New research has suggested that tranexamic acid has the potential to prevent people dying from head injuries. The CRASH-2 Intracranial Bleeding Study highlighting the potential of the cheap, off-patent drug to help people suffering from brain trauma is published online by the BMJ today.
According to the collaborators – led by the London School of Hygiene & Tropical Medicine - the results provide strong grounds to test the effect of this treatment in a larger and definitive study. The forthcoming CRASH-3 trial (http://crash3.lshtm.ac.uk/) will determine reliably the effectiveness of tranexamic acid in patients with head injury.
Every year millions of people world-wide are treated for head injury. Unfortunately, currently there is no proven effective treatment for this life threatening condition, which affects mainly young working people. One of the frequent complications occurring after head injury is bleeding into the head. Usually this bleeding progresses in the first hours after the injury and produces more brain damage. Because tranexamic acid reduces clot breakdown the investigators hypothesised that this drug could reduce bleeding into the brain and therefore improve patients' outcomes.
The CRASH-2 Intracranial Bleeding Study was the first to evaluate the effect of tranexamic acid on head injury patients. The results showed that patients who receive tranexamic acid were less likely to have bleeding progression, they survive more and with less disability.
Dr Pablo Perel, who is based in the Clinical Trials Unit at LSHTM, says: "Although the results are not definitive they provide hope about the potential effectiveness of this simple drug for head injury patients. If such an inexpensive and widely practicable treatment were found to improve patient outcomes after head injury this would have major implications for clinical care."
**Source: London School of Hygiene & Tropical Medicine
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04 July 2011
Mass. General team identifies new class of antiangiogenesis drugs
Massachusetts General Hospital (MGH) researchers have discovered the first of an entirely new class of antiangiogenesis drugs – agents that interfere with the development of blood vessels. In a report in Proceedings of the National Academy of Sciences/Early Edition, the investigators describe how a compound derived from a South American tree was able, through a novel mechanism, to interfere with blood vessel formation in animal models of normal development, wound healing and tumor growth. "Most of the FDA-approved antiangiogenesis drugs inhibit the pathway controlled by vascular endothelial growth factor or VEGF, which directly stimulates blood vessel development," says Igor Garkavtsev, MD, PhD, of the Steele Laboratory for Tumor Biology at MGH, lead author of the study. "Although these drugs have become standard treatments for several types of cancer, they only provide modest benefit in terms of extending patient survival, so more effective drugs targeting tumor vasculature are needed."
While tumors need to generate and maintain their own blood supply to keep growing, tumor vasculature tends to be highly disorganized, which interferes with the effectiveness of traditional treatments like radiation and chemotherapy. Drugs that target the VEGF pathway can "normalize" tumor vasculature and improve the effectiveness of other therapies, but in addition to their limited effect on patient survival, such agents also can generate resistance or have toxic effects.
In their search for drugs that block blood vessel growth in different ways, Garkavtsev and his colleagues focused on pathways involved with the adhesion of endothelial cells that line blood vessels to the outer vessel wall. Appropriate cellular adhesion is essential to blood vessel function, and cells lining the tangled vessels characteristic of tumors often exhibit altered adhesion. Using a novel two-step strategy, the team first screened 50,000 compounds to find those affecting cellular adhesion and then analyzed identified compounds for toxicity and for their effects on actin, a protein essential to cellular structure.
One of two compounds identified by this process was dehydro-alpha-lapachone (DAL), derived from Tabebuia avellanedae, a tree native to Argentina and Brazil. Since DAL has structural similarities to another agent with antitumor activities and did not appear to be toxic, it was chosen for further investigation. The researchers first showed that DAL administration interfered with blood vessel formation in zebrafish, both during embryonic development and wound healing. They then found that it reduced the vascular density of tumors implanted in mice and, with daily treatment, significantly reduced tumor growth with no signs of toxicity.
Experiments with endothelial cells from human umbilical veins revealed that DAL administration altered the size and shape of the cells by changing the organization of the actin cytoskeleton; blocked formation of new vascular networks and reorganized existing networks; and interfered with the movement of cells required for wound healing. Further investigation found that DAL produces these effects by decreasing the activity of Rac1, a protein known to be important to cellular adhesion and cytoskeletal organization.
