A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues

A20 Modulates Lipid Metabolism and Energy Production to Promote Liver Regeneration

Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-$\kappa$B inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.$\beta$galactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-$\kappa$B, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation

Finding a Needle in the Virus Metagenome Haystack - Micro-Metagenome Analysis Captures a Snapshot of the Diversity of a Bacteriophage Armoire

Viruses are ubiquitous in the oceans and critical components of marine microbial communities, regulating nutrient transfer to higher trophic levels or to the dissolved organic pool through lysis of host cells. Hydrothermal vent systems are oases of biological activity in the deep oceans, for which knowledge of biodiversity and its impact on global ocean biogeochemical cycling is still in its infancy. In order to gain biological insight into viral communities present in hydrothermal vent systems, we developed a method based on deep-sequencing of pulsed field gel electrophoretic bands representing key viral fractions present in seawater within and surrounding a hydrothermal plume derived from Loki's Castle vent field at the Arctic Mid-Ocean Ridge. The reduction in virus community complexity afforded by this novel approach enabled the near-complete reconstruction of a lambda-like phage genome from the virus fraction of the plume. Phylogenetic examination of distinct gene regions in this lambdoid phage genome unveiled diversity at loci encoding superinfection exclusion- and integrase-like proteins. This suggests the importance of fine-tuning lyosgenic conversion as a viral survival strategy, and provides insights into the nature of host-virus and virus-virus interactions, within hydrothermal plumes. By reducing the complexity of the viral community through targeted sequencing of prominent dsDNA viral fractions, this method has selectively mimicked virus dominance approaching that hitherto achieved only through culturing, thus enabling bioinformatic analysis to locate a lambdoid viral “needle" within the greater viral community “haystack". Such targeted analyses have great potential for accelerating the extraction of biological knowledge from diverse and poorly understood environmental viral communities

Validación de la versión brasileña y colombiana de la escala CCAENA (continuidad de la atención en todos los niveles de atención): Irene Garcia-Subirats

Introducción El cuestionario de continuidad de la atención en todos los niveles de atención (CCAENA en español) evalúa los tres tipos de continuidad de la atención (relacional, informativa, gerencial) en todos los niveles de atención desde la perspectiva del paciente. Había sido validado para el contexto sanitario español. Objetivo: evaluar las propiedades psicométricas de la versión abreviada de la escala CCAENA en el contexto colombiano y brasileño. Métodos Estudio transversal mediante encuesta de población en municipios de Colombia (n = 2,163) y Brasil (n = 2,167). Los datos se recopilaron en 2011 mediante un cuestionario que incluía 14 ítems de la escala CCAENA adaptados a ambos contextos (y traducidos). Se evaluaron la validez de constructo (análisis factorial exploratorio), la consistencia interna (alfa de Cronbach) y la multidimensionalidad (coeficientes de correlación de Spearman). Resultados Al igual que en la versión original, el análisis factorial mostró que los ítems se agruparon en tres factores: la continuidad entre los niveles de atención y la relación entre el proveedor de atención primaria y el proveedor de atención secundaria. El alfa de Cronbach indicó una buena consistencia interna (Colombia: 0.87, 0.91, 0.87; Brasil: 0.86, 0.89, 0.86). Los coeficientes de correlación sugieren que los tres factores pueden interpretarse como escalas separadas (<0.70). Conclusión La validez y la confiabilidad de la versión abreviada de CCAENA son adecuadas en ambos países, manteniendo una alta equivalencia con la versión original, por lo tanto, es una herramienta útil para evaluar la continuidad de la atención en estos contextos. Mensajes clave Este estudio demuestra buenas propiedades psicométricas (validez y confiabilidad) de la versión abreviada de la escala CCAENA adaptada al contexto colombiano y brasileño. Esta herramienta será útil para proveedores e investigaciones para evaluar los tres tipos de continuidad de la atención en todos los niveles de atención desde la perspectiva del paciente en Colombia y Brasil. The Author 2014. Publicado por Oxford University Press en nombre de la Asociación Europea de Salud Pública. Todos los derechos reservados.Introduction The questionnaire of continuity of care across care levels (CCAENA in Spanish) assesses the three types of continuity of care (relational, informational, managerial) across care levels from the patient’s perspective. It had been validated for the Spanish health care context. Objective: To evaluate the psychometric properties of shortened version of the CCAENA scale in the Colombian and Brazilian context. Methods Cross-sectional study by means of a population survey in municipalities of Colombia (n = 2,163) and Brazil (n = 2,167). Data were collected in 2011 using a questionnaire that included 14 items of the CCAENA scale adapted to both contexts (and translated). Construct validity (exploratory factor analysis), internal consistency (Cronbach’s alpha) and multidimensionality (Spearman correlation coefficients) were assessed. Results As in the original version, the factor analysis showed that the items grouped into three factors: continuity across care levels and patient-primary care provider and -secondary care provider relationship. Cronbach’s alpha indicated good internal consistency (Colombia: 0.87, 0.91, 0.87; Brazil: 0.86, 0.89, 0.86). The correlation coefficients suggest that the three factors can be interpreted as separated scales (<0.70). Conclusion Validity and reliability of the shortened version of CCAENA are adequate in both countries – maintaining high equivalence with the original version – thus, is a useful tool to assess continuity of care in these contexts. Key messages This study demonstrates good psychometric properties - validity and reliability- of the shortened version of CCAENA scale adapted to the Colombian and Brazilian context. This tool will be useful for providers and researches to assess the three types of continuity of care across care levels from the patient’s perspective in Colombia and Brazil. The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved

Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting similar to 1 in 2500-4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program

Reciprocal influence of ethylene and gibberellins on response-gene expression in Arabidopsis thaliana

Item does not contain fulltextThe complexity of hormonal responses and their functional overlap support the presence of an intensive cross-talk between hormone signalling pathways. A detailed analysis of responses induced by ethylene and gibberellin (GA) in a GA-insensitive mutant (gai), an ethylene-resistant mutant (etr1-3), the gai etr1-3 double-mutant, and in wild-type Arabidopsis thaliana plants, revealed multiple interactions between ethylene and GA signal transduction pathways. Ethylene insensitive mutants and wild-type plants treated with 1-methylcyclopropene (1-MCP), an ethylene perception inhibitor, displayed a stronger responsiveness of genes differentially regulated by GA. In addition, microarray-analysis showed that the GA-response in an ethylene-insensitive background is different from that in the wild-type, confirming the importance of ethylene in a plant's response towards GA. In this paper, we present a number of genes with an altered response-pattern as a direct consequence of cross-talk between ethylene and GA