Factor V Leiden and Inflammation

Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation

Relacion entre el indice de variabilidad lexica y la edad en ninos con desarrollo tipico del lenguaje

54 p.El propósito del presente trabajo fue conocer la relación existente entre el Índice de Variabilidad Léxica (IVL) y la edad de niños de la ciudad de Talca con desarrollo típico del lenguaje, específicamente en niños de 6 años a 6 años 11 meses de edad. La hipótesis planteada es “el Índice de Variabilidad Léxica (IVL) en niños con desarrollo típico del lenguaje de 6 años a 8 años 11 meses de edad pertenecientes a la ciudad de Talca en la Región del Maule, se correlaciona directa y positivamente con la edad”. Así, se seleccionó una muestra aleatoria y representativa de niños pertenecientes a establecimientos educacionales particular subvencionados de la ciudad de Talca, en la Región del Maule. Los resultados indican que no existe una relación estrecha entre el índice de variabilidad léxica y la edad de estos niños, es decir, a medida que aumenta la edad no aumenta la habilidad para producir palabras nuevas, e incrementar así la totalidad de palabras que conforman sus enunciados. Finalmente se discuten las proyecciones clínicas de la presente investigación

Probability-Based Dynamic Time Warping for Gesture Recognition on RGB-D Data

Dynamic Time Warping (DTW) is commonly used in gesture recognition tasks in order to tackle the temporal length variability of gestures. In the DTW framework, a set of gesture patterns are compared one by one to a maybe infinite test sequence, and a query gesture category is recognized if a warping cost below a certain threshold is found within the test sequence. Nevertheless, either taking one single sample per gesture category or a set of isolated samples may not encode the variability of such gesture category. In this paper, a probability-based DTW for gesture recognition is proposed. Different samples of the same gesture pattern obtained from RGB-Depth data are used to build a Gaussian-based probabilistic model of the gesture. Finally, the cost of DTW has been adapted accordingly to the new model. The proposed approach is tested in a challenging scenario, showing better performance of the probability-based DTW in comparison to state-of-the-art approaches for gesture recognition on RGB-D data

Influence of ABO locus on PFA-100 collagen-ADP closure time is not totally dependent on the von willebrand factor. Results of a GWAS on gait-2 project phenotypes

(1) Background: In a previous study, we found that two phenotypes related to platelet reactivity, measured with the PFA-100 system, were highly heritable. The aim of the present study was to identify genetic determinants that influence the variability of these phenotypes: Closure time of collagen-ADP (Col-ADP) and of collagen-epinephrine (Col-Epi). (2) Methods: As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia (2) Project, 935 individuals from 35 large Spanish families were studied. A genome-wide association study (GWAS) with ≈ 10 M single nucleotide polymorphisms (SNPs) was carried out with Col-ADP and Col-Epi phenotypes. (3) Results: The study yielded significant genetic signals that mapped to the ABO locus. After adjusting both phenotypes for the ABO genotype, these signals disappeared. After adjusting for von Willebrand factor (VWF) or for coagulation factor VIII (FVIII), the significant signals disappeared totally for Col-Epi phenotype but only partially for Col-ADP phenotype. (4) Conclusion: Our results suggest that the ABO locus exerts the main genetic influence on PFA-100 phenotypes. However, while the effect of the ABO locus on Col-Epi phenotype is mediated through VWF and/or FVIII, the effect of the ABO locus on Col-ADP phenotype is partly produced through VWF and/or FVIII, and partly through other mechanisms

Impacto de la gestión inmobiliaria en la articulación de la oferta comercial de los ejes comerciales prime en ciudades turísticas europeas: el caso de Barcelona

El artículo parte del hecho de que en las principales calles comerciales de las ciudades turísticas europeas se implantan establecimientos comerciales con una oferta comercial de lujo, de lujo asequible y de “mass market”. Posteriormente se define y justifica el concepto “Ejes Comerciales Prime” como aquellas calles comerciales con los precios de alquiler de los locales comerciales más elevados de la ciudad y por tener máxima demanda turística y tráfico peatonal. En el caso de Barcelona, las calles que cumplen los criterios anteriores son Passeig de Gràcia y Av. Portal de l’Àngel. Asimismo, en la investigación se constata que el precio de alquiler de los locales comerciales impacta en la cuenta de explotación de los establecimientos comerciales a través de la tasa de esfuerzo, y además impacta también en la rentabilidad de los inversores de locales comerciales en dichos ejes comerciales Prime. Por primera vez en la literatura científica, se analiza el impacto del mercado inmobiliario de locales comerciales en la articulación de la oferta comercial de los ejes comerciales Prime denode las principales ciudades turísticas europeas, provocando una concentración sectorial, empresarial y de la propiedad. El análisis se centra en la ciudad de Barcelona.Postprint (published version

Burden of multimorbidity, socioeconomic status and use of health services across stages of life in urban areas: a cross-sectional study