"This work is the first to discover the antivascular effects of DAL and its target Rac1, and our data strongly suggest that DAL promotes Rac1 degradation," says Rakesh Jain, PhD, director of the Steele Lab and senior author of the study. "DAL has the potential to improve treatment of many types of cancer and of other diseases characterized by abnormal blood vessels." Jain is the Cook Professor of Radiation Oncology (Tumor Biology) and Garkavtsev is an assistant professor of Radiation Oncology at Harvard Medical School
**Source: Massachusetts General Hospital
While tumors need to generate and maintain their own blood supply to keep growing, tumor vasculature tends to be highly disorganized, which interferes with the effectiveness of traditional treatments like radiation and chemotherapy. Drugs that target the VEGF pathway can "normalize" tumor vasculature and improve the effectiveness of other therapies, but in addition to their limited effect on patient survival, such agents also can generate resistance or have toxic effects.
In their search for drugs that block blood vessel growth in different ways, Garkavtsev and his colleagues focused on pathways involved with the adhesion of endothelial cells that line blood vessels to the outer vessel wall. Appropriate cellular adhesion is essential to blood vessel function, and cells lining the tangled vessels characteristic of tumors often exhibit altered adhesion. Using a novel two-step strategy, the team first screened 50,000 compounds to find those affecting cellular adhesion and then analyzed identified compounds for toxicity and for their effects on actin, a protein essential to cellular structure.
One of two compounds identified by this process was dehydro-alpha-lapachone (DAL), derived from Tabebuia avellanedae, a tree native to Argentina and Brazil. Since DAL has structural similarities to another agent with antitumor activities and did not appear to be toxic, it was chosen for further investigation. The researchers first showed that DAL administration interfered with blood vessel formation in zebrafish, both during embryonic development and wound healing. They then found that it reduced the vascular density of tumors implanted in mice and, with daily treatment, significantly reduced tumor growth with no signs of toxicity.
Experiments with endothelial cells from human umbilical veins revealed that DAL administration altered the size and shape of the cells by changing the organization of the actin cytoskeleton; blocked formation of new vascular networks and reorganized existing networks; and interfered with the movement of cells required for wound healing. Further investigation found that DAL produces these effects by decreasing the activity of Rac1, a protein known to be important to cellular adhesion and cytoskeletal organization.
"This work is the first to discover the antivascular effects of DAL and its target Rac1, and our data strongly suggest that DAL promotes Rac1 degradation," says Rakesh Jain, PhD, director of the Steele Lab and senior author of the study. "DAL has the potential to improve treatment of many types of cancer and of other diseases characterized by abnormal blood vessels." Jain is the Cook Professor of Radiation Oncology (Tumor Biology) and Garkavtsev is an assistant professor of Radiation Oncology at Harvard Medical School
**Source: Massachusetts General Hospital
MADRID Y ANDALUCÍA, LAS COMUNIDADES CON MAS DEFICIENCIAS ASISTENCIALES PEDIÁTRICAS, SEGÚN LA AEPAP
Las Comunidades Autónomas más deficientes en la calidad asistencial pediátrica son Andalucía y Madrid, y además con "tres puntos negros", seguidas de Cataluña y Murcia con dos, según la AEPAP, que expresa su apoyo al recién creado "Observatorio Pediátrico de Atención Primaria" en la Comunidad madrileña.
Para la Asociación Española de Pediatría de Atención Primaria, AEPAP, "puntos negros" son las características más desfavorables, como son las plazas de pediatría de AP cubiertas por profesionales sin la especialidad, la escasez de enfermería pediátrica, los horarios que dificultan la conciliación de la vida familiar y laboral, los sueldos bajos y las dificultades en el acceso a Internet en las consultas.
Según esta asociación científica, "corresponde a la administración sanitaria mejorar estas diferencias o se crearán divergencias insalvables en los recursos adjudicados a la asistencia sanitaria de los niños y adolescentes, dependiendo del lugar donde residan". En este sentido, la Dra. Begoña Domínguez, presidenta de AEPAP, considera necesaria "extender a todas las CC.AA. la iniciativa del Observatorio Pediátrico de Atención Primaria, lo que ha sido trasladado a todas las vocalías autonómicas que conforman la Asociación". Cabe recordar que la finalidad de este Observatorio es vigilar y alertar sobre la problemática asistencial y laboral de los pediatras de los Centros de Salud de Madrid, a fin de optimizar la calidad de la asistencia a los niños y adolescentes de esta Comunidad
Para la Asociación Española de Pediatría de Atención Primaria, AEPAP, "puntos negros" son las características más desfavorables, como son las plazas de pediatría de AP cubiertas por profesionales sin la especialidad, la escasez de enfermería pediátrica, los horarios que dificultan la conciliación de la vida familiar y laboral, los sueldos bajos y las dificultades en el acceso a Internet en las consultas.
Según esta asociación científica, "corresponde a la administración sanitaria mejorar estas diferencias o se crearán divergencias insalvables en los recursos adjudicados a la asistencia sanitaria de los niños y adolescentes, dependiendo del lugar donde residan". En este sentido, la Dra. Begoña Domínguez, presidenta de AEPAP, considera necesaria "extender a todas las CC.AA. la iniciativa del Observatorio Pediátrico de Atención Primaria, lo que ha sido trasladado a todas las vocalías autonómicas que conforman la Asociación". Cabe recordar que la finalidad de este Observatorio es vigilar y alertar sobre la problemática asistencial y laboral de los pediatras de los Centros de Salud de Madrid, a fin de optimizar la calidad de la asistencia a los niños y adolescentes de esta Comunidad
Taller women more likely to have twins
Taller women are more likely to have dizygotic (non-identical) twin pregnancies after double embryo transfer (DET), researchers from The Netherlands have found. Dr. Marieke Lambers, from VUMC, Gynaecology Obstetrics and Reproductive Medicine, Amsterdam, told the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that the findings could help doctors decide whether to transfer one or two embryos in order to minimise multiple pregnancies without compromising pregnancy rates. “This is a further step towards the development of tailor-made personalised IVF treatment,” she said. The researchers say that this is the first time the effect of maternal height on multiple implantation has been shown. “In natural dizygotic twinning it is not possible to distinguish between multiple ovulation and implantation,” said Dr. Lambers “whereas by studying pregnancies in mothers who have undergone DET we know exactly how many embryos were transferred and can therefore draw firm conclusions about the factors that influence the development of twin pregnancies.” The researchers studied data from the 19840 women in The Netherlands who underwent IVF treatment between 1983 and 1995 (the OMEGA study group). They selected all first fresh (unfrozen) IVF and ICSI cycles using DET that resulted in the delivery of a single or twin baby, both living and stillborn. Excluded from the analysis were cases where there were insufficient data from medical files, patients who used donated oocytes or who had undertaken fertility treatment besides IVF and ICSI, those who had had an abortion, an ectopic pregnancy, or a miscarriage. The remaining group was analysed using a dependent variable – whether or not the pregnancy was single or multiple – and a number of independent variables: BMI, weight, height, maternal age, number of oocytes retrieved, use of alcohol, level of education and parity. Of the 6589 patients who completed their first IVF cycle, 2357 women had DET, resulting in 371 singleton and 125 twin pregnancies. “When we came to analyse the twin group, we found that a maternal height of over 1.74cm and more than 11 oocytes retrieved were independently associated with twin pregnancies,” said Dr. Lambers. “The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos. But the association between increased height and multiple pregnancy is more difficult to explain. Previous studies have shown that women who are prone to conceive twins after IVF have a higher level of vascular endothelial growth factor-A (VEGF-A), which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEGF-A levels,” she said. “Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births,” said Dr. Lambers. “We hope that our work could be used in future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is an important topic, since multiple pregnancies involve a higher risk of problems for the mother, such as pre-eclampsia, and also for the baby due to pre-term or immature delivery.”
