11 November 2011
Knocking out key protein in mice boosts insulin sensitivity
By knocking out a key regulatory protein, scientists at the University of California, San Diego School of Medicine and the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland dramatically boosted insulin sensitivity in lab mice, an achievement that opens a new door for drug development and the treatment of diabetes. The research, published in the November 11 issue of the journal Cell, reveals a new and previously unsuspected role for nuclear receptor corepressor (NCoR), a transcriptional coregulatory protein found in a wide variety of cells.
"Different transcription factors stimulate genes, turning them on and off, by bringing in co-activators or co-repressors," said Jerrold M. Olefsky, MD, associate dean for Scientific Affairs and Distinguished Professor of Medicine at UC San Diego and senior author of the paper. "All transcriptional biology is a balance of these co-activators and co-repressors."
Olefsky and colleagues focused their attention on NCoR, which was known to be a major co-repressor of Peroxisome Proliferator-Activated Receptor gamma or PPAR-gamma, a ubiquitous protein that regulates fatty acid storage and glucose metabolism, but which also appeared to act on other receptors as well.
"It seemed to be a general purpose co-repressor," said Olefsky. "It's unusual for one protein to do so many things. It's not very efficient and you don't see it too much in biology."
The scientists created a knock-out mouse model whose adipocytes or fat cells lacked NCoR. Though bred to be obese and prone to diabetes, Olefsky said the glucose tolerance improved in the NCoR knock-out mice. Moreover, they displayed enhanced insulin sensitivity in liver, muscle and fat, and decreased systemic inflammation. Resistance to insulin, a hormone central to regulating carbohydrate and fat metabolism, is a hallmark of diabetes, as is chronic inflammation.
"When NCoR was deleted, insulin sensitivity in the whole animal increased dramatically compared to normal obese mice, which remained insulin resistant. The sensitivity occurred not just in adipocytes, but in all cells," said Olefsky. "With NCoR knocked out of adipocytes, PPAR-gamma becomes active. This produces a robust increase in systemic insulin sensitivity."
Phosphorylation is a biochemical process in which a phosphate group is added to a protein or other organic molecule, activating or deactivating many protein enzymes. It turns out that NCoR facilitates phosphorylation of PPAR-gamma, so that without NCoR, the receptor remains unphosphorylated and active.
In related work also published in the same issue of Cell, EPFL scientists found that knocking out NCoR in muscle cells produced a surprising effect. It did not repress PPAR-gamma, but rather generated a different phenotype or set of results.
"In adipocytes, NCoR repressed PPAR-gamma, but in other cells, it appears to repress other transcription factors," Olefsky said. "That's a new principle: A repressor that's found in many cells, but performs a specific, different function depending on the cell type."
Though NCoR's role as a major co-repressor was known, it was considered a poor drug target because inhibiting it could cause unwanted de-repression in some cell types, producing adverse side effects. Olefsky said the newly discovered specificity of NCoR revitalizes the idea that NCoR may be an excellent drug target for type 2 diabetes and other insulin resistant diseases.
"If researchers can make a drug that's tissue-specific, repressing NCoR could be a powerful way to boost insulin sensitivity. It's doable. Already, we can create drugs that specifically target fat and liver cells. That might be good enough to produce a system-wide benefit."
"Different transcription factors stimulate genes, turning them on and off, by bringing in co-activators or co-repressors," said Jerrold M. Olefsky, MD, associate dean for Scientific Affairs and Distinguished Professor of Medicine at UC San Diego and senior author of the paper. "All transcriptional biology is a balance of these co-activators and co-repressors."
Olefsky and colleagues focused their attention on NCoR, which was known to be a major co-repressor of Peroxisome Proliferator-Activated Receptor gamma or PPAR-gamma, a ubiquitous protein that regulates fatty acid storage and glucose metabolism, but which also appeared to act on other receptors as well.
"It seemed to be a general purpose co-repressor," said Olefsky. "It's unusual for one protein to do so many things. It's not very efficient and you don't see it too much in biology."
The scientists created a knock-out mouse model whose adipocytes or fat cells lacked NCoR. Though bred to be obese and prone to diabetes, Olefsky said the glucose tolerance improved in the NCoR knock-out mice. Moreover, they displayed enhanced insulin sensitivity in liver, muscle and fat, and decreased systemic inflammation. Resistance to insulin, a hormone central to regulating carbohydrate and fat metabolism, is a hallmark of diabetes, as is chronic inflammation.
