Cancer avatars for personalized medicine help researchers find genomic signatures of cancers

 

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Researchers at University of California, San Diego School of Medicine and Moores Cancer Center have used computer simulations of cancer cells -- cancer avatars -- to identify drugs most likely to kill cancer cells isolated from patients' brain tumors.

The findings, published in May 21 online issue of the Journal of Translational Medicine, may help researchers stratify cancer patients for clinical trials according to their cancers' genomic signatures and predicted sensitivities to different cancer drugs.

Such an approach would allow scientists to selectively test cancer drugs on those who would be most likely to respond to them, while simultaneously reducing patients' exposures to toxic drugs that would likely be ineffective.

"Genomics tells us that cancers are a lot like snowflakes. No two cancers are alike so it does not make sense to give all patients the same drugs. This is the idea behind personalizing therapies for cancer," said lead author Sandeep Pingle, MD, PhD, a project scientist in the laboratory of Santosh Kesari, MD, PhD, chief of the division of Neuro-Oncology, professor in the department of neurosciences, director of Neuro-Oncology at UC San Diego Moores Cancer Center and the study's senior author.

"With the virtual cell model, we can take into account all the complexity of cellular processes to predict which drugs will be the most effective against a particular tumor based on its genomic profile," Pingle said. "This is a first step toward personalized medicine."

Researchers developed a virtual cell that represents the internal workings of a normal, healthy cell, depicting them as a complex collection of signaling pathways and metabolic networks. The virtual healthy cell can be made cancerous. Indeed, it can be turned into any kind of cancer cell by distorting specific points and pathways in the system. These cellular distortions represent a person's so-called cancer avatar. Once the avatar is generated, a computer model predicts which drugs, based upon their known functions, are most likely to kill a real cancer cell.

For the study, researchers generated cancer avatars for cells obtained from patients with glioblastoma, a highly aggressive cancer of the brain's glial cells. The condition has a five-year survival rate of about 10 percent. The computer generated predictions were then "truth-checked" against standard, cultured cells in drug-sensitivity experiments.

"The advantage of computational modeling is the ability to incorporate the wealth of genomic and proteomic information on cancer cells and to screen drugs and combinations of drugs much faster and cost effectively," said Kesari. "Our ultimate goal is to take this technology to the clinic to identify the best drugs for treating each individual cancer patient."

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Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.

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Journal Reference:

1. Sandeep C Pingle, Zeba Sultana, Sandra Pastorino, Pengfei Jiang, Rajesh Mukthavaram, Ying Chao, Ila Bharati, Natsuko Nomura, Milan Makale, Taher Abbasi, Shweta Kapoor, Ansu Kumar, Shahabuddin Usmani, Ashish Agrawal, Shireen Vali, Santosh Kesari. In silico modeling predicts drug sensitivity of patient-derived cancer cells. Journal of Translational Medicine, 2014; 12 (1): 128 DOI: 10.1186/1479-5876-12-128

Tiny muscles help bats fine-tune flight, stiffen wing skin

 

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Fine-tuning flight. Hair-thin muscles embedded in the skin of their wings allow bats like this Jamaican fruit bat to change the stiffness and curvature of their wings at different points of the wing stroke. That observation could help improve design of mechanical flight surfaces.

Bats appear to use a network of hair-thin muscles in their wing skin to control the stiffness and shape of their wings as they fly, according to a new study. The finding provides new insight about the aerodynamic fine-tuning of membrane wings, both natural and human-made.

A new study of bats reveals a capability within their wondrous wings that may help them fine-tune their flight.

Bats employ a network of nearly hair-thin muscles embedded in the membrane of their inherently floppy wing skin to adjust the wings' stiffness and curvature while they fly, Brown University researchers report. Birds and insects have stiff wings, but the new evidence suggests bats have evolved this muscular means of preserving or adjusting wing shape.

"Aerodynamic performance depends upon wing shape," said Brown biology graduate student Jorn Cheney, lead author of the newly published paper in Bioinspiration and Biomimetics. "The shape of a membrane wing might initially begin flat but as soon as it starts producing lift it's not going to remain flat because it has to deform in response to that aerodynamic load.

"The shape it adopts could be a terrible one -- it could make the animal crash -- or it could be beneficial," Cheney said. "But they are not locked into that shape. Because bats have these muscles in their wings, and also bones that can control the general shape as well, they can adopt any number of profiles."

Membrane muscle measurements

Cheney wasn't sure what to make of the tiny muscles, called plagiopatagiales, heading into the experiments reported in the paper. They have been known for more than a century but their function has never been demonstrated.

When Cheney considered the muscle function, he estimated that each individual muscle would be too weak to reshape the wing. That led him to form two competing hypotheses: either that the muscles would activate together to enhance force or that these oddly shaped, weak muscles might exist solely as sensors of stretch.

Only experiments could settle the question, so Cheney attached electrode sensors to a few muscles on the wings of a few Jamaican fruit bats and filmed them as they flew in the lab's wind tunnel.

Three key findings emerged from the data. They all point to the plagiopatagiales modulating skin stiffness.

One result was that the muscle activation and relaxation follows a distinct pattern during flight: They tense on the downstroke and relax on the upstroke.

"This is the first study showing that bats turn these muscles on and off during a typical wingbeat cycle," said co-author Sharon Swartz, professor of biology at Brown.

.Another finding was that the muscles don't act individually. Instead they exert their force in synchrony, providing enough collective strength to stiffen the wing.

Finally, Cheney found, the muscles appeared to activate with different timing at different flight speeds. As the bats flew faster, they tensed the muscles sooner in the upstroke-downstroke cycle.

In other words, the data suggested that the muscles do not behave passively but actively and collectively in keeping with conditions of flight.

None of the data, however, preclude the muscles from serving a sensory function as well.

Technological insight, too

Cheney's findings fit into a larger program of research at Brown between the labs of biologist Swartz and co-author Kenneth Breuer, professor of engineering, in which, as Breuer puts it, they are "using biology to inspire engineering and using engineering to inspire biology."

In parallel with studies of real bats, the team has also built a robotic bat wing that incorporates their biological observations. Then they use the wing to generate data from experiments that they could never do with living creatures, such as precisely varying kinematic parameters like wingbeat frequency and amplitude, or the degree of wing folding during flapping.

In a separate paper in the same edition of Bioinspiration and Biomimetics, Swartz, Breuer, and former student Joe Bahlman report on how energy costs and aerodynamic forces changed as they varied several kinematic parameters in the robotic bat wing. They found that to generate a given force, such as lift, each of several parameters requires about the same amount of energy, but that the timing and extent of wing folding varies the ratio between lift and power significantly.

The group is now improving the robotic wing by integrating the new findings about how plagiopatagiales impact wing stiffness and shape.

"When one tries to build an engineered flying vehicle, you want to have control over its aerodynamic properties," Breuer said. "This is one more knob that we have to turn now. To be able to use these membrane wings and be able to control the properties in the way that we suspect bats do, using these muscles, is a great opportunity for biomimetic systems."

The group has a paper in press showing that controlling membrane tension in this way controls aerodynamic properties.

In addition to Cheney, Breuer, and Swartz, the paper's other authors are Erika Giblin, Nicolai Konow, and Thomas Roberts at Brown and Kevin Middleton at the University of Missouri.

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Story Source:

The above story is based on materials provided by Brown University. Note: Materials may be edited for content and length.

Straw from oilseed as a new source of biofuels

 

May 23 / 2014

Norwich BioScience Institutes

Straw from crops such as wheat, barley, oats and oilseed rape is seen as a potential source of biomass for second generation biofuel production. Currently the UK produces around 12 million tonnes of straw. Although much is used for animal bedding, mushroom compost and energy generation, there still exists a vast surplus. Preliminary lab findings are pointing at ways that the process of turning straw from oilseed rape into biofuel could be made more efficient, as well as how the straw itself could be improved.

