The health burden of an Asian strain of the parasitic flatworm schistosomiasis is more damaging to the global health burden than previously thought, according to a study published on March 5, 2008 in the open-access journal PLoS Neglected Tropical Diseases.
Schistosomiasis, a parasitic flatworm of the genus Schistosoma, can localize in several parts of the body but commonly affects the intestines. Symptoms include abdominal pain, fever, cough, diarrhea, abnormally high eosinophil count, and enlargement of the liver and spleen, and it is transmitted through certain species of snails. It primarily infects people in developing countries, infecting an estimated 207 million people in 76 (mostly developing) countries. There are several species of the Schistosoma genus that affect humans -- this study focused on Schistosomiasis japonica, found in China and the Philippines.
Through the Global Burden of Disease project, the World Health Organization (WHO) estimates the incidence, prevalence, severity, and length of over 130 major causes of illness, injury, and death throughout the world. A statistical measure known as the disability-adjusted life year (DALY) is used, which means to estimate the number of years of life lost due to premature death and any years lost in disability. This data is often used by policy makers to determine the level of funding for prevention programs, treatment efforts, and research.
According to the WHO, schistosomiasis has a low disease burden, with a 0.005 DALY score on a scale of 0 (for perfect health) to 1 (for death.) However, the burder of schistosomiasis has not been examined in more than a decade. To this end, the researchers performed a literature search to find data, and a decision model approach to re-examine the burden of this disease. The researchers calculated that the symptoms of Schistosomiasis japonica is 7 to 46 times greater than the current estimate. The team arrived at an estimate of 0.098 to 0.186. This study is the first to focus on one strain of the disease, and it is part of an ever growing group of evidence that this common parasitic disease is more damaging than previously estimated for global health.
"Schistosomiasis has a detrimental impact on nutrition and growth and development and can lead to major organ damage and death," study author Julia Finkelstein , of the Harvard School of Public Health, Boston, USA, says. "Current measures may severely underestimate the disability-related impact of the infection and need to be revised."
Dr. Charles King, of Case Western Reserve University, Cleveland, USA, who was not involved in the study but wrote an accompanying Expert Commentary article, predicted that, "Ultimately, these new measures of schistosomiasis-associated disability will translate into a greater priority to control schistosomiasis." Integrating new approaches and discoveries with these old estimates will, he says,"be essential to providing a balanced and fair assessment of neglected tropical diseases, and for properly setting disease control priorities for these disabling diseases of poverty."
About PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases (http://www.plosntds.org/) is a peer-reviewed, open-access journal devoted to the pathology, epidemiology, prevention, treatment, and control of the neglected tropical diseases, as well as public policy relevant to this group of diseases. All works published in PLoS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available subject only to the condition that the original authorship and source are properly attributed. The Public Library of Science uses the Creative Commons Attribution License, and copyright is retained by the authors.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.
Saturday, March 15, 2008
Physical Activity Of Adolescent Girls Could Be Increased By After-School Programs
Afterschool programs can modestly increase the amount of physical activity among girls in middle school, according to new results from the Trial of Activity for Adolescent Girls (TAAG), a multiple site, community based study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.
Results are published in the article, "Promoting Physical Activity in Middle School Girls," in the March issue of the American Journal of Preventive Medicine.
The study found that programs which linked schools in 6 geographic regions of the U.S. with community partners (such as the YMCA or YWCA, local health clubs, and community recreation centers) increased time spent in moderate-to-vigorous physical activity among the middle-school female students by about 2 minutes per day, or 80 calories a week. This finding occurred after three years of the intervention but not after two years. Physical activity was measured using accelerometers (a device for measuring the acceleration of motion), rather than self-reported. The authors write that results suggest this improved level of activity could prevent excess weight gain of about 2 pounds per year (or 0.82 kg per year), which, if sustained, could prevent a girl from becoming overweight as a teenager or adult.
In addition, TAAG showed a reduction of 8.2 minutes of sedentary behavior in girls in the intervention schools. Furthermore, the best results were seen in programs offered between 2 p.m. and 5 p.m. on weekdays, which suggest that afterschool programs are more effective than programs offered at other times, such as morning weekdays and weekends. The study results support the need for schools and community programs to work together to provide opportunities for physical activity programs in afterschool settings.
Researchers have found that as youth, especially girls, become adolescents, their level of physical activity decreases, putting them at risk for becoming overweight.
Results are published in the article, "Promoting Physical Activity in Middle School Girls," in the March issue of the American Journal of Preventive Medicine.
The study found that programs which linked schools in 6 geographic regions of the U.S. with community partners (such as the YMCA or YWCA, local health clubs, and community recreation centers) increased time spent in moderate-to-vigorous physical activity among the middle-school female students by about 2 minutes per day, or 80 calories a week. This finding occurred after three years of the intervention but not after two years. Physical activity was measured using accelerometers (a device for measuring the acceleration of motion), rather than self-reported. The authors write that results suggest this improved level of activity could prevent excess weight gain of about 2 pounds per year (or 0.82 kg per year), which, if sustained, could prevent a girl from becoming overweight as a teenager or adult.