Vista completa||Volver a mensajesTaller women more likely to have twins
Taller women are more likely to have dizygotic (non-identical) twin pregnancies after double embryo transfer (DET), researchers from The Netherlands have found. Dr. Marieke Lambers, from VUMC, Gynaecology Obstetrics and Reproductive Medicine, Amsterdam, told the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that the findings could help doctors decide whether to transfer one or two embryos in order to minimise multiple pregnancies without compromising pregnancy rates. “This is a further step towards the development of tailor-made personalised IVF treatment,” she said. The researchers say that this is the first time the effect of maternal height on multiple implantation has been shown. “In natural dizygotic twinning it is not possible to distinguish between multiple ovulation and implantation,” said Dr. Lambers “whereas by studying pregnancies in mothers who have undergone DET we know exactly how many embryos were transferred and can therefore draw firm conclusions about the factors that influence the development of twin pregnancies.” The researchers studied data from the 19840 women in The Netherlands who underwent IVF treatment between 1983 and 1995 (the OMEGA study group). They selected all first fresh (unfrozen) IVF and ICSI cycles using DET that resulted in the delivery of a single or twin baby, both living and stillborn. Excluded from the analysis were cases where there were insufficient data from medical files, patients who used donated oocytes or who had undertaken fertility treatment besides IVF and ICSI, those who had had an abortion, an ectopic pregnancy, or a miscarriage. The remaining group was analysed using a dependent variable – whether or not the pregnancy was single or multiple – and a number of independent variables: BMI, weight, height, maternal age, number of oocytes retrieved, use of alcohol, level of education and parity. Of the 6589 patients who completed their first IVF cycle, 2357 women had DET, resulting in 371 singleton and 125 twin pregnancies. “When we came to analyse the twin group, we found that a maternal height of over 1.74cm and more than 11 oocytes retrieved were independently associated with twin pregnancies,” said Dr. Lambers. “The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos. But the association between increased height and multiple pregnancy is more difficult to explain. Previous studies have shown that women who are prone to conceive twins after IVF have a higher level of vascular endothelial growth factor-A (VEGF-A), which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEGF-A levels,” she said. “Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births,” said Dr. Lambers. “We hope that our work could be used in future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is an important topic, since multiple pregnancies involve a higher risk of problems for the mother, such as pre-eclampsia, and also for the baby due to pre-term or immature delivery.”
03 July 2011
Treatment approach to human Usher syndrome: Small molecules ignore stop signals
Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day life. While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease. In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options. Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA base, resulting in premature termination of protein synthesis.
The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal Human Gene Therapy. The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.
"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.
Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.
The translational biomedical research on readthrough of nonsense mutations aimed at developing a treatment for Usher syndrome is being funded by the FAUN foundation and the "Syscilia" project of the Seventh Framework Program of the European Union. It is part of the Research Training Group 1044 "Developmental and Disease-Induced Modifications of the Nervous System," funded by the German Research Foundation (DFG). The group has recently joined the Translational Neurosciences Research Focus of Johannes Gutenberg University Mainz.
**Source: Johannes Gutenberg Universitaet Mainz
The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal Human Gene Therapy. The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.
"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.
Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.
The translational biomedical research on readthrough of nonsense mutations aimed at developing a treatment for Usher syndrome is being funded by the FAUN foundation and the "Syscilia" project of the Seventh Framework Program of the European Union. It is part of the Research Training Group 1044 "Developmental and Disease-Induced Modifications of the Nervous System," funded by the German Research Foundation (DFG). The group has recently joined the Translational Neurosciences Research Focus of Johannes Gutenberg University Mainz.
**Source: Johannes Gutenberg Universitaet Mainz
Unos investigadores piden ciudades mejor adaptadas a la meteorología
Caminar media hora al día es uno de los mejores ejercicios, repiten continuamente los médicos. Bastan 30 minutos a buen paso para cuidar un poco la salud. Pero ¿qué hacer en verano, cuando las autoridades sanitarias recomiendan no salir -mucho menos andar- en las horas centrales del día, o en invierno cuando la nieve hace imposible este ejercicio? Unos investigadores de la Universidad McGill (Montreal, Canadá) han analizado cómo influye el clima en los paseos ciudadanos.