"When NCoR was deleted, insulin sensitivity in the whole animal increased dramatically compared to normal obese mice, which remained insulin resistant. The sensitivity occurred not just in adipocytes, but in all cells," said Olefsky. "With NCoR knocked out of adipocytes, PPAR-gamma becomes active. This produces a robust increase in systemic insulin sensitivity."
Phosphorylation is a biochemical process in which a phosphate group is added to a protein or other organic molecule, activating or deactivating many protein enzymes. It turns out that NCoR facilitates phosphorylation of PPAR-gamma, so that without NCoR, the receptor remains unphosphorylated and active.
In related work also published in the same issue of Cell, EPFL scientists found that knocking out NCoR in muscle cells produced a surprising effect. It did not repress PPAR-gamma, but rather generated a different phenotype or set of results.
"In adipocytes, NCoR repressed PPAR-gamma, but in other cells, it appears to repress other transcription factors," Olefsky said. "That's a new principle: A repressor that's found in many cells, but performs a specific, different function depending on the cell type."
Though NCoR's role as a major co-repressor was known, it was considered a poor drug target because inhibiting it could cause unwanted de-repression in some cell types, producing adverse side effects. Olefsky said the newly discovered specificity of NCoR revitalizes the idea that NCoR may be an excellent drug target for type 2 diabetes and other insulin resistant diseases.
"If researchers can make a drug that's tissue-specific, repressing NCoR could be a powerful way to boost insulin sensitivity. It's doable. Already, we can create drugs that specifically target fat and liver cells. That might be good enough to produce a system-wide benefit."
**Source: University of California - San Diego
Parkinsonian worms may hold the key to identifying drugs for Parkinson's disease
Researchers at The University of Texas at Austin have devised a simple test, using dopamine-deficient worms, for identifying drugs that may help people with Parkinson's disease. The worms are able to evaluate as many as 1,000 potential drugs a year. The researchers have received federal funding that could increase that to one million drug tests a year.
The test is based on the difficulty that these "parkinsonian" C. elegans worms have in switching from swimming to crawling when they're taken out of water.
"They can crawl fine," says Jon Pierce-Shimomura, assistant professor of neurobiology. "They go into a puddle and can swim fine. But as soon as the puddle goes away they crash. In some cases an individual will remain rigid for about a half hour."
Pierce-Shimomura led a team of researchers, including Andres Vidal-Gadea, Stephen Topper and Layla Young, to identify this "motor switching" problem. Their findings were published last month in the Proceedings of the National Academy of Science.
"We take these motor transitions for granted," says Pierce-Shimomura, "like getting up out of a chair or walking through a doorway from one surface to another. But people with Parkinson's have a terrible time with this. They freeze at the threshold. It looks like we have a very simple worm model for this now."
To identify potential therapeutics, Pierce-Shimomura begins with worms that have been mutated to be deficient in producing dopamine. It's the loss of dopamine-producing cells in the brain that causes Parkinson's disease in humans.
The dopamine-deficient worms are put through the same paces that lead to the immobility, but in the presence of a drug.
If they become immobile as they normally would when water is removed, the researchers move on to the next drug. But if somehow a drug helps the worms' brains overcome the dopamine deficiency and they transition to crawling, the lab has a potential therapeutic.
Pierce-Shimomura says that although humans have a vastly more complex nervous system than the worms, the two species share an "ancient and conserved" genetic structure to their dopaminergic systems. What works to overcome a dopamine deficiency in the worms may do something similar in humans, and it can be tested in worms with extraordinary speed.
Pierce-Shimomura has already begun testing potential drugs for Parkinson's. So far he's found one compound that shows promising effects in the worms. The particular compound has already been approved for use in humans for treatment of another condition.
Working with the university's Office of Technology Commercialization, he's filed a patent application for the worm model for testing of neurodegenerative diseases such as Alzheimer's and Parkinson's.
About half a million Americans suffer from Parkinson's disease, a degenerative disorder of the central nervous system. Early symptoms of the disease include shaking, rigidity, and slowness of movement. As it progresses, the physical symptoms can advance to the point of incapacity, and cognitive impairments, including early dementia, can arise as well.