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Pilot Steam Explosion Unit in the Biorefinery Centre.

The bright yellow fields of oilseed rape are a familiar sight at this time of year, but for scientists what lies beneath is just as exciting.

Researchers at the Institute of Food Research are looking at how to turn straw from oilseed rape into biofuel. Preliminary findings are pointing at ways the process could be made more efficient, as well as how the straw itself could be improved.

Straw from crops such as wheat, barley, oats and oilseed rape is seen as a potential source of biomass for second generation biofuel production. Currently the UK produces around 12 million tonnes of straw. Although much is used for animal bedding, mushroom compost and energy generation, there still exists a vast surplus.

Straw contains a mix of sugars that could be used as a source of biofuels that do not compete with food production but instead represent a sustainable way of utilizing waste. However, the sugars are in a form that makes them inaccessible to the enzymes that release them for conversion into biofuels, so pre-treatments are needed. The pre-treatments make the complex carbohydrates more accessible to enzymes that convert them to glucose, in a process called saccharification. This is then fermented by yeast into ethanol.

Using the facilities at the Biorefinery Centre on the Norwich Research Park, Professor Keith Waldron and his team have been looking at the steps needed to unlock the sugars tied up in the tough straw structure. In particular, they have looked at the pre-treatment stage, focusing on steam explosion, which involves 'pressure-cooking' the biomass, to drive a number of chemical reactions. A rapid pressure-release then causes the material to be ripped open, to further improve accessibility.

They varied the temperature and duration of steam explosion and then used a variety of physical and biochemical techniques to characterise what effects varying the pre-treatments had on the different types of sugars before and after saccharification.

The amount of cellulose converted to glucose increased with the severity of the pretreatment. Saccharification efficiency is also associated with the loss of specific sugars, and subsequent formation of sugar breakdown products.

In a further study funded by the BBSRC / EPSRC Integrated Biorefining Research and Technology Club, the scientists discovered the key factors that determine the efficiency of saccharification. One particular compound, uronic acid, limited the rate at which enzymes worked. The final sugar yield was closely related to the removal of xylan, a common component of plant cell walls. The abundance of lignin, a 'woody' cell wall component, was positively related to the amount of available sugars.

These findings will help improve the efficiency by which straw can be converted to biofuels. For example, adding enzymes that more effectively remove xylan should improve yield. Controlling the level of lignin in the material should also help.

It may even be possible to improve the straw itself, for example to reduce the uronic acid content in the biomass, as suggested by these findings. In the main, oilseed rape has been bred to improve oilseed yield and disease resistance, without paying much attention to the straw. The IFR is working with colleagues at the University of York and the John Innes Centre to see whether there are ways of breeding more "biofuel-ready" varieties of oilseed rape, with the same yields of oilseed but with more amenable straw. In addition, a full understanding of the polysaccharides and other compounds made available during pretreatment may mean other valuable co-products, like platform chemicals, may be viably produced from the surplus straw.

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Story Source:

The above story is based on materials provided by Norwich BioScience Institutes. Note: Materials may be edited for content and length.

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Journal References:

1. Ian P. Wood, Adam Elliston, Sam R.A. Collins, David Wilson, Ian Bancroft, Keith W. Waldron. Steam explosion of oilseed rape straw: Establishing key determinants of saccharification efficiency. Bioresource Technology, 2014; 162: 175 DOI: 10.1016/j.biortech.2014.03.115
2. Peter Ryden, Alizée Gautier, Nikolaus Wellner, Henri S. Tapp, Svein J. Horn, Vincent G.H. Eijsink, Keith W. Waldron. Changes in the composition of the main polysaccharide groups of oil seed rape straw following steam explosion and saccharification. Biomass and Bioenergy, 2014; 61: 121 DOI: 10.1016/j.biombioe.2013.12.003

Breakthrough method for making Janus or patchy capsules

 

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Paul Dommersnes, left, from the University of Paris, Diderot, and Jon Otto Fossum, from the Norwegian University of Science and Technology, were among the team that has come up with a novel way to create patchy capsules.

Hollow capsules that have a selectively permeable shell are promising candidates as tiny containers for molecules, particles or bubbles, and are becoming increasingly important in a wide variety of applications. But making these kinds of capsules with more than one kind of substance on their shells has been challenging -- until now.

In a article in the latest edition of Nature Communications, NTNU researcher Jon Otto Fossum and Paul Dommersnes from the University of Paris, Diderot, were part of a team that showed that both Janus and more advanced patchy capsules can be assembled by combining electro-coalescence and electro-hydrodynamic flow in leaky dielectric emulsion drops. This technique can be used with any type of insulating or weakly conductive particles.

Their work is the realization of one possible direction foreseen by the same researchers in a publication in Nature Communications in 2013.

Hollow capsules with two or more substances on their surface are able to organize themselves in specific ways, which means they could be used to grow human skin or other body tissues, or to make porous tissues and composites. They can also be used to transport a variety of substances and release them in specific environments.

Janus capsules, named for the two-faced Roman god, have just two different substances in their shells. They are a sub-group of patchy capsules, which can have more than two different substances in their shells. The researchers were able to make both Janus capsules, with two different substances, and patchy capsules, which had stripes or flecks on them.

Janus and patchy capsules are distinct from Janus and patchy particles, which are solid. These capsules combine the characteristics of Janus or patchy particles, and those of capsules such as colloidosomes.

The different characteristics on the shells of the capsules make them attractive to each other in different ways, depending on the composition of the capsule shells, which means they can create scaffolds suitable for biomedical applications, for assembling electric circuits or optical structures such as photonic crystals, and as vehicles for liquid or molecular transport.

The researchers foresee that their route for designing patchy capsules will facilitate the foundation for many advanced applications, for example, by using microfluidic methods.

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Story Source:

The above story is based on materials provided by Norwegian University of Science and Technology. Note: Materials may be edited for content and length.

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Journal Reference:

1. Zbigniew Rozynek, Alexander Mikkelsen, Paul Dommersnes, Jon Otto Fossum. Electroformation of Janus and patchy capsules. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4945

Measuring fine dust concentration via smartphone

 

May 23 / 2014

Karlsruhe Institute of Technology

Big cities in the smog: Photos from Beijing and, more recently, Paris clearly illustrate the extent of fine dust pollution. But what about our direct environment? What is the pollution concentration near our favorite jogging route? Scientists are developing a sensor that can be connected easily to smartphones. In the future, users are to take part in drawing up a pollution map via participatory sensing. The precision of the map will be the higher, the more people will take part.

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Clean air alongside busy roads? The smartphone fine dust sensor is intended to measure concentration in real time.

Big cities in the smog: Photos from Beijing and, more recently, Paris clearly illustrate the extent of fine dust pollution. But what about our direct environment? What is the pollution concentration near our favorite jogging route? Scientists of Karlsruhe Institute of Technology (KIT) are developing a sensor that can be connected easily to smartphones. In the future, users are to take part in drawing up a pollution map via participatory sensing. The precision of the map will be the higher, the more people will take part.

The principle of fine dust measurements using a smartphone corresponds to that of simple optical sensors. "Instead of the conventional infrared LED in the sensor, the flashlight of the smartphone emits light into the measurement area. This light is scattered by the possibly existing dust or smoke. The camera serves as a receptor and takes a picture representing the measurement result. The brightness of the pixels can then be converted into the dust concentration," computer scientist Matthias Budde explains. He has developed the system as a member of the research group TECO of KIT's Chair for Pervasive Computing.

The computer scientists have carried out comparative measurements to prove that the principle works. The smartphone sensors are not yet as precise as specialized instruments. However, their costs are much lower. "Detectors at the official measurement stations operated by the Baden-Württemberg State Agency for the Environment, Measurement, and Nature Conservation are very precise, but also very large, very expensive, and static. In Karlsruhe, for instance, only two measurement stations have been established," Budde says. He plans to enhance accuracy by a high measurement density. Measurements of many, closely adjacent sensors may be combined to results of reduced inaccuracy. Thus, measurement errors could be reduced. Due to their close vicinity, the sensors might also be calibrated against each other. Budde thinks that a potential application scenario is joint measurement or participatory sensing: Interested citizens measure data at various places in their city and share them. These data may then be used to draw up a fine dust pollution map for the respective city in real time.