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Background The burden of chronic conditions and multimorbidity is a growing health problem in developed countries. The study aimed to determine the estimated prevalence and patterns of multimorbidity in urban areas of Catalonia, stratified by sex and adult age groups, and to assess whether socioeconomic status and use of primary health care services were associated with multimorbidity. Methods A cross-sectional study was conducted in Catalonia. Participants were adults (19+ years) living in urban areas, assigned to 251 primary care teams. Main outcome: multimorbidity (≥2 chronic conditions). Other variables: sex (male/female), age (19–24; 25–44; 45–64; 65–79; 80+ years), socioeconomic status (quintiles), number of health care visits during the study. Results We included 1,356,761 patients; mean age, 47.4 years (SD: 17.8), 51.0% women. Multimorbidity was present in 47.6% (95% CI 47.5-47.7) of the sample, increasing with age in both sexes but significantly higher in women (53.3%) than in men (41.7%). Prevalence of multimorbidity in each quintile of the deprivation index was higher in women than in men (except oldest group). In women, multimorbidity prevalence increased with quintile of the deprivation index. Overall, the median (interquartile range) number of primary care visits was 8 (4–14) in multimorbidity vs 1 (0–4) in non-multimorbidity patients. The most prevalent multimorbidity pattern beyond 45 years of age was uncomplicated hypertension and lipid disorder. Compared with the least deprived group, women in other quintiles of the deprivation index were more likely to have multimorbidity than men until 65 years of age. The odds of multimorbidity increased with number of visits in all strata. Conclusions When all chronic conditions were included in the analysis, almost 50% of the adult urban population had multimorbidity. The prevalence of multimorbidity differed by sex, age group and socioeconomic status. Multimorbidity patterns varied by life-stage and sex; however, circulatory-endocrine-metabolic patterns were the most prevalent multimorbidity pattern after 45 years of age. Women younger than 80 years had greater prevalence of multimorbidity than men, and women’s multimorbidity prevalence increased as socioeconomic status declined in all age groups. Identifying multimorbidity patterns associated with specific age-related life-stages allows health systems to prioritize and to adapt clinical management efforts by age group.Ministry of Science and Innovation through the Instituto Carlos III (ISCiii)ISCiii-RETICSISCiiiInstitut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol

Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

BACKGROUND: Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. METHODS: To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. RESULTS: In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. CONCLUSIONS: MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment

Facial emotion processing in patients with social anxiety disorder and Williams-Beuren syndrome: an fMRI study

Background: social anxiety disorder (SAD) and Williams-Beuren syndrome (WBS) are 2 conditions with major differences in terms of genetics, development and cognitive profiles. Both conditions are associated with compromised abilities in overlapping areas, including social approach, processing of social emotional cues and gaze behaviour, and to some extent they are associated with opposite behaviours in these domains. We examined common and distinct patterns of brain activation during a facial emotion processing paradigm in patients with SAD and WBS. Methods: we examined patients with SAD and WBS and healthy controls matched by age and laterality using functional MRI during the processing of happy, fearful and angry faces. Results: we included 20 patients with SAD and 20 with WBS as well as 20 matched controls in our study. Patients with SAD and WBS did not differ in the pattern of limbic activation. We observed differences in early visual areas of the face processing network in patients with WBS and differences in the cortical prefrontal regions involved in the top-down regulation of anxiety and in the fusiform gyrus for patients with SAD. Compared with those in the SAD and control groups, participants in the WBS group did not activate the right lateral inferior occipital cortex. In addition, compared with controls, patients with WBS hypoactivated the posterior primary visual cortex and showed significantly less deactivation in the right temporal operculum. Participants in the SAD group showed decreased prefrontal activation compared with those in the WBS and control groups. In addition, compared with controls, participants with SAD showed decreased fusiform activation. Participants with SAD and WBS also differed in the pattern of activation in the superior temporal gyrus, a region that has been linked to gaze processing. Limitations: the results observed in the WBS group are limited by the IQ of the WBS sample; however, the specificity of findings suggests that the pattern of brain activation observed for WBS is more likely to reflect a neurobiological substrate rather than intellectual impairment per se. Conclusion: patients with SAD and WBS showed common and specific patterns of brain activation. Our results highlight the role of cortical regions during facial emotion processing in individuals with SAD and WBS

Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program.

Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bonematrix. This encasement limits their access to nutrients and likely affects their differentiation, a pro-cess that remains poorly defined. Here, we show that restriction in glucose supply promotes the oste-ocyte transcriptional program while also being associated with increased mitochondrial DNA levels.Glucose deprivation triggered the activation of the AMPK/PGC-1 pathway. AMPK and SIRT1 activa-tors or PGC-1aoverexpression are sufficient to enhance osteocyte gene expression in IDG-SW3 cells,murine primary osteoblasts, osteocytes, and organotypic/ex vivobone cultures. Conversely, osteo-blasts and osteocytes deficient inPpargc1aandbwere refractory to the effects of glucose restriction.Finally, conditional ablation of both genes in osteoblasts and osteocytes generate osteopenia andreduce osteocytic gene expression in mice. Altogether, we uncovered a role for PGC-1 in the regula-tion of osteocyte gene expression

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaig