more significantly linked to CAP were: HIV (OR [95% CI]: 5.21 [4.35 to 6.27]), chronic obstructive pulmonary disease (COPD) (2.97 [2.84 to 3.12]), asthma (2.16 [2.07,2.26]), smoking (1.96 [1.91 to 2.02]) and poor dental hygiene (1.45 [1.41 to 1.49]). Average prevalence of any RF was 82.2% in cases and 69.2% in controls (2.05 [2.00 to 2.10]). CAP rate increased with the accumulation of RF and age: risk associated with 1RF was 1.42 (1.37 to 1.47) in 18-60-year-old individuals vs 1.57 (1.49 to 1.66) in >60 years of age, with 2RF 1.88 (1.80 to 1.97) vs 2.35 (2.23, 2.48) and with ≥ 3 RF 3.11 (2.95, 3.30) vs 4.34 (4.13 to 4.57)., Discussion: Prevalence of RF in adult CAP in primary care is high. Main RFs associated are HIV, COPD, asthma, smoking and poor dental hygiene. Our risk stacking results could help clinicians identify patients at higher risk of pneumonia., Competing Interests: Competing interests: FM-T and/or his institution has received research grants and/or honoraria as a consultant/advisor and/or speaker and for conducting vaccine trials from GlaxoSmithKline, Sanofi Pasteur, MSD, Pfizer, Novartis, Novavax, Regeneron, Janssen and MedImmune Inc. ER has received honoraria as a consultant/advisor and/or speaker, as well as grants for attending to conferences and practical courses from GlaxoSmithKline, Sanofi Pasteur MSD, Merck, Sanofi Pasteur, Pfizer and Novartis. IR-C has received honoraria as a consultant/advisor and/or speaker, as well as grants for attending to conferences and practical courses from GlaxoSmithKline, Sanofi Pasteur, MSD, Merck and Pfizer. EM has received honoraria as a consultant/advisor and/or speaker as well as grants for attending to conferences and practical courses from GlaxoSmithKline, Pfizer and Novartis. JM has received honoraria as a consultant/advisor and/or speaker, as well as grants for attending to conferences and practical courses from Astra-Zeneca, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi. None declared for the rest of the authors.

The bidirectional relationship between infectious diseases and diabetes is well-known. On the one hand, diabetes patients are at a higher risk of presenting with infectious diseases, possibly with more severity, and on the other hand, infectious diseases impair metabolic control in patients with diabetes. Population ageing arises partly due to an increased survival rate in chronic diseases, of which diabetes is amongst them. Improving infectious disease prevention could reduce complications arising from the former diseases, consequences of decompensated diabetes condition (morbidity, incapacity, hospital admissions, healthcare costs, and mortality rates) and result in improved quality of life in patients with diabetes. The current review presents the treatment of infectious diseases in patients with diabetes and the dealing with immuno-preventable diseases with the currently advised vaccinations., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: upper gastrointestinal bleeding (UGIB) is one of the main causes of hospital admission in gastroenterology departments and is associated with a significant morbidity and mortality. Rebleeding after initial endoscopic therapy occurs in 10-20% of cases and therefore, there is a need to define predictive factors for rebleeding., Aim: the aim of our study was to analyze risk factors and outcomes in a population of patients who suffered a rebleed., Methods: five hundred and seven patients with gastrointestinal bleeding were included. Clinical and biochemical data, as well as procedures and outcome six months after admission, were all collected. Documented clinical outcome included in-hospital and six-month delayed mortality, rebleeding and six-month delayed hemorrhagic and cardiovascular events., Results: according to a logistic regression analysis, high creatinine levels were independent risk factors for rebleeding of non-variceal and variceal UGIB. In non-variceal UGIB, tachycardia was an independent risk factor, whereas albumin levels were an independent protective factor. Rebleeding was associated with in-hospital mortality (29.5% vs 5.5%; p < 0.0001). In contrast, rebleeding was not related to six-month delayed mortality or delayed cardiovascular and hemorrhagic events., Conclusions: tachycardia and high creatinine and albumin levels were independent factors associated with rebleeding, suggestive of a potential predictive role of these parameters. The incorporation of these variables into predictive scores may provide improved results for patients with UGIB. Further validation in prospective studies is required.