The sensor is planned to be attached to the smartphone by means of a magnet, for instance. Adaptation of electronics will not be required. Users who want to join participatory sensing will have to download the corresponding app. At the measurement point desired, the sensor is attached to the cell phone and the users take a photo or a video for measurement. The images can be evaluated locally or transmitted to a computer system that combines these data with other measurements and sends them back. Then, the fine dust concentration is displayed by the phone.

Presently, the smartphone sensor can measure concentrations of about one microgram per cubic meter. This is sufficient for detecting coarse dust and smoke, but not for typical fine dust concentrations in the microgram range. The scientists now plan to further increase the sensitivity of the sensors. This can be achieved among other means by ideally bundling the flashlight in the sensor by using hemispherical lenses. This principle is realized in a recently produced, far smaller second prototype. In addition, the evaluation algorithms and the smartphones themselves will be further developed. In the future, the devices will no longer compress the photos automatically, but also be able to supply raw data. This promises to increase the accuracy of the measurement results even further. Budde reckons that a smartphone sensor able to detect typical fine dust will have been developed in the course of next year.

The doctoral thesis of the computer scientist, however, does not only deal with the further development of the sensor and the possibilities of generating a map from the measurement points, but also with the question of how citizens can be motivated to participate. "Many people are intrinsically interested in such offers, because they see a benefit for themselves and others," Budde says. For those, who like games, a gamification system might be feasible. Users might score points for the collection of data or measurements at certain locations. Also, data protection is an important aspect of participatory sensing. "Users have to be sure that the operator protects their data from being tracked or stolen and uses them for nothing but the pollution map." An option is data aggregation, by means of which data are combined and bundled such that they can no longer be traced back to an individual person. But the central idea of participatory sensing is the joint benefit resulting from an increased information quality -- which increases with the number of measurements.

KIT Video on measuring fine dust concentration via smartphone: http://www.kit.edu/videos/feinstaub_messen

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Story Source:

The above story is based on materials provided by Karlsruhe Institute of Technology. Note: Materials may be edited for content and length

Electricity use slashed with efficiency controls for heating, cooling

 

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Commercial buildings could cut their heating and cooling electricity use by an average of 57 percent with advanced energy-efficiency controls, according to a year-long trial of the controls at malls, grocery stores and other buildings across the country. The study demonstrated higher energy savings than what was predicted in earlier computer simulations by the same researchers.

"We've long known that heating and cooling are among the biggest energy consumers in buildings, largely because most buildings don't use sophisticated controls," said the study's lead researcher, engineer Srinivas Katipamula of the Department of Energy's Pacific Northwest National Laboratory. "But our tests of controls installed at real, working commercial buildings clearly demonstrate how much more energy efficient air-conditioning systems can be."

This research was supported by DOE's Office of Energy Efficiency & Renewable Energy and the Bonneville Power Administration.

Sitting on the roofs of many commercial buildings are shiny metal boxes containing heating, cooling, ventilation and air conditioning (also known as HVAC) units. These are pre-made in a factory and have all their components inside a box, leading the industry to call them "packaged" HVAC units. Another kind of commercial HVAC, called air handling units, have long used sophisticated controls to ensure they work as efficiently as possible. But packaged units are often allowed to run for hours on end, even if they aren't needed, and receive little maintenance.

Packaged HVAC units consume the same amount of electricity each year as 8 million U.S. residents, or about 2,600 trillion British thermal units of energy. All those ignored and often-inefficient HVAC systems add up, creating higher power bills and contributing to the nation's greenhouse gas emissions.

Putting an idea to the test

Katipamula and his PNNL colleagues have spent their careers thinking up ways to reduce energy use in buildings. In 2011, they set out to adapt the controls already found in air handling HVAC units for use in packaged rooftop HVAC units. The goal was to enable packaged units to automatically adjust their operations based on conditions inside and outside a building. Using sensors and variable-speed motors, the controls decide when and how fast ventilation fans should run, and if the units can use naturally cold air from the outside instead of mechanically cooling indoor air.

While the PNNL team was evaluating how these controls could work, they learned a few companies were simultaneously and independently in the process of developing such advanced controls. During the summer of 2012, the team installed one of the commercially available control kits on 66 rooftop HVAC units at eight volunteer commercial buildings in Washington state, Ohio, California and Pennsylvania. The buildings included shopping malls, grocery stores, big-box stores and a medical clinic. The installed devices, manufactured by Transformative Wave of Kent, Wash., were chosen because they most closely resembled the advanced controls PNNL had envisioned.

Real energy savings

Katipamula and his colleagues found that, compared to standard operations, the HVAC units using advanced controls cut their energy use by an average of 57 percent. The actual energy savings ranged from 20 to 90 percent. Larger buildings such as malls, which need bigger HVAC units, saved more energy than smaller buildings. And buildings that ran ventilation fans more, such as stores open long hours, tended to save more energy.

Translating the energy savings into dollars saved depended on local power costs. Nationwide, energy costs an average of 10 cents per kilowatt-hour, though areas with abundant and inexpensive power supplies often pay less and large cities with greater energy needs generally pay more. When using the national average, researchers found all the field-tested HVAC units would have saved an average of $1,489 annually per unit. The team calculated it would take a building owner three years to recoup the cost of buying and installing advanced controls with that average cost savings. Commercial buildings often have multiple rooftop HVAC units, so actual savings per building would depend on the number of units used.

But the exact payback period depends on several factors. To help building owners weigh the costs, the research team developed a table that lays out which specific combinations of an HVAC unit's size, the number of hours its fan runs daily and the local energy rate would result in a three-year or less payback period. The team concluded installing advanced controls in smaller units with a capacity of 15 tons or less could achieve a three-year payback in areas where energy costs 12 cents per kilowatt-hour or more, or where sufficient utility incentives were available.

"I'm proud to see the advanced controls my colleagues and I evaluated not only work in the real world, but produce significant energy savings," Katipamula said. "We hope commercial building owners will be inspired by these tangible savings and install advanced controls in their rooftop HVAC units."

The reports are available at:

S. Katipamula, W. Wang and M. Vowles, "Improving Operating Efficiency of Packaged Air Conditioners & Heat Pumps," ASHRAE Journal, March 2014, http://buildingsystems.pnnl.gov/documents/036-043_Katipamula.pdf.

W. Wang, S. Katipamula, H. Ngo, R. Underhill, D. Taasevigen and R. Lutes, "Advanced Rooftop Control (ARC) Retrofit: Field-Test Results," report for DOE, July 2013, http://www.pnl.gov/main/publications/external/technical_reports/PNNL-22656.pdf

Pulsed electrical fields destroy antibiotic-resistant bacteria infecting burn injuries

 

Application of electrical fields (left) is believed to destroy bacteria by inducing the formation of large holes (right) in bacterial membranes.

Application of a technology currently used to disinfect food products may help to get around one of the most challenging problems in medicine today, the proliferation of bacteria resistant to antibiotics and other antimicrobial drugs. In a paper appearing in the June issue of the journal Technology and already released online, investigators from the Massachusetts General Hospital (MGH) Center for Engineering in Medicine describe how the use of microsecond-pulsed, high-voltage non-thermal electric fields successfully killed resistant bacteria infecting experimentally induced burns in mice, reducing bacterial levels up to 10,000-fold.

"Pulsed electrical field technology has the advantages of targeting numerous bacterial species and penetrating the full thickness of a wound," says Alexander Golberg, PhD, of the MGH Center for Engineering in Medicine (MGH-CEM), first author of the paper. "This could lead to a completely new means of burn wound disinfection without using antibiotics, which can increase bacterial resistance."

