Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception.

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream).

The isolation of circulating tumour cells (CTCs) in colorectal cancer (CRC) mostly relies on the expression of epithelial markers such as EpCAM, and phenotypic characterisation is usually performed under fluorescence microscopy with only one or two additional markers. This limits the ability to detect different CTC subpopulations based on multiple markers. The aim of this work was to develop a novel protocol combining two platforms (IsoFluxTM and ImageStream®X) to improve CTC evaluation. Cancer cell lines and peripheral blood from healthy donors were used to evaluate the efficiency of each platform independently and in combination. Peripheral blood was extracted from 16 early CRC patients (before loco-regional surgery) to demonstrate the suitability of the protocol for CTC assessment. Additionally, peripheral blood was extracted from nine patients one month after surgery to validate the utility of our protocol for identifying CTC subpopulation changes over time. Results: Our protocol had a mean recovery efficiency of 69.5% and a limit of detection of at least four cells per millilitre. We developed an analysis method to reduce noise from magnetic beads used for CTC isolation. CTCs were isolated from CRC patients with a median of 37 CTCs (IQ 13.0-85.5) at baseline. CTCs from CRC patients were significantly (p < 0.0001) larger than cytokeratin (CK)-negative cells, and patients were stratified into two groups based on BRAFV600E and PD-L1 expression on CK-positive cells. The changes observed over time included not only the number of CTCs but also their distribution into four different subpopulations defined according to BRAFV600E and PD-L1 positivity. We developed a novel protocol for semi-automatic CTC isolation and phenotypic characterisation by combining two platforms. Assessment of CTCs from early CRC patients using our protocol allowed the identification of two clusters of patients with changing phenotypes over time.

Telomere Instability in Lynch Syndrome Families Leads to Some Shorter Telomeres in MSH2+/- Carriers.

Lynch syndrome (LS) is an inherited predisposition to early onset of various cancers, caused by mutation in a DNA mismatch repair (MMR) gene. In heterozygous MMR+/- carriers, somatic mutation, loss or silencing of the wild type allele increases the mutation rate, facilitating the initiation of MMR-defective cancers. These cancers are characterized by instability at short tandem repeats (STRs) and in telomeric DNA. We have investigated telomere length in saliva DNA from LS and control families, using single telomere analysis at XpYp and 12q and by qPCR to measure total telomeric DNA. Single telomere analysis showed a trend for shorter XpYp telomeres in MSH2+/- carriers compared to MLH1+/- carriers or controls, but this was masked in the comparative analysis of total telomeric DNA. Comparison of age-adjusted telomere length within families showed that neither MSH2+/- or MLH1+/- children had consistently shorter or longer telomeres than their MMR+/- parent, indicating the absence of an inter-generational effect on telomere length. Unexpectedly however, wildtype children in families with MSH2 mutations, had significantly longer XpYp telomeres than their MMR+/- parent. Altogether our data suggest that MMR insufficiency, particularly in MSH2+/- carriers, increases telomere instability and somatic cell turnover during the lifetime of LS mutation carriers but has minimal consequences for telomere length in the germline.

The Polemic Diagnostic Role of TP53 Mutations in Liquid Biopsies from Breast, Colon and Lung Cancers.

Being minimally invasive and thus allowing repeated measures over time, liquid biopsies are taking over traditional solid biopsies in certain circumstances such as those for unreachable tumors, very early stages or treatment monitoring. However, regarding TP53 mutation status analysis, liquid biopsies have not yet substituted tissue samples, mainly due to the lack of concordance between the two types of biopsies. This needs to be examined in a study-dependent manner, taking into account the particular type of liquid biopsy analyzed, that is, circulating tumor cells (CTCs) or cell-free DNA (cfDNA), its involvement in the tumor biology and evolution and, finally, the technology used to analyze each biopsy type. Here, we review the main studies analyzing TP53 mutations in either CTCs or cfDNA in the three more prevalent solid tumors: breast, colon and lung cancers. We evaluate the correlation for mutation status between liquid biopsies and tumor tissue, suggesting possible sources of discrepancies, as well as evaluating the clinical utility of using liquid biopsies for the analysis of TP53 mutation status and the future actions that need to be undertaken to make liquid biopsy analysis a reality for the evaluation of TP53 mutations.

