77 research outputs found
Valor clínico de la tomografía de emisión de positrones con F-18-FDG en el seguimiento de pacientes con cáncer de ovario
Background. Positron emission tomography with fluor-
18-deoxyglucose (PET-FDG) is an efficient technique for the
detection of tumoural tissue. The aim of the paper is to
evaluate the PET-FDG in the diagnosis of residual disease or
relapse in patients with cancer of the ovary.
Methods. A total of 24 patients, diagnosed and treated for
cancer of the ovary with surgery and subsequent
chemotherapy, were included. With 12 patients the study was
carried out prior to second-look surgery, and with the other 12
after objectivising an increase of the tumoural marker in the
follow up. Abdominal-pelvic CAT, determination of the seric
levels of CA-125 and PET-FDG of thorax, abdomen and pelvis
were carried out on all patients. The PET-FDG was evaluated
in a qualitative way through the visual study of the images,
and quantitatively through the SUV or standard uptake value.
The definitive diagnosis was confirmed through an anatomopathological
study in 13 cases and through clinical follow
up in the rest with an average of 11.2±5.4 months (range 6-24).
Results. A CA-125 value higher than 35 UI/ml was
considered positive, obtaining a sensitivity of 77% and a
specificity of 100%. The sensitivity of the CAT was 23% and the
specificity 91%. With the FDG-PET sensitivity was 92% and the
specificity 90%. A SUV value ≥ 3 was considered pathological,
obtaining the same results as with the visual evaluation. The
FDG-PET was positive in 5 patients with non-conclusive CAT, 4
with negative CAT and 2 with negative CA-125.
Conclusion. These preliminary results suggest that the
FDG-PET could be useful in the follow up of patients treated
for cancer of the ovary. The FDG-PET could be efficient in the
differentiation between residual disease or recurrence, as
opposed to sequels to the treatment, when the CAT is not
conclusive due to anatomical distortion. The FDG-PET could
be more sensitive than an increased marker value, and facing
an increase of the latter it permits a non-invasive localisation
of the disease
Methylation alterations are not a major cause of PTTG1 missregulation
Background: On its physiological cellular context, PTTG1 controls sister chromatid segregation
during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity
for which gained the over name of securin. PTTG1 was found to promote malignant transformation
in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently,
PTTG1 has been also related to different processes such as DNA repair and found to trans-activate
different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has
been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be
excluded that this effect may also occur in other tumor types. Despite the clinical relevance and
the increasing molecular characterization of PTTG1, the reason for its up-regulation remains
unclear.
Method: We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell
lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also
tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential
methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1
immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix
50 K microarray technology and FRET analysis to search for allelic imbalances comprising the
PTTG1 locus.
Conclusion: Our data suggest that neither methylation alterations nor LOH are involved in
PTTG1 over-expression. These data, together with those previously reported, point towards a
post-transcriptional level of missregulation associated to PTTG1 over-expression.This project was funded by The Fundación de Investigación Biomédica Mutua Madrileña Automovilista. Neocodex have been partially funded by the Ministerio de Educación y Ciencia of Spain (FIT-010000-2004-69, PTQ04-1-0006, PTQ2003-0549, PTQ2003-0546 and PTQ2003-0783). MAJ was also supported by SAF2005- 07713-C03-03 and CS by FIS 06/757
Circulating circRNA as biomarkers for dilated cardiomyopathy etiology
Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing - involving genetics, imaging, or cardiovascular techniques - makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed differentially among etiology-based DCM. The study was based on a case-control multicentric study. We enrolled 130 subjects: healthy controls (n = 20), idiopathic DCM (n = 30), ischemic DCM (n = 20), and familial DCM patients which included pathogen variants of (i) LMNA gene (n = 30) and (ii) BCL2-associated athanogene 3 (BAG3) gene (n = 30). Differentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and correlated to relevant systolic and diastolic parameters. The pathophysiological implications were explored through bioinformatics tools. Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confirm the discriminative capacity of circRNAs. The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker. Key messages The limitations of cardiac diagnostic imaging and the absence of a robust biomarker reveal the need for a diagnostic tool for dilated cardiomyopathy (DCM). The circular RNA (circRNA) expression pattern is paramount for categorizing the DCM etiologies. Our peripheral circRNAs fingerprint discriminates between various among etiology-based DCM and correlates with some echocardiographic parameters. We provide a potential non-invasive biomarker for the etiology-based diagnosis of LMNA-related DCM and ischemic DCM.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants in the framework of the European Regional Development Fund (ERDF) Integrated Territorial Initiative (ITI PI0048-2017 and ITI0033_2019), a clinical research grant from the Spanish Society of Cardiology for Basic Research in cardiology (PI0012_2019), COST (European Cooperation in Science and Technology) Action EUCardioRNA CA17129, and the Portuguese Foundation for Science and Technology (FCT) under the framework of the research grant PTDC-MED-GEN-29389-2017
Conducting Anilate-Based Mixed-Valence Fe(II)Fe(III) Coordination Polymer: Small-polaron Hopping Model for Oxalate-Type Fe(II)Fe(III) 2D Networks
The mixed-valence FeIIFeIII 2D coordination polymer formulated as [TAG][FeIIFeIII(ClCNAn)3]·(solvate) 1 (TAG = tris(amino)-guanidinium, ClCNAn2− = chlorocyanoanilate dianionic ligand) crystallized in the polar trigonal space group P3. In the solid-state structure, determined both at 150 and at 10 K, anionic 2D honeycomb layers [FeIIFeIII(ClCNAn)3]− establish in the ab plane, with an intralayer metal−metal distance of 7.860 Å, alternating with cationic layers of TAG. The similar Fe−O distances suggest electron delocalization and an average oxidation state of +2.5 for each Fe center. The cation imposes its C3 symmetry to the structure and engages in intermolecular N−H···Cl hydrogen bonding with the ligand. Magnetic susceptibility characterization indicates magnetic ordering below 4 K and the presence of a hysteresis loop at 2 K with a coercive field of 60 Oe. Mössbauer measurements are in agreement with the existence of Fe(+2.5) ions at RT and statistic charge localization at 10 K. The compound shows semiconducting behavior with the in-plane conductivity of 2 × 10−3 S/cm, 3 orders of magnitude higher than the perpendicular one. A small-polaron hopping model has been applied to a series of oxalate-type FeIIFeIII 2D coordination polymers, providing a clear explanation on the much higher conductivity of the anilate-based systems than the oxalate ones
Patterns of adherence to and compliance with the Portuguese smoke-free law in the leisure-hospitality sector
CIEC – Research Centre on Child Studies, UM (FCT R&D 317)Background: In 2008, the Portuguese smoke-free law came into effect including partial bans in the leisure-hospitality (LH)
sector. The objective of the study is to assess the prevalence of smoking control policies (total ban, smoking permission and
designated smoking areas) adopted by the LH sector in Portugal. The levels of noncompliance with each policy are
investigated as well as the main factors associated with smoking permission and noncompliance with the law.
Methods: Cross-sectional study conducted between January 2010 and May 2011. A random sample of venues was selected
from the Portuguese LH sector database, proportionally stratified according to type, size and geographical area. All venues
were assessed in loco by an observer. The independent effects of venues’ characteristics on smoking permission and the
level of noncompliance with the law were explored using logistic regression.
Results: Overall, 1.412 venues were included. Total ban policy was adopted by 75.9% of venues, while 8.4% had designated
smoking areas. Smoking ban was more prevalent in restaurants (85.9%). Only 29.7% of discos/bars/pubs opted for complete
ban. Full or partial smoking permission was higher in discos/bar/pubs (OR = 7.37; 95%CI 4.87 to 11.17). Noncompliance with
the law was higher in venues allowing smoking and lower in places with complete ban (33.6% and 7.6% respectively, p,
0.001). Discos/bars/pubs with full smoking permission had the highest level of noncompliance (OR = 3.31; 95%CI 1.40 to
7.83).
