The multifunctional role of phospho-calmodulin in pathophysiological processes

Calmodulin (CaM) is a versatile Ca 2+ -sensor/transducer protein that modulates hundreds of enzymes, channels, transport systems, transcription factors, adaptors and other structural proteins, controlling in this manner multiple cellular functions. In addition to its capacity to regulate target proteins in a Ca 2+ -dependent and Ca 2+ -independent manner, the posttranslational phosphorylation of CaM by diverse Ser/Thr- and Tyr-protein kinases has been recognized as an important additional manner to regulate this protein by fine-tuning its functionality. In this review, we shall cover developments done in recent years in which phospho-CaM has been implicated in signalling pathways that are relevant for the onset and progression of diverse pathophysiological processes. These include diverse systems playing a major role in carcinogenesis and tumour development, prion-induced encephalopathies and brain hypoxia, melatonin-regulated neuroendocrine disorders, hypertension, and heavy metal-induced cell toxicity.Original work in the author laboratory was funded by the Secretaría de Estado de Investigación, Desarrollo e Innovación [SAF2014-52048-R], and the Consejería de Educación, Juventud y Deportes – Comunidad de Madrid [B2017/BMD-36]

Detection of the largest population susceptible to prescription of a program of exercises in Primary Care to prevent frailty

Aim: Identify the population over 70 year's old treated in primary care who should participate in a physical exercise program to prevent frailty. Analyze the concordance among 2 criteria to select the beneficiary population of the program. Design: Population-based cross-sectional study. Settings: Primary Care. Participants: Elderly over 70 years old, living in the Peñagrande neighborhood (Fuencarral district of Madrid) from the Peñagrande cohort, who accepted to participate in 2015 (n = 332). Main measurements: The main variable of the study is the need for exercise prescription in people over 70 years old at the Primary Care setting. It was identified through 2 different definitions: Prefrail (1-2 of 5 Fried criteria) and Independent individuals with physical performance limited, defined by Consensus on frailty and falls prevention among the elderly (independent and with a total SPPB score &lt;10). Results: The 63,8% of participants (n = 196) need exercise prescription based on criteria defined by Fried and/or the consensus for prevention of frailty and falls in the elderly. In 82 cases the 2 criteria were met, 80 were prefrail with normal physical performance and 34 were robust with a limited physical performance. The concordance among both criteria is weak (kappa index 0, 27). Conclusion: Almost 2 thirds of the elderly have some kind of functional limitation. The criteria of the consensus document to prevent frailty detect half of the pre-frail individuals in the community.Objetivo: Identificar a la población mayor de 70 años atendida en Atención Primaria, susceptible de participar en un programa de ejercicio físico para prevenir fragilidad. Analizar la concordancia entre 2 criterios para seleccionar la población beneficiaria del programa. Diseño: Estudio transversal de base poblacional. Emplazamiento: Atención Primaria. Participantes: Mayores de 70 años no frágiles residentes del Barrio Peñagrande (distrito Fuencarral, Madrid) pertenecientes a la cohorte de Peñagrande localizables en 2015 y que aceptaron participar (n = 307). Mediciones principales: La variable principal del estudio es la necesidad de prescripción de ejercicio en Atención Primaria en personas mayores de 70 a˜nos; se identificó a través de 2 definiciones diferentes: personas prefrágiles (1 o 2 de los 5 criterios de Fried) y personas independientes con desempeño físico limitado, definida por los criterios del documento de consenso sobre prevención de fragilidad y caídas en la persona mayor (mayor de 70 años independiente y con puntuación total del SPPB < 10). Resultados: El 63,84% de los participantes (n = 196) necesitan prescripción del ejercicio por ser prefrágiles y/o por cumplir los criterios definidos en el documento de consenso. En 82 casos cumplían los 2 criterios (prefragilidad y desempeño físico disminuido), 80 eran prefrágiles con desempeño físico normal y 34 eran robustos con desempeño físico limitado. La concordancia entre ambos criterios es débil (índice kappa 0,27).Conclusión: Casi 2 tercios de los mayores presentan algún tipo de limitación funcional. Los criterios del documento de consenso para prevenir la fragilidad detectan a la mitad de los individuos prefrágiles de la comunidad.Este proyecto está parcialmente financiado con una subvención del Ministerio de Salud, Instituto de Salud Carlos III (FIS:PI 09/2143) y RETICEF (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, RD 06/0013/1013)

Association between proximity to industrial chemical installations and cancer mortality in Spain

It is likely that pollution from chemical facilities will affect the health of any exposed population; however, the majority of scientific evidence available has focused on occupational exposure rather than environmental. Consequently, this study assessed whether there could have been an excess of cancerrelated mortality associated with environmental exposure to pollution from chemical installations e for populations residing in municipalities in the vicinity of chemical industries. To this end, we designed an ecological study which assessed municipal mortality due to 32 types of cancer in the period from 1999 to 2008. The exposure to pollution was estimated using distance from the facilities to the centroid of the municipality as a proxy for exposure. In order to assess any increased cancer mortality risk in municipalities potentially exposed to chemical facilities pollution (situated at a distance of 5 km from a chemical installation), we employed Bayesian Hierarchical Poisson Regression Models. This included two Bayesian inference methods: Integrated Nested Laplace Approximations (INLA) and Markov Chain Monte Carlo (MCMC, for validation). The reference category consisted of municipalities beyond the 5 km limit. We found higher mortality risk (relative risk, RR; estimated by INLA, 95% credible interval, 95%CrI) for both sexes for colorectal (RR, 1.09; 95%CrI, 1.05e1.15), gallbladder (1.14; 1.03e1.27), and ovarian cancers (1.10; 1.02e1.20) associated with organic chemical installations. Notably, pleural cancer (2.27; 1.49e3.41) in both sexes was related to fertilizer facilities. Associations were found for women, specifically for ovarian (1.11; 1.01e1.22) and breast cancers (1.06; 1.00e1.13) in the proximity of explosives/pyrotechnics installations; increased breast cancer mortality risk (1.10; 1.03e1.18) was associated with proximity to inorganic chemical installations. The results suggest that environmental exposure to pollutants from some types of chemical facilities may be associated with increased mortality from several different types of cancerThe study was partially supported by research grants from the Spanish Health Research Fund, Carlos III Institute of Health (ISCIII), Spain (FIS CP11/00112, FIS PI14CIII/00065, FIS PI17CIII/00040) and by Scientific Foundation of the Spanish Association Against Cancer (AECC), Spain (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) e EVP-1178/14