Circulating miR-200c and miR-141 and outcomes in patients with breast cancer

Research article[Abstract] Background. The deregulation of microRNAs in both tumours and blood has led to the search for microRNAs to indicate the presence of cancer and predict prognosis. We hypothesize the deregulation of miR-200c/miR-141 in the whole blood can identify breast cancer (BC), and could be developed into a prognostic signature. Methods. The expression of miR-200c and miR-141 were examined in bloods (57 stage I-IV BC patients and 20 age-matched controls) by quantitative reverse-transcription PCR. The associations of circulating microRNAs with clinic and pathological characteristics were analysed. Their effects on survival were analysed by the Kaplan-Meier method and Cox regressions. Results. MiR-200c was down regulated (P < 0.0001) in the blood of BC patients, yielded an area under the ROC curve of 0.79 (90% sensitivity, 70.2% specificity) in discriminating BC from controls. Circulating miR-141 was not discriminating. MiR-200c and miR-141 in the blood of BC patients were inversely correlated (P = 0.019). The miR-200c levels were numerically higher in stage IV and tumours with lower MIB-1. MiR-141 was significantly higher in the blood of patients with stage I-III, lymph node metastasis, and HER2 negative tumours. High blood expression of miR-200c and/or low expression of miR-141 was associated with unfavourable overall survival (hazard ratio, 3.89; [95% CI: 1.28-11.85]) and progression-free survival (3.79 [1.41–10.16]) independent of age, stage and hormonal receptors. Conclusions. Circulating miR-200c and miR-141 were deregulated in BC comparing with controls. Furthermore, miR-200c and miR-141 were independent prognostic factors and associated with distinct outcomes of BC patients.Instituto de Salud Carlos III (España); PI06-154

Evaluation of the in vitro antimicrobial activity of extracts of Persea americana (Avocado) variety Choquette on the growth of Staphylococcus aureus and Escherichia coli

Las enfermedades infecciosas se encuentran entre las primeras causas de muerte a nivel mundial y la situación se agravada por la aparición progresiva de resistencia a las terapias farmacológicas convencionales. La Persea americana (aguacate), posee sustancias activas que regulan la proliferación de algunos microorganismos patógenos. El objetivo de esta investigación fue evaluar la actividad antimicrobiana y concentración mínima inhibitoria de extractos de Persea americana variedad Choquette sobre el crecimiento de S. aureus ATCC 29213 y E. coli ATCC 25922. La presente fue una investigación de tipo experimental en la que se utilizaron extractos de la cáscara, pulpa y semilla a partir de solventes orgánicos. Se determinó la concentración mínima inhibidora (CMI) y bactericida (CMB) de cada extracto utilizando placas de agar Mueller Hinton las cuales fueron inoculadas con la suspensión bacteriana ajustada. La CMI y CMB para la E. coli. Tratada con la cáscara (solvente hexano y el cloroformo) fue de (1/2)1000 mg/ml; la CMI y CMB para el S. aureus (con los solventes cloroformo y acetato de etilo) fue de (1/2)1000 mg/ml, el extracto de la pulpa no presentó actividad antimicrobiana para ambos microorganismos. Los resultados reflejan actividad antimicrobiana en cascara y semilla, por lo que se propone desarrollar nuevas investigaciones orientadas hacia la caracterización de estos compuestos con miras al desarrollo de fármacos antimicrobianos.Infectious diseases are among the leading causes of death worldwide and the situation is aggravated by the progressive emergence of resistance to conventional drug therapies. The Persea americana (avocado), has active substances that regulate the proliferation of some pathogenic microorganisms. The objective of this research was to evaluate the antimicrobial activity and minimum inhibitory concentration of extracts of Persea americana variety Choquette on the growth of S. aureus ATCC 29213 and E. coli ATCC 25922. The present was an experimental investigation using extracts of the shell, pulp and seed from organic solvents. The minimum inhibitory (MIC) and bactericidal (MIB) concentration of each extract was determined using Mueller Hinton agar plates which were inoculated with the adjusted bacterial suspension. The MIC and CMB for E. coli. Treated with the shell (hexane solvent and chloroform) was (1/2)1000 mg/ml; the MIC and CMB for S. aureus (with the solvents chloroform and ethyl acetate) was (1/2)1000 mg/ml, the pulp extract did not present antimicrobial activity for both microorganisms. The results reflect antimicrobial activity in shell and seed, so it is proposed to develop further research aimed at the characterization of these compounds for the development of antimicrobial drugs