In addition, TAAG showed a reduction of 8.2 minutes of sedentary behavior in girls in the intervention schools. Furthermore, the best results were seen in programs offered between 2 p.m. and 5 p.m. on weekdays, which suggest that afterschool programs are more effective than programs offered at other times, such as morning weekdays and weekends. The study results support the need for schools and community programs to work together to provide opportunities for physical activity programs in afterschool settings.
Researchers have found that as youth, especially girls, become adolescents, their level of physical activity decreases, putting them at risk for becoming overweight.
Heparin Investigation Update By Baxter
As reported in previous updates, Baxter's sophisticated analytical procedures, including capillary electrophoresis and nuclear magnetic resonance spectroscopy, identified an unknown material in some lots of the active pharmaceutical ingredient (API) for heparin, which is supplied to Baxter by Scientific Protein Laboratories (SPL).
I. Further analysis of contaminant rules out proteins, dioxins and other chemicals
The heparin impurity that has been found in the API lots associated with adverse clinical events is chemically very similar to the heparin molecule itself. Heparin is called a polysaccharide because it is composed of many sugar-like units, and likewise, the impurity contains polysaccharides. One reason it has been difficult to determine the precise chemical structure of the impurity is because it is so similar to heparin, making it hard to separate the two in sophisticated chemical analyses.
Through its research to date, Baxter has ruled out protein impurities in the suspect heparin API. Therefore, bacterial-derived protein molecules such as pertussis, botulinum, shiga, diphtheria, cholera, and tetanus toxin, to name a few, can be ruled out as the heparin impurity. Other chemicals such as tetrodotoxin (from puffer fish), lead and dioxins (formed when hydrocarbons with chlorine are burned) also do not match the identified heparin impurity.
While Baxter's analysis is not complete, the company has evidence that the unknown material is a highly sulfated glucosaminoglycan-like (GAG-like) material. While heparinlike, the material is structurally different from naturally-occurring heparin. The unknown material has approximately the same molecular weight as heparin and is similar in other ways, which is why standard testing would not detect its presence.
II. Investigation focus turns to supply chain and determining causality of allergic reactions
"In this investigation, there are three key questions that we are trying to answer - what exactly is the contaminant, where in the supply chain was it introduced, and can we prove that this contaminant is in fact causing the reactions we've seen," explained Norbert G. Riedel, corporate vice president and chief scientific officer of Baxter International Inc.
Dozens of Baxter scientists, manufacturing and quality experts have been working seven days a week since late December 2007, when the company began to see the increase in heparin-related adverse event reports. More than 40 different laboratory methodologies and hundreds of different tests have been employed in these investigations, including state-of-the-art analytical instrumentation such as nuclear magnetic resonance spectroscopy, which Baxter is now using on a continuous basis.
III. No fatalities have been confirmed by medical evidence to be caused by allergic reactions to Baxter heparin
At this point in time, neither Baxter nor the U.S. Food and Drug Administration (FDA) investigations have confirmed that Baxter heparin has caused any fatalities as a result of an allergic reaction. Baxter has received reports of a number of deaths. The company determined that there are four cases in which patients received Baxter heparin and suffered an allergic-type reaction to heparin that may have contributed to the adverse outcome, though there is not yet enough medical data available to draw a firm conclusion that the reaction caused death. In each of these cases, the patient had multiple underlying complex medical conditions and patients in three of these four cases had either undergone, or were in the process of undergoing, invasive cardiac surgery.
The company has received approximately 600 heparin-related adverse reaction reports to date.
"Patient safety is Baxter's highest priority, and we take our responsibility to investigate any report we receive seriously," Riedel said. "The company investigates as thoroughly as possible, contacting the person or institution that reported the event, checking sales records, medical records, and visiting the institution for further inquiry when appropriate. Baxter will continue its diligent investigation into the reports it receives."
"The continued collaboration between Baxter, FDA and SPL, as well as the consolidators, workshops and other links in the supply chain, is critical to putting all of the pieces together and determining root cause," Riedel said. "Baxter remains committed to facilitating this collaboration and providing the technical expertise necessary to resolve this issue. We stand ready to assist SPL and regulatory authorities in implementing additional measures to ensure that this does not happen again."
"We are confident that through our quick actions, significant resources and technological capabilities, we have been able to materially assist the FDA and other countries' regulatory agencies in identifying and resolving this issue before it manifested itself more widely in the industry," concluded Riedel.
I. Further analysis of contaminant rules out proteins, dioxins and other chemicals
The heparin impurity that has been found in the API lots associated with adverse clinical events is chemically very similar to the heparin molecule itself. Heparin is called a polysaccharide because it is composed of many sugar-like units, and likewise, the impurity contains polysaccharides. One reason it has been difficult to determine the precise chemical structure of the impurity is because it is so similar to heparin, making it hard to separate the two in sophisticated chemical analyses.
Through its research to date, Baxter has ruled out protein impurities in the suspect heparin API. Therefore, bacterial-derived protein molecules such as pertussis, botulinum, shiga, diphtheria, cholera, and tetanus toxin, to name a few, can be ruled out as the heparin impurity. Other chemicals such as tetrodotoxin (from puffer fish), lead and dioxins (formed when hydrocarbons with chlorine are burned) also do not match the identified heparin impurity.