About 500,000 individuals are treated for burn injuries in the U.S. each year. Standard burn treatment involves removal of burned tissue, skin grafts, and the application of antiseptic and antimicrobial dressings to prevent and treat infection. The growing prevalence of antibiotic-resistant bacteria -- including strains of Acinetobacter baumannii and Staphylococcus aureus -- is behind the frequent failure of antibiotic treatment, necessitating novel approaches to eliminate infecting pathogens.

Pulsed electrical fields (PEFs) have been used for decades to preserve food by destroying bacteria, presumably by causing the formation of large pores in the bacterial membrane; and more recently PEF's have been used to treat solid tumors. Members of the MGH research team, led by Martin Yarmush, MD, PhD, director of the MGH-CEM, have previously used PEF to study scarless skin regeneration and are currently investigating use of the technology to improve wound healing. Theorizing that the procedure could improve management of wound infection, the researchers designed the current study.

The investigators applied a multidrug resistant strain of A. baumannii to small third-degree burns that had been made on the backs of anesthetized mice. After 40 minutes, during which imaging of the fluorescent bacteria confirmed the established infection, the burned area was treated with an electrical field generated by placing the damaged skin between two electrodes. Each animal received two 40-pulse treatments five minutes apart, one group receiving 250 V/mm pulses and another receiving 500 V/mm pulses.

Images taken right after each treatment showed pronounced drops in bacterial levels. While images taken three hours later showed some bacterial regrowth, the overall results confirmed a persistent reduction in bacterial levels, ranging from a 500-fold reduction after 80 pulses at 250 V/mm volts to a more than 10,000-fold reduction after 80 pulses at 500 V/mm. The researchers also found that increasing the number of pulses per treatment had a greater effect on bacterial reduction than did increasing the strength of the electric field. Additional investigation is needed to confirm the safety of the tested voltage levels and the treatment's effectiveness against deep infections and other species of resistant bacteria.

"Currently available technologies have not been able to solve the problem of multidrug-resistant burn wound infections, and lasers are unable to treat infections deep within a wound because of the scattering and absorption of light," says Yarmush, who is senior author of the Technology paper. "Pulsed electric fields are a previously unexplored technique that has the potential to provide a chemical-free way of disinfecting burns and other wound infections."

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The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

Radiofrequency ablation, complete endoscopic resection equally effective for dysplastic Barrett's esophagus

 

May 21 / 2014

American Society for Gastrointestinal Endoscopy

Radiofrequency ablation and complete endoscopic resection are equally effective in the short-term treatment of dysplastic Barrett's esophagus, according to a new systematic review article, but adverse event rates are higher with complete endoscopic resection. Barrett's esophagus is a condition in which the lining of the esophagus changes and becomes more like the lining of the small intestine. It is believed that Barrett's esophagus (BE) occurs because of chronic inflammation resulting from long-standing Gastroesophageal Reflux Disease.

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According to a new systematic review article, radiofrequency ablation and complete endoscopic resection are equally effective in the short-term treatment of dysplastic Barrett's esophagus, but adverse event rates are higher with complete endoscopic resection. The article comparing the two treatments appears in the May issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy (ASGE).

Barrett's esophagus is a condition in which the lining of the esophagus changes and becomes more like the lining of the small intestine. It is believed that Barrett's esophagus (BE) occurs because of chronic inflammation resulting from long-standing Gastroesophageal Reflux Disease (GERD). Barrett's esophagus is more common in Caucasian males older than the age of 50 who have had GERD for greater than five years. Most patients with Barrett's esophagus will not develop cancer. However, in some patients further precancerous change in the tissue, called dysplasia, will develop. Those patients that develop dysplasia, especially high grade dysplasia, are significantly more likely to develop esophageal cancer.

Esophagectomy (surgery to remove part or all of the esophagus) has previously been the recommended treatment for BE with high grade dysplasia (HGD) or intramucosal cancer (cancer limited to the most superficial layer of the esophagus), but this surgery is associated with significant morbidity and mortality. As a result, endoscopic therapies for treatment of HGD or superficial cancers have been developed which minimize treatment-related morbidity. Ideally, endoscopic treatments need to target the entire segment of Barrett's mucosa (lining of the esophagus) in order to maximally reduce the risk of developing esophageal cancer.

To date, two distinct endoscopic approaches have been widely used for this purpose. The first is complete endoscopic mucosal resection (EMR) where the BE mucosa is resected or removed endoscopically. This has the advantage of providing a large histologic specimen, which can then be evaluated for unrecognized, more advanced pathology, and may be curative. The other approach is ablation of the BE mucosa by using a variety of techniques such as photodynamic therapy, argon plasma coagulation (APC), and more recently, radiofrequency ablation (RFA). RFA uses a focal heat process to destroy the Barrett's tissue. In recent years, RFA has become the ablative treatment of choice in the management of dysplastic BE, with early studies suggesting excellent efficacy and low rates of adverse events.

"Only one trial to date has directly compared complete EMR and RFA in treating dysplastic BE. The aim of this systematic review was to compare the efficacy and safety of these two techniques. This is important because RFA is substantially more expensive than complete EMR and may require multiple procedures over six months or more, making it less acceptable to patients. Therefore, in order to justify the use of RFA in the future it must be convincingly proven to be superior to complete EMR, in terms of both efficacy and risk of adverse events," said study lead author Georgina Chadwick, MRCP, The Royal College of Surgeons of England. "We found that RFA and complete EMR are equally effective in the short-term treatment of dysplastic BE, but adverse event rates are higher with complete EMR."

Methods

This article was a systematic review of literature to compare the efficacy and safety of complete EMR and radiofrequency ablation in the treatment of dysplastic BE. Patients had a diagnosis of BE with HGD or intramucosal cancer treated with either complete EMR or RFA. Main outcome measurements included complete eradication of dysplasia and intestinal metaplasia at the end of treatment and after more than 12 months' follow-up, as well as short and long-term adverse event rates associated with either treatment.

Results

A total of 22 studies met the inclusion criteria. Only one trial directly compared the two techniques; most studies were observational case series. Dysplasia was effectively eradicated at the end of treatment in 95 percent of patients after complete EMR and 92 percent after RFA. After a median follow-up of 23 months for complete EMR and 21 months for RFA, eradication of dysplasia was maintained in 95 percent of patients treated with complete EMR and 94 percent of patients treated with RFA. Short-term adverse events were seen in 12 percent of patients treated with complete EMR, but in only 2.5 percent of those treated with RFA. Esophageal strictures were long-term adverse events in 38 percent of patients treated with complete EMR, compared with 4 percent of those treated with RFA. Progression to cancer appeared to be rare after either treatment, although follow-up was short.

The authors concluded that both complete EMR and RFA have proven efficacy in eradication of BE with HGD or intramucosal cancer, but both short and long-term adverse events are significantly greater after complete EMR. The results of this review suggest that RFA, with prior resection of any nodules, is the endoscopic treatment of choice for dysplastic BE. But further research needs to be done to prove the long-term durability of both treatments in order to confirm their superiority over surgery in the management of dysplastic BE. Though low, the risk of recurrence of dysplasia and intestinal metaplasia after treatment reiterates the need for continuing endoscopic surveillance. Further research needs to determine the optimal surveillance regimen after successful eradication.

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Story Source:

The above story is based on materials provided by American Society for Gastrointestinal Endoscopy. Note: Materials may be edited for content and length.

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Journal Reference:

1. Georgina Chadwick, Oliver Groene, Sheraz R. Markar, Jonathan Hoare, David Cromwell, George B. Hanna. Systematic review comparing radiofrequency ablation and complete endoscopic resection in treating dysplastic Barrett's esophagus: a critical assessment of histologic outcomes and adverse events. Gastrointestinal Endoscopy, 2014; 79 (5): 718 DOI: 10.1016/j.gie.2013.11.030

Managing diabetes: How can online games help patients make healthier choices?

 

May 21 / 2014

Journal of Consumer Research, Inc.

Type 2 diabetes is a chronic disease of global relevance. Due to the fear that comes with the long-term bodily degenerative processes, people with the disease often do not actively seek information on the health risks. According to a new study, modern day technologies like interactive games and virtual reality platforms can help people with Type 2 diabetes make better choices and monitor their health on a regular basis.

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Type 2 diabetes is a chronic disease of global relevance. Due to the fear that comes with the long-term bodily degenerative processes, people with the disease often do not actively seek information on the health risks. According to a new study in the Journal of Consumer Research, modern day technologies like interactive games and virtual reality platforms can help people with Type 2 diabetes make better choices and monitor their health on a regular basis.

"Our findings bring to light the unrealized power of information communication technologies as social platforms," write authors Kelly Tian (University of Wyoming), Pookie Sautter, Derek Fisher (both New Mexico State University), Sarah Fischbach (University of Hawaii at Manoa), Cuauhtemoc Luna-Nevarez (Sacred Heart University), Kevin Boberg, Jim Kroger (both New Mexico State University), and Richard Vann (University of Wyoming).

The authors found that when people engage in interactive social platforms that are capable of building and hosting online therapeutic communities, they develop empathy for the people who are living day-to-day with a chronic disease. As the online therapeutic communities are developed, the players become peers who mentor one another in making better choices about their health.

For companies interested in funding grants that support the healthcare industry, study results support the need for establishing online therapeutic communities where visual platforms foster community engagement and create markets for new technologies. The authors also point out a need for reforming patient education and the design and distribution of information related to a chronic disease like Type 2 diabetes.

"Emerging bio-health companies that develop monitoring products may also benefit from allowing customer input featured in their product designs," the authors conclude. "Patient visions of how these features can help alleviate trauma and improve lives show the power of the therapeutic community."

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Story Source:

The above story is based on materials provided by Journal of Consumer Research, Inc.. Note: Materials may be edited for content and length.

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Journal Reference:

1. Kelly Tian, Pookie Sautter, Derek Fisher, Sarah Fischbach, Cuauhtemoc Luna-Nevarez, Kevin Boberg, Jim Kroger, and Richard Vann. Transforming Health Care: Empowering Therapeutic Communities through Technology-Enhanced Narratives. Journal of Consumer Research, August 2014

Exclusive: EBay initially believed user data safe after cyberattack

 

 

(Reuters) - EBay Inc initially believed that its customers' data was safe as forensic investigators reviewed a network security breach discovered in early May and made public this week, a senior executive told Reuters on Friday.

EBay has come under fire over its handling of the cyberattack, in which hackers accessed personal data of all 145 million users, ranking it among the biggest such attacks launched on a corporation to date.

"For a very long period of time we did not believe that there was any eBay customer data compromised," global marketplaces chief Devin Wenig said, in the first comments by a top eBay executive since the e-commerce company disclosed the breach on Wednesday.

EBay moved "swiftly to disclose" the breach after it realized customer data was involved, he said.

Wenig would not say when the company first realized that the cyberattackers accessed customer data, nor how long it took to prepare Wednesday's announcement.

He said hackers got in using the credentials of three corporate employees, eventually making their way to the user database.

Hackers accessed email addresses and encrypted passwords belonging to all eBay users. "Millions" of users have since reset their passwords and the company had begun notifying users, though it would take some time to complete that task, Wenig said.

"You would imagine that anyone who has ever touched eBay is a large number," he said. "So we're going to send all of them an email, but sending that number all at once is not operationally possible."

At least three U.S. states are investigating the company's security practices. Customers have complained on social media about delayed notification emails. And New York's attorney general called on eBay to provide free credit monitoring services to users.

But the Internet retail giant has no plans to compensate customers or offer free credit monitoring for now because it had detected no financial fraud, Wenig said.

Wenig declined comment when asked if he thought eBay had good security prior to the breach. He said the company would now bolster its security systems, and has mobilized senior executives in a subsequent investigation of the attack.

"We want to make sure it doesn't happen again so we're going to continue to look our procedures, harden our operational environment and add levels of security where it's appropriate."

The breach marked the latest headache for eBay this year. In January, it crossed swords publicly with activist investor Carl Icahn, who mounted a campaign to get it to spin out PayPal. Then in April, the e-commerce company disappointed investors with a weak second-quarter outlook, pressuring its shares.

AVOIDING BACK DOORS

Buying and selling activity on eBay remained "fairly normal" though eBay is still working out the cost of the breach, which included hiring a number of security firms. Wenig, who was previously a senior executive at Thomson Reuters Corp, declined to comment on whether the cost could be material to eBay's results.

Wenig's revelation that the company initially believed that no customer data had been compromised might take some of the heat off eBay's executive team.

Cyber forensics experts said it's not uncommon for large companies to take weeks to grasp the full impact of an attack, because hackers are often able to steal data without leaving obvious clues.

"In some cases you go in and find the smoking gun immediately. Other times, it takes a few days or even a few weeks," said Kevin Johnson, a cyber-forensics expert who was not involved in the eBay investigation but has worked for other Fortune 500 companies.

Daniel Clemens, a forensics expert and CEO of Packet Ninjas, said investigators often ask companies to hold off on disclosure until they believe they understand the full extent of an attack. Otherwise, they risk tipping off attackers who might cover their tracks or leave "back doors" so they can return after the investigators complete their probe.

On Wednesday, the e-commerce company announced that hackers raided its network between late February and early March. The company said financial information was not compromised and its payments unit PayPal was not affected.

When eBay first discovered the network breach in early May, the senior team was immediately involved and held multiple daily calls on the issue. EBay staff have been working around the clock since Wednesday.

Wenig said he could not provide much more detail about what happened in the attack beyond the scant information given out so far.

He declined to provide further specifics, citing ongoing investigations by the Federal Bureau of Investigation and several forensics firms including FireEye Inc's Mandiant division.

(Editing by Edwin Chan, Lisa Shumaker and Andrew Hay)

Researchers to study whether mobile phones affect teenage brains

 

 

(Reuters) - British researchers are launching the largest study in the world to investigate whether using mobile phones and other wireless gadgets might affect children's brain development.

The Study of Cognition, Adolescents and Mobile Phones, or SCAMP, project will focus on cognitive functions such as memory and attention, which continue to develop into adolescence - just the age when teenagers start to own and use personal phones.

While there is no convincing evidence that radio waves from mobile phones affect health, to date most scientific research has focused on adults and the potential risk of brain cancers.

Because of that, scientists are uncertain as to whether children's developing brains may be more vulnerable than adults' brains - partly because their nervous systems are still developing, and partly because they are likely to have a higher cumulative exposure over their lifetimes.

"Scientific evidence available to date is reassuring and shows no association between exposure to radiofrequency waves from mobile phone use and brain cancer in adults in the short term - i.e. less than 10 years of use," said Paul Elliott, director of the Centre for Environment and Health at Imperial College London, who will co-lead the research.

"But the evidence available regarding long term heavy use and children's use is limited and less clear."

Mobile phone use is ubiquitous, with the World Health Organisation estimating 4.6 billion subscriptions globally. In Britain, some 70 percent of 11 to 12 year-olds now own a mobile phone, and that figure rises to 90 percent by age 14.

COGNITIVE ABILITIES

Elliott and the study's principal investigator, Mireille Toledano, aim to recruit around 2,500 11 to 12 year-old school children and follow their cognitive development over two years whilst collecting data on how often, for what, and for how long they use mobile or smart phones and other wireless devices.

Parents and pupils who agree to take part in the study will answer questions about the children's use of mobile devices and wireless technologies, well-being and lifestyle. Pupils will also undertake classroom-based computerised tests of the cognitive abilities behind functions like memory and attention.

