Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms

Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma

Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma

In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical management remains challenging; thus, novel and more efficacious treatment strategies are needed. Evidence-based medicine supports the role of the immune system to treat neoplastic diseases. Besides, immunotherapy offers the possibility of a precise medicinal approach to treat cancer. In recent years, multiple immunotherapeutic strategies have been developed, and are now recognized as a pillar of treatment. In addition, dogs represent a good model for translational medicine purposes. This review will cover the most relevant immunotherapeutic strategies for the treatment of canine malignant melanoma, divided among five different categories, namely, monoclonal antibodies, nonspecific immunotherapy activated by bacteria, vaccines, gene therapy, and lymphokine-activated killer cell therapy

Physiological, hormonal and molecular mechanisms regulating chilling injury in horticultural species. Postharvest technologies applied to reduce its impact

The storage of fruits and vegetables at low temperature near the freezing point is the foremost technology applied to retard postharvest ripening and to extend the shelf-life period of agricultural products. However, most tropical and subtropical produce is sensitive to chilling injury, which constitutes a set of physiological alterations caused by exposure to low temperatures for variable time periods, to the detriment of quality. This article is a thorough review of the physiological, hormonal and molecular mechanisms involved in the induction and development of this physiopathy. Also, the different postharvest technologies of a chemical, physical or biotechnological nature assayed in research or applied in the agro-food industry with the aim of inhibiting or delaying the emergence of chilling injury in sensitive plant produce of agricultural interest are reviewed. © 2009 Society of Chemical Industry.Peer Reviewe

Aproximación proteómica al estudio de la respuesta diferencial del metabolismo energético al estrés por bajas temperaturas en tomate y pimiento

Trabajo presentado al congreso "III Jornadas Bienales de jóvenes investigadores en proteómica" celebrado en Santiago de Compostela del 9 al 10 de febrero de 2012.Tomate (Solanum lycopersicum) y pimiento (Capsicum annuum), son dos especies hortofrutícolas pertenecientes a la familia Solanaceae susceptibles a sufrir daños por frío cuando se almacenan a bajas temperaturas, lo que afecta seriamente a la calidad de los frutos, siendo causa de importantes pérdidas económicas en el sector agro-alimentario. Una de las principales respuestas celulares al estrés por bajas temperaturas consiste en el mantenimiento de la homeostasis osmótica por la acumulación de osmolitos compatibles, para lo que tiene lugar la reprogramación de metabolismos energéticos como la glicólisis, el ciclo de Calvin y el ciclo de Krebs. Se ha abordado este estudio desde una perspectiva proteómica, comparando el proteoma de tomate y de pimiento sometidos a daños por frío para investigar las diferentes respuestas del metabolismo energético a las bajas temperaturas en frutos de estas dos especies. El análisis proteómico se ha realizado mediante electroforesis 2D-DIGE seguida de la identificación de las proteínas diferencialmente expresadas por MALDI-TOF-MS. Previamente a comparar los perfiles proteómicos de ambas especies, dentro de cada una de ellas se ha realizado una comparativa del perfil de frutos conservados a temperatura que inducen daños por frío y de frutos conservados a temperatura que no inducen dichos daños, con el fin de identificar las proteínas diferencialmente expresadas debido a la fisiopatía. Se han observado alteraciones en la fermentación y en el ciclo de Calvin en pimiento y cambios en el metabolismo de carbohidratos compuestos sacarosa), metabolismo de monosacáridos (glucosa) y cadena de transporte de electrones en tomate. En ambos frutos se han detectado modificaciones en la expresión de enzimas de la glicolisis y del ciclo de Krebs por efecto de la conservación refrigerada, hecho que pone de manifiesto la importancia que estos dos metabolismos parecen tener en la respuesta a los daños por frío.Este trabajo de investigación ha sido financiado por el Ministerio de Ciencia e Innovación (MICINN) (proyecto PIE2009-40I080), y por la Agencia de Ciencia y Tecnología de la Región de Murcia (Fundación SENECA) (proyecto 04553/GERM/06). PSB y ISE están contratadas en el marco del programa JAE-DOC del CSIC.Peer Reviewe

Understanding the mechanisms of chilling injury in bell pepper fruits using the proteomic approach

In order to advance in the understanding of CI in pepper fruits, the cell ultrastructure alterations induced by CI and the physiological and metabolic changes have been studied along with the proteomic study. When stored at low temperatures bell pepper (Capsicum annuum) fruits exhibited visual CI symptoms and important alterations within the cell ultrastructure, since peroxisomes and starch grains were not detected and the structure of the chloroplast was seriously damaged in chilled tissues. Physiological and metabolic disorders were also observed in chilled fruits, such as higher ethylene production, increased MDA content, changes in sugar and organic acids and enzymatic activities. The comparative proteomic analysis between control and chilled fruits reveals that the main alterations induced by CI in bell pepper fruits are linked to redox homeostasis and carbohydrate metabolism. Thus, protein abundance in the ascorbate-glutathione cycle is altered and catalase is down-regulated. Key proteins from glycolysis, Calvin cycle and Krebs cycle are also inhibited in chilled fruits. Enolase and GAPDH are revealed as proteins that may play a key role in the development of chilling injury. This study also provides the first evidence at the protein level that cytosolic MDH is involved in abiotic stress. © 2012 Elsevier B.V.P.S.B. and I.E. were supported by a postdoctoral position from the JAE-Doc program of the National Research Council (CSIC). This work was supported by the Spanish Ministry of Science and Innovation (MICINN) [grants AGL2007-60447 and PIE2009-40I080], and by the Council of Science and Technology from the Region of Murcia (Spain) (Fundación SENECA) [grant 04553/GERM/06].Peer Reviewe

An engineered plant that accumulates higher levels of heavy metals than Thlaspi caerulescens, with yields of 100 times more biomass in mine soils

8 pages, 3 figures, 2 tables.Nicotiana glauca transformed with TaPCS1 was tested for its application in phytoremediation. When plantlets were grown in mine soils containing Cu, Zn, and Pb (42, 2600, and 1500 mg kg−1) the plant showed high levels of accumulation especially of Zn and Pb. Adult plants growing in mine soils containing different heavy metal concentrations showed a greater accumulation as well as an extension to a wider range of elements, including Cd, Ni and B. The overexpressed gene confers up to 9 and 36 times more Cd and Pb accumulation in the shoots under hydroponic conditions, and a 3- and 6-fold increase in mining soils. When the hyperaccumulator Thlaspi caerulescens was compared, the results were higher values of heavy metal and Boron accumulation, with a yield of 100 times more biomass. Thlaspi was unable to survive in mining soils containing either a level higher than 11 000 mg kg−1 of Pb and 4500 mg kg−1 of Zn, while engineered plants yielded an average of 0.5 kg per plant.This research was supported by FEDER project IFD97 1469-C04-03, for which the authors are deeply indebted.Navarro-Aviñó was financed by ‘‘Social European Funds’’.Peer reviewe