The Ninth Interactive Infectious Disease workshop TIPICO was held on November 22-23, 2018, in Santiago de Compostela, Spain. This 2-day academic experience addressed current and topical issues in the field of infectious diseases and vaccination. Summary findings of the meeting include: cervical cancer elimination will be possible in the future, thanks to the implementation of global vaccination action plans in combination with appropriate screening interventions. The introduction of appropriate immunization programs is key to maintain the success of current effective vaccines such as those against meningococcal disease or rotavirus infection. Additionally, reduced dose schedules might improve the efficiency of some vaccines (i.e., PCV13). New vaccines to improve current preventive alternatives are under development (e.g., against tuberculosis or influenza virus), while others to protect against infectious diseases with no current available vaccines (e.g., enterovirus, parechovirus and flaviviruses) need to be developed. Vaccinomics will be fundamental in this process, while infectomics will allow the application of precision medicine. Further research is also required to understand the impact of heterologous vaccine effects. Finally, vaccination requires education at all levels (individuals, community, healthcare professionals) to ensure its success by helping to overcome major barriers such as vaccine hesitancy and false contraindications.

Chromosomal translocations represent frequent events in leukemia. In t(8;21)+ acute myeloid leukemia, RUNX1 is fused to nearly the entire ETO protein, which contains four conserved nervy homology regions, NHR1-4. Furthermore RUNX1/ETO interacts with ETO-homologous proteins via NHR2, thereby multiplying NHR domain contacts. As shown recently, RUNX1/ETO retains oncogenic activity upon either deletion of the NHR3 + 4 N-CoR/SMRT interaction domain or substitution of the NHR2 tetramer domain. Thus, we aimed to clarify the specificities of the NHR domains. A C-terminally NHR3 + 4 truncated RUNX1/ETO containing a heterologous, structurally highly related non-NHR2 tetramer interface translocated into the nucleus and bound to RUNX1 consensus motifs. However, it failed to interact with ETO-homologues, repress RUNX1 targets, and transform progenitors. Surprisingly, transforming capacity was fully restored by C-terminal fusion with ETO's NHR4 zinc-finger or the repressor domain 3 of N-CoR, while other repression domains failed. With an inducible protein assembly system, we further demonstrated that NHR4 domain activity is critically required early in the establishment of progenitor cultures expressing the NHR2 exchanged truncated RUNX1/ETO. Together, we can show that NHR2 and NHR4 domains can be replaced by heterologous protein domains conferring tetramerization and repressor functions, thus showing that the NHR2 and NHR4 domain structures do not have irreplaceable functions concerning RUNX1/ETO activity for the establishment of human CD34+ cell expansion. We could resemble the function of RUNX1/ETO through modular recomposition with protein domains from RUNX1, ETO, BCR and N-CoR without any NHR2 and NHR4 sequences. As most transcriptional repressor proteins do not comprise tetramerization domains, our results provide a possible explanation as to the reason that RUNX1 is recurrently found translocated to ETO family members, which all contain tetramer together with transcriptional repressor moieties.

Introduction: The aim of this systematic review is to summarize epidemiological data and areas of future acute pancreatitis research in Spain., Methods: We conduct an independent search in PubMed and Web of Science and analyse articles by Spanish researchers from 2008 to 2018., Results: We identified an overall incidence of 72/100,000 person-years, with biliary pancreatitis as the most common etiology. BISAP was useful but suboptimal for predicting severity and some biomarkers such as Oleic acid chlorohydrin have shown promising results. The modified determinant-based classification can help to classify patients admitted to intensive care units. Ringer's lactate solution is currently the fluid of choice and classic surgery has been surpassed by minimally-invasive approaches. Starting a full-caloric diet is safe when bowel sounds are present., Discussion: There are numerous well-defined research fields in Spain. Future multicentre studies should focus on management, predicting severity and cost-effectiveness., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Introduction: The essence of Enhanced Recovery After Surgery (ERAS) programs is the multimodal approach, and many authors have demonstrated safety and feasibility in fast track bariatric surgery. According to this concept, a multidisciplinary ERAS program for bariatric surgery has been developed by the Spanish Fast Track Group (ERAS Spain). The aim of this study was to analyze the initial implementation of this Spanish National ERAS protocol in bariatric surgery, comparing it with a historical cohort receiving standard care. Material and methods: A multi-centric prospective study was performed, including 233 consecutive patients undergoing bariatric surgery during 2015 and following ERAS protocol. It was compared with a historical cohort of 286 patients, who underwent bariatric surgery at the same institutions between 2013 and 2014 and following standard care. Compliance with the protocol, morbidity, mortality, hospital stay and readmission were evaluated. Results: Bariatric techniques performed were Roux-en-Y gastric bypass and sleeve gastrectomy. There were no significant differences in complications, mortality and readmission. Postoperative pain and hospital stay were significantly lower in the ERAS group. The total compliance to protocol was 80%. Conclusion: The Spanish National ERAS protocol is a safe issue, obtaining similar results to standard care in terms of complications, reoperations, mortality and readmissions. It is associated with less postoperative pain and earlier hospital discharge.

Objective: Seasonal influenza epidemics are a major public health concern. They are caused by the influenza A and B viruses; although the A virus is more prominent, influenza B virus infection causes a disease with similar characteristics. There are two phylogenetically distinct influenza B lineages (B/Victoria and B/Yamagata), only one of which is present in the trivalent vaccine formulated each season., Methods: Epidemiological data from the Spanish Influenza Surveillance System for 2007 to 2017 were reviewed to establish the relative proportion of each type of virus and the characterization of the B lineages in relation to the composition of the trivalent vaccine., Results: The median proportion of B (2007-2017) was 27.2% (0.7%-74.8%) vs. 16.3% (0.4%-98.6%) for A-H3 and 44.2% (0.1%-98.0%) for pandemic A-H1N1 (20092017). The B lineages co-circulated in 8/10 seasons and there was mismatch with the B vaccine strain in 4/10 seasons. The B virus was dominant in 2007/08 and 2012/13 throughout Spain. There was a combination of dominance/codominance of influenza B and mismatch with the vaccine lineage in at least one third of epidemic seasons reviewed., Conclusions: Epidemiological information on influenza B has been less compiled in comparison with data on the A virus. Influenza virus type B is responsible for a significant number of cases in almost all seasons. The predominant B lineage in each season is unpredictable, affecting the protection conferred by the seasonal vaccine. Spanish epidemiological data support the rationale for a quadrivalent vaccine with both B virus lineages similarly to data from other settings., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the 2016 practical prevention guidelines for CAP through vaccination in Spain, based on the available vaccines, as well as the evidence using a literature review and expert opinion. Vaccines against pneumococcus and influenza continue to be the main prevention tools available against CAP, and can contribute to reduce the burden of disease due to CAP and its associated complications. The available evidence supports the priority indications established in these guidelines, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The aim of this study was to determine the prevalence and type of thyroid hormone levels alterations in patients with acute pancreatitis (AP) and analyze if variations are useful AP progression predictors., Methods: Three groups of patients were analyzed: AP patients (n = 90), abdominal pain patients (n = 30), and healthy control subjects (n = 40). Usual blood parameters for AP diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels were analyzed., Results: Thyroid hormone level alterations were detected only within the AP group (41% of total cases), being the reduction in T3 levels the most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases). Alterations were not influenced by age or sex. Free thyroxine average values were also significantly higher in the AP group, compared with the healthy control group (P = 0.0005), resulting as independent predictors of both severity and mortality. Mortality in this group was 50%, with deceased patients showing FT4 levels above the reference limit., Conclusions: Our results show that FT4 level determination during the initial clinical evaluation of patients admitted to the emergency service with AP can be included as a severity indicator to help determine the differential care of these cases.

This work studies the morphological changes taking place in the Dama dama rumen during prenatal development using histomorphometrics, surface microstructure and immunohistochemistry analysis as well as carrying out a comparative analysis of this species with other wild (red deer) and domestic-type ruminants. A total of 25 fallow deer embryos and fetuses were used, from the first stage of prenatal life until birth. The appearance of the rumen from the primitive gastric tube was observed at 51 days of prenatal life (CRL 3 cm, 21% gestation). By 57 days (CRL 4.3 cm, 24% gestation) the ruminal wall comprised three layers: an internal epithelial layer, a middle layer of pluripotential blastemic tissue and an external layer or serosa. Ruminal pillars were visible at 72 days (CRL 6 cm, 30% gestation), and by 85 days (CRL 7.2 cm, 35% gestation) ruminal papillae were starting to appear. Under scanning electron microscopy, by 80 days (CRL 7 cm, 33% gestation) small ruminal papillae were observed protruding from the surface. Morphometric results showed accelerated growth of the epithelial layer and the tunica muscularis at 180 days (75% gestation). By contrast, the growth-rate of the lamina propria and submucosa declined from the early embryonic stages until birth. The serosa maintained a steady rate of growth until birth. Neuroendocrine cells (synaptophysin) were detected at 85 days (CRL 7.2 cm CRL, 35% gestation), while glial cell markers (glial fibrillary acidic protein and vimentin) were found at 108 days (CRL 31 cm, 45% gestation) and 63 days (CRL 4.4 cm, 26% gestation) respectively. Neuropeptide Y and vasoactive intestinal polypeptide were detected immunohistochemically at 180 days (CRL 33 cm, 75% gestation) and 192 days (CRL 35 cm, 80% gestation) respectively. In comparison to other wild and domestic-type ruminants, histomorphogenesis of the rumen in Dama dama was similar to that reported in red deer and goats, but rather slower than that observed for sheep or cattle.

