Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7-/- mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7-/- mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late-onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. Conclusions Our data suggest that loss of integrin α7 causes a novel form of adult-onset cardiac dysfunction indicating a critical role for the integrin α7β1 in normal cardiac function and highlights the need for long-term cardiac monitoring in patients with ITGA7-related congenital myopathy

Exploring Mexican adolescents' perceptions of environmental health risks: a photographic approach to risk analysis

The objective of this study was to explore Mexican adolescents' perceptions of environmental health risks in contaminated urban areas, and to test the environmental photography technique as a research tool for engaging adolescents in community-based health research. The study was conducted with 74 adolescents from two communities in the city of San Luis Potosi, Mexico. Participants were provided with disposable cameras and asked to take photographs of elements and situations which they believed affected their personal health both at home and outside their homes. They were also asked to describe each photograph in writing. Photographs and written explanations were analyzed by using quantitative and qualitative content analysis. Risk perception plays a crucial role in the development of Risk Communication Programs (RCPs) aimed at the improvement of community health. The photography technique opens up a promising field for environmental health research since it affords a realistic and concise impression of the perceived risks. Adolescents in both communities perceived different environmental health risks as detrimental to their well-being, e.g. waste, air pollution, and lack of hygiene. Yet, some knowledge gaps remain which need to be addressed

Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity

10.1186/s13395-020-00227-4Skeletal Muscle101

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice

BACKGROUND: Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. METHODS AND RESULTS: In this study, we described skeletal and cardiac muscle pathology in Itga7−/− mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7−/− mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late-onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. CONCLUSIONS: Our data suggest that loss of integrin α7 causes a novel form of adult-onset cardiac dysfunction indicating a critical role for the integrin α7β1 in normal cardiac function and highlights the need for long-term cardiac monitoring in patients with ITGA7-related congenital myopathy

Efectos a la salud y exposición a p,p'-DDT y p,p'-DDE: el caso de México Human health effects and p,p'-DDE and p,p'-DDT exposure: the case of Mexico

Basado en la revisión sistemática de 32 artículos publicados en PubMed-Medline hasta enero del 2006 y utilizando como palabras clave DDT exposure, human, milk y Mexico; este estudio analiza la situación acerca de la exposición en México a difenildicloroetano (DDT) y su principal metabolito p,p,'-DDE, así como, su posible repercusión sobre la salud humana. Aún cuando, el uso del DDT se suspendió en 1999, los estudios evaluados reportan niveles importantes de p,p'-DDE, en muestras biológicas de suero, tejido adiposo y leche materna de poblaciones no ocupacionalmente expuestas. Así mismo, existen evidencias sobre daños a la salud, especialmente relacionados con el área reproductiva masculina, la lactancia materna y más recientemente daños a nivel celular, así como, alteración en el desarrollo psicomotor de niños expuestos in utero. Aún cuando existen muchas lagunas, acerca de otros efectos adversos a la salud relacionados con la exposición a DDT o sus metabolitos, la experiencia lograda hasta ahora, debe ser tomada en cuenta en México y el resto de Latinoamérica, para que considerando el principio precautorio se legisle sobre el DDT y otros contaminantes orgánicos persistente que tienen actividad y características similares al DDT o sus metabolitos.<br>Based on the systematic revision of 32 articles published in PubMed-Medline until January of 2006 and using like key words DDT exposure, human, milk and Mexico; this study analyzes the situation about the exposure of difenildicloroetano (DDT) and its main metabolite p,p,'-DDE in Mexico, as well as, their possible repercussion on the human health. Even though, the use of the DDT in Mexico was banned in 1999, the evaluated studies report significant levels of p, p'-DDE, in biological samples of serum, adipose tissue and maternal milk of populations not occupationally exposed. Also, there are evidences on damages to the health, specially related to the reproductive area, and more recently damages at cellular level, as well as, alteration in the psychomotor development of children exposed in uterus. Even though many gaps exist concerning the other adverse effects on health, relating to DDT exposure and its metabolites, experience accumulated at this point, must be taken into account in Mexico and the rest from Latin America, so that following this precautionary principle they should legislate against DDT and other persistent organic contaminants with characteristics similar to those of DDT and its metabolites