Dinámica de la inflación y sus componentes en Argentina: una historia a dos velocidades: 1995-2001 vs 2005-2019

Fil: Zarzosa Valdivia, Fernando. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Moreno Halberstadt, Kassandra. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Este trabajo analiza, para Argentina, la dinámica de inflación y sus componentes en dos períodos 1995M01- 2001M12 y 2005M10 – 2019M04. La suma de los coeficientes autorregresivos sugiere que la inercia, en general, ha aumentado pasando de ser nula a 0.864 en el caso de la inflación general. Además, encontramos evidencia de persistencia o ‘long-memory’ en los rubros transporte y comunicaciones, vivienda y servicios básicos, en equipamiento y mantenimiento del hogar y en bienes y servicios varios. Con respecto a la duración de los efectos de un shock que golpea a los precios encontramos que el promedio de períodos en que desaparece el efecto (o el 50% del mismo) pasa de 48 (9) meses en la primera etapa a 86 (16) meses en la segunda.Fil: Zarzosa Valdivia, Fernando. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Moreno Halberstadt, Kassandra. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Economía, Econometrí

Dickkopf Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role

Dickkopf; Wnt antagonists; Wnt signalingDickkopf; Antagonistes Wnt; Senyalització WntDickkopf; Antagonistas Wnt; Señalización WntThe Wnt signaling pathway regulates crucial aspects such as cell fate determination, cell polarity and organogenesis during embryonic development. Wnt pathway deregulation is a hallmark of several cancers such as lung, gastric and liver cancer, and has been reported to be altered in others. Despite the general agreement reached by the scientific community on the oncogenic potential of the central components of the pathway, the role of the antagonist proteins remains less clear. Deregulation of the pathway may be caused by overexpression or downregulation of a wide range of antagonist proteins. Although there is growing information related to function and regulation of Dickkopf (DKK) proteins, their pharmacological potential as cancer therapeutics still has not been fully developed. This review provides an update on the role of DKK proteins in cancer and possible potential as therapeutic targets for the treatment of cancer; available compounds in pre-clinical or clinical trials are also reviewed.This work was supported by grants from Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and PI21/00640); La Marató de TV3 (201937); Fundació A.BOSCH; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Eric Abidal Foundation and Mi compañero de viaje

Analysis of Cancer Genomic Amplifications Identifies Druggable Collateral Dependencies within the Amplicon

Cancer; Drug development; Gene amplificationsCáncer; Desarrollo de fármacos; Amplificaciones de genesCàncer; Desenvolupament de medicaments; Amplificacions de gensThe identification of novel therapeutic targets for specific cancer molecular subtypes is crucial for the development of precision oncology. In the last few years, CRISPR/Cas9 screens have accelerated the discovery and validation of new targets associated with different tumor types, mutations, and fusions. However, there are still many cancer vulnerabilities associated with specific molecular features that remain to be explored. Here, we used data from CRISPR/Cas9 screens in 954 cancer cell lines to identify gene dependencies associated with 16 common cancer genomic amplifications. We found that high-copy-number genomic amplifications generate multiple collateral dependencies within the amplified region in most cases. Further, to prioritize candidate targets for each chromosomal region amplified, we integrated gene dependency parameters with both druggability data and subcellular location. Finally, analysis of the relationship between gene expression and gene dependency led to the identification of genes, the expression of which may constitute predictive biomarkers of dependency. In conclusion, our study provides a set of druggable targets specific for each amplification, opening the possibility to specifically target amplified tumors on this basis.This research was funded by grants from Institut Català d’Oncologia (ICO), Instituto de Salud Carlos III (PI21/00640), AGAUR (2021 FI_B 00088), Fundació BOSCH, Iniciativa Tot per tu, Fundació Amics Joan Petit, and Mi compañero de viaje