"Cognition is essentially how we think, how we make decisions, and how we process and recall information," said Toledano, who is also at Imperial College's centre for Environment and Health.

"It is linked to intelligence and educational achievement and forms the building blocks of the innovative and creative potential of every individual and therefore society as a whole."

The World Health Organisation says a large number of studies have been performed over the past two decades to assess whether mobile phones pose a potential health risk, and to date, no adverse health effects have been established.

Still, the electromagnetic fields produced by mobile phones are classified by the International Agency for Research on Cancer as "possibly carcinogenic to humans", and the global health agency has said more research into the issue is vital.

Current British health policy guidelines say children under 16 should be encouraged to use mobile phones for essential purposes only, and where possible use a hands-free kit or text.

But Toledano said this advice was "given in the absence of available evidence - and not because we have evidence of any harmful effects".

"As mobile phones are a new and widespread technology central to our lives, ... the SCAMP study is important ... to provide the evidence base ... through which parents and their children can make informed life choices," she said.

(Editing by Alison Williams)

Comments (1)

Art16 wrote:

I am sure the challenge to many is the theft of the teenage attention span in real time. The communications revolution has created teenage social groups which can continue their group “activities” at their leisure practically 24/7 and not have to physically gather to talk, gossip, flirt, spread rumors, and all the things in which the teen years find important. The upshot is that teenagers have less time to devote to schoolwork, reading, self development, and those activities that help the learning process and cognitive ability to develop. Not all teens are a slave to their cellphones, but the role model of adults with cellphones at or in their ears does not help.

The alleged health effects advertised by some people and organizations have no foundation in the scientific method, and are, in my book, just another manifestation of the fine art of fear mongering with less than honorable attentions. My 35 years or so at being involved in electromagnetic energy safety in the IEEE C95 standards committees gives me the confidence to say to not worry about these claims and only if you see me running for the door, then you should follow. Besides, the FDA is at the door watching for harmful effects of cellphones as well, as they do with all kinds of things that could impact the public adversely in real ways.

Bill to put warning label on sugary drinks advances in California

 

(Reuters) - A measure to require sugary soft drinks to carry labels warning of obesity, diabetes and tooth decay advanced in the California state legislature on Friday, the latest move by lawmakers nationwide aimed at persuading people to drink less soda.

The legislation, if enacted, would put California, which banned sodas and junk food from public schools in 2005, in the vanguard of a growing national movement to curb the consumption of high-calorie beverages medical experts say are largely to blame for an epidemic of childhood obesity.

"This is a major victory for public health advocates, community groups, physicians, and dentists,” said Democratic state senator Bill Monning, author of the bill. "By informing consumer choice, we can improve the health of Californians.”

In 2012, New York City Mayor Michael Bloomberg spearheaded a citywide ban on sales of oversized sugary soft drinks, but the move was declared illegal by a state judge after a legal challenge by makers of soft drinks and a restaurant group. New York's highest court has agreed to hear an appeal.

The California measure, passed on Friday by a 5-2 vote in the state senate's appropriations committee, marks the second time that Monning, who represents the central coastal area around Carmel, has tried to influence consumers' drink choices.

The bill next goes to the senate floor, where it could have its final senate vote as early as Wednesday.

Last year, Monning backed an unsuccessful measure that would have taxed the drinks.

Efforts to curtail consumption of sugary drinks through taxes and other efforts have met fierce resistance from the U.S. food and beverage industry, which opposes the labeling bill.

Lisa Katic, who testified on behalf of the California Nevada Soft Drink Association in April, said the proposal, while well intentioned, "will do nothing to prevent obesity, diabetes or tooth decay, and may even make problems worse."

According to Katic, the main source of added sugars in American diets are sandwiches and hamburgers, and not sodas or other soft drinks.

(editing by Gunna Dickson)

How Tomatoes Can Help Fight Cancer

 

by: Michael Roizen, MD, and Mehmet Oz, MD

Whether it’s a thick juicy slice of beefsteak tomato, a puree into luscious pasta sauce, spicy salsa, or as an extract in your green drink, tomatoes and tomato extract lower heart disease risks by decrease atherosclerotic plaque in the arteries of your heart, brain and legs. And if that’s not enough, here’s another good reason to love your tomato; this magical fruit (it’s not a vegetable) also decreases cancer risk.

One report reveals that lycopene -- the powerful carotenoid that gives tomatoes their fiery hue and disease-fighting prowess -- also boosts levels of an important cancer-quelching hormone called adiponectin. Like a Swiss Army Knife, lycopene does it all -- helps you maintain healthy blood sugar, burn fat, cool inflammation, it discourages cancer cell growth, and throws up roadblocks when tumors try to grow their own arteries. Adiponectin even encourages cancer cells to die.

Related: How to Get the Most out of Your Tomatoes

In the study, women who got 25 milligrams of lycopene a day from tomato products (equivalent to a half-cup of your favorite sauce) boosted levels of adiponectin by 9 percent -- reducing their breast cancer risk. Higher “A” levels are also linked to lower risk for diabetes and heart disease.

Along with boosting adiponectin, lycopene has been associated with reducing risk for prostate, lungs and stomach cancer, reducing LDL (lousy) cholesterol levels while helping to control blood pressure.

So we think this message -- EAT MORE LYCOPENE! -- is for everyone.

Here are six delicious ways to get more into your daily diet:

1. Go Italian -- and beyond. The human body absorbs the most lycopene from cooked tomato products eaten with a smidge of healthy fat -- like the olive oil in tomato sauce. You’ll get 25 milligrams of lycopene from a half-cup of tomato puree or tomato sauce. Top off your whole-wheat pasta with tomato marinara, dunk whole-grain bread in tomato sauce, but don’t stop there. Ladle sauce over black or red beans, spaghetti squash, or your favorite veggies, too.
2. Sip soup or juice. A cup of tomato soup or vegetable juice cocktail also delivers your lycopene quota. Choose reduced or low-sodium varieties. (Read those labels when shopping for sauce and puree!)
3. Treat yourself to pink fruit. Enjoy a slice of juicy watermelon (13 milligrams) or half of a pink grapefruit (1.7 milligrams). 
4. Choose red toppings. Add five chopped, sundried tomatoes (5 milligrams) to your salad topping. Upgrade your veggie burger with 2 tablespoons of chili sauce (6.7 milligrams) or catsup (5 milligrams), dunk steamed shrimp in cocktail sauce (5.9 milligrams in two tablespoons), add a big dollop of salsa to your burrito (4.8 milligrams in 3 tablespoons).
5. Munch a tomato. A whole, fresh tomato has 5 milligrams of lycopene. That number jumps to 7.5 if you cook it for five minutes, even higher the longer it simmers.
6. Put tomato in your green drink. Tomato extract takes the essences of the tomato and lets you add it to drinks or healthy smoothies you prepare.  Read the label to insure your getting a real tomato extract.

Related: Drink Your Greens in this Smoothie

4 More Ways to Boost Adiponectin

Remember that healthy “A” hormone, adiponectin, that is increased by lycopene?

Your body boosts available levels when you do these things:

1. Move your muscles. Muscle cells make adiponectin when you use ’em. A brisk, daily walk plus strength-training exercises twice a week can accentuate your “A levels” significantly.
2. Find fiber.  For optimal adiponectin levels, aim for at least 27 grams of fiber daily. (Two to three servings of whole grains plus five to seven servings of produce.) People who hit that fiber quotient have adiponectin levels 24% higher than those who get less than 17 grams of fiber a day.
3. Nibble nuts. Crunching a small handful five days a week could boost your adiponectin levels 12 percent. See if your home town made our top 10 nuttiest cities in the U.S.
4. Stop sugar. Sugary drinks and added sugars and syrups can reduce levels of adiponectin. Having fruit and fiber–four servings a day--can do the opposite and raise your “A” about 10 percent.

source: www.sharecare.com

Wound-healing role for microRNAs in colon offer new insight to inflammatory bowel diseases

 

The findings, first discovered in mice and later reproduced in human cells, could provide a fresh avenue for investigating chronic digestive diseases and for potentially repairing damage in these and other disease or injury settings.

"We identified a novel role for microRNAs in regulating wound healing in the intestine. This finding has important implications for diseases such as ulcerative colitis and Crohn's disease and may be relevant to wound healing mechanisms in other tissues," said Dr. Joshua Mendell, CPRIT Scholar in Cancer Research, Professor of Molecular Biology, and member of the UT Southwestern Harold C. Simmons Cancer Center.

Ulcerative colitis and Crohn's disease -- the two most common inflammatory bowel diseases affecting an estimated 1.5 million in the U.S. -- stem from an abnormal immune response, which results in the body mistakenly attacking cells in the intestine. The resulting chronic injury to the colon also is considered a risk factor for colon cancer. Understanding the cellular pathways involved could eventually lead to potential therapeutic treatments.

MicroRNAs serve as brakes that help regulate how much of a protein is made, which, in turn, determines how cells respond to various stimuli. Approximately 500 to 1000 microRNAs are encoded in the genomes of mammals. Dr. Mendell's laboratory studies how these tiny regulators work normally and how diseases such as cancer arise when they function in an abnormal manner.

These latest findings, which appear in the journal Cell, focus on two microRNAs: miR-143 and miR-145. While there is extensive literature implicating these microRNAs in colon cancer, little is known about their natural function in the colon. So Dr. Guanglu Shi, postdoctoral researcher in Molecular Biology, and other researchers began their five-year investigation by removing or "knocking out" the gene that produces these two microRNAs in mouse models.

The researchers found that the cells that normally increase their growth to make repairs, called epithelial cells, fail under stress in the knockout animals. Epithelial cells line the intestines where food is digested, separating the contents from the rest of the body and absorbing needed nutrients.

"The epithelial cells of the colon normally proliferate quickly to fill in the wounds from an injury. Without these microRNAs, the epithelial cells are unable to switch into this repair mode, so they never heal the wounds and the mice are not able to survive," Dr. Shi said.

In addition, the research upended traditional thinking about where the tiny microRNAs reside, discovering to everyone's surprise that they reside in supporting cells, called mesenchymal cells, instead of the epithelial cells themselves as previously thought.

"This was surprising because colon cancers derive from the epithelial cells, so it was assumed that the microRNAs must function within them," Dr. Mendell said. "If these microRNAs do participate in colon cancer, they must do so by acting from outside the epithelium."

Identifying the accurate location of the microRNAs is essential to locating the pathways they regulate and eventually, to determining whether they can be manipulated for therapeutic purposes.

Dr. Mendell's team collaborated with a group of surgeons at UT Southwestern including Dr. Joselin Anandam, Assistant Professor of Surgery, Dr. Abier Abdelnaby, Assistant Professor of Surgery, Dr. Glen Balch, Assistant Professor of Surgery, and Dr. John Mansour, Assistant Professor of Surgery, and Dr. Adam Yopp, Assistant Professor of Surgery, who provided human tissue specimens. "The ability to work closely with an outstanding clinical team enabled us to confirm that our findings in mice extend to humans," Dr. Mendell said.

In addition, the researchers say they have worked out one of the many pathways regulated by these microRNAs, called the insulin-like growth factor signaling pathway.

"This pathway is involved in many different processes in the body, but one function is to stimulate wound healing responses," Dr. Mendell explained. "Increasing the amount of insulin-like growth factor signaling improves wound healing in the intestine."

Knocking out miR-143 and miR-145 counteracts that effect.

Poor diet before pregnancy linked with preterm birth

 

May 23 / 2014

University of Adelaide

For the first time, researchers have confirmed that women who eat a poor diet before they become pregnant are around 50% more likely to have a preterm birth than those on a healthy diet. The study shows that women who consistently ate a diet high in protein and fruit prior to becoming pregnant were less likely to have a preterm birth, while those who consistently ate high fat and sugar foods, and take-out food were about 50% more likely to have a preterm birth.

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This is the first study of its kind to assess women's diet prior to conception and its association with outcomes at birth.

University of Adelaide research has for the first time confirmed that women who eat a poor diet before they become pregnant are around 50% more likely to have a preterm birth than those on a healthy diet.

Researchers at the University of Adelaide's Robinson Research Institute investigated the dietary patterns of more than 300 South Australian women to better understand their eating habits before pregnancy.

It's the first study of its kind to assess women's diet prior to conception and its association with outcomes at birth.

The results, published in The Journal of Nutrition, show that women who consistently ate a diet high in protein and fruit prior to becoming pregnant were less likely to have a preterm birth, while those who consistently ate high fat and sugar foods and takeaway were about 50% more likely to have a preterm birth.

"Preterm birth is a leading cause of infant disease and death and occurs in approximately one in 10 pregnancies globally. Anything we can do to better understand the conditions that lead to preterm birth will be important in helping to improve survival and long-term health outcomes for children," says the lead author of the paper, Dr Jessica Grieger, Posdoctoral Research Fellow with the Robinson Research Institute, based at the Lyell McEwin Hospital.

"In our study, women who ate protein-rich foods including lean meats, fish and chicken, as well as fruit, whole grains and vegetables, had significantly lower risk of preterm birth.

"On the other hand, women who consumed mainly discretionary foods, such as takeaway, potato chips, cakes, biscuits, and other foods high in saturated fat and sugar were more likely to have babies born preterm," Dr Grieger says.

"It is important to consume a healthy diet before as well as during pregnancy to support the best outcomes for the mum and baby," Dr Grieger says.

"Diet is an important risk factor that can be modified. It is never too late to make a positive change. We hope our work will help promote a healthy diet before and during pregnancy. This will help to reduce the number of neonatal deaths and improve the overall health of children," she says.

Dr Grieger will present her research findings at the upcoming SA Annual Scientific Meeting of the Australian Society for Medical Research during ASMR Medical Research Week on Wednesday 4 June.

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Story Source:

The above story is based on materials provided by University of Adelaide. Note: Materials may be edited for content and length.

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Journal Reference:

1. J. A. Grieger, L. E. Grzeskowiak, V. L. Clifton. Preconception Dietary Patterns in Human Pregnancies Are Associated with Preterm Delivery. Journal of Nutrition, 2014; DOI: 10.3945/jn.114.190686

Breakthrough in RSV research to help infected children

 

May 23 / 2014

Le Bonheur Children's Hospital

A drug has been shown to safely reduce the viral load and clinical illness of healthy adult volunteers intranasally infected with respiratory syncytial virus. RSV is the most common cause of lower respiratory tract infections in young children in the United States and worldwide. It hospitalizes 125,000 children in the United States each year, and has been the cause for 1.5 million outpatient visits.

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Researchers at Le Bonheur Children's Hospital and the University of Tennessee Health Science Center announced results today from a clinical trial of a drug shown to safely reduce the viral load and clinical illness of healthy adult volunteers intranasally infected with respiratory syncytial virus (RSV).

Detailed results of this study were presented by lead researcher Infectious Disease Specialist John DeVincenzo, MD, this week during a poster discussion session at the American Thoracic Society 2014 International Conference in San Diego. He serves as medical director of the Molecular and Viral Diagnostics Laboratories at Le Bonheur Children's Hospital and also serves as a professor of Pediatrics and professor of Microbiology, Immunology, and Biochemistry at the University of Tennessee College of Medicine.

RSV is the most common cause of lower respiratory tract infections in young children in the United States and worldwide. It hospitalizes 125,000 children in the United States each year, and was the cause for 1.5 million outpatient visits, according to the Centers for Disease Control and Prevention (CDC). DeVincenzo and his fellow researchers have been part of virtually every experimental therapeautic advancement, developmental pathway and antiviral therapy created to tackle the virus in the past 15 years.