While Baxter's analysis is not complete, the company has evidence that the unknown material is a highly sulfated glucosaminoglycan-like (GAG-like) material. While heparinlike, the material is structurally different from naturally-occurring heparin. The unknown material has approximately the same molecular weight as heparin and is similar in other ways, which is why standard testing would not detect its presence.
II. Investigation focus turns to supply chain and determining causality of allergic reactions
"In this investigation, there are three key questions that we are trying to answer - what exactly is the contaminant, where in the supply chain was it introduced, and can we prove that this contaminant is in fact causing the reactions we've seen," explained Norbert G. Riedel, corporate vice president and chief scientific officer of Baxter International Inc.
Dozens of Baxter scientists, manufacturing and quality experts have been working seven days a week since late December 2007, when the company began to see the increase in heparin-related adverse event reports. More than 40 different laboratory methodologies and hundreds of different tests have been employed in these investigations, including state-of-the-art analytical instrumentation such as nuclear magnetic resonance spectroscopy, which Baxter is now using on a continuous basis.
III. No fatalities have been confirmed by medical evidence to be caused by allergic reactions to Baxter heparin
At this point in time, neither Baxter nor the U.S. Food and Drug Administration (FDA) investigations have confirmed that Baxter heparin has caused any fatalities as a result of an allergic reaction. Baxter has received reports of a number of deaths. The company determined that there are four cases in which patients received Baxter heparin and suffered an allergic-type reaction to heparin that may have contributed to the adverse outcome, though there is not yet enough medical data available to draw a firm conclusion that the reaction caused death. In each of these cases, the patient had multiple underlying complex medical conditions and patients in three of these four cases had either undergone, or were in the process of undergoing, invasive cardiac surgery.
The company has received approximately 600 heparin-related adverse reaction reports to date.
"Patient safety is Baxter's highest priority, and we take our responsibility to investigate any report we receive seriously," Riedel said. "The company investigates as thoroughly as possible, contacting the person or institution that reported the event, checking sales records, medical records, and visiting the institution for further inquiry when appropriate. Baxter will continue its diligent investigation into the reports it receives."
"The continued collaboration between Baxter, FDA and SPL, as well as the consolidators, workshops and other links in the supply chain, is critical to putting all of the pieces together and determining root cause," Riedel said. "Baxter remains committed to facilitating this collaboration and providing the technical expertise necessary to resolve this issue. We stand ready to assist SPL and regulatory authorities in implementing additional measures to ensure that this does not happen again."
"We are confident that through our quick actions, significant resources and technological capabilities, we have been able to materially assist the FDA and other countries' regulatory agencies in identifying and resolving this issue before it manifested itself more widely in the industry," concluded Riedel.
DEET Inhibits The Receptors That Allow Insects To Smell Their Human Prey
Fifty years have passed since the United States Department of Agriculture and the U.S. Army invented DEET to protect soldiers from disease-transmitting insects (and, in the process, made camping trips and barbecues more pleasant for the rest of us civilians). But despite decades of research, scientists still didn't know precisely how it worked. Now, by pinpointing DEET's molecular target in insects, researchers at Rockefeller University have definitively shown that the widely used bug repellent acts like a chemical cloak, masking human odors that blood-feeding insects find attractive. The research, which will be published in the March 13 issue of Science Express, now makes it possible not only to systematically improve upon the repellent properties of DEET but also to make it a safer chemical.
"For all these years, there were a lot of theories but no consensus on how DEET worked," says Leslie Vosshall, head of the Laboratory of Neurogenetics and Behavior. "Does it smell bad to mosquitoes or does it blind them to odors" It was a great unsolved problem."
Mosquitoes are strongly attracted to odors in human breath and sweat, including carbon dioxide, lactic acid and an alcohol-based compound called 1-octen-3-ol. Different receptors within their olfactory system detect these odors, among others, and lead them to their prey. DEET simply interferes with the proper functioning of odorant receptors, making the hunt for a tasty meal all the more difficult.
But this interference is selective.
To see DEET's effect on different odorant receptors, the researchers recorded the electrical activity of cells in the mosquito olfactory system while exposing the insects to the chemical. They found that DEET only shuts down those receptors that work in tandem with a smell coreceptor called Or83b, which is present in all insects. Whereas DEET shuts down the receptor pairs that detect 1-octen-3-ol and two other sweaty odors, it doesn't affect the lone receptor that detects carbon dioxide. That's because this carbon dioxide receptor doesn't require Or83b to function, whereas the sweaty-odor receptors do. "Each receptor complex has different properties," says Vosshall. "And the idea is that DEET is acting on the uniqueness of this complex."
Since mosquitoes that lack this coreceptor have yet to be genetically engineered, Vosshall and her group used fruit fly mutants that do not have the coreceptor. While normal flies avoid a vial treated with DEET, the researchers found that flies without the coreceptor ventured into the vials, suggesting that Or83b is required to detect this potent chemical. Vosshall then proved that DEET specifically affected the receptor/coreceptor as a unit by isolating the RNA of each and injecting both into a frog egg. As expected, DEET inhibited the odorant receptor/coreceptor complex even in this environment, which was isolated from the olfactory system.
By targeting the coreceptor complex rather than the coreceptor alone, DEET doesn't shut down the entire olfactory system, says Vosshall. "Instead, it seems to shut down strategically different parts of it. It just shuts down enough of these receptors to confuse the mosquito or blind it to the odors it finds attractive."
Although DEET is widely used, concerns about its potential health risks have prompted scientists to pursue alternatives, though so far none have proven to be significantly more effective than DEET. "We now know how DEET works, and this is the first step in making significantly better insect repellents," says Vosshall.
"For all these years, there were a lot of theories but no consensus on how DEET worked," says Leslie Vosshall, head of the Laboratory of Neurogenetics and Behavior. "Does it smell bad to mosquitoes or does it blind them to odors" It was a great unsolved problem."
Mosquitoes are strongly attracted to odors in human breath and sweat, including carbon dioxide, lactic acid and an alcohol-based compound called 1-octen-3-ol. Different receptors within their olfactory system detect these odors, among others, and lead them to their prey. DEET simply interferes with the proper functioning of odorant receptors, making the hunt for a tasty meal all the more difficult.
But this interference is selective.
To see DEET's effect on different odorant receptors, the researchers recorded the electrical activity of cells in the mosquito olfactory system while exposing the insects to the chemical. They found that DEET only shuts down those receptors that work in tandem with a smell coreceptor called Or83b, which is present in all insects. Whereas DEET shuts down the receptor pairs that detect 1-octen-3-ol and two other sweaty odors, it doesn't affect the lone receptor that detects carbon dioxide. That's because this carbon dioxide receptor doesn't require Or83b to function, whereas the sweaty-odor receptors do. "Each receptor complex has different properties," says Vosshall. "And the idea is that DEET is acting on the uniqueness of this complex."
Since mosquitoes that lack this coreceptor have yet to be genetically engineered, Vosshall and her group used fruit fly mutants that do not have the coreceptor. While normal flies avoid a vial treated with DEET, the researchers found that flies without the coreceptor ventured into the vials, suggesting that Or83b is required to detect this potent chemical. Vosshall then proved that DEET specifically affected the receptor/coreceptor as a unit by isolating the RNA of each and injecting both into a frog egg. As expected, DEET inhibited the odorant receptor/coreceptor complex even in this environment, which was isolated from the olfactory system.
By targeting the coreceptor complex rather than the coreceptor alone, DEET doesn't shut down the entire olfactory system, says Vosshall. "Instead, it seems to shut down strategically different parts of it. It just shuts down enough of these receptors to confuse the mosquito or blind it to the odors it finds attractive."
Although DEET is widely used, concerns about its potential health risks have prompted scientists to pursue alternatives, though so far none have proven to be significantly more effective than DEET. "We now know how DEET works, and this is the first step in making significantly better insect repellents," says Vosshall.
New Research On The Origins Of Asthma And Allergies Presented At Annual Meeting
Viral illnesses that produce wheezing are very common in early childhood, but not all children who wheeze in the first several years of life go on to develop asthma. D.J. Jackson, MD and colleagues at the University of Wisconsin, Madison presented their study at the 2008 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Philadelphia.
Wheezing with respiratory syncytial virus (RSV) infections has previously been associated with increased risk of developing asthma later in childhood. Jackson and colleagues confirmed this finding, but discovered a novel finding as well: wheezing illnesses during the first three years of life caused by rhinovirus, the most common cause of "colds" in children and adults, were the strongest predictor of asthma at age 6 years.
Exposure to diesel exhaust particles and indoor endotoxin during early childhood increases the risk for persistent wheeze at age three
Diesel exhaust particles (DEP) and endotoxin, found in bacteria, may act together to promote wheezing in young children, according to a new study presented at the 2008 AAAAI Annual Meeting in Philadelphia.
Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a NIEHS sponsored study, were evaluated at age 3. Exposure to high levels of DEP prior to age 1 was associated with a two-fold increased risk for wheezing. Children exposed to both DEP and high levels of endotoxin were at risk for wheezing at age three.
Patrick Ryan, PhD and colleagues at the University of Cincinnati in Cincinnati, Ohio concluded that children exposed to DEP during infancy may be at increased risk for the development of wheezing at age 3, and this relationship is modified by indoor exposure to endotoxin.
Allergens in urban elementary schools and homes of children with asthma
William Sheehan, MD and colleagues at Children's Hospital Boston, Boson, MA studied the association between allergens in schools and childhood asthma. They investigated allergen exposure in schools compared to homes with a specific focus on children with asthma. This new study was presented at the 2008 AAAAI Annual Meeting in Philadelphia.
The study was based on collecting 66 samples from various rooms in four Northeastern US urban elementary schools and 38 student bedrooms. Samples were analyzed for cat, dog, cockroach, dust mites, and mouse urinary protein.
The study, presented at the 2008 AAAAI Annual Meeting in Philadelphia, shows higher levels of mouse urine, but lower levels of dust mites in schools versus homes. It is important to recognize that children with asthma may encounter varying levels of allergens in environments outside the home, such as schools.
Exposure to mouse allergens in US homes is associated with asthma symptoms
Asthma, which remains a significant public health concern in the U.S., affects millions of Americans. To evaluate the importance of mouse allergen in asthma, Päivi Salo, PhD and colleagues at the National Institute of Environmental Health Sciences examined whether elevated levels of mouse allergen were associated with asthma among the study participants.