A huge barrier to preventing or treating diseases such as Parkinson's is the amount of time it takes to identify drugs that work effectively. Typically, drugs are tested on mice -- a process that is expensive and requires one to two years for mice to age while testing just a few dozen drugs at a time.
With the help of a few undergraduates Pierce-Shimomura believes that he can test about 1,000 drugs a year. The number could rise to one million a year if the process can be automated.
He recently received a $3 million Transformative Research Projects Award from the National Institutes of Health with mechanical engineering professor Adela Ben-Yakar, to develop just such an automation process for parkinsonian worms as well as worms mutated to have other neurodegenerative diseases, including a C. elegans version of Alzheimer's.
"These worms are so simple to work with, we can do these drug screens at massive scale," says Pierce-Shimomura. "Right now the more hands we have, the more targets we can test."
**Source: University of Texas at Austin
The test is based on the difficulty that these "parkinsonian" C. elegans worms have in switching from swimming to crawling when they're taken out of water.
"They can crawl fine," says Jon Pierce-Shimomura, assistant professor of neurobiology. "They go into a puddle and can swim fine. But as soon as the puddle goes away they crash. In some cases an individual will remain rigid for about a half hour."
Pierce-Shimomura led a team of researchers, including Andres Vidal-Gadea, Stephen Topper and Layla Young, to identify this "motor switching" problem. Their findings were published last month in the Proceedings of the National Academy of Science.
"We take these motor transitions for granted," says Pierce-Shimomura, "like getting up out of a chair or walking through a doorway from one surface to another. But people with Parkinson's have a terrible time with this. They freeze at the threshold. It looks like we have a very simple worm model for this now."
To identify potential therapeutics, Pierce-Shimomura begins with worms that have been mutated to be deficient in producing dopamine. It's the loss of dopamine-producing cells in the brain that causes Parkinson's disease in humans.
The dopamine-deficient worms are put through the same paces that lead to the immobility, but in the presence of a drug.
If they become immobile as they normally would when water is removed, the researchers move on to the next drug. But if somehow a drug helps the worms' brains overcome the dopamine deficiency and they transition to crawling, the lab has a potential therapeutic.
Pierce-Shimomura says that although humans have a vastly more complex nervous system than the worms, the two species share an "ancient and conserved" genetic structure to their dopaminergic systems. What works to overcome a dopamine deficiency in the worms may do something similar in humans, and it can be tested in worms with extraordinary speed.
Pierce-Shimomura has already begun testing potential drugs for Parkinson's. So far he's found one compound that shows promising effects in the worms. The particular compound has already been approved for use in humans for treatment of another condition.
Working with the university's Office of Technology Commercialization, he's filed a patent application for the worm model for testing of neurodegenerative diseases such as Alzheimer's and Parkinson's.
About half a million Americans suffer from Parkinson's disease, a degenerative disorder of the central nervous system. Early symptoms of the disease include shaking, rigidity, and slowness of movement. As it progresses, the physical symptoms can advance to the point of incapacity, and cognitive impairments, including early dementia, can arise as well.
A huge barrier to preventing or treating diseases such as Parkinson's is the amount of time it takes to identify drugs that work effectively. Typically, drugs are tested on mice -- a process that is expensive and requires one to two years for mice to age while testing just a few dozen drugs at a time.
With the help of a few undergraduates Pierce-Shimomura believes that he can test about 1,000 drugs a year. The number could rise to one million a year if the process can be automated.
He recently received a $3 million Transformative Research Projects Award from the National Institutes of Health with mechanical engineering professor Adela Ben-Yakar, to develop just such an automation process for parkinsonian worms as well as worms mutated to have other neurodegenerative diseases, including a C. elegans version of Alzheimer's.
"These worms are so simple to work with, we can do these drug screens at massive scale," says Pierce-Shimomura. "Right now the more hands we have, the more targets we can test."
**Source: University of Texas at Austin
UT MD Anderson study finds acupuncture can prevent radiation-induced chronic dry mouth
When given alongside radiation therapy for head and neck cancer, acupuncture has shown for the first time to reduce the debilitating side effect of xerostomia, according to new research from The University of Texas MD Anderson Cancer Center and Fudan University Shanghai Cancer Center. The study, published in the journal Cancer, reported findings from the first randomized controlled trial of acupuncture for the prevention of xerostomia.
Xerostomia, or severe dry mouth, is characterized by reduced salivary flow, which commonly affects patients receiving radiotherapy for head and neck cancer. Most current treatments are palliative and offer limited benefit, according to Lorenzo Cohen, Ph.D., professor in MD Anderson's Departments of General Oncology and Behavioral Science and director of the Integrative Medicine Program.
The condition impairs quality of life for patients, as it creates difficulties eating, speaking and sleeping, while also increasing the risk for oral infections.
"There have been a number of small studies examining the benefits of acupuncture after xerostomia develops, but no one previously examined if it could prevent xerostomia," said Cohen, who is also the study's principal investigator. "We found incorporating acupuncture alongside radiotherapy diminished the incidence and severity of this side effect."
Cohen and his colleagues examined 86 patients with nasopharyngeal carcinoma, treated at Fudan University Shanghai Cancer Center. Forty patients were randomized to acupuncture and 46 to the standard of care. Those in the treatment arm received acupuncture therapy three times per week during the seven-week course of radiotherapy. Patients were evaluated before radiotherapy, weekly during radiotherapy, and then again one and six months later.
The results were based on data derived from two self-report questionnaires and measuring actual saliva flow. Patients completed the Xerostomia Questionnaire (XQ), an eight-item survey which assessed symptoms consistent with the condition. XQ scores under 30 corresponded to mild or no symptoms of xerostomia.
The second measure, MD Anderson Symptom Inventory Head and Neck (MDASI-HN), ranked the severity of cancer-related symptoms, other than xerostomia, and their interference with quality of life. The team also measured saliva flow rates using standardized sialometry collection techniques.
Benefits Noticed Quickly
"What was quite remarkable was that we started to see group differences as early as three weeks into radiotherapy for the development of xerostomia, cancer-related symptoms that interfere with quality of life, and saliva flow rates -- an important objective measure," said Zhiqiang Meng, M.D., Ph.D., co-principle investigator of the study and deputy chair of the Department of Integrative Oncology, Fudan University Shanghai Cancer Center.
The largest group differences in XQ scores were seen by the end of radiotherapy, but the differences persisted over time. By one month after the end of radiotherapy, 54.3 percent of the acupuncture group reported XQ scores greater than 30, compared to the control group at 86.1 percent. By six months after radiotherapy, the numbers dropped to 24.1 percent in the acupuncture group and 63.6 percent of the control group still reporting symptoms of xerostomia. Saliva flow rates were also greater in the acupuncture group, starting at three weeks into radiotherapy and persisting through the one and six month follow-up.
Acupuncture also helped cancer-related symptoms, other than xerostomia, as measured by the MDASI-HN questionnaire, with differences that emerged in week three and continued through six months.
"The medical implications are quite profound in terms of quality of life, because while chronic dry mouth may sound benign, it has a significant impact on sleeping, eating and speaking," Cohen said. "Without saliva, there can be an increase in microbial growth, possible bone infection and irreversible nutritional deficits."
Additional studies are needed to determine the mechanisms for the benefits of acupuncture, and while the study didn't examine this issue, Cohen said it may have an impact on local blood flux, specifically at the parotid gland.
Further research is planned, including a large trial conducted at MD Anderson in collaboration with Fudan University Shanghai Cancer Center. Both centers will enroll 150 patients undergoing radiotherapy for head and neck cancer: 50 will receive acupuncture, 50 sham acupuncture and 50 will be enrolled in a control group. Researchers will also examine saliva constituents and a number of other measures to better determine the mechanisms of acupuncture.
Xerostomia, or severe dry mouth, is characterized by reduced salivary flow, which commonly affects patients receiving radiotherapy for head and neck cancer. Most current treatments are palliative and offer limited benefit, according to Lorenzo Cohen, Ph.D., professor in MD Anderson's Departments of General Oncology and Behavioral Science and director of the Integrative Medicine Program.
The condition impairs quality of life for patients, as it creates difficulties eating, speaking and sleeping, while also increasing the risk for oral infections.
"There have been a number of small studies examining the benefits of acupuncture after xerostomia develops, but no one previously examined if it could prevent xerostomia," said Cohen, who is also the study's principal investigator. "We found incorporating acupuncture alongside radiotherapy diminished the incidence and severity of this side effect."
Cohen and his colleagues examined 86 patients with nasopharyngeal carcinoma, treated at Fudan University Shanghai Cancer Center. Forty patients were randomized to acupuncture and 46 to the standard of care. Those in the treatment arm received acupuncture therapy three times per week during the seven-week course of radiotherapy. Patients were evaluated before radiotherapy, weekly during radiotherapy, and then again one and six months later.
The results were based on data derived from two self-report questionnaires and measuring actual saliva flow. Patients completed the Xerostomia Questionnaire (XQ), an eight-item survey which assessed symptoms consistent with the condition. XQ scores under 30 corresponded to mild or no symptoms of xerostomia.
The second measure, MD Anderson Symptom Inventory Head and Neck (MDASI-HN), ranked the severity of cancer-related symptoms, other than xerostomia, and their interference with quality of life. The team also measured saliva flow rates using standardized sialometry collection techniques.
Benefits Noticed Quickly
"What was quite remarkable was that we started to see group differences as early as three weeks into radiotherapy for the development of xerostomia, cancer-related symptoms that interfere with quality of life, and saliva flow rates -- an important objective measure," said Zhiqiang Meng, M.D., Ph.D., co-principle investigator of the study and deputy chair of the Department of Integrative Oncology, Fudan University Shanghai Cancer Center.
The largest group differences in XQ scores were seen by the end of radiotherapy, but the differences persisted over time. By one month after the end of radiotherapy, 54.3 percent of the acupuncture group reported XQ scores greater than 30, compared to the control group at 86.1 percent. By six months after radiotherapy, the numbers dropped to 24.1 percent in the acupuncture group and 63.6 percent of the control group still reporting symptoms of xerostomia. Saliva flow rates were also greater in the acupuncture group, starting at three weeks into radiotherapy and persisting through the one and six month follow-up.
Acupuncture also helped cancer-related symptoms, other than xerostomia, as measured by the MDASI-HN questionnaire, with differences that emerged in week three and continued through six months.
"The medical implications are quite profound in terms of quality of life, because while chronic dry mouth may sound benign, it has a significant impact on sleeping, eating and speaking," Cohen said. "Without saliva, there can be an increase in microbial growth, possible bone infection and irreversible nutritional deficits."
Additional studies are needed to determine the mechanisms for the benefits of acupuncture, and while the study didn't examine this issue, Cohen said it may have an impact on local blood flux, specifically at the parotid gland.
Further research is planned, including a large trial conducted at MD Anderson in collaboration with Fudan University Shanghai Cancer Center. Both centers will enroll 150 patients undergoing radiotherapy for head and neck cancer: 50 will receive acupuncture, 50 sham acupuncture and 50 will be enrolled in a control group. Researchers will also examine saliva constituents and a number of other measures to better determine the mechanisms of acupuncture.
En EEUU logran monitorizar los pensamientos de tres personas en aparente situación irreversible
Hasta hace relativamente poco, la ciencia creía que los pacientes con daños cerebrales graves no podían responder ante estímulos externos. En los últimos años se ha demostrado que la inconsciencia no siempre va asociada al estado vegetativo. Hay estudios que consiguen que los pacientes se comuniquen a través de pruebas que monitorizan sus pensamientos. En 2010, un equipo dirigido por el doctor Adrian Owen, un neurocientífico británico de la Universidad de Ontario, consiguió que los participantes de su estudio respondieran a preguntas sencillas. Para ello trabajaron con los pacientes para asociar un tipo de pensamiento, el cual activa una zona del cerebro, con la respuesta «sí»; y otro tipo de pensamiento, el cual activa otra zona completamente diferente, con el «no». Varios pacientes consiguieron responder a las preguntas siguiendo esa fórmula.