Targeting the Hedgehog Pathway in Rhabdomyosarcoma

Embryonic pathways; Paediatric cancer; Soft tissue sarcomasVies embrionàries; Càncer pediàtric; Sarcomes de teixits tousVías embrionarias; Cáncer pediátrico; Sarcomas de tejidos blandosAberrant activation of the Hedgehog (Hh) signalling pathway is known to play an oncogenic role in a wide range of cancers; in the particular case of rhabdomyosarcoma, this pathway has been demonstrated to be an important player for both oncogenesis and cancer progression. In this review, after a brief description of the pathway and the characteristics of its molecular components, we describe, in detail, the main activation mechanisms that have been found in cancer, including ligand-dependent, ligand-independent and non-canonical activation. In this context, the most studied inhibitors, i.e., SMO inhibitors, have shown encouraging results for the treatment of basal cell carcinoma and medulloblastoma, both tumour types often associated with mutations that lead to the activation of the pathway. Conversely, SMO inhibitors have not fulfilled expectations in tumours—among them sarcomas—mostly associated with ligand-dependent Hh pathway activation. Despite the controversy existing regarding the results obtained with SMO inhibitors in these types of tumours, several compounds have been (or are currently being) evaluated in sarcoma patients. Finally, we discuss some of the reasons that could explain why, in some cases, encouraging preclinical data turned into disappointing results in the clinical setting.This article was funded by grants from: Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and FI18/00178); ACCIÓ (COMRDI15-1-0014); Fundació la Marató de TV3; Fundació Albert Bosch; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Fundation Amics Joan Petit; Del Hospital a la cathedral Initiative by Xavi Vallès; and Mi compañero de viaje Association

TRIB3 silencing promotes the downregulation of Akt pathway and PAX3-FOXO1 in high-risk rhabdomyosarcoma

Fusion protein; RhabdomyosarcomaProteïna de fusió; RabdomiosarcomaProteína de fusión; RabdomiosarcomaRhabdomyosarcoma (RMS), such as other childhood tumors, has witnessed treatment advancements in recent years. However, high-risk patients continue to face poor survival rates, often attributed to the presence of the PAX3/7-FOXO1 fusion proteins, which has been associated with metastasis and treatment resistance. Despite efforts to directly target these chimeric proteins, clinical success remains elusive. In this study, the main aim was to address this challenge by investigating regulators of FOXO1. Specifically, we focused on TRIB3, a potential regulator of the fusion protein in RMS. Our findings revealed a prominent TRIB3 expression in RMS tumors, highlighting its correlation with the presence of fusion protein. By conducting TRIB3 genetic inhibition experiments, we observed an impairment on cell proliferation. Notably, the knockdown of TRIB3 led to a decrease in PAX3-FOXO1 and its target genes at protein level, accompanied by a reduction in the activity of the Akt signaling pathway. Additionally, inducible silencing of TRIB3 significantly delayed tumor growth and improved overall survival in vivo. Based on our analysis, we propose that TRIB3 holds therapeutic potential for treating the most aggressive subtype of RMS. The findings herein reported contribute to our understanding of the underlying molecular mechanisms driving RMS progression and provide novel insights into the potential use of TRIB3 as a therapeutic intervention for high-risk RMS patients.This research was funded by grants from Institut Català d’Oncologia (ICO), Instituto de Salud Carlos III (PI21/00640), Fundació la Marató de TV3, Fundació BOSCH, Iniciativa Tot per tu, Fundació Amics Joan Petit, Fundación Inocente, and Mi compañero de viaje

Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma

Dissemination; Paediatric cancer; Solid tumoursDiseminación; Cáncer pediátrico; Tumores sólidosDisseminació; Càncer pediàtric; Tumors sòlidsThe majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.This research was supported by grants from: Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and FI18/00178); ACCIÓ (COMRDI15-1-0014); Fundació la Marató de TV3; Fundació A. BOSCH; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Eric Abidal Foundation; Del Hospital a la catedral Initiative by Xavi Vallès; and Mi compañero de viaje Association

Statement of the Spanish Interdisciplinary Cardiovascular Prevention Committee (CEIPC ) on the 2012 European Cardiovascular Prevention Guidelines