Results from a national survey demonstrate that elevated mouse allergen levels in the home are associated with asthma symptoms in allergic individuals. The National Survey of Lead and Allergens (NSLAH) was the first study to estimate mouse allergen levels and examine residential exposure to mouse allergen in a nationally representative sample of U.S. households. The study confirms that mouse allergen is an important household allergen and aggravates asthma symptoms among asthma sufferers.
Although mouse allergen is a well-recognized allergen in occupational settings, it has only recently been recognized as an important allergen in homes. To date, the majority of the research has focused on inner-city homes in which mouse allergen has been found to be ubiquitous. The findings from the NSLAH suggest that the presence of mouse allergen in U.S. homes is surprisingly common even outside urban areas. Of the surveyed homes, 82% had detectable levels of mouse allergen and, in 35% of the homes; allergen concentrations exceeded a level that has been associated with increased mouse allergen sensitization rates. Elevated levels were most commonly found in high-rise apartments and mobile homes, older homes, and low-income homes.
The results showed that in allergic individuals, higher levels of mouse allergen significantly increased the likelihood of having asthma symptoms. Because elevated levels of the allergen were not restricted to inner-city areas, this study suggests that mouse allergen is an important household allergen outside of urban environments. For allergic individuals, reducing allergen levels in the home is an essential part of asthma control and treatment. Therefore, mice may not be welcome visitors in homes where allergic and asthmatic individuals reside.
Health care utilization is higher among patients whose asthma is not well-controlled
The study by Theresa Guilbert, MD and colleagues aimed to determine whether asthma control is associated with increased healthcare resource utilization. This new study was present at the 2008 AAAAI Annual Meeting.
The study interviewed patients receiving any prescription asthma treatment in the past year. Patients whose asthma was not well-controlled at baseline had a higher risk of an asthma-related event compared to patients with controlled asthma. Adults with asthma that was not well-controlled were at 4-times greater risk for office visits and 4.5 times greater risk for ER visits. Children with asthma that was not well-controlled were at 4-times greater risk for office visits and tended to have an increased risk of ER visits.
Asthma that is not well-controlled is associated with increased healthcare resource utilization. Asthma control determination using ACT/C-ACT may help clinicians and patients decrease the risk of these events. Additional studies to determine if monitoring asthma control could lead to reduced healthcare resource utilization could be valuable.
These studies were presented at the 2008 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI). The AAAAI is the largest professional medical specialty organization in the United States representing allergists, asthma specialists, clinical immunologists, allied health professionals and others with special interest in the research and treatment of allergic disease.
Allergy/immunology specialists are pediatric or internal medicine physicians who have elected an additional two years of training to become specialized in the treatment of asthma, allergy and immunologic disease.
The AAAAI represents allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic disease. Allergy/immunology specialists are pediatric or internal medicine physicians who have elected an additional two years of training to become specialized in the treatment of asthma, allergy and immunologic disease. Established in 1943, the AAAAI has more than 6,500 members in the United States, Canada and 60 other countries.
Wheezing with respiratory syncytial virus (RSV) infections has previously been associated with increased risk of developing asthma later in childhood. Jackson and colleagues confirmed this finding, but discovered a novel finding as well: wheezing illnesses during the first three years of life caused by rhinovirus, the most common cause of "colds" in children and adults, were the strongest predictor of asthma at age 6 years.
Exposure to diesel exhaust particles and indoor endotoxin during early childhood increases the risk for persistent wheeze at age three
Diesel exhaust particles (DEP) and endotoxin, found in bacteria, may act together to promote wheezing in young children, according to a new study presented at the 2008 AAAAI Annual Meeting in Philadelphia.
Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a NIEHS sponsored study, were evaluated at age 3. Exposure to high levels of DEP prior to age 1 was associated with a two-fold increased risk for wheezing. Children exposed to both DEP and high levels of endotoxin were at risk for wheezing at age three.
Patrick Ryan, PhD and colleagues at the University of Cincinnati in Cincinnati, Ohio concluded that children exposed to DEP during infancy may be at increased risk for the development of wheezing at age 3, and this relationship is modified by indoor exposure to endotoxin.
Allergens in urban elementary schools and homes of children with asthma
William Sheehan, MD and colleagues at Children's Hospital Boston, Boson, MA studied the association between allergens in schools and childhood asthma. They investigated allergen exposure in schools compared to homes with a specific focus on children with asthma. This new study was presented at the 2008 AAAAI Annual Meeting in Philadelphia.
The study was based on collecting 66 samples from various rooms in four Northeastern US urban elementary schools and 38 student bedrooms. Samples were analyzed for cat, dog, cockroach, dust mites, and mouse urinary protein.
The study, presented at the 2008 AAAAI Annual Meeting in Philadelphia, shows higher levels of mouse urine, but lower levels of dust mites in schools versus homes. It is important to recognize that children with asthma may encounter varying levels of allergens in environments outside the home, such as schools.
Exposure to mouse allergens in US homes is associated with asthma symptoms
Asthma, which remains a significant public health concern in the U.S., affects millions of Americans. To evaluate the importance of mouse allergen in asthma, Päivi Salo, PhD and colleagues at the National Institute of Environmental Health Sciences examined whether elevated levels of mouse allergen were associated with asthma among the study participants.