The 3D culture of human mesenchymal stem cells (hMSCs) represents a more physiological environment than classical 2D culture and has been used to enhance the MSC secretome or extend cell survival after transplantation. Here we describe a simple and affordable method to generate 3D spheroids of hMSCs by seeding them at high density in a low-binding 96-well plate. Spheroids of hMSCs cultured in low-binding 96-well plates can be used to study the basic biology of the cells and to generate conditioned media or spheroids to be used in transplantation therapeutic approaches. These MSCs or their secretome can be used as a regenerative therapy and for tissue repair across multiple disease areas, including neurodegeneration. In comparison to other methods (hanging drop, use of gels or biomaterials, magnetic levitation, etc. ), the method described here is simple and affordable with no need to use specialized equipment, expensive materials or complex reagents., Competing Interests: Conflicts of interest statement: The authors declare that there are no conflicts of interest or competing interests.

Due to the increasing intake of raw fish, the appearance of keriorrhea in our environment has become more and more frequent. We present three clinical cases in order to aknowledge this sign and avoid unnecesary diagnostic tests.

Mesenchymal stem cells (MSCs) hold great potential as a regenerative therapy for stroke, leading to increased repair and functional recovery in animal models of cerebral ischaemia. While it was initially hypothesised that cell replacement was an important mechanism of action of MSCs, focus has shifted to their paracrine actions or the so called "bystander" effect. MSCs secrete a wide array of growth factors, chemokines, cytokines and extracellular vesicles, commonly referred to as the MSC secretome. There is evidence suggesting the MSC secretome can promote repair through a number of mechanisms including preventing cell apoptosis, modulating the inflammatory response and promoting endogenous repair mechanisms such as angiogenesis and neurogenesis. In this review, we will discuss the in vitro approaches currently being employed to drive the MSC secretome towards a more anti-inflammatory and regenerative phenotype. We will then examine the role of the secretome in promoting repair and improving recovery in preclinical models of cerebral ischaemia.

We present a number of comments about the recently published paper by Aziz et al. about the epidemiology of Functional Dyspepsia in USA, Canada and UK in comparison with previous studies in our country.

Background: Detailed analyses of mortality after upper gastrointestinal (GI) bleeding are lacking. Follow-up rarely extends beyond 30 days., Aims: Our aim was to analyze in-hospital and delayed 6-months mortality, identifying risk factors., Methods: This was a prospective study on patients with upper GI bleeding over 36 months. Clinical outcomes were in-hospital and delayed-6 month-mortality., Results: Four hundred and forty-none patients were included. Overall inpatient mortality was 9.8% but mortality directly related to bleeding was 5.1%. Patients who died presented lower systolic blood pressures, platelet recounts, prothrombin times and lower levels of hemoglobin, calcium, albumin, urea, creatinine and total proteins. Cirrhosis and neoplasms determined a higher in-hospital mortality. Albumin levels were protective, whereas creatinine and an active bleeding were risk factors for in-hospital death in multivariate analysis. Up to 12.6% of patients discharged died in the first 6 months. Neoplasms, chronic kidney disease, coronary disease and esophageal varices were related to delayed mortality. Coronary disease and neoplasms were independent risk factors for mortality, but albumin levels were protective in multivariate analysis., Conclusion: Comorbidities were risk factors for delayed mortality, whereas albumin levels were a protective factor for in-hospital and delayed deaths. Six months mortality is proportionately as important as in-hospital mortality. Half of the delayed deaths might be preventable.

Inflammation is an established contributor to disease and the NLRP3 inflammasome is emerging as a potential therapeutic target. A number of small molecule inhibitors of the NLRP3 pathway have been described. Here we analysed the most promising of these inhibitor classes side by side to assess relative potency and selectivity for their respective putative targets. Assessed using ASC inflammasome-speck formation, and release of IL-1β, in both human monocyte/macrophage THP1 cells and in primary mouse microglia, we compared the relative potency and selectivity of P2X7 inhibitors, inflammasome inhibitors (diarylsulfonylurea vs. the NBC series), and caspase-1 inhibitors. In doing so we are now able to provide a well characterised small molecule tool kit for interrogating and validating inflammasome-dependent responses with a range of nanomolar potency inhibitors against established points in the inflammasome pathway.

Objectives: Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course., Methods: One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1β, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α., Results: Significant differences were found between patients with severe AP and those with mild or moderately severe AP in IFN-γ (P < 0.001), IL6 (P < 0.001), TNF-α (P = 0.002), GM-CSF (P < 0.001), IL4 (P = 0.002), IL1b (P = 0.017), and IL13 (P < 0.001) concentrations. Interferon-γ, IL6, and TNF-α were associated with severe AP, whereas GM-CSF, IL4, IL1b, and IL13 were associated with mild or moderately severe AP. The IL13/IFNγ ratio was significantly higher in patients with mild AP (P = 7.36 × 10)., Conclusions: A TH1 profile was associated with severe AP and a TH2 profile with mild or moderately severe AP. We report an IL13/IFNγ ratio of potential value to predict the prognosis in AP.

The capnodynamic method is a minimally invasive method continuously calculating effective pulmonary blood flow (CO EPBF ), equivalent to cardiac output when intra pulmonary shunt flow is low. The capnodynamic equation joined with a ventilator pattern containing cyclic reoccurring expiratory holds, provides breath to breath hemodynamic monitoring in the anesthetized patient. Its performance however, might be affected by changes in the mixed venous content of carbon dioxide (C v CO 2 ). The aim of the current study was to evaluate CO EPBF during rapid measurable changes in mixed venous carbon dioxide partial pressure (P v CO 2 ) following ischemia-reperfusion and during sustained hypercapnia in a porcine model. Sixteen pigs were submitted to either ischemia-reperfusion (n = 8) after the release of an aortic balloon inflated during 30 min or to prolonged hypercapnia (n = 8) induced by adding an instrumental dead space. Reference cardiac output (CO) was measured by an ultrasonic flow probe placed around the pulmonary artery trunk (CO TS ). Hemodynamic measurements were obtained at baseline, end of ischemia and during the first 5 min of reperfusion as well as during prolonged hypercapnia at high and low CO states. Ischemia-reperfusion resulted in large changes in P v CO 2 , hemodynamics and lactate. Bias (limits of agreement) was 0.7 (-0.4 to 1.8) L/min with a mean error of 28% at baseline. CO EPBF was impaired during reperfusion but agreement was restored within 5 min. During prolonged hypercapnia, agreement remained good during changes in CO. The mean polar angle was -4.19° (-8.8° to 0.42°). Capnodynamic CO EPBF is affected but recovers rapidly after transient large changes in P v CO 2 and preserves good agreement and trending ability during states of prolonged hypercapnia at different levels of CO.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Background: Mesenchymal stem cells (MSCs) are one of the most promising candidates for the treatment of major neurological disorders. Desirable therapeutic properties of MSCs include reparative and regenerative potential but, despite their proven safety, the efficacy of MSCs remains controversial. Therefore, it is essential to optimise culture protocols to enhance the therapeutic potential of the MSC secretome. Here we aimed to: assess the increase in secretion of cytokines that may induce repair, regeneration, or immunomodulation when cultured in three dimensions; study the effect of interleukin (IL)-1 priming on two- (2D) and three-dimensional (3D) cultures of MSC; and evaluate the potential use of the modified secretome using microglial-MSC co-cultures., Methods: We established a 3D spheroid culture of human MSCs, and compared the secretome in 2D and 3D cultures under primed (IL-1) and unprimed conditions. BV2 microglial cells were stimulated with lipopolysaccharide (LPS) and treated with spheroid conditioned media (CM) or were co-cultured with whole spheroids. Concentrations of secreted cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Protein arrays were used to further evaluate the effect of IL-1 priming in 2D and 3D cultures., Results: 3D culture of MSCs significantly increased secretion of the IL-1 receptor antagonist (IL-1Ra), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF) compared with 2D culture, despite priming treatments with IL-1 being more effective in 2D than in 3D. The addition of CM of 3D-MSCs reduced LPS-induced tumour necrosis factor (TNF)-α secretion from BV2 cells, while the 3D spheroid co-cultured with the BV2 cells induced an increase in IL-6, but had no effect on TNF-α release. Protein arrays indicated that priming treatments trigger a more potent immune profile which is necessary to orchestrate an effective tissue repair. This effect was lost in 3D, partly because of the overexpression of IL-6., Conclusions: Increased secretion of anti-inflammatory markers occurs when MSCs are cultured in 3D, but this specific secretome did not translate into anti-inflammatory effects on LPS-treated BV2 cells in co-culture. These data highlight the importance of optimising priming treatments and culture conditions to maximise the therapeutic potential of MSC spheroids.

Electrochemical tyrosinase biosensors for tyramine determination were developed by the immobilization of the enzyme in calcium phosphate materials (CaPs) followed by cross-linking with glutaraldehyde. Tyramine was detected by the electrochemical reduction at -0.1V of the o- enzymatically-formed dopaquinone. Three different CaPs were explored as immobilization systems, monetite, brushite and brushite cement. Biosensors based on brushite matrices provide better analytical properties than the monetite one. Compared to brushite, a 10-fold increase of sensitivity was obtained with the brushite cement-based biosensor, which highlights the effect of brushite crystal formation in the presence of the enzyme in the biosensor performance. Several variables involved in the enzyme immobilization method such as glutaraldehyde cross-linking time, PPO/brushite ratio and thickness of the brushite-enzyme film were investigated. Furthermore, the effects of pH and temperature on biosensor performance were also optimized. Brushite cement-PPO-GA biosensor resulted in a reliable, highly sensitive, fast, inexpensive and easy analytical method for tyramine detection. Under optimal conditions (time of 15min, a ratio of 1.0 and 50μg of the brushite-enzyme mixture, 20°C and pH 6,0), a linear range of 5.8 × 10 -7 to 1.6 × 10 -5 , sensitivity 1.50 × 10 3 mAM -1 cm -2 , detection limit, 4.85 × 10 -8 M and a response time, 6s were obtained. The suitability of the proposed biosensor to determine the tyramine content in cheese samples has been explored. The mean analytical recovery of added tyramine in gouda and brie cheeses were found to be 95.5±5.8 and 96.9±7.5 respectively. A study of the tyramine content evolution over the course of a week under inadequate storage showed the importance of monitoring the degradation of certain foods., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In order to gain insight of the modifications that freezing and thawing cause to the surviving population of spermatozoa, changes in the potential of the plasma membrane (Em) and intracellular Na + content of stallion spermatozoa were investigated using flow cytometry. Moreover, caspase 3 activity was also investigated and the functionality of the Na + -K + ATPase pump was investigated before and after freezing and thawing. Cryopreservation caused a significant (p < 0.001) increase in the subpopulation of spermatozoa with depolarized sperm membranes, concomitantly with an increase (p < 0.05) in intracellular Na + . These changes occurred in relation to activation of caspase 3 (p < 0.001). Cryopreservation reduced the activity of the Na-K + pump and inhibition of the Na + -K + ATPase pump with ouabain-induced caspase 3 activation. It is concluded that inactivation of Na + -K + ATPase occurs during cryopreservation, an inhibition that could play a role explaining the accelerated senescence of the surviving population of spermatozoa., (© 2017 American Society of Andrology and European Academy of Andrology.)

The aim of this study is to describe differences in the ontogenesis of the abomasum in sheep (domestic ruminant) and deer (wild ruminant). Histomorphometric and immunohistochemical analysis were carried out on 50 embryos and fetuses of the sheep and 50 red deer from the first prenatal stages until birth. To compare similar periods of gestation in both species, we calculate the percentages of gestation. The appearance of the abomasum was earlier in the red deer (22% gestation) than in the sheep (25% gestation). Throughout development the epithelium happened sequentially, being of the types pseudostratified to simple cylindrical. This important modification was earlier in the red deer than the sheep. At 46% gestation in red deer and 50% in sheep, gastric pits were observed on the surface of abomasal folds. Our studies suggest a close link between the initial formation of these pseudoglandular structures and the clear separation of lamina propria and submucosa separated by de muscularis mucosae. At 54% gestation in red deer and at 60% in sheep, in the bottom of these pits the first outlines of glands were distinguishable. Finally, the presence of neuroendocrine and glial cells were detected in deer at earlier stages than in sheep., (© 2017 Japanese Society of Animal Science.)