Las guías europeas de prevención cardiovascular contemplan dos sistemas de evaluación de la evidencia (SEC y GRADE) y recomiendan combinar las estrategias poblacional y de alto riesgo, interviniendo en todas las etapas de la vida, con la dieta como piedra angular de la prevención. La valoración del RCV incorpora los niveles de HDL y los factores psicosociales, una categoría de muy alto riesgo y el concepto edad-riesgo. Se recomienda e luso de métodos cognitivo-conductuales (entrevistamotivadora, intervenciones psicológicas), aplicados por profesionales sanitarios, con la participación de familiares de los pacientes, para contrarrestar el estrés psicosocial y reducir el RCV mediante dietas saludables, entrenamiento físico, abandono del tabaco y cumplimiento terapéutico. También se requieren medidas de salud pública, como la prohibición de fumar en lugares públicos o eliminar los ácidos grasos trans de la cadena alimentaria. Otras novedades consisten en desestimar el tratamiento antiagregante en prevención primaria y la recomendación de mantener la PA dentro del rango13-139/80-85 mmHg en pacientes diabéticos o con RCV alto. Se destaca el bajo cumplimiento terapéutico observado, porque influye en el pronóstico de los pacientes y en los costes sanitarios. Para mejorar la prevención cardiovascular se precisa una verdadera alianza entre políticos, administraciones, asociaciones científicas y profesionales de la salud, fundaciones de salud, asociaciones de consumidores, pacientes y sus familias, que impulse las estrategias poblacional e individual, mediante el uso de toda la evidencia científica disponible, desde ensayos clínicos hasta estudios observacionales y modelo matemáticos para evaluar intervenciones a nivel poblacional, incluyendo análisis de coste-efectividadBased on the two main frameworks for evaluating scientific evidence—SEC and GRADE—European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL level and psycho-social factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g.,motivational interviewing, psychological interventions, led by health professionals and with the participation of the patient’s family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions—such as smoking ban in public areas or the elimination of trans fatty acids from the food chain—are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure (BP) within the1 30-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally ,due to the significant impact on patient progress and medical costs, special emphasisis given to the low therapeutic adherence levels observed . In sum ,improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage o the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyse

Handbook of Active Ageing and Quality of Life: From Concepts to Applications

La edición de este libro estuvo a cargo de Fermina Rojo-Pérez y Gloria Fernández-Mayoralas.El documento adjunto contiene la cubierta, portada e índice del libro.This handbook presents an overview of studies on the relationship of active ageing and quality of life. It addresses the new challenges of ageing from the paradigm of positive ageing (active, healthy and successful) for a better quality of life. It provides theoretical perspectives and empirical studies, including scientific knowledge as well as practical experiences about the good ageing and the quality of later life around the world, in order to respond to the challenges of an aged population. The handbook is structured in 4 sections covering theoretical and conceptual perspectives, social policy issues and research agenda, methods, measurement instrument-scales and evaluations, and lastly application studies including domains and geographical contexts.Peer reviewe

The histochemical profiles of fibre types in porcine skeletal muscle

Using a variety of histochemical methods -mATPase staining after alkaline and acid preincubations, NADH-TR and a-MGPDH- we have investigated the fibre types in porcine skeletal muscle. The results reveal that four major fibre types -1, IIA, IIB and II*- can be separated histochemically in Longissimus lumborum muscle of Landrace pigs. The histochemical properties of the muscle fibre type 11* are very similar to that of type IIX described in other mammals. The existence of IIX fibres in pig muscle has been recently demonstrated by molecular biology techniques and our results validate the use of histochemistry (mATPase) as an easy methodology to differentiate the three fast myosins (type 11 fibres) in pig muscle

ESTUDIO HISTOQUÍMICO DE LA MUSCULATURA LATERAL DE LA CARPA (CYPRINUS CARPIO) (1989)

By means of the histoenzymologicaltechniques the hislochemical and morphological characteristics of the lateral muscle of carp (Cyprinus carpio) were analysed; il has been identified different fiber types. We have observed the presence of the superficial red muscle formed by fiber of high and low mATPase activity, a deep white mucle shaped al the mosaic pattern and a pink muscle where the histochemical and morphological characteristics of the fiber types are so variables.Mediante técnicas histoenzimáticas se analizan las características histoquímicas y morfológicas de la musculatura laleral de la carpa (Cyprinus carpio) identificándose los distintos tipos de libras. Se ha constatado la existencia de un músculo rojo superficial integrado por fibras de alta y baja actividad mATPasa, un músculo blanco profundo con fibras en modelo de mosaico y un músculo rosa donde las características histoquímicas y morfológicas de los tipos de fibras que lo integran son muy variables