Results from a national survey demonstrate that elevated mouse allergen levels in the home are associated with asthma symptoms in allergic individuals. The National Survey of Lead and Allergens (NSLAH) was the first study to estimate mouse allergen levels and examine residential exposure to mouse allergen in a nationally representative sample of U.S. households. The study confirms that mouse allergen is an important household allergen and aggravates asthma symptoms among asthma sufferers.
Although mouse allergen is a well-recognized allergen in occupational settings, it has only recently been recognized as an important allergen in homes. To date, the majority of the research has focused on inner-city homes in which mouse allergen has been found to be ubiquitous. The findings from the NSLAH suggest that the presence of mouse allergen in U.S. homes is surprisingly common even outside urban areas. Of the surveyed homes, 82% had detectable levels of mouse allergen and, in 35% of the homes; allergen concentrations exceeded a level that has been associated with increased mouse allergen sensitization rates. Elevated levels were most commonly found in high-rise apartments and mobile homes, older homes, and low-income homes.
The results showed that in allergic individuals, higher levels of mouse allergen significantly increased the likelihood of having asthma symptoms. Because elevated levels of the allergen were not restricted to inner-city areas, this study suggests that mouse allergen is an important household allergen outside of urban environments. For allergic individuals, reducing allergen levels in the home is an essential part of asthma control and treatment. Therefore, mice may not be welcome visitors in homes where allergic and asthmatic individuals reside.
Health care utilization is higher among patients whose asthma is not well-controlled
The study by Theresa Guilbert, MD and colleagues aimed to determine whether asthma control is associated with increased healthcare resource utilization. This new study was present at the 2008 AAAAI Annual Meeting.
The study interviewed patients receiving any prescription asthma treatment in the past year. Patients whose asthma was not well-controlled at baseline had a higher risk of an asthma-related event compared to patients with controlled asthma. Adults with asthma that was not well-controlled were at 4-times greater risk for office visits and 4.5 times greater risk for ER visits. Children with asthma that was not well-controlled were at 4-times greater risk for office visits and tended to have an increased risk of ER visits.
Asthma that is not well-controlled is associated with increased healthcare resource utilization. Asthma control determination using ACT/C-ACT may help clinicians and patients decrease the risk of these events. Additional studies to determine if monitoring asthma control could lead to reduced healthcare resource utilization could be valuable.
These studies were presented at the 2008 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI). The AAAAI is the largest professional medical specialty organization in the United States representing allergists, asthma specialists, clinical immunologists, allied health professionals and others with special interest in the research and treatment of allergic disease.
Allergy/immunology specialists are pediatric or internal medicine physicians who have elected an additional two years of training to become specialized in the treatment of asthma, allergy and immunologic disease.
The AAAAI represents allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic disease. Allergy/immunology specialists are pediatric or internal medicine physicians who have elected an additional two years of training to become specialized in the treatment of asthma, allergy and immunologic disease. Established in 1943, the AAAAI has more than 6,500 members in the United States, Canada and 60 other countries.
$7.6 Million Grant To Develop Novel Treatment For Parkinson's Disease Awarded To Scripps Florida
Philip LoGrasso, associate professor and senior director for drug discovery at Scripps Florida, will lead the project as principal investigator. LoGrasso, who joined Scripps Florida in 2005, previously held positions at Merck and the NIH.
The new five-year grant will fund research to develop a compound to treat neurodegeneration in Parkinson's disease. The goal of the project is to bring the potential treatment to the point where Scripps Research and potential partners can file an application for an investigational new drug - the first step in the lengthy clinical trials process required by the U.S. Food and Drug Administration.
An estimated one million Americans are believed to suffer from Parkinson's disease, according to the Parkinson's Disease Foundation; approximately 40,000 new cases are reported annually. Patients with Parkinson's suffer from a loss of dopaminergic neurons, the source of dopamine, a neurotransmitter that plays a key role in motor reflexes and cognitition. While some loss of dopaminergic neurons is common, Parkinson's patients routinely lose more than half.
"Development of a drug that prevents dopaminergic neurodegeneration would be a quantum leap in the clinical treatment of Parkinson's disease," LoGrasso said. "All current therapies treat only the symptoms of the disease, not the underlying pathologies. Current treatments also tend to lose therapeutic efficacy over time, or have adverse side effect profiles that make their long-term use difficult."
A Classic Approach
To develop the new small-molecule compound, LoGrasso will work with a team of Scripps Research scientists. Together, the team represents a range of experience in pharmaceutical preclinical drug development, encompassing the fields of medicinal chemistry, biochemistry, cell biology, structural biology, behavioral pharmacology, drug metabolism and pharmacokinetics, and toxicology.
The team will use what LoGrasso calls a classical pharmaceutical approach to drug development, which involves annual milestones and multiple compound tracking.
"Our research plan is designed to mitigate the risk of developing a single compound that may fail due to specific problems, and to maximize the chance for clinical success by having back-up compounds," LoGrasso said. "We believe that using this approach to optimize small-molecule inhibitors will create a series of compounds with favorable pharmacokinetic properties and safety profiles."