The Phase 2a challenge study of Gilead Sciences Inc.'s GS-5806, an investigational oral RSV fusion inhibitor, achieved primary and secondary endpoints of lower viral load, improvements in total mucus weight and symptom diary score compared to placebo. Volunteers in the study were given the oral drug after being infected with RSV using the experimental challenge model -- based on a clinical isolate from an infant hospitalized with RSV bronchiolitis which can be safely used to infect adults, and that was developed by DeVincenzo in 2007 to test proof-of-concept antivirals.

"No effective antiviral treatments currently exist for RSV, which is the leading cause of severe childhood respiratory infections, and is increasingly recognized as a major cause of serious adult respiratory infections," said DeVincenzo. "Based on the reductions in viral load, reduced clinical symptoms, as well as the safety profile observed in this adult challenge study, clinical trials in naturally infected patients should now be explored."

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Story Source:

The above story is based on materials provided by Le Bonheur Children's Hospital. Note: Materials may be edited for content and length.

Body clock and its biological impact: Fruit fly research to provide new insight

 

May 23 / 2014

University of Southampton

How animals keep time through their internal circadian rhythms could help us understand why we sleep and how we cope with jet lag. Using the fruit fly Drosophila melanogaster as an experimental model, researchers have discovered that the molecular and cellular ‘clock’ mechanisms of insects closely resemble those of mammals, including humans. As these biological clock systems not only control sleep, but also influence functions such as blood pressure and metabolic rate, they could give us greater insight into many medical conditions.

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New research at the University of Southampton into how animals keep time through their internal circadian rhythms could help us understand why we sleep and how we cope with jet lag.

Biological scientist Dr Herman Wijnen uses the fruit fly Drosophila melanogaster as an experimental model as the molecular and cellular 'clock' mechanisms of insects closely resemble those of mammals, including humans. As these biological clock systems not only control sleep, but also influence functions such as blood pressure and metabolic rate, they could give us greater insight into many medical conditions.

Dr Wijnen, who has just been awarded two new grants collectively worth around £500,000 to support his research, says: "This project has the potential of discovering new aspects of the timing of sleep/wake rhythms in both animals and humans."

The €100,000 European Union Marie Curie Career Integration Grant will allow a new PhD researcher to follow up on studies of sleep/wake behaviour by current Southampton postgraduate researcher, Karolina Mirowska. Together with other members of Dr Wijnen's laboratory, Karolina discovered a developmental role in flies for one of the molecular clock components that is also found in humans.

The availability of powerful assays and convenient culture conditions make the fruit fly system ideally suited for the planned laboratory research.

In addition, Dr Wijnen has been awarded approximately £431,000 from the Biotechnology and Biological Sciences Research Council (BBSRC) to study the way that fruit flies synchronise their rhythms to daily environmental temperature cycles. He explains that "This research could provide valuable insights in the way that the behaviour and life cycle of harmful insects, such as agricultural pests and disease vectors, is governed by temperature. What's more, the clocks of flies and humans are connected to temperature response mechanisms by the same regulatory component. So we may even learn something about the way that our own body temperature rhythms are used as daily time cues."

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Story Source:

The above story is based on materials provided by University of Southampton. Note: Materials may be edited for content and length.

Bacterial adaptation contributes to pneumococcal threat in sickle cell disease patients

 

May 23 / 2014

St. Jude Children's Research Hospital

Differences in the genetic code of pneumococcal bacteria have been identified by researcher that may explain why it poses such a risk to children with sickle cell disease and why current vaccines don’t provide better protection against the infection. The findings will aid efforts to improve vaccine effectiveness and inform research into new ways to protect young sickle cell disease patients from life-threatening pneumococcal infections that can lead to pneumonia, meningitis, bloodstream infections and other problems.

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Researchers have identified differences in the genetic code of pneumococcal bacteria that may explain why it poses such a risk to children with sickle cell disease and why current vaccines don't provide better protection against the infection. St. Jude Children's Research Hospital scientists led the study, which appeared earlier this month in the journal Cell Host & Microbe.

The findings will aid efforts to improve vaccine effectiveness and inform research into new ways to protect young sickle cell disease patients from life-threatening pneumococcal infections that can lead to pneumonia, meningitis, bloodstream infections and other problems. Despite advances in preventive care, including vaccination and prophylactic antibiotic therapy, pneumococcal infections still pose a serious health risk to children with sickle cell disease, who are at a much greater risk of possibly fatal infection than are members of the general public.

The results followed whole genome sequencing of hundreds of pneumococcal bacteria collected from the public and patients with sickle cell disease. The genome is carried in the DNA molecule and includes the instructions necessary to assemble and sustain life.

The analysis showed the bacteria have adapted to sickle cell patients, including measures aimed at preventing infection. As a result, disease-causing strains of the bacteria differ in children with and without sickle cell disease. For example, the pneumococcal strains collected from sickle cell patients in this study differed from the 13 pneumococcal strains included in the current vaccine recommended for children age 5 and younger.

"The results help explain why current vaccines haven't been as successful at protecting children with sickle cell disease from pneumococcal infections as they have in protecting other children," said Joshua Wolf, M.D., an assistant member of the St. Jude Department of Infectious Diseases and one of the study's lead authors. The other first authors are Robert Carter, Ph.D., of the St. Jude Computational Biology department, and Tim van Opijnen, formerly of Tufts University School of Medicine, Boston, and now of Boston College.

Work is already underway on vaccines that take a different approach to priming the disease-fighting immune system to protect high-risk groups, including children with sickle cell disease, said the study's corresponding author, Jason Rosch, Ph.D., an assistant member of the St. Jude Infectious Diseases department. "These results will help guide vaccine design going forward," he said.

Sickle cell disease is caused by an inherited mutation in the gene that carries instructions for making hemoglobin. That is the protein red blood cells use to carry oxygen. The mutation leaves red blood cells prone to the sickled shape that gives the disease its name and is also responsible for the episodes of intense pain, organ damage and other problems associated with the life-shortening disease. About 300,000 infants are born with sickle cell disease each year, making it the world's most common genetic disorder.

For this study, scientists compared the genomes of 322 pneumococcal bacteria collected from sickle cell patients between 1994 and 2011 to DNA from 327 strains obtained from individuals without sickle cell disease.

The analysis revealed that over time, the genomes of bacteria isolated from sickle cell patients shrank as genes and the corresponding DNA were discarded or combined. A comparison of the bacterial genomes from individuals with and without sickle cell disease suggested the changes reflected bacterial adaptation to their sickle cell host and contributed to the bacteria's ability to persist despite advances in preventive care.

Using a technique called transposon sequencing (Tn-seq), researchers showed that the bacteria's ability to cause widespread infection in mice with and without sickle cell disease was dramatically affected by changes in 60 different bacterial genes. The results demonstrated that bacteria faced different conditions in animals with and without sickle cell disease.

When researchers checked those same genes in bacteria isolated from sickle cell patients, they found six that were missing or altered in a significant percentage of samples. The list included genes involved in transporting iron into bacteria, bacterial metabolism and other processes that are likely altered in patients with sickle cell disease.

"We demonstrated that genes necessary to cause disease in the general public are expendable in patients with sickle cell disease," Rosch said.

The same methods used in this study could also be used to better understand the genetics behind other pneumococcal high-risk groups, including in individuals who are past retirement age or are obese.

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Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.

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Journal Reference:

1. Robert Carter, Joshua Wolf, Tim van Opijnen, Martha Muller, Caroline Obert, Corinna Burnham, Beth Mann, Yimei Li, Randall T. Hayden, Tamara Pestina, Derek Persons, Andrew Camilli, Patricia M. Flynn, Elaine I. Tuomanen, Jason W. Rosch. Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions. Cell Host & Microbe, 2014; 15 (5): 587 DOI: 10.1016/j.chom.2014.04.005