El innovador estudio utilizó complejos escáneres creados «ad hoc» que complican que este tipo de pruebas se generalicen por su elevado coste. Ahora Owen y su equipo han dado un paso más. En su último estudio, realizado en las universidades de Cambridge y Lieja, han demostrado que se pueden obtener resultados similares utilizando sencillamente un electroencefalograma, al alcance en cualquier hospital. En esta ocasión, los doctores pidieron a sus pacientes que imaginaran primero que movían los dedos de las manos y después los dedos de los pies, ante lo que tres de los dieciséis pacientes mostró actividad cerebral. «Fue posible detectar que estos pacientes estaban conscientes a pesar de haber sido diagnosticados como completamente inconscientes», señaló Owen.
Con esta prueba, Adrian Owen ha hecho patente que muchos de los diagnósticos que determinan si una persona está en estado vegetativo son erróneos y espera que al hacer más preciso el diagnóstico también se pueda mejorar el tratamiento de estos pacientes.
**Publicado en "ABC"
El innovador estudio utilizó complejos escáneres creados «ad hoc» que complican que este tipo de pruebas se generalicen por su elevado coste. Ahora Owen y su equipo han dado un paso más. En su último estudio, realizado en las universidades de Cambridge y Lieja, han demostrado que se pueden obtener resultados similares utilizando sencillamente un electroencefalograma, al alcance en cualquier hospital. En esta ocasión, los doctores pidieron a sus pacientes que imaginaran primero que movían los dedos de las manos y después los dedos de los pies, ante lo que tres de los dieciséis pacientes mostró actividad cerebral. «Fue posible detectar que estos pacientes estaban conscientes a pesar de haber sido diagnosticados como completamente inconscientes», señaló Owen.
Con esta prueba, Adrian Owen ha hecho patente que muchos de los diagnósticos que determinan si una persona está en estado vegetativo son erróneos y espera que al hacer más preciso el diagnóstico también se pueda mejorar el tratamiento de estos pacientes.
**Publicado en "ABC"
Woodsmoke from cooking fires linked to pneumonia, cognitive impacts
A new study led by University of California, Berkeley, researchers spotlight the human health effects of exposure to smoke from open fires and dirty cookstoves, the primary source of cooking and heating for 43 percent, or some 3 billion members, of the world's population. Women and young children in poverty are particularly vulnerable. In the first study, the researchers found a dramatic one-third reduction in severe pneumonia diagnoses among children in homes with smoke-reducing chimneys on their cookstoves. The second study uncovered a surprising link between prenatal maternal exposure to woodsmoke and poorer performance in markers for IQ among school-aged children.
The findings on pneumonia, the chief cause of death for children five and under, will be published in the journal The Lancet on Nov. 10, two days before World Pneumonia Day. While previous research has linked exposure to household cooking smoke to respiratory infections, the latest results come from the first-ever randomized controlled trial -- the gold standard of scientific experiments -- on air pollution.
"This study is critically important because it provides compelling evidence that reducing household woodsmoke exposure is a public health intervention that is likely on a par with vaccinations and nutrition supplements for reducing severe pneumonia, and is worth investing in," said Kirk Smith, professor of global environmental health at UC Berkeley's School of Public Health and principal investigator of the RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) study. "There is a huge burden of disease and death due to child pneumonia, and there aren't a lot of good interventions out there," added Dr. Arthur Reingold, a UC Berkeley professor of epidemiology and an internationally recognized expert on infectious diseases, who was not part of the RESPIRE trial. "Randomized controlled trials are frequently demanded by funding agencies and decision makers before they are willing to make substantial investments in new technologies or strategies, and this study provides the needed evidence of an intervention that works."
In the RESPIRE study -- which includes partners from Guatemala's Universidad Del Valle, the U.S. Centers for Disease Control and Prevention, University of Liverpool, Norway's University of Bergen and the World Health Organization -- researchers worked with rural communities in the Western Highlands of Guatemala. Households with a pregnant woman or young infant were randomly assigned to either receive a woodstove with a chimney or to continue cooking with traditional open woodfires.
The researchers found that using chimneys to vent cooking smoke outside homes led to a more striking decrease in cases of severe pneumonia compared with total pneumonia cases, possibly because the reduction in smoke with the chimney stoves was insufficient to significantly reduce all risk.
"The amount of smoke exposure babies were getting from the open woodfire stoves is comparable to having them smoke three to five cigarettes a day," said Smith, whose research in this field began 30 years ago. "The chimney stoves reduced that smoke exposure by half, on average."