The scientists will examine small-molecule compounds that inhibit c-jun-N-terminal kinase 2/3 (JNK 2/3). Pronounced Junk, JNK 2/3 is an important contributor to stress-induced apoptosis (cell death) and has been shown to play a significant role in neuronal survival. As such, the kinase is a highly viable target for drugs to treat neurodegenerative disorders like Parkinson's disease.
Previous research has shown that small-molecule and peptide inhibitors of the JNK target protect dopaminergic neurons in both acute and chronic models of Parkinson's disease. Previous research has also shown that the JNK2/3 knockout mouse models - mice that lack the gene for JNK2/3 - suffer fewer Parkinson's-like symptoms.
The scientists hope to identify approximately three compounds that demonstrate in vivo efficacy by the third year, and a top compound by year four of the research program.
"When we're finished, our aim it is to have a safe, efficacious compound with sufficient preclinical safety data to support human clinical studies," LoGrasso said.
The new five-year grant will fund research to develop a compound to treat neurodegeneration in Parkinson's disease. The goal of the project is to bring the potential treatment to the point where Scripps Research and potential partners can file an application for an investigational new drug - the first step in the lengthy clinical trials process required by the U.S. Food and Drug Administration.
An estimated one million Americans are believed to suffer from Parkinson's disease, according to the Parkinson's Disease Foundation; approximately 40,000 new cases are reported annually. Patients with Parkinson's suffer from a loss of dopaminergic neurons, the source of dopamine, a neurotransmitter that plays a key role in motor reflexes and cognitition. While some loss of dopaminergic neurons is common, Parkinson's patients routinely lose more than half.
"Development of a drug that prevents dopaminergic neurodegeneration would be a quantum leap in the clinical treatment of Parkinson's disease," LoGrasso said. "All current therapies treat only the symptoms of the disease, not the underlying pathologies. Current treatments also tend to lose therapeutic efficacy over time, or have adverse side effect profiles that make their long-term use difficult."
A Classic Approach
To develop the new small-molecule compound, LoGrasso will work with a team of Scripps Research scientists. Together, the team represents a range of experience in pharmaceutical preclinical drug development, encompassing the fields of medicinal chemistry, biochemistry, cell biology, structural biology, behavioral pharmacology, drug metabolism and pharmacokinetics, and toxicology.
The team will use what LoGrasso calls a classical pharmaceutical approach to drug development, which involves annual milestones and multiple compound tracking.
"Our research plan is designed to mitigate the risk of developing a single compound that may fail due to specific problems, and to maximize the chance for clinical success by having back-up compounds," LoGrasso said. "We believe that using this approach to optimize small-molecule inhibitors will create a series of compounds with favorable pharmacokinetic properties and safety profiles."
The scientists will examine small-molecule compounds that inhibit c-jun-N-terminal kinase 2/3 (JNK 2/3). Pronounced Junk, JNK 2/3 is an important contributor to stress-induced apoptosis (cell death) and has been shown to play a significant role in neuronal survival. As such, the kinase is a highly viable target for drugs to treat neurodegenerative disorders like Parkinson's disease.
Previous research has shown that small-molecule and peptide inhibitors of the JNK target protect dopaminergic neurons in both acute and chronic models of Parkinson's disease. Previous research has also shown that the JNK2/3 knockout mouse models - mice that lack the gene for JNK2/3 - suffer fewer Parkinson's-like symptoms.
The scientists hope to identify approximately three compounds that demonstrate in vivo efficacy by the third year, and a top compound by year four of the research program.
"When we're finished, our aim it is to have a safe, efficacious compound with sufficient preclinical safety data to support human clinical studies," LoGrasso said.
Wasps Offer Clues To Which Came First, Social Dominance Or Big Brains
There's new evidence supporting the idea that bigger brains are better. A study of a tropical wasp suggests that the brainpower required to be dominant drives brain capacity.
University of Washington researchers have found that key processing regions in the brains of both males and females of one wasp species not only increased in size with age but were also associated with being dominant. The study also showed different patterns of brain development in males and females. Certain subregions were larger in males and others were larger in females. This matched expectations based on males' greater use of vision and females' greater reliance on their antennae.
UW researchers Sean O'Donnell and Yamile Molina found increased brain growth in areas of the insects' brains called the mushroom bodies, which vaguely resemble the cerebrum in humans and other vertebrates. A mushroom body sits atop each hemisphere of the wasp brain. The mushroom bodies process input from the eyes and antennae, and are involved in learning and memory.
The social paper wasp that was studied, Mischocyttarus mastigorphorus, is unusual because males are dominant over females, a rarity among social insects, said O'Donnell, a UW associate professor of psychology. Most social insect societies - bees, ants and wasps - are predominantly female, with males short-lived and subordinate.
O'Donnell and Molina, a UW doctoral student, focused on a part of the insects' mushroom body, called the calyx, where neural connections are made. While the overall size of the calyces did not differ between the males and females, specific subregions were larger in each sex. Males rely on vision when they leave the nest for mating opportunities, and the part of the calyx that receives visual input was larger. In contrast, most female interaction takes place on the nest, where tactile and odor senses are important and the part of the calyx that received input from the antennae was bigger among the females.