Background and Aim: The study aims to assess and compare the predicting ability of some scores and biomarkers in acute pancreatitis., Methods: We prospectively collected data from 269 patients diagnosed of acute pancreatitis, admitted to Virgen de las Nieves University Hospital between June 2010 and June 2012. Blood urea nitrogen (BUN), C-reactive protein, and creatinine were measured on admission and after 48 h, lactate and bedside index for severity acute pancreatitis (BISAP) only on admission and RANSON within the first 48 h. Definitions from 2012 Atlanta Classification were used. Area under the curve (AUC) was calculated for each scoring system for predicting severe acute pancreatitis (SAP), mortality, and intensive care unit (ICU) admission, obtaining optimal cut-off values from the receiver operating characteristic curves., Results: Eight (3%) patients died, 17 (6.3%) were classified as SAP, and 10 (3.7%) were admitted in ICU. BISAP was the best predictor on admission for SAP, mortality, and ICU admission with an AUC of 0.9 (95% CI 0.83-0.97); 0.97 (95% CI 0.95-0.99); and 0.89 (95% CI 0.79-0.99), respectively. After 48 h, BUN 48 h was the best predictor of SAP (AUC = 0.96 CI: 0.92-0.99); BUN 48 h and BISAP were the best predictors for mortality (AUC = 0.97 CI: 0.95-0.99) and creatinine 48 h for ICU admission (AUC = 0.96 CI: 0.92-0.99). Lactate showed an AUC of 0.79 (CI: 0.71-0.88), 0.87 (CI: 0.78-0.96), and 0.77 (CI: 0.67-0.87) for SAP, mortality, and ICU admission, respectively. All parameters were predictors for SAP, mortality, and ICU admission, but C-reactive protein on admission was only a significant predictor of SAP., Conclusion: Bedside index for severity acute pancreatitis is a good predictive system for SAP, mortality, and ICU admission, being useful for triaging patients for ICU management. Lactate could be useful for developing new scores., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Competing Interests: Competing interests: None declared.

Background: Treatment of gastric cancer is based on accurate staging. Emerging methods, such as PET-CT, are increasingly being used for this purpose. Our aim was to analyze the results of EUS and PET-CT in staging and restaging our patients with gastric cancer, comparing both of them with the histological results., Methods: Patients with confirmed gastric cancer were prospectively enrolled. Inclusion criteria for the final analysis included only patients who finally received a surgical resection. All patients underwent preoperative TNM staging by means of EUS and PET-CT within 21 days prior to the surgical treatment., Results: A total of 256 patients were included. The overall EUS accuracy for T staging was 78% and 80.2% in restaging. EUS showed its best accuracy when distinguishing T1-T2 tumors vs. T3-T4, with an increased accuracy in restaging. Regarding N staging, the overall accuracy of EUS was 76.2%, and 72.5% for PET-CT ( p  = 0.02). With regards to restaging, accuracy of EUS and PET-CT for N staging was 88.5% and 69%, respectively, with significant differences ( p  < 0.0001)., Conclusions: EUS performed better than PET-CT in gastric cancer N staging and restaging. EUS accuracy in this setting is still suboptimal and probably more than one single diagnostic procedure should be used.

Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression ( ABCB1, CCNG2 and TUBB2B ). In addition, PTOV1 induced prostatospheres formation and self-renewal genes expression ( ALDH1A1, LIN28A, MYC and NANOG ). In contrast, Du145 and PC3 cells knockdown for PTOV1 significantly accumulated in the G2/M phase, presented a concomitant increased subG1 peak, and cell death by apoptosis. These effects were enhanced in docetaxel-resistant cells. Analyses of tumor datasets show that PTOV1 expression significantly correlated with prostate tumor grade, drug resistance ( CCNG2 ) and self-renewal ( ALDH1A1, MYC ) markers. These genes are concurrently overexpressed in most metastatic lesions. Metastases also show PTOV1 genomic amplification in significant co-occurrence with docetaxel-resistance and self-renewal genes. Our findings identify PTOV1 as a promoter of docetaxel-resistance and self-renewal characteristics for castration resistant prostate cancer. The concomitant increased expression of PTOV1 , ALDH1A1 and CCNG2 in primary tumors, may predict metastasis and bad prognosis., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment., (Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)