In all there were 265 children in the chimney-stove homes and 253 children in the control homes. During the study, the researchers reported 149 children in the chimney-stove homes and 180 in the open-fire homes with physician-diagnosed pneumonia. For severe pneumonia, characterized by low blood oxygenation, there were 72 cases in the chimney-stove group and 101 in the control group.
The findings on pneumonia, the chief cause of death for children five and under, will be published in the journal The Lancet on Nov. 10, two days before World Pneumonia Day. While previous research has linked exposure to household cooking smoke to respiratory infections, the latest results come from the first-ever randomized controlled trial -- the gold standard of scientific experiments -- on air pollution.
"This study is critically important because it provides compelling evidence that reducing household woodsmoke exposure is a public health intervention that is likely on a par with vaccinations and nutrition supplements for reducing severe pneumonia, and is worth investing in," said Kirk Smith, professor of global environmental health at UC Berkeley's School of Public Health and principal investigator of the RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) study. "There is a huge burden of disease and death due to child pneumonia, and there aren't a lot of good interventions out there," added Dr. Arthur Reingold, a UC Berkeley professor of epidemiology and an internationally recognized expert on infectious diseases, who was not part of the RESPIRE trial. "Randomized controlled trials are frequently demanded by funding agencies and decision makers before they are willing to make substantial investments in new technologies or strategies, and this study provides the needed evidence of an intervention that works."
In the RESPIRE study -- which includes partners from Guatemala's Universidad Del Valle, the U.S. Centers for Disease Control and Prevention, University of Liverpool, Norway's University of Bergen and the World Health Organization -- researchers worked with rural communities in the Western Highlands of Guatemala. Households with a pregnant woman or young infant were randomly assigned to either receive a woodstove with a chimney or to continue cooking with traditional open woodfires.
The researchers found that using chimneys to vent cooking smoke outside homes led to a more striking decrease in cases of severe pneumonia compared with total pneumonia cases, possibly because the reduction in smoke with the chimney stoves was insufficient to significantly reduce all risk.
"The amount of smoke exposure babies were getting from the open woodfire stoves is comparable to having them smoke three to five cigarettes a day," said Smith, whose research in this field began 30 years ago. "The chimney stoves reduced that smoke exposure by half, on average."
In all there were 265 children in the chimney-stove homes and 253 children in the control homes. During the study, the researchers reported 149 children in the chimney-stove homes and 180 in the open-fire homes with physician-diagnosed pneumonia. For severe pneumonia, characterized by low blood oxygenation, there were 72 cases in the chimney-stove group and 101 in the control group.
**Source: University of California - Berkeley
More fiber, but not necessarily less fat, good for teen diets
A diet high in fiber -- but not necessarily one low in saturated fat or cholesterol -- is tied to a lower risk of heart disease and type-2 diabetes in teenagers, according to new findings from Michigan State University. A study led by Joseph Carlson of MSU's Division of Sports and Cardiovascular Nutrition suggests to reduce metabolic syndrome -- a collection of risk factors including high blood pressure and a large waistline -- it is more important to emphasize diets including fiber-rich, nutrient-dense, plant-based foods than focus on restricting foods high in cholesterol or saturated fat.
The research is published in Journal of the American Dietetic Association.
"What we found is that as fiber intake increases, the risk for metabolic syndrome decreases," said Carlson, a registered dietitian and associate professor at MSU. "High-fiber, nutrient-dense foods are packed with heart healthy vitamins, minerals and chemicals that can positively affect many cardiovascular risk factors.
"It may be better to focus on including these foods than to focus, as is commonly done, on excluding foods high in saturated fat."
That does not mean, however, that teens should have carte blanche in eating foods high in saturated fat and cholesterol, Carlson said.
"It is well established that saturated fat can raise bad cholesterol," he said. "What this data suggest is the importance of including foods high in dietary fiber."
With the high availability of processed foods today, Carlson said, it is possible for teens to eat a diet that is low in saturated fat and cholesterol but that also is low in fiber and nutrient-rich, plant-based foods. Recent national data indicates up to 30 percent of teens' dietary intake comes from beverages and sugar-rich snacks.