Desde noviembre hasta mayo observaron el gusto por las caminatas de los habitantes de nueve ciudades del hemisferio norte: Santa Cruz de La Palma en Gran Canaria, Kilmarnock y Glasgow en Escocia, Rousse en Bulgaria, Gliwice en Polonia, Oulu y Jakobstad en Finlandia, Sion en Suiza e Ítaca en EEUU. De las estudiadas, la ciudad española es la más pequeña, con 18.000 ciudadanos, mientras que Glasgow es la más numerosa, con una población de 1,2 millones de personas. Oulu es el lugar más frío de todos, con temperaturas por debajo de los 0ºC la mayoría de los días estudiados.
Los resultados del trabajo, publicados en 'Environment and Behavior' muestran que cuando hace frío, un aumento de 5ºC en la temperatura incrementa el número de peatones un 14% y cuando deja de nevar el incremento es del 23%. Y, lo que más desanima a quienes quieren pasear es la lluvia. En Rousse, en los días lluviosos, el número de caminantes descendía un 42%. El aire, sin embargo, tiene menos influencia que otros factores del clima.
Además de la alternativa de los gimnasios o, en el verano, aprovechar las primeras o las últimas horas del día, los investigadores afirman que "muchas más personas caminarían si quienes diseñan los planes urbanísticos de las ciudades tuvieran en cuenta el clima y utilizaran superficies que absobieran bien el agua, un sistema de alcantarillado que desagüe en condiciones o partes cubiertas en determinados tramos de la ciudad, así como servicios que retiren la nieve acumulada con rapidez".
"Nuestro estudio demuestra que la gente camina cuando está preparada para aguantar la temperatura . Es un ejercicio que no requiere un gran cambio de actitud, porque las personas están dispuestas, pero sí necesitan que el paisaje urbano ofrezca unas condiciones óptimas para hacerlo", indica Luc de Montigny, del Departamento de Epidemiología de la Universidad y principal firmante de la investigación. "Dada la epidemia de obesidad que afecta a todos los países, facilitar el paseo a sus ciudadanos es lo menos que las autoridades pueden hacer", concluye.
**Publicado en "EL MUNDO"
Desde noviembre hasta mayo observaron el gusto por las caminatas de los habitantes de nueve ciudades del hemisferio norte: Santa Cruz de La Palma en Gran Canaria, Kilmarnock y Glasgow en Escocia, Rousse en Bulgaria, Gliwice en Polonia, Oulu y Jakobstad en Finlandia, Sion en Suiza e Ítaca en EEUU. De las estudiadas, la ciudad española es la más pequeña, con 18.000 ciudadanos, mientras que Glasgow es la más numerosa, con una población de 1,2 millones de personas. Oulu es el lugar más frío de todos, con temperaturas por debajo de los 0ºC la mayoría de los días estudiados.
Los resultados del trabajo, publicados en 'Environment and Behavior' muestran que cuando hace frío, un aumento de 5ºC en la temperatura incrementa el número de peatones un 14% y cuando deja de nevar el incremento es del 23%. Y, lo que más desanima a quienes quieren pasear es la lluvia. En Rousse, en los días lluviosos, el número de caminantes descendía un 42%. El aire, sin embargo, tiene menos influencia que otros factores del clima.
Además de la alternativa de los gimnasios o, en el verano, aprovechar las primeras o las últimas horas del día, los investigadores afirman que "muchas más personas caminarían si quienes diseñan los planes urbanísticos de las ciudades tuvieran en cuenta el clima y utilizaran superficies que absobieran bien el agua, un sistema de alcantarillado que desagüe en condiciones o partes cubiertas en determinados tramos de la ciudad, así como servicios que retiren la nieve acumulada con rapidez".
"Nuestro estudio demuestra que la gente camina cuando está preparada para aguantar la temperatura . Es un ejercicio que no requiere un gran cambio de actitud, porque las personas están dispuestas, pero sí necesitan que el paisaje urbano ofrezca unas condiciones óptimas para hacerlo", indica Luc de Montigny, del Departamento de Epidemiología de la Universidad y principal firmante de la investigación. "Dada la epidemia de obesidad que afecta a todos los países, facilitar el paseo a sus ciudadanos es lo menos que las autoridades pueden hacer", concluye.
**Publicado en "EL MUNDO"
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