Educación emocional en la educación para la salud: cuestión de Salud Pública / Emotional education in health education: a matter of Public Health

El modelo holístico de salud exige incluir las emociones en las estrategias de prevención y promoción. Para comprobar la extensión de su consideración en la educación para la salud, se realizó una revisión sistemática en las bases de datos Medline, PsycInfo y ERIC. Se aceptaron 66 de los 648 artículos revisados, hallándose gran diversidad temática, teórica y terminológica respecto a la salud emocional. Por tanto, la representación en la literatura científica de las estrategias de educación para la salud que incluyen las emociones es todavía pequeña. Asimismo, aquellas que sí las incluyen presentan una gran variedad terminológica y teórica que dificulta la difusión del conocimiento y la generalización de resultados. Se pone de manifiesto la necesidad de implementación de un modelo de formación para la salud en el que se incluya la educación emocional como componente fundamental de la misma, en sintonía con los recientes avances científicos

The holistic model of health requires the inclusion of emotions in prevention and promotion policies. A systematic review was carried out in databases Medline, PsychInfo, and ERIC to check the extent to which emotions are covered in health education. Sixty-six of the 648 papers reviewed were accepted, presenting a wide range of topics, theories, and terms regarding emotional health. Therefore, health education strategies that take emotions into consideration are still underrepresented in scie.jpgic literature. Moreover, a great terminological and theorical diversity is found among the ones that incorporate emotional health, hindering knowledge dissemination and generalization of results. The need for an implementation of a health education model where emotional education is included as an essential part of it, according to recent scie.jpgic advances is clearly shown

Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for treatment response assessment in metastatic colorectal cancer patients.

BACKGROUND: The use of circulating tumor cells (CTCs) as indicators of treatment response in metastatic colorectal cancer (mCRC) needs to be clarified. The objective of this study is to compare the Response Evaluation Criteria in Solid Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on the presence and phenotypic characterization of CTCs, as indicators of FOLFOX-bevacizumab treatment response. METHODS: 77 mCRC blood samples from FOLFOX-bevacizumab treated patients were analyzed to isolate CTCs before and after (12 and 24 weeks) treatment, using an immunomagnetic separation method. VEGFR expression was identified by double immunostaining. RESULTS: We observed a decrease of CTCs (42.8 vs. 18.2%) and VEGFR positivity (69.7% vs. 41.7%) after treatment. According to RECIST, 6.45% of the patients did not show any clinical benefit, whereas 93.55% patients showed a favorable response at 12 weeks. According to CyCAR, 29% had a non-favorable response and 71% patients did not. No significant differences were found between the response assessment by RECIST and CyCAR at 12 or 24 weeks. However, in the multivariate analysis, RECIST at 12 weeks and CyCAR at 24 weeks were independent prognostic factors for OS (HR: 0.1, 95% CI 0.02-0.58 and HR: 0.35, 95% CI 0.12-0.99 respectively). CONCLUSIONS: CyCAR results were comparable to RECIST in evaluating the response in mCRC and can be used as an alternative when the limitation of RECIST requires additional response analysis techniques.

Digit loss in archosaur evolution and the interplay between selection and constraints.

Evolution involves interplay between natural selection and developmental constraints. This is seen, for example, when digits are lost from the limbs during evolution. Extant archosaurs (crocodiles and birds) show several instances of digit loss under different selective regimes, and show limbs with one, two, three, four or the ancestral number of five digits. The 'lost' digits sometimes persist for millions of years as developmental vestiges. Here we examine digit loss in the Nile crocodile and five birds, using markers of three successive stages of digit development. In two independent lineages under different selection, wing digit I and all its markers disappear. In contrast, hindlimb digit V persists in all species sampled, both as cartilage, and as Sox9- expressing precartilage domains, 250 million years after the adult digit disappeared. There is therefore a mismatch between evolution of the embryonic and adult phenotypes. All limbs, regardless of digit number, showed similar expression of sonic hedgehog (Shh). Even in the one-fingered emu wing, expression of posterior genes Hoxd11 and Hoxd12 was conserved, whereas expression of anterior genes Gli3 and Alx4 was not. We suggest that the persistence of digit V in the embryo may reflect constraints, particularly the conserved posterior gene networks associated with the zone of polarizing activity (ZPA). The more rapid and complete disappearance of digit I may reflect its ZPA-independent specification, and hence, weaker developmental constraints. Interacting with these constraints are selection pressures for limb functions such as flying and perching. This model may help to explain the diverse patterns of digit loss in tetrapods. Our study may also help to understand how selection on adults leads to changes in development.

Evaluación de la aplicación del protocolo de prevención de la sepsis neonatal precoz por estreptococo del grupo B en el Hospital “Doce de Octubre” de Madrid / Evaluation of the application of the protocol for prevention of early neonatal group B Streptococcal sepsis at Hospital Doce de Octubre in Madrid, Spain

Objetivo: Evaluar la aplicación del protocolo de profilaxis antibiótica intraparto (PAI) para la prevención de las enfermedades perinatales por estreptococo del grupo B (EGB) en el Hospital “Doce de Octubre” de Madrid. Métodos: Se realizó un estudio observacional, descriptivo y transversal que evaluó el cumplimiento de la PAI frente al EGB en un total de 425 partos atendidos en el Hospital “Doce de Octubre” durante un período de tiempo comprendido entre el 10 de febrero y el 10 de marzo de 2004, a través de tres indicadores: porcentaje de mujeres con cribado realizado, porcentaje de mujeres con indicación de profilaxis efectuada y porcentaje de mujeres que recibieron la PAI entre aquellas a las que se indicó según el protocolo.Resultados: Se practicó la prueba de cribado al 73,7% de mujeres (308) que lo requerían. Se reflejó el resultado del exudado en el informe de seguimiento de la gestación en el 58,7% de los casos (181) y en el 90,9% de los pacientes (280) en los informes de ingreso en el hospital. Se indicó la profilaxis en el 89,4% de los casos (84) que lo requerían. Se administró en el 95,2% de las mujeres en las que estaba indicada.Conclusiones: La monitorización del programa de prevención establecido en el hospital “Doce de Octubre” permite establecer unas propuestas de mejora en la aplicación del mismo. Las propuestas principales son: realización del exudado vaginorrectal de modo universal a todas las gestantes entre las semanas 35 y 37 de gestación; protocolizar en la historia clínica la constatación del resultado del exudado y la edad gestacional en que se realizó; si está indicada la quimioprofilaxis, iniciar siempre su administración de forma inmediata tras el ingreso

Objective: To evaluate the protocol for intrapartum antibiotic prophylaxis (IAP) for prevention of perinatal group B streptococcal (GBS) infection at Hospital Doce de Octubre in Madrid, Spain.Methods: The authors carried out a descriptive, cross-sectional, observational study to evaluate compliance with the IAP for the prevention of GBS infection in 425 births occurring at Hospital Doce de Octubre between February 10 and March 10, 2004, in terms of three indicators: percentage of women screened, percentage of women in whom prophylaxis was indicated and percentage of women who received IAP among those in whom prophylaxis was indicated according to the protocol.Results: The screening test was performed in 73.7% (308) of the women who requested it. The results of the analysis of the exudates were recorded in the pregnancy follow-up in 58.7% of the cases (181) and in the hospital admission records in 90.9% (280). Prophylaxis was indicated in 89.4% (84) of the cases in which it was requested, and was administered in 95.2% of the cases in which it was indicated.Conclusiones: The monitoring of the prevention program underway at Hospital Doce de Octubre makes it possible to stablish proposals for improving the application of said program. The major proposals are: analysis of the recto-vaginal exudates in all pregnant women between weeks 35 and 37 of gestation; application of a protocol for the inclusion of the results of the analysis of the exudates and the gestational age at which it was performed in the clinical record; if chemoprophylaxis is indicated, administration should always begin immediately after admission