Due to low intakes of fruits, vegetables, whole grains and beans, the total dietary fiber intake in teens is about 13 grams per day, well below the recommendation of 26 grams and 38 grams for female and male adolescents, respectively.
In addition, obesity and other key risk factors associated with metabolic syndrome are on the rise in youth; more than 70 percent of teens in the study had at least one of the five risk factors used to assess metabolic syndrome: high blood pressure, high levels of sugar and fat in the blood, low levels of good cholesterol and a large waistline (a person having three or more of the factors are classified as having the syndrome).
"One of the takeaways is that our study reinforced the current dietary recommendations for dietary fiber intake by including a variety of plant-based foods," Carlson said. "A strategy of emphasizing fiber-rich foods may improve adherence to dietary recommendations."
The next step, he said, is to figure out the best methods to boost dietary fiber intakes to levels that will improve or sustain a desirable cardiovascular risk factor status. For example, if a person daily has three servings of fruit and vegetables (12 grams of fiber), one serving of beans (seven grams), and three servings of whole grain, they will be at about 30 grams of dietary fiber.
"The trick is getting people in the groove finding the foods that they both enjoy and are convenient," Carlson said.
As part of the cross-sectional study, Carlson and his team focused on data collected as part of the National Health and Nutrition Examination Survey done from 1999-2002. They analyzed the diets of more than 2,100 boys and girls ages 12 to 19, looking at whether the teens had three or more conditions that make up metabolic syndrome.
The study found there was a three-fold increase in the number of children that had metabolic syndrome when the group of children receiving the least fiber was compared with the group receiving the most. There was not a significant relationship with either saturated fat or cholesterol intake.
**Source: Michigan State University
The research is published in Journal of the American Dietetic Association.
"What we found is that as fiber intake increases, the risk for metabolic syndrome decreases," said Carlson, a registered dietitian and associate professor at MSU. "High-fiber, nutrient-dense foods are packed with heart healthy vitamins, minerals and chemicals that can positively affect many cardiovascular risk factors.
"It may be better to focus on including these foods than to focus, as is commonly done, on excluding foods high in saturated fat."
That does not mean, however, that teens should have carte blanche in eating foods high in saturated fat and cholesterol, Carlson said.
"It is well established that saturated fat can raise bad cholesterol," he said. "What this data suggest is the importance of including foods high in dietary fiber."
With the high availability of processed foods today, Carlson said, it is possible for teens to eat a diet that is low in saturated fat and cholesterol but that also is low in fiber and nutrient-rich, plant-based foods. Recent national data indicates up to 30 percent of teens' dietary intake comes from beverages and sugar-rich snacks.
Due to low intakes of fruits, vegetables, whole grains and beans, the total dietary fiber intake in teens is about 13 grams per day, well below the recommendation of 26 grams and 38 grams for female and male adolescents, respectively.
In addition, obesity and other key risk factors associated with metabolic syndrome are on the rise in youth; more than 70 percent of teens in the study had at least one of the five risk factors used to assess metabolic syndrome: high blood pressure, high levels of sugar and fat in the blood, low levels of good cholesterol and a large waistline (a person having three or more of the factors are classified as having the syndrome).
"One of the takeaways is that our study reinforced the current dietary recommendations for dietary fiber intake by including a variety of plant-based foods," Carlson said. "A strategy of emphasizing fiber-rich foods may improve adherence to dietary recommendations."
The next step, he said, is to figure out the best methods to boost dietary fiber intakes to levels that will improve or sustain a desirable cardiovascular risk factor status. For example, if a person daily has three servings of fruit and vegetables (12 grams of fiber), one serving of beans (seven grams), and three servings of whole grain, they will be at about 30 grams of dietary fiber.
"The trick is getting people in the groove finding the foods that they both enjoy and are convenient," Carlson said.
As part of the cross-sectional study, Carlson and his team focused on data collected as part of the National Health and Nutrition Examination Survey done from 1999-2002. They analyzed the diets of more than 2,100 boys and girls ages 12 to 19, looking at whether the teens had three or more conditions that make up metabolic syndrome.
The study found there was a three-fold increase in the number of children that had metabolic syndrome when the group of children receiving the least fiber was compared with the group receiving the most. There was not a significant relationship with either saturated fat or cholesterol intake.
**Source: Michigan State University
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