"When you are dominant among insects you get more food," O'Donnell said, "and in this case it gives males more energy to leave the nest and mate. The fact that the males are dominant and long-lived makes this species interesting from a neurobiological standpoint. We think they have pretty sophisticated cognition compared to males of other wasp species."
The researchers studied five wasp colonies in a tropical cloud forest near Monteverde, Costa Rica. They first marked all resident adult wasps on the nests and these individuals were excluded from further analyses. Newly emerged wasps then were captured and marked over the next several days and returned to their nest. Each colony then was observed in the morning and afternoon every three days over the course of more than a month. Behavioral data such as giving and receiving aggression were collected, as well as time spent on and off the nest. After this observation period, sections of the wasps' brains were examined under a microscope.
Among the unanswered questions stemming from this study include how long these wasps live and how long these patterns of brain growth continued.
"We only followed them for 42 days, so we don't know how long they live," said O'Donnell. "We also don't know if their brain development is similar to humans in terms of if and when they start to decline cognitively.
He said an exciting new idea - the social challenge hypothesis - suggests that large human brains evolved in response to the demands of complex social interactions. The wasp work extends this idea to individual brain variation.
"Do you get to be dominant because of a big brain or does being dominant drive brain size? That's still an open question and we don't know which comes first," said O'Donnell. "This study suggests the high cognitive demands of being dominant drive brain capacity and supports the social brain hypothesis. The next step is to broaden the scope of the research by looking at more species of paper wasps. We are interested in how brains evolve in concert with social evolution. There is the intriguing possibility that there are similar patterns across wide spans of evolutionary time. My goal is to get a bigger sample of social wasp species and examine this."
"You are looking at super-distant animals when you compare wasps and people. Yet there may be an interesting commonality between them. Increased brainpower may be part of being social, no matter who you are. What makes this exciting is we see some common patterns in how brains change as societies evolve. As we see changes in social complexity, there are changes in brain structure. If it is good for people it should be good for wolves, dolphins and paper wasps."
University of Washington researchers have found that key processing regions in the brains of both males and females of one wasp species not only increased in size with age but were also associated with being dominant. The study also showed different patterns of brain development in males and females. Certain subregions were larger in males and others were larger in females. This matched expectations based on males' greater use of vision and females' greater reliance on their antennae.
UW researchers Sean O'Donnell and Yamile Molina found increased brain growth in areas of the insects' brains called the mushroom bodies, which vaguely resemble the cerebrum in humans and other vertebrates. A mushroom body sits atop each hemisphere of the wasp brain. The mushroom bodies process input from the eyes and antennae, and are involved in learning and memory.
The social paper wasp that was studied, Mischocyttarus mastigorphorus, is unusual because males are dominant over females, a rarity among social insects, said O'Donnell, a UW associate professor of psychology. Most social insect societies - bees, ants and wasps - are predominantly female, with males short-lived and subordinate.
O'Donnell and Molina, a UW doctoral student, focused on a part of the insects' mushroom body, called the calyx, where neural connections are made. While the overall size of the calyces did not differ between the males and females, specific subregions were larger in each sex. Males rely on vision when they leave the nest for mating opportunities, and the part of the calyx that receives visual input was larger. In contrast, most female interaction takes place on the nest, where tactile and odor senses are important and the part of the calyx that received input from the antennae was bigger among the females.
"When you are dominant among insects you get more food," O'Donnell said, "and in this case it gives males more energy to leave the nest and mate. The fact that the males are dominant and long-lived makes this species interesting from a neurobiological standpoint. We think they have pretty sophisticated cognition compared to males of other wasp species."
The researchers studied five wasp colonies in a tropical cloud forest near Monteverde, Costa Rica. They first marked all resident adult wasps on the nests and these individuals were excluded from further analyses. Newly emerged wasps then were captured and marked over the next several days and returned to their nest. Each colony then was observed in the morning and afternoon every three days over the course of more than a month. Behavioral data such as giving and receiving aggression were collected, as well as time spent on and off the nest. After this observation period, sections of the wasps' brains were examined under a microscope.
Among the unanswered questions stemming from this study include how long these wasps live and how long these patterns of brain growth continued.
"We only followed them for 42 days, so we don't know how long they live," said O'Donnell. "We also don't know if their brain development is similar to humans in terms of if and when they start to decline cognitively.
He said an exciting new idea - the social challenge hypothesis - suggests that large human brains evolved in response to the demands of complex social interactions. The wasp work extends this idea to individual brain variation.
"Do you get to be dominant because of a big brain or does being dominant drive brain size? That's still an open question and we don't know which comes first," said O'Donnell. "This study suggests the high cognitive demands of being dominant drive brain capacity and supports the social brain hypothesis. The next step is to broaden the scope of the research by looking at more species of paper wasps. We are interested in how brains evolve in concert with social evolution. There is the intriguing possibility that there are similar patterns across wide spans of evolutionary time. My goal is to get a bigger sample of social wasp species and examine this."
"You are looking at super-distant animals when you compare wasps and people. Yet there may be an interesting commonality between them. Increased brainpower may be part of being social, no matter who you are. What makes this exciting is we see some common patterns in how brains change as societies evolve. As we see changes in social complexity, there are changes in brain structure. If it is good for people it should be good for wolves, dolphins and paper wasps."
Subscribe to:
Posts (Atom)