Conclusions: Our findings show a high adherence to smoking ban policy by the Portuguese LH sector. Nonetheless, one
quarter of the venues is fully or partially permissive towards smoking, with the discos/bars/pubs considerably contributing
to this situation. Venues with smoking permission policies were less compliant with the legislation. The implementation of a
comprehensive smoke-free law, without any exceptions, is essential to effectively protect people from the second hand
smoke.The work is part of a large Epidemiological Study on the Portuguese Tobacco Control Policy, developed by the Instituto de Medicina Preventiva da Faculdade de Medicina de Lisboa and supported, in its preliminary part, by the Direccao Geral da Saude (DGS) and, in the second part, by the national funding institution Fundacao para a Ciencia e Tecnologia (FCT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Genetic Structure of the Spanish Population
<p>Abstract</p> <p>Background</p> <p>Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias.</p> <p>Results</p> <p>In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts.</p> <p>Conclusions</p> <p>In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.</p
Neurofilament light chain level is a weak risk factor for the development of MS
Altres ajuts: T Jens Kuhle was supported by an ECTRIMS Research Fellowship Programme and by the Forschungsfonds of the University of Basel, Switzerland.To determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual. Data were acquired from 2 CIS cohorts. The screening phase evaluated patients developing clinically definite MS (CIS-CDMS) and patients who remained as CIS during a 2-year minimum follow-up (CIS-CIS). We determined levels of neurofascin, semaphorin 3A, fetuin A, glial fibrillary acidic protein, and neurofilament light (NfL) and heavy chains in CSF (estimated mean [95% confidence interval; CI]). We evaluated associations between biomarker levels, conversion, disability, and magnetic resonance parameters. In the replication phase, we determined NfL levels (n = 155) using a 900 ng/L cutoff. Primary endpoints in uni- and multivariate analyses were CDMS and 2010 McDonald MS. The only biomarker showing significant differences in the screening was NfL (CIS-CDMS 1,553.1 [1,208.7-1,897.5] ng/L and CIS-CIS 499.0 [168.8-829.2] ng/L, p < 0.0001). The strongest associations were with brain parenchymal fraction change (r = −0.892) and percentage brain volume change (r = −0.842) at 5 years. NfL did not correlate with disability. In the replication phase, more NfL-positive patients, according to the cutoff, evolved to MS. Every 100-ng/L increase in NfL predicted CDMS (hazard ratio [HR] = 1.009, 95% CI 1.005-1.014) and McDonald MS (HR = 1.009, 95% CI 1.005-1.013), remaining significant for CDMS in the multivariate analysis (adjusted HR = 1.005, 95% CI 1.000-1.011). This risk was lower than the presence of oligoclonal bands or T2 lesions. NfL is a weak independent risk factor for MS. Its role as an axonal damage biomarker may be more relevant as suggested by its association with medium-term brain volume changes
Collagen XIX Alpha 1 improves prognosis in amyotrophic lateral sclerosis
The identification of more reliable diagnostic or prognostic biomarkers in age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), is urgently needed. The objective in this study was to identify more reliable prognostic biomarkers of ALS mirroring neurodegeneration that could be of help in clinical trials. A total of 268 participants from three cohorts were included in this study. The muscle and blood cohorts were analyzed in two cross-sectional studies, while the serial blood cohort was analyzed in a longitudinal study at 6-monthly intervals. Fifteen target genes and fourteen proteins involved in muscle physiology and differentiation, metabolic processes and neuromuscular junction dismantlement were studied in the three cohorts. In the muscle biopsy cohort, the risk for a higher mortality in an ALS patient that showed high Collagen type XIX, alpha 1 (COL19A1) protein levels and a fast progression of the disease was 70.5% (P < 0.05), while in the blood cohort, this risk was 20% (P < 0.01). In the serial blood cohort, the linear mixed model analysis showed a significant association between increasing COL19A1 gene levels along disease progression and a faster progression during the follow-up period of 24 months (P < 0.05). Additionally, higher COL19A1 levels and a faster progression increased 17.9% the mortality risk (P < 0.01). We provide new evidence that COL19A1 can be considered a prognostic biomarker that could help the selection of homogeneous groups of patients for upcoming clinical trial and may be pointed out as a promising therapeutic target in ALS
Therapeutic implications of selecting the SCORE (European) versus the D'AGOSTINO (American) risk charts for cardiovascular risk assessment in hypertensive patients
Background: No comparisons have been made of scales estimating cardiovascular mortality and overall cardiovascular morbidity and mortality. The study objectives were to assess the agreement between the Framingham-D'Agostino cardiovascular risk (CVR) scale and the chart currently recommended in Europe (SCORE) with regard to identification of patients with high CVR, and to describe the discrepancies between them and the attendant implications for the treatment of hypertension and hyperlipidaemia. Methods: A total of 474 hypertensive patients aged 40-65 years monitored in primary care were enrolled into the study. CVR was assessed using the Framingham-D'Agostino scale, which estimates the overall cardiovascular morbidity and mortality risk, and the SCORE chart, which estimates the cardiovascular mortality risk. Cardiovascular risk was considered to be high for values ≥ 20% and ≥ 5% according to the Framingham-D'Agostino and SCORE charts respectively. Kappa statistics was estimated for agreement in classification of patients with high CVR. The therapeutic recommendations in the 2007 European Guidelines on Cardiovascular Disease Prevention were followed. Results
HisAK70: Progress towards a vaccine against different forms of leishmaniosis
Background: Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods: Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results: HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions: The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-17394 and AGL2013-44100R) and PLATESA (P2013/ABI-2906) from the Comunidad de Madrid (Spain).Peer Reviewe
- …