Forest Biodiversity Assessment in Peruvian Andean Montane Cloud Forest

Cloud forests are unusual and fragile habitats, being one of the least studied and least understood ecosystems. The tropical Andean dominion is considered one of the most significant places in the world as rega rds biological diversity, with a very high level of endemism. The biodiversity was analysed in an isolated remnant area of a tropical montane cloud forest known as the ?Bosque de Neblina de Cuyas?, in the North of the Peruvian Andean range. Composition, structure and dead wood were measured or estimated. The values obtained were compared with other cloud forests. The study revealed a high level of forest biodiversity, although the level of biodiversity differs from one area to another: in the inner areas, where human pressure is almost inexistent, the biodiversity values increase. The high species richness and the low dominance among species bear testimony to this montane cloud forest as a real enclave of biodiversity

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

High prevalence and diversity of HIV-1 non-B genetic forms due to immigration in southern Spain: A phylogeographic approach

Phylogenetic studies are a valuable tool to understand viral transmission patterns and the role of immigration in HIV-1 spread. We analyzed the spatio-temporal relationship of different HIV-1 non-B subtype variants over time using phylogenetic analysis techniques. We collected 693 pol (PR+RT) sequences that were sampled from 2005 to 2012 from naïve patients in different hospitals in southern Spain. We used REGA v3.0 to classify them into subtypes and recombinant forms, which were confirmed by phylogenetic analysis through maximum likelihood (ML) using RAxML. For the main HIV-1 non-B variants, publicly available, genetically similar sequences were sought using HIV-BLAST. The presence of HIV-1 lineages circulating in our study population was established using ML and Bayesian inference (BEAST v1.7.5) and transmission networks were identified. We detected 165 (23.4%) patients infected with HIV-1 non-B variants: 104 (63%) with recombinant viruses in pol: CRF02_AG (71, 43%), CRF14_BG (8, 4.8%), CRF06_cpx (5, 3%) and nine other recombinant forms (11, 6.7%) and unique recombinants (9, 5.5%). The rest (61, 37%) were infected with non-recombinant subtypes: A1 (30, 18.2%), C (7, [4.2%]), D (3, [1.8%]), F1 (9, 5.5%) and G (12, 7.3%). Most patients infected with HIV-1 non-B variants were men (63%, p < 0.001) aged over 35 (73.5%, p < 0.001), heterosexuals (92.2%, p < 0.001), from Africa (59.5%, p < 0.001) and living in the El Ejido area (62.4%, p<0.001). We found lineages of epidemiological relevance (mainly within Subtype A1), imported primarily through female sex workers from East Europe. We detected 11 transmission clusters of HIV-1 non-B Subtypes, which included patients born in Spain in half of them. We present the phylogenetic profiles of the HIV-1 non-B variants detected in southern Spain, and explore their putative geographical origins. Our data reveals a high HIV-1 genetic diversity likely due to the import of viral lineages that circulate in other countries. The highly immigrated El Ejido area acts as a gateway through which different subtypes are introduced into other regions, hence the importance of setting up epidemiological control measures to prevent future outbreaks

Phylodynamic and Phylogeographic Profiles of Subtype B HIV-1 Epidemics in South Spain

Since 1982, HIV-1 epidemics have evolved to different scenarios in terms of transmission routes, subtype distribution and characteristics of transmission clusters. We investigated the evolutionary history of HIV-1 subtype B in south Spain.We studied all newly diagnosed HIV-1 subtype B patients in East Andalusia during the 2005-2012 period. For the analysis, we used the reverse transcriptase and protease sequences from baseline resistance, and the Trugene® HIV Genotyping kit (Siemens, Barcelona, Spain). Subtyping was done with REGA v3.0. The maximum likelihood trees constructed with RAxML were used to study HIV-1 clustering. Phylogeographic and phylodynamic profiles were studied by Bayesian inference methods with BEAST v1.7.5 and SPREAD v1.0.6.Of the 493 patients infected with HIV-1 subtype B, 234 grouped into 55 clusters, most of which were small (44 clusters ≤ 5 patients, 31 with 2 patients, 13 with 3). The rest (133/234) were grouped into 11 clusters with ≥ 5 patients, and most (82%, 109/133) were men who have sex with men (MSM) grouped into 8 clusters. The association with clusters was more frequent in Spanish (p = 0.02) men (p< 0.001), MSM (p<0.001) younger than 35 years (p = 0.001) and with a CD4+ T-cell count above 350 cells/ul (p<0.001). We estimated the date of HIV-1 subtype B regional epidemic diversification around 1970 (95% CI: 1965-1987), with an evolutionary rate of 2.4 (95%CI: 1.7-3.1) x 10-3 substitutions/site/year. Most clusters originated in the 1990s in MSMs. We observed exponential subtype B HIV-1 growth in 1980-1990 and 2005-2008. The most significant migration routes for subtype B went from inland cities to seaside locations.We provide the first data on the phylodynamic and phylogeographic profiles of HIV-1 subtype B in south Spain. Our findings of transmission clustering among MSMs should alert healthcare managers to enhance preventive measures in this risk group in order to prevent future outbreaks

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases