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Natural cure for Herpes Simplex

HSV or Herpes Simplex Virus, the etiological agent for Herpes has been a complexity for doctors and scientists for decades. Finally, cure for Herpes has been discovered in the most amazing place of all – nature. As seen on
Herpessecrets, there is a natural safe and effective remedy available that not only cures your Herpes but also provides fast symptom relief and stops further outbreaks.

The main cause of Herpes that causes genital ulcer diseases is a sexually transmitted virus known as the Herpes simplex virus type 2 (HSV-2). This virus also increases your susceptibility to HIV-1. The only options available to these patients are antiviral medications but limited success has been seen with these. Till date there is no cure available and even vaccines are at a premature stage of development.

Increasing evidence from research has shown that people affected with Herpes go through brief shedding episodes even when they have no symptoms. This alarming finding sheds light on the high transmission rates seen.

 

Pathogenesis

HSV virus enters the body thought inoculation through the mucosal surface as well as through skin cracks. The most common cause of this is by sexual transmission. Once inside the body, this virus starts replicating and destroying tissues resulting in its cytopathic effect.  HSV virus escapes immunity by entering the sensory root ganglia and climbs the peripheral sensory nerves. The reason for its recurrence is reactivation of this virus from latently infected sacral nerve root ganglia.

 

Clinical

Clinically Herpes presents as a first episode and subsequently recurrent outbreaks. This commonly starts in the genitals where HSV 1 or 2 has been shown to have similar severity and result in painful genital or extra-genital lesions. Besides the commonly known genital infection, HSV is known to cause other complications including Meningits, Pharygitis, as well as autonomic nervous system sacral radiculopathy. Also headaches and photophobia has been seen in patients infected with HSV.


Transmission.

HSV is transmitted both during outbreaks as well as during asymptomatic periods though viral shedding. Although common in both sexes, asymptomatic shedding is seen more in women.  Transmission also occurs from a mother to a child through the vaginal passage delivery.

 

Detection

The established way of diagnosing HSV is through cell culture with HSV-1 and 2 typing. Monoclonal antibodies directed towards type specific antigens are used to subtype this virus.  Newer developments include DNA detection tests as well as PCR of HSV.

 

Treatment

Although so much is known about this virus, there is an absolute lack of treatments available. Current options available are Acyclovir, famciclovir,penciclovir and intravenous foscarnet. None of these drugs have been shown to cure Herpes and only cause (if at all) a brief, symptomatic relief.

Introducing natural cure.

As seen on Herpessecrets there are proven natural cures that have shown amazing results. This has helped not just provide cure but also helps in the psychological and emotional turmoil faced by Herpes patients. To know more visit Herpessecrets

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Turn unwanted cell phones to cash

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Unwanted Smartphones - today people and businesses have unwanted smartphones and unlike trading in a phone for very little value - We sell phones for our clients and charge a variable fee - on average we return 258% more after our fees than trade in companies. Can we sell a phone for you today? Call us toll free at 800 320-601

Visit http://simplysellphones.com/

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Marmo TV - Get updates about your favorite shows

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Television and movies are moving online more than ever before. According to Adobe, online viewership has increased over 146% in the last year itself. Viewers want to break free of getting stuck with their TV sets and mobile technology makes it possible to do that.

More movies and episodic content is available online and has seen a growth much higher than watching sports online. With so much content showing up on the Internet there was a dire need of a platform that could make it easier to know when your shows come online.

Finally there is one service that consolidates and tracks these shows called Marmo TV. Marmo TV was conceived by enthusiasts who loved watching shows online but could not find a way to know when their favorite programs were available. The result was a fantastic product called Marmo TV. Currently the Marmo TV group can be seen at their facebook page www.facebook.com/marmotv as well as on twitter at @Marmo_TV

With the ease of access using different devices like computers, laptops, tablets and mobile phones, users expectations are rising. Content providers and distributors are doing their best to catch up with fulfilling these expectations. Marmo TV is a growing service that is already seen as indispensable by their users. The beauty of this service is that it is a one-stop-shop to know when and where the programs you are waiting for become online.

Marmo TV goes beyond just a regular set of shows. They are growing not just because they love what they do but they are doing it for their users.  Users are able to post requests for what they are seeking for and Marmo TV is the first to find for them as soon as those shows are Internet-aired.

Marmo TV is a platform that will soon be seen as necessary not just by the vast number of users but also by the entire showbiz industry.

The media and entertainment industry are making strides into the digital world - Marmo TV is the guide to when that happens.

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The Science Behind Phototherapy

 

Our skin has the ability to absorb LED light and use it as a source of energy to stimulate cellular regeneration. LED light therapy, first researched by NASA for use in the U.S. Space Program, can reverse and control the visible signs of aging and help you look years younger without harsh chemical treatments or invasive surgical procedures. Tightening of skin, disappearing blemishes, smoothing of wrinkles and rough spots, softening of redness, and shrinking of pore size can be achieved with this natural light treatment.

 

Why Does Light Therapy Work?

Red light easily penetrates the skin, boosts circulation and brings more blood and nutrients to the area. It also stimulates vital collagen and elastin production. Collagen helps plump the skin, while elastin firms the skin.
The red light is energizing and repairing damaged cells, stimulating collagen and elastin and giving the skin back its youthful look. Developed by NASA to heal wounds, red light therapy was found to promote and speed up skin regeneration.
 


Cells in the skin absorb wavelengths between 590 and 950 nanometers. Our cells convert this light energy into “fuel” that is used to increase cellular metabolism. Research by the National Aeronautics and Space Administration (NASA) has shown that light therapy increases cellular growth up to 200%.

(*NASA Light-Emitting Diode Technology Brings Relief In Clinical Trials)

While the NASA study focused on healing injuries, the effect of light therapy on skin is exactly the same. The increased cellular activity stimulates formation of new collagen and elastin — the building blocks of healthy skin. This is what makes red light therapy so effective in removing scars and general skin rejuvenating.

 

 

Different Wavelengths, Different Solutions

Yellow/Amber Light Therapy:

Amber light therapy can be referred to as yellow or orange light therapy. It encompasses the range of wavelengths from 570 nm to 600 nm.

Amber light has quite a shallow skin penetration but is effective in the treatment of skin issues involving redness, such as spider veins. Though it is not typically used for tissue healing or collagen/elastin production, where it excels is in the treatment of problems such as sun damage. It is often considered to be an ideal therapy for sensitive skin, as its therapy is calming and soothing.

Amber light therapy is frequently recommended as a drug free alternative treatment for skin redness and flushing, irritation, rosacea, UV radiation damage, and reducing the appearance of the tiny blood vessels on the nose and face. It helps to flush waste from the skin, boost lymphatic flow, and increase cellular growth.

Red Light Therapy:

Visible red light is capable of penetrating the skin to a depth of about 8 to 10 mm. Once absorbed, the light energy is converted to cellular energy, stimulating the body’s natural processes on a cellular level:

  • Increased circulation and the formation of new capillaries. 
  • Increased lymph system activity.
  • Increased production of collagen and fibroblasts. 
  • Increased release of ATP, or raw cellular energy. 
  • Increased phagocytosis, or cellular clean up.
  • Tissue granulation stimulated.
  • Inflammation reduced. 

All of these things work together to produce many benefits for you in the areas of anti-aging, the healing of wounds and injuries, and the relief of pain, as we’ll see below. But no matter what the application, red and infrared light therapy share the same benefits overall.

Blue Light Therapy

Blue light is right next to UV light on the electromagnetic spectrum, and science has found that it retains some of the antibacterial properties of UV light, but without the risks associated with UV overexposure. Blue light was found to kill acne bacteria, and was FDA approved for that purpose around 2002.

Green Light Therapy:

Green light therapy typically falls in the wavelength range of 515 nm to 520 nm and is most frequently used for skin treatments and anti-aging therapies, such as an LED photofacial.

The rejuvenating benefits of green light therapy can help to improve pigmentation issues that have come from causes such as sun damage. This treatment can help to fade the appearance of freckles, as well as age spots, sun spots, reddish and brown patches, and liver spots. Other forms of hyper pigmentation and melanin problems that are caused by age can also be lightened through the use of light in these wavelengths.

Green light affects the melanocytes (the cells that produce the melanin, which is the pigmentation in the bottom layer of the epidermis), reducing its production. Over time, spots simply fade away for a younger looking, rejuvenated, and more even complexion.

To order Vivi advanced phototherapy device click here

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A Hofstede cultural analysis between the US and Nigeria for the purpose of ministry

M. Mooney, ministry practitioner

Reporting for National Association of Christian Ministers 


 

God is doing great things among us, far exceeding our expectations and requests!


 

"Now to him who is able to do far more abundantly than all that we ask or think, according to the power at work within us, to him be glory in the church and in Christ Jesus throughout all generations, forever and ever. Amen" (Eph 3:20-21 ESV).


 

 

Executive Elders Gregory Roberson and Michael Mooney are scheduled to hold lectures during a ministerial conference being held at the Freewater Institute of Pastoral Ministry in Kogi State, Nigeria. The provost, Brother Freewater Issah is a member of the National Association of Christian Ministers, and the Bible college holds a spiritual alliance with the NACM.  Some 45 graduates are scheduled to receive ordination by the laying on of hands and ministerial licensing into during this event.  Elders Roberson and Mooney are humbled by the privilege to partake in this ceremony, while representing the NACM internationally.  With these things in mind, the following cultural analysis has been conducted for report.

Purpose of Report 

The purpose of this report is to establish background information in preparation for a missions trip to Nigeria.  The objective of the trip is to conduct a ministerial leadership workshop designed to equip emerging native pastors to effectively lead others in the 21st century.  Herein, the cultural differences and similarities between American and Nigerian perspectives of leadership are considered.  This report is written to prepare the traveling ministers with the knowledge necessary to position themselves appropriately within the culture; thereby, increasing the probability of successful communications, and interpersonal relations. 

How this Information May Assist Future Missions 

Missionaries from US cultures are often sent to Nigeria to establish new churches, and or to offer training to Nigerian pastors already overseeing established churches.  The information herein may be utilized to increase the effectiveness of Kingdom objectives during their expedition. 

Expectations for Leadership Acceptance 

Leadership training is likely to be well received by Nigerians within the concept of its definition and scope.  That is defining leadership as a process toward fellow persuasion within the domains of generating inspiration, developing and casting vision, modeling leadership behavior, and providing regular encouragement accompanied with feedback.  However, there are striking contrasts between American and Nigerian perceptions of power distances between authority, and appreciation for individuality.  For these reasons, special attention may be necessary when communicating leadership principles which emphasize originality, innovation, challenges to traditions, and prioritization of organizational goals above communal well being.

Rationale 

Leadership is a process by which initiators persuade members toward organizational objectives, visions and goals (Weathersby, 1999).  In other words, “leadership is a process whereby an individual influences a group of individuals to achieve a common goal” (Northouse, p. 3, 2010).  Kouzes and Posner (2002, 1987) describe leadership as something which occurs through modeling, inspiring, challenging, enabling, and encouraging constitutes. This approach to visionary leadership has been more specifically defined within the quantifiable behaviors of: 

1. Challenging traditional process, 
2. Inspiring a Shared Vision, 
3. Inspiring others to take positive action, 
4. Modeling the “way” of leadership, and 
5. Encouraging the heats of those around us 

Following these five attributes, research by Zagorsek, Jaklic, and Stough (2004) found little differences between American and Nigerian approaches to leadership when samples were taken from MBA students in both countries.  The utility of this finding is that there may be a reasonable level of acceptance for charismatic approaches to leadership.  Although, it still should be anticipated that there will be differences regarding cultural attitudes  in areas such as power distance, individuality, and gender roles. In order to maintain mutual understanding, Americans should maintain a respect for those holding traditional mindsets toward gender and political power. Americans should be sensitive to varying opinions and careful not to assume that such cultural element are somehow wrong or discriminatory –in light of their US afforded freedoms.  Further, they should not attempt to undermine these dynamics while expecting to maintain welcomed communications.

Cultural Dimensions 

Geert Hofstede offers a systematic approach to cultural analysis which has become a standard in global relations.  His method seeks to view cultures through the lenses of five categories: 

1. Power Distance (PDI), 
2. Individualism (IDV), 
3. Masculinity (MAS), 
4. Uncertainty Avoidance (UAI) and 
5. Long Term Orientation (LTO) (Northouse, 2010).  

According to the Hofstede Centre (2013), the cultural dimensions between Nigeria and the US are as follows: PDI 80/40, IDV 30/91, MAS 60/62, and UAI 55/46, LTO 16/29.  Each score is an assigned number out of 100.  These numbers are generally interpreted as existing in one of two categories: high or low.  A score is high when it is above 50, and low when below 50.  Comparisons and contrasts between two cultures are generally considered as being either similar or not similar. Below are the results between Nigerians and North Americans.

Nigerian & American Power Distance: Not similar 

Power Distance (PDI) describes the levels of social tolerance toward the gaps that exist between authorities and subordinates –in other words the lack of social equality.  Nigeria holds a high score at 80 vs. the US position of 40.  The implications are that Nigerians are much more accepting of social classes, and much more accepting of autocratic authority which clearly defines objectives (Hofstede, 2012).


 

 

Nigerian & American Individualism: Not similar 

Individualism (IDV) considers societal preferences for communal solidarity.  Nigeria holds a low score in this category at 30 vs. the US at 91.  The implications are that Nigeria is a collectivist country, holding high regard for community, group membership, shared responsibility, and loyalty that at times supersedes rationality.  Even in matters of organizational promotions of leadership, decisions may be most influenced by family connections or group membership –as opposed to qualifications (Hofstede, 2012).  This position stands in contrast to the self-promoted society of the US.  Yet, there are many biblical similarities with the Nigerian concept of community, and their culture may be a good model for how church members should prefer one another.

Nigerian & American Masculinity: Similar 

Masculinity (MAS) describes the extent to which a society is competitive, results driven, and achievement oriented, as opposed to femininity, which describes success in terms of overall quality of life. Nigeria scores a 62 in this category, which is very similar to the US holding a 60.  Therefore, the implications are that both cultures are predominately masculine, while maintaining an appreciation for femininity (Hofstede, 2012).  

Nigerian & American Uncertainty Avoidance: Not Similar


 

Uncertainty Avoidance (UAI) determines the extent to which a society is comfortable with undefined leadership roles, and how anxiety relates to unpredictable events (Jones, & Alony, 2007).  In other words, it is projected that people with high scores in this area are inclined to seek situations where circumstances are predictable.  Nigeria scores a 55 in this area, and the US a 46.  The implications are that Nigerians are prone to hold strict codes of behavior, prone to structure, highly regard punctuality, and value security as a great priority (Hofstede, 2012).  

Nigerian & American Long Term Orientation: Similar  

Long Term Orientation (LTO) is descriptive of a society’s view of the future in terms of something hopeful, innovative, and in need of preparation –as opposed to the short term orientation which holds high regard for tradition, enjoys quick results, and less likely to save for future endeavors.  Nigeria holds a score of 16 in this domain vs. the US which is a 29.  The implications are that Nigerians and Americans are typically interested in quick results and are often motivated to keep up with the social wealth of their neighbors (Hofstede, 2012).  


 

How to Use this Information in Ministry  


 

 

From this analysis it may be concluded that Nigerians and Americans hold similar attitudes in areas of ambition, competition, results orientation, and achievement.  Ministers of the gospel may uses these as points by which to establish rapport and mutual understanding during times of general communication, formal training sessions, and selection of content for illustrations.  

Further, there is a shared interest in “quick fixes” and avoiding the pain of delayed gratification.  This information may be a useful launching pad by which ministers may point out their perusal weaknesses and lack of patience; thereby also developing opportunities to gain rapport while teaching from scripture.

Nevertheless, Nigerians and Americans hold different perspectives regarding social equality, individuality, and the willingness to take risks.  Therefore, careful attention should be given to these areas in order to enjoy the potential associated with effective communication.  Additionally, Americans may have a few things to learn from Nigerians in the virtues of their selfless contributions as members of greater communities.



References 

Hofstede, G. (2013). Geert Hofstede cultural dimensions: Greece. Retrieved June 1, 2013, from http://geert-hofstede.com/nigeria.html

Hugo Zagorsek, Marko Jaklic, & Stanley J. Stough. (2004). Comparing leadership practices between the united states, nigeria, and slovenia: Does culture matter? Cross Cultural Management: An International Journal, 11(2), 16-34. doi:10.1108/13527600410797774

Jones, M., & Alony, I. (2007, January). The Cultural Impact of Information Systems -- Through the Eyes of Hofstede -- A Critical Journey. Issues in Informing Science & Information Technology, 4(13), 407.

Kouzes, J., Posner, B. 2002. The Leadership Challenge. Jossey-Bass Publishing. 

Kouzes, J.M. & Posner, B.Z. (1987) The Leadership Challenge: How to Get Extraordinary Things Done in Organizations. San Francisco: Jossey-Bass.

Northouse, P. G.  (2010).  Leadership: Theory and Practice (5th ed.).  Thousand Oaks, CA: Sage Publications.  ISBN: 978-1-4129-7488-2.

Weathersby, G. (1999). Leadership vs. Management. Management Review, 88(3), 5. 

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A butler to help save your money

Its not easy to save money. You can search around the web for coupons, go to price comparison sites and/or check deal sites. And if you are lucky, you will find the product you are looking for. But there is always that question – Could I have found it cheaper?

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The site to learn about Lab automations

The market of laboratory robotics and automation solutions is growing fast. Not a single laboratory is left, which does not automate processes and makes use of computerised systems to evolve and grow. LabAutomations.com is the place where the industry meets their customers, introduce them to products and shares valuable information about new innovations. With a commitment to neutrality and an organisational flair, LabAutomations is the right place to search for opportunities and get informed about laboratory automation news. Visit: https://labautomations.com
 

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Biologists find an early sign of cancer

Source: newsoffice.mit.edu

Years before they show any other signs of disease, pancreatic cancer patients have very high levels of certain amino acids in their bloodstream, according to a new study from MIT, Dana-Farber Cancer Institute, and the Broad Institute.

This finding, which suggests that muscle tissue is broken down in the disease’s earliest stages, could offer new insights into developing early diagnostics for pancreatic cancer, which kills about 40,000 Americans every year and is usually not caught until it is too late to treat.

The study, which appears today in the journal Nature Medicine, is based on an analysis of blood samples from 1,500 people participating in long-term health studies. The researchers compared samples from people who were eventually diagnosed with pancreatic cancer and samples from those who were not. The findings were dramatic: People with a surge in amino acids known as branched chain amino acids were far more likely to be diagnosed with pancreatic cancer within one to 10 years.

“Pancreatic cancer, even at its very earliest stages, causes breakdown of body protein and deregulated metabolism. What that means for the tumor, and what that means for the health of the patient — those are long-term questions still to be answered,” says Matthew Vander Heiden, an associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the paper’s senior authors.

The paper’s other senior author is Brian Wolpin, an assistant professor of medical oncology at Dana-Farber. Wolpin, a clinical epidemiologist, assembled the patient sample from several large public-health studies. All patients had their blood drawn when they began participating in the studies and subsequently filled out annual health questionnaires.

Working with researchers at the Broad Institute, the team analyzed blood samples for more than 100 different metabolites — molecules, such as proteins and sugars, produced as the byproducts of metabolic processes.

“What we found was that this really interesting signature fell out as predicting pancreatic cancer diagnosis, which was elevation in these three branched chain amino acids: leucine, isoleucine, and valine,” Vander Heiden says. These are among the 20 amino acids — the building blocks for proteins — normally found in the human body.

Some of the patients in the study were diagnosed with pancreatic cancer just one year after their blood samples were taken, while others were diagnosed two, five, or even 10 years later.

“We found that higher levels of branched chain amino acids were present in people who went on to develop pancreatic cancer compared to those who did not develop the disease,” Wolpin says. “These findings led us to hypothesize that the increase in branched chain amino acids is due to the presence of an early pancreatic tumor.”

Early protein breakdown

Vander Heiden’s lab tested this hypothesis by studying mice that are genetically programmed to develop pancreatic cancer. “Using those mouse models, we found that we could perfectly recapitulate these exact metabolic changes during the earliest stages of cancer,” Vander Heiden says. “What happens is, as people or mice develop pancreatic cancer, at the very earliest stages, it causes the body to enter this altered metabolic state where it starts breaking down protein in distant tissues.”

“This is a finding of fundamental importance in the biology of pancreatic cancer,” says David Tuveson, a professor at the Cancer Center at Cold Spring Harbor Laboratory who was not involved in the work. “It really opens a window of possibility for labs to try to determine the mechanism of this metabolic breakdown.”

The researchers are now investigating why this protein breakdown, which has not been seen in other types of cancer, occurs in the early stages of pancreatic cancer. They suspect that pancreatic tumors may be trying to feed their own appetite for amino acids that they need to build cancerous cells. The researchers are also exploring possible links between this early protein breakdown and the wasting disease known as cachexia, which often occurs in the late stages of pancreatic cancer.

Also to be answered is the question of whether this signature could be used for early detection. The findings need to be validated with more data, and it may be difficult to develop a reliable diagnostic based on this signature alone, Vander Heiden says. However, he believes that studying this metabolic dysfunction further may reveal additional markers, such as misregulated hormones, that could be combined to generate a more accurate test.

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Modeling shockwaves through the brain New scaling law helps estimate humans' risk of blast-induced traumatic brain injury.

Source: newsoffice.mit.edu

Since the start of the military conflicts in Iraq and Afghanistan, more than 300,000 soldiers have returned to the United States with traumatic brain injury (TBI) caused by exposure to bomb blasts — and in particular, exposure to improvised explosive devices, or IEDs. Symptoms of traumatic brain injury can range from the mild, such as lingering headaches and nausea, to more severe impairments in memory and cognition.

Since 2007, the U.S. Department of Defense has recognized the critical importance and complexity of this problem, and has made significant investments in traumatic brain injury research. Nevertheless, there remain many gaps in scientists’ understanding of the effects of blasts on the human brain; most new knowledge has come from experiments with animals.

Now MIT researchers have developed a scaling law that predicts a human’s risk of brain injury, based on previous studies of blasts’ effects on animal brains. The method may help the military develop more protective helmets, as well as aid clinicians in diagnosing traumatic brain injury — often referred to as the “invisible wounds” of battle.

“We’re really focusing on mild traumatic brain injury, where we know the least, but the problem is the largest,” says Raul Radovitzky, a professor of aeronautics and astronautics and associate director of the MIT Institute for Soldier Nanotechnologies (ISN). “It often remains undetected. And there’s wide consensus that this is clearly a big issue.”

While previous scaling laws predicted that humans’ brains would be more resilient to blasts than animals’, Radovitzky’s team found the opposite: that in fact, humans are much more vulnerable, as they have thinner skulls to protect much larger brains.

A group of ISN researchers led by Aurélie Jean, a postdoc in Radovitzky’s group, developed simulations of human, pig, and rat heads, and exposed each to blasts of different intensities. Their simulations predicted the effects of the blasts’ shockwaves as they propagated through the skulls and brains of each species. Based on the resulting differences in intracranial pressure, the team developed an equation, or scaling law, to estimate the risk of brain injury for each species.

“The great thing about doing this on the computer is that it allows you to reduce and possibly eventually eliminate animal experiments,” Radovitzky says.

The MIT team and co-author James Q. Zheng, chief scientist at the U.S. Army’s soldier protection and individual equipment program, detail their results this week in the Proceedings of the National Academy of Sciences.

Air (through the) head

A blast wave is the shockwave, or wall of compressed air, that rushes outward from the epicenter of an explosion. Aside from the physical fallout of shrapnel and other chemical elements, the blast wave alone can cause severe injuries to the lungs and brain. In the brain, a shockwave can slam through soft tissue, with potentially devastating effects.

In 2010, Radovitzky’s group, working in concert with the Defense and Veterans Brain Injury Center, a part of the U.S. military health system, developed a highly sophisticated, image-based computational model of the human head that illustrates the ways in which pressurized air moves through its soft tissues. With this model, the researchers showed how the energy from a blast wave can easily reach the brain through openings such as the eyes and sinuses — and also how covering the face with a mask can prevent such injuries. Since then, the team has developed similar models for pigs and rats, capturing the mechanical response of brain tissue to shockwaves.

In their current work, the researchers calculated the vulnerability of each species to brain injury by establishing a mathematical relationship between properties of the skull, brain, and surrounding flesh, and the propagation of incoming shockwaves. The group considered each brain structure’s volume, density, and celerity — how fast stress waves propagate through a tissue. They then simulated the brain’s response to blasts of different intensities.

“What the simulation allows you to do is take what happens outside, which is the same across species, and look at how strong was the effect of the blast inside the brain,” Jean says.

In general, they found that an animal’s skull and other fleshy structures act as a shield, blunting the effects of a blast wave: The thicker these structures are, the less vulnerable an animal is to injury. Compared with the more prominent skulls of rats and pigs, a human’s thinner skull increases the risk for traumatic brain injury.

Shifting the problem

This finding runs counter to previous theories, which held that an animal’s vulnerability to blasts depends on its overall mass, but which ignored the role of protective physical structures. According to these theories, humans, being more massive than pigs or rats, would be better protected against blast waves.

Radovitzky says this reasoning stems from studies of “blast lung” — blast-induced injuries such as tearing, hemorrhaging, and swelling of the lungs, where it was found that mass matters: The larger an animal is, the more resilient it may be to lung damage. Informed by such studies, the military has since developed bulletproof vests that have dramatically decreased the number of blast-induced lung injuries in recent years.

“There have essentially been no reported cases of blast lung in the last 10 years in Iraq or Afghanistan,” Radovitzky notes. “Now we’ve shifted that problem to traumatic brain injury.”

In collaboration with Army colleagues, Radovitzky and his group are performing basic research to help the Army develop helmets that better protect soldiers. To this end, the team is extending the simulation approach they used for blast to other types of threats.

His group is also collaborating with audiologists at Massachusetts General Hospital, where victims of the Boston Marathon bombing are being treated for ruptured eardrums.

“They have an exact map of where each victim was, relative to the blast,” Radovitzky says. “In principle, we could simulate the event, find out the level of exposure of each of those victims, put it in our scaling law, and we could estimate their risk of developing a traumatic brain injury that may not be detected in an MRI.” 

Joe Rosen, a professor of surgery at Dartmouth Medical School, sees the group’s scaling law as a promising window into identifying a long-sought mechanism for blast-induced traumatic brain injury. 

“Eighty percent of the injuries coming off the battlefield are blast-induced, and mild TBIs may not have any evidence of injury, but they end up the rest of their lives impaired,” says Rosen, who was not involved in the research. “Maybe we can realize they’re getting doses of these blasts, and that a cumulative dose is what causes [TBI], and before that point, we can pull them off the field. I think this work will be important, because it puts a stake in the ground so we can start making some progress.”

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Chemists recruit anthrax to deliver cancer drugs

Source: newsoffice.mit.edu

Bacillus anthracis bacteria have very efficient machinery for injecting toxic proteins into cells, leading to the potentially deadly infection known as anthrax. A team of MIT researchers has now hijacked that delivery system for a different purpose: administering cancer drugs.

“Anthrax toxin is a professional at delivering large enzymes into cells,” says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT. “We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells.”

In a paper appearing in the journal ChemBioChem, Pentelute and colleagues showed that they could use this disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. This is the first demonstration of effective delivery of antibody mimics into cells, which could allow researchers to develop new drugs for cancer and many other diseases, says Pentelute, the senior author of the paper.

Hitching a ride

Antibodies — natural proteins the body produces to bind to foreign invaders — are a rapidly growing area of pharmaceutical development. Inspired by natural protein interactions, scientists have designed new antibodies that can disrupt proteins such as the HER2 receptor, found on the surfaces of some cancer cells. The resulting drug, Herceptin, has been successfully used to treat breast tumors that overexpress the HER2 receptor.

Several antibody drugs have been developed to target other receptors found on cancer-cell surfaces. However, the potential usefulness of this approach has been limited by the fact that it is very difficult to get proteins inside cells. This means that many potential targets have been “undruggable,” Pentelute says.

“Crossing the cell membrane is really challenging,” he says. “One of the major bottlenecks in biotechnology is that there really doesn’t exist a universal technology to deliver antibodies into cells.”

For inspiration to solve this problem, Pentelute and his colleagues turned to nature. Scientists have been working for decades to understand how anthrax toxins get into cells; recently researchers have started exploring the possibility of mimicking this system to deliver small protein molecules as vaccines.

The anthrax toxin has three major components. One is a protein called protective antigen (PA), which binds to receptors called TEM8 and CMG2 that are found on most mammalian cells. Once PA attaches to the cell, it forms a docking site for two anthrax proteins called lethal factor (LF) and edema factor (EF). These proteins are pumped into the cell through a narrow pore and disrupt cellular processes, often resulting in the cell’s death.

However, this system can be made harmless by removing the sections of the LF and EF proteins that are responsible for their toxic activities, leaving behind the sections that allow the proteins to penetrate cells. The MIT team then replaced the toxic regions with antibody mimics, allowing these cargo proteins to catch a ride into cells through the PA channel.

‘A prominent advance’

The antibody mimics are based on protein scaffolds that are smaller than antibodies but still maintain structural diversity and can be designed to target different proteins inside a cell. In this study, the researchers successfully targeted several proteins, including Bcr-Abl, which causes chronic myeloid leukemia; cancer cells in which that protein was disrupted underwent programmed cell suicide. The researchers also successfully blocked hRaf-1, a protein that is overactive in many cancers.

“This work represents a prominent advance in the drug-delivery field,” says Jennifer Cochran, an associate professor of bioengineering at Stanford University. “Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated.”

The MIT team is now testing this approach to treat tumors in mice and is also working on ways to deliver the antibodies to specific types of cells.

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Chemists recruit anthrax to deliver cancer drugs With some tinkering, a deadly protein becomes an efficient carrier for antibody drugs.

Source: newsoffice.mit.edu

Bacillus anthracis bacteria have very efficient machinery for injecting toxic proteins into cells, leading to the potentially deadly infection known as anthrax. A team of MIT researchers has now hijacked that delivery system for a different purpose: administering cancer drugs.

“Anthrax toxin is a professional at delivering large enzymes into cells,” says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT. “We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells.”

In a paper appearing in the journal ChemBioChem, Pentelute and colleagues showed that they could use this disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. This is the first demonstration of effective delivery of antibody mimics into cells, which could allow researchers to develop new drugs for cancer and many other diseases, says Pentelute, the senior author of the paper.

Hitching a ride

Antibodies — natural proteins the body produces to bind to foreign invaders — are a rapidly growing area of pharmaceutical development. Inspired by natural protein interactions, scientists have designed new antibodies that can disrupt proteins such as the HER2 receptor, found on the surfaces of some cancer cells. The resulting drug, Herceptin, has been successfully used to treat breast tumors that overexpress the HER2 receptor.

Several antibody drugs have been developed to target other receptors found on cancer-cell surfaces. However, the potential usefulness of this approach has been limited by the fact that it is very difficult to get proteins inside cells. This means that many potential targets have been “undruggable,” Pentelute says.

“Crossing the cell membrane is really challenging,” he says. “One of the major bottlenecks in biotechnology is that there really doesn’t exist a universal technology to deliver antibodies into cells.”

For inspiration to solve this problem, Pentelute and his colleagues turned to nature. Scientists have been working for decades to understand how anthrax toxins get into cells; recently researchers have started exploring the possibility of mimicking this system to deliver small protein molecules as vaccines.

The anthrax toxin has three major components. One is a protein called protective antigen (PA), which binds to receptors called TEM8 and CMG2 that are found on most mammalian cells. Once PA attaches to the cell, it forms a docking site for two anthrax proteins called lethal factor (LF) and edema factor (EF). These proteins are pumped into the cell through a narrow pore and disrupt cellular processes, often resulting in the cell’s death.

However, this system can be made harmless by removing the sections of the LF and EF proteins that are responsible for their toxic activities, leaving behind the sections that allow the proteins to penetrate cells. The MIT team then replaced the toxic regions with antibody mimics, allowing these cargo proteins to catch a ride into cells through the PA channel.

‘A prominent advance’

The antibody mimics are based on protein scaffolds that are smaller than antibodies but still maintain structural diversity and can be designed to target different proteins inside a cell. In this study, the researchers successfully targeted several proteins, including Bcr-Abl, which causes chronic myeloid leukemia; cancer cells in which that protein was disrupted underwent programmed cell suicide. The researchers also successfully blocked hRaf-1, a protein that is overactive in many cancers.

“This work represents a prominent advance in the drug-delivery field,” says Jennifer Cochran, an associate professor of bioengineering at Stanford University. “Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated.”

The MIT team is now testing this approach to treat tumors in mice and is also working on ways to deliver the antibodies to specific types of cells.

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Benefits of statins slightly outweigh diabetes risk

Source: www.newkerala.com

A new study has revealed the benefits of taking cholesterol-lowering drugs such as statins are far greater than the risks and the diabetes risk of taking the drug was "small".

According to the researchers from UCL and the University of Glasgow, among nearly 130 000 participants from clinical trials that previously tested the effect of statins on heart disease and stroke (major vascular events), those assigned statins vs. placebo, or higher vs. lower doses of statins, were noted to have a small increase in risk of developing type 2 diabetes of about 12 percent over a four-year period, and also to gain an excess of 240g (around half a pound) in weight.

David Preiss of the University of Glasgow Institute of Cardiovascular and Medical Sciences, said that weight gain is a risk factor for diabetes which might help explain the small increased risk of diabetes observed in people taking statins.

The researchers who also studied the mechanism of action found that Statins work by reducing the efficiency of a liver enzyme involved in cholesterol production, which causes liver cells to trap more low-density lipoprotein (LDL-) cholesterol from the bloodstream, reducing its circulating level. This mechanism is thought to underlie the efficacy of statins in lowering the risk of major vascular events.

The researchers added that the effects of the genetic variants are orders of magnitude lower than the effects of statins. There is also no indication from this study that an individual's genetic make-up will meaningfully affect their clinical response to statin treatment. Statin drugs should continue to be prescribed without the need for any form of genetic testing.

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Healthy Grid: Fight Cavities With Sweet Treats

Source: www.bio-medicine.org

Healthy Grid announced the impending release of two new tools to fight cavities. Lolozlollipops will use herbs to fight the bacteria that cause tooth decay and Xylitol hard candies will also fight bacteria while stimulating saliva production.

“We're very excited to be rolling these out close together,” said Andrew Clapp of Healthy Grid. “Even though personal dental care is on the upswing, we know that people can always use a little more prevention. Cavities are painful and expensive but these treats are tasty and easy to use. We hope to help people get better news at the dentist and longer use out of their teeth.”

Loloz lollipops are the brainchild of UCLA professor Wenyuan Shi as well as the result of centuries of Chinese herbal remedies. As chair of the Oral Biology Section at UCLA's School of Dentistry, Shi has sought to bring better dental care to underserved portions of the population including impoverished people, geographically isolated people, children, and the elderly. Many people don't have access to the right tools and education and many don't have the physical capacity to adequately floss and brush.

Shi thought that the answer might be found in traditional Chinese herbs. After more than 50,000 trials, he concluded that licorice root would fight the streptococcus bacteria that causes tooth decay. Because the extract would need a few minutes of exposure to kill the bacteria, Shi decided to make it into a lollipop. Licorice root in this form doesn't produce the flavor associated with the name so orange was elected as the initial flavor.

 

“For Loloz, and this is the case with Xylitol too, it's important to not bite through the candy,” says Clapp. “Number one, your dentist will be disappointed if you're biting through any hard candy. Number two, these things take a couple of minutes to have their intended effect. Let them melt in your mouth.”

Loloz will be available from theDental Optimizer site. The recommended schedule is two lollipops per day for ten days and Healthy Grid suggests that this should be repeated four times per year.

Healthy Grid is currently offering Xylitol Tooth-Friendly Candies to help the fight against tooth decay. Xylitol is a sugar substitute that is widely known for its flavor and consistency in cooking. According to Healthy Grid, Xylitol works by depriving bacteria of the sucrose it needs to grow.

“Forgive the technical-speak here,” said Clapp, “Regular sugar feeds the bacteria and fosters growth leading to tooth decay and gum disease. Xylitol's different chemical makeup doesn't feed the bacteria and since it stimulates saliva production bad particles clear out more quickly. Your mouth becomes more hostile to the harmful bacteria.”

Other benefits come to the users of Xylitol as well. It contains fewer calories per serving than sugar so it's beneficial to those seeking both weight loss and a treat. It also metabolizes more slowly than sugar so it is likely better for people with diabetes.

The experts at Healthy Grid recommend enjoying Tooth-Friendly Xylitol candies around 5 times per day and, like the Loloz, they recommend letting them dissolve and not biting through them.

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Stop Taking Patients in Cardiac Arrest to Hospital, Says Expert

Source:medimoon.com

It’s time to stop taking patients in cardiac arrest to hospital and let ambulance crews deliver the best possible care at the scene, argues a senior UK doctor in The BMJ this week. But a senior US doctor warns that avoidingambulance transport could result in unacceptable deaths.

Cardiac Arrest:

Cardiac arrest outside of hospital is a common and catastrophic medical emergency experienced by about 60,000 people a year in the UK. Less than 10% survive to discharge from hospital.

Immediate cardiopulmonary resuscitation (CPR) offers the best chance of survival and ambulance services throughout the developed world tend to take patients in cardiac arrest to hospital, with CPR ongoing.

Cardiac arrest (Photo credit)

Full Study:

This seems intuitive, writes Jonathan Benger, Professor of Emergency Care at the University of the West of England, and Consultant at University Hospitals Bristol NHS Foundation Trust, but he says “hospitals have nothing to offer almost all such patients beyond the care that is provided by a well trained and equipped ambulance service.”

Furthermore, taking such patients to hospital may be actively harmful, he warns.

He believes this has to stop. “Ambulance staff must be empowered to use their skills to optimise CPR, achieve early defibrillation, and deliver the best possible care at the scene, with no thought of transport until spontaneous circulation has returned or until it becomes clear that the patient has no chance of survival,” he writes.

Once spontaneous circulation has returned, the patient should be stabilised and transported to a “heart attack” centre for ongoing care. And if spontaneous circulation does not return then the patient’s death “should be accepted and made as dignified as possible.”

He acknowledges that, in rare circumstances, transport to hospital is justified, but says this should be delivered by a specialist team.

“For the vast majority of patients, however, it is time to call a halt to transport in cardiac arrest and to concentrate on providing the best possible resuscitation skills at scene, empowering and supporting ambulance staff. More must also be done to educate staff and the public about best possible care and what to expect when cardiac arrest occurs outside hospital,” he concludes.

But Bruce Adams, Chair of emergency medicine at the University of Texas HealthSciences Center, says rules for deciding when to stop resuscitation are fallible and can result in unacceptable deaths.

He points out that the quality of CPR and survival outcomes “vary strikingly with geography, further complicating the application of guidelines on when to stop resuscitation.”

And he argues that the costs of CPR survival are overstated. “Avoiding ambulance transport of every patient with a cardiac arrest who died in the emergency room would save the US Medicare programme only $58m, which is less than 0.1% of its total annual losses from fraud alone,” he explains.

The rate of ambulance crashes with full lights and sirens is 46 per 100,000 patient journeys, he says. “We would need to halt 2,178 ambulance transports to prevent asingle injury, but that effort would result in more than 20 unnecessary deaths.”

Furthermore, the fear that CPR creates long term neurovegetative survivors is not borne out by the data, he adds. “For the most part, patients that are destined to die do so fairly soon.”

Meanwhile, an estimated 5% of all organs harvested are from legally brain dead patients who received CPR, “so reducing ambulance transport of patients in cardiac arrest could diminish organ donations.”

Finally, he points to emerging advances in CPR research, saying “these promising hospital based resuscitative strategies may change our definition of who is and who is not salvageable.”

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Shorebird’s beak inspires UT Arlington research on water collection

A UT Arlington engineering professor and his doctoral student have designed a device based on a shorebird’s beak that can accumulate water collected from fog and dew.

The device could provide water in drought-stricken areas of the world or deserts around the globe.

Xin Heng, PhD student, and Cheng Luo

Xin Heng, left, a doctoral student in Mechanical and Aerospace Engineering, and Cheng Luo, MAE professor, have made a device that can use fog and dew to collect water.

Cheng Luo, professor in the Mechanical & Aerospace Engineering Department, and Xin Heng, PhD candidate in the same College of Engineering department, published “Bioinspired Plate-Based Fog Collectors” in the Aug. 25 edition of ACS’ (American Chemical Society) Applied Materials & Interfaces journal. ACS also included the research in its Public Affairs Weekly release this week.

The idea began when Heng saw an article that explained the physical mechanism shorebirds use to collect their food – driving food sources into their throats by opening and closing their beaks. Luo said that inspired the team to try to replicate the natural beak in the lab.

“We wanted to see if we could do that first,” Luo said. “When we made the artificial beaks, we saw that multiple water drops were transported by narrow, beak-like glass plates. That made us think of whether we could harvest the water from fog and dew.”

Their experiments were successful. They found out they could harvest about four tablespoons of water in a couple of hours from glass plates that were about 26 centimeters long by 10 centimeters wide.

Shorebirds refers to a general category of bird that lives on the world’s shorelines. They typically have long, hinged beaks that are designed to ferret around for prey whether in the sand or the water.

Luo said the hinged, non-parallel artificial beaks the team made in the lab mimic the shorebirds’ beaks, forcing the condensation to the point where the two glass plates meet. The water is pumped through a channel, and then the process is repeated.

Luo and Heng said more sustainable methods are needed for accumulating water in arid or semi-arid places, which make up about half of the world’s land mass.

“And really, if this method could be mass-produced, it could be used anywhere in the world fog or dew exist,” Luo said.

Khosrow Behbehani, dean of the College of Engineering, said the research could help drought-stricken areas like Texas and California.

“The research shows innovative ideas can be triggered by careful observation of seemingly unrelated phenomenon,” Behbehani said. “Collecting water from existing fog or dew using this novel method offers another alternative for communities that are strapped for our most precious resource.”

- See more at: http://www.uta.edu/news/releases/2014/09/birdbeak-water-luo.php#sthash.a1ztfBR7.dpuf

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Stanford scientists track the rise and fall of brain volume throughout life

Source: news.stanford.edu
Stanford scientists have shown how the brain changes throughout life, and created a standard curve that can be used to assess whether patients are maturing and aging normally. This resource could help diagnose or monitor people with mental health conditions, learning delays or other diseases.

We can witness our bodies mature, then gradually grow wrinkled and weaker with age, but it is only recently that scientists have been able to track a similar progression in the nerve bundles of our brains. That tissue increases in volume until around age 40, then slowly shrinks. By the end of our lives the tissue is about the volume of a 7-year-old.

So finds a team of Stanford scientists who used a new magnetic resonance imaging technique to show, for the first time, how human brain tissue changes throughout life. Knowing what's normal at different ages, doctors can now image a patient's brain, compare it to this standard curve and be able to tell if a person is out of the normal range, much like the way a growth chart can help identify kids who have fallen below their growth curve. The researchers have already used the technique to identify previously overlooked changes in the brain of people with multiple sclerosis.

"This allows us to look at people who have come into the clinic, compare them to the norm and potentially diagnose or monitor abnormalities due to different diseases or changes due to medications," said Jason Yeatman, a graduate student in psychology and first author on a paper published today in Nature Communications. Aviv Mezer, a research associate, was senior author on the paper. Both collaborated with Brian Wandell, a professor of psychology, and his team.

For decades scientists have been able to image the brain using magnetic resonance imaging (MRI) and detect tumors, brain activity or abnormalities in people with some diseases, but those measurements were all subjective. A scientist measuring some aspect of the brain in one lab couldn't directly compare findings with someone in another lab. And because no two scans could be compared, there was no way to look at a patient's image and know whether it fell outside the normal range.

Limitation overcome

"A big problem in MRI is variation between instruments," Mezer said. Last year Mezer and Wandell led an interdisciplinary team to develop a technique that can be used to compare MRI scans quantitatively between labs, described in Nature Medicine. "Now with that method we found a way to measure the underlying tissue and not the instrumental bias. So that means that we can measure 100 subjects here and Jason can measure another 100 in Seattle (where he is now a postdoctoral fellow) and we can put them all in a database for the community."

The technique the team had developed measures the amount of white matter tissue in the brain. That amount of white matter comes primarily from an insulating covering called myelin that allows nerves to fire most efficiently and is a hallmark of brain maturation, though the white matter can also be composed of other types of cells in the brain.

White matter plays a critical role in brain development and decline, and several diseases including schizophrenia and autism are associated with white matter abnormalities. Despite its importance in normal development and disease, no metric existed for determining whether any person's white matter fell within a normal range, particularly if the people were imaged on different machines.

Mezer and Yeatman decided to use the newly developed quantitative technique to develop a normal curve for white matter levels throughout life. They imaged 24 regions within the brains of 102 people ages 7 to 85, and from that established a set of curves showing the increase and then eventual decrease in white matter in each of the 24 regions throughout life.

What they found is that the normal curve for brain composition is rainbow-shaped. It starts and ends with roughly the same amount of white matter and peaks between ages 30 and 50. But each of the 24 regions changes a different amount. Some parts of the brain, like those that control movement, are long, flat arcs, staying relatively stable throughout life.

Others, like the areas involved in thinking and learning, are steep arches, maturing dramatically and then falling off quickly. (The group did point out that their samples started at age 7 and a lot of brain development had already occurred.)

Continued collaboration

"Regions of the brain supporting high-level cognitive functions develop longer and have more degradation," Yeatman said. "Understanding how that relates to cognition will be really important and interesting." Yeatman is now a postdoctoral scholar at the University of Washington, and Mezer is now an assistant professor at the Hebrew University of Jerusalem. They plan to continue collaborating with each other and with other members of the Wandell lab, looking at how brain composition correlates with learning and how it could be used to diagnose diseases, learning disabilities or mental health issues.

The group has already shown that they can identify people with multiple sclerosis (MS) as falling outside the normal curve. People with MS develop what are known as lesions – regions in the brain or spinal cord where myelin is missing. In this paper, the team showed that they could identify people with MS as being off the normal curve throughout regions of the brain, including places where there are no visible lesions. This could provide an alternate method of monitoring and diagnosing MS, they say.

Wandell has had a particular interest in studying the changes that happen in the brain as a child learns to read. Until now, if a family brought a child into the clinic with learning disabilities, Wandell and other scientists had no way to diagnose whether the child's brain was developing normally, or to determine the relationship between learning delays and white matter abnormalities.

"Now that we know what the normal distribution is, when a single person comes in you can ask how their child compares to the normal distribution. That's where this is headed," said Wandell, who is also the Isaac and Madeline Stein Family professor and a Stanford Bio-X affiliate. Wandell runs the Center for Cognitive and Neurobiological Imaging (CNI), where Mezer and the team developed the MRI technique to quantify white matter, and where the scans for this study were conducted.

The ability to share data among scientists is an issue Wandell has championed at the CNI and has been promoting in his work helping the Stanford Neurosciences Institute plan the computing strategy for their new facility. "Sharing of data and computational methods is critical for scientific progress," Wandell said. In line with that goal, the new standard curve for white matter is something scientists around the world can use and contribute data to.

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Artificial sweetners not so sweet for your health.

Source: Weizmann Institute of Science
@WeizmannScience Study finds Increase Glucose intolerance with the use of Artificial sweetners.

Artificial sweeteners, promoted as aids to weight loss and diabetes prevention, could actually hasten the development of glucose intolerance and metabolic disease; and they do it in a surprising way: by changing the composition and function of the gut microbiota – the substantial population of bacteria residing in our intestines. These findings, the results of experiments in mice and humans, were published today in Nature. Among other things, says Dr. Eran Elinav of the Weizmann Institute's Immunology Department, who led this research together with Prof. Eran Segal of Computer Science and Applied Mathematics Department, the widespread use of artificial sweeteners in drinks and food may be contributing to the obesity and diabetes epidemic that is sweeping much of the world.

For years researchers have been puzzling over the fact that non-caloric artificial sweeteners do not seem to assist in weight loss, and some studies have suggested they may even have an opposite effect. Graduate student Jotham Suez in Elinav's lab, who led the study, collaborated with graduate students Tal Korem and David Zeevi in Segal's lab and Gili Zilberman-Shapira in Elinav's lab in discovering that artificial sweeteners, even though they do not contain sugar, nonetheless have a direct effect on the body's ability to utilize glucose. Glucose intolerance – generally thought to occur when the body cannot cope with large amounts of sugar in the diet – is the first step on the path to metabolic syndrome and adult-onset diabetes.

The scientists gave mice water laced with the three most commonly used artificial sweeteners – in the equivalent amounts to those permitted by the FDA. These mice developed glucose intolerance, as compared to mice that drank water, or even sugar water. Repeating the experiment with different types of mice and different doses of the sweeteners produced the same results – these substances were somehow inducing glucose intolerance.

Next, the researchers investigated a hypothesis that the gut microbiota are involved in this phenomenon. They thought the bacteria might do this by reacting to new substances like artificial sweeteners, which the body itself may not recognize as "food." Indeed, artificial sweeteners are not absorbed in the gastrointestinal tract, but in passing through they encounter trillions of the bacteria in the gut microbiota.

The researchers treated mice with antibiotics to eradicate many of their gut bacteria; this resulted in a full reversal of the artificial sweeteners' effects on glucose metabolism. Next, they transferred the microbiota from mice that consumed artificial sweeteners to 'germ-free' mice – resulting in a complete transmission of the glucose intolerance into the recipient mice. This, in itself, was conclusive proof that changes to the gut bacteria are directly responsible for the harmful effects to their host's metabolism. The group even found that incubating the microbiota outside the body, together with artificial sweeteners, was sufficient to induce glucose intolerance in the sterile mice. A detailed characterization of the microbiota in these mice revealed profound changes to their bacterial populations, including new microbial functions that are known to infer a propensity to obesity, diabetes and complications of these problems in both mice and humans.

Does the human microbiome function in the same way? Elinav and Segal had a means to test this as well. As a first step, they looked at data collected from their Personalized Nutrition Project, the largest human trial to date to look at the connection between nutrition and microbiota. Here, they uncovered a significant association between self-reported consumption of artificial sweeteners, personal configurations of gut bacteria and the propensity for glucose intolerance. They next conducted a controlled experiment, asking a group of volunteers who did not generally eat or drink artificially sweetened foods to consume them for a week and then undergo tests of their glucose levels as well as their gut microbiota compositions.

The findings showed that many – but not all – of the volunteers had begun to develop glucose intolerance after just one week of artificial sweetener consumption. The composition of their gut microbiota explained the difference: The researchers discovered two different populations of human gut bacteria – one that induced glucose intolerance when exposed to the sweeteners, the second that had no effect either way. Elinav believes that certain bacteria in the guts of those who developed glucose intolerance reacted to the chemical sweeteners by secreting substances that then provoked an inflammatory response similar to sugar overdose, promoting changes in the body's ability to utilize sugar.

Segal: "The results of our experiments highlight the importance of personalized medicine and nutrition to our overall health. We believe that an integrated analysis of individualized 'big data' from our genome, microbiome and dietary habits could transform our ability to understand how foods and nutritional supplements affect a person's health and risk of disease."

Elinav: "Our relationship with our own individual mix of gut bacteria is a huge factor in determining how the food we eat affects us. Especially intriguing is the link between use of artificial sweeteners – through the bacteria in our guts – to a tendency to develop the very disorders they were designed to prevent; this calls for reassessment of today's massive, unsupervised consumption of these substances."

 

###

Also participating in this research were Christoph A. Thaiss, Ori Maza, and Dr. Hagit Shapiro of Elinav's group; Dr. Adina Weinberger of Segal's group; Dr. Ilana Kolodkin-Gal of the Molecular Genetics Department; Prof. Alon Harmelin and Dr. Yael Kuperman of the Veterinary Resources Department; Dr. Shlomit Gilad of the Nancy and Stephen Grand Israel National Center for Personalized Medicine; Prof. Zamir Halperin and Dr. Niv Zmora of Tel Aviv Sourasky Medical Center and Tel Aviv University; and Dr. David Israeli of Kfar Shaul Hospital Jerusalem Center for Mental Health.

Dr. Eran Elinav's research is supported by the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Benoziyo Endowment Fund for the Advancement of Science; the Gurwin Family Fund for Scientific Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; Yael and Rami Ungar, Israel; the Crown Endowment Fund for Immunological Research; John L. and Vera Schwartz, Pacific Palisades, CA; the Rising Tide Foundation; Alan Markovitz, Canada; Cynthia Adelson, Canada; the estate of Jack Gitlitz; the estate of Lydia Hershkovich; the European Research Council; the CNRS - Centre National de la Recherche Scientifique; the estate of Samuel and Alwyn J. Weber; and Mr. and Mrs. Donald L. Schwarz, Sherman Oaks, CA. Dr. Elinav is the Incumbent of the Rina Gudinski Career Development Chair.

Prof. Eran Segal's research is supported by the Kahn Family Research Center for Systems Biology of the Human Cell; the Carolito Stiftung; the Cecil and Hilda Lewis Charitable Trust; the European Research Council; and Mr. and Mrs. Donald L. Schwarz, Sherman Oaks, CA.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

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Tobacco that cures - New use promises treatment of Ebola

Credit: Reuters/WHO/Tarik Jasarevic/Handout via Reuters

Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.

The treatment, which had been tested only in lab animals before being given to two American medical workers in Liberia, consists of proteins called monoclonal antibodies that bind to and inactivate the Ebola virus.

For decades biotech companies have produced such antibodies by growing genetically engineered mouse cells in enormous metal bioreactors. But in the case of the new Ebola treatment ZMapp, developed by Mapp Pharmaceuticals, the antibodies were produced in tobacco plants at Kentucky Bioprocessing, a unit of tobacco giant Reynolds American.

The tobacco-plant-produced monoclonals have been dubbed "plantibodies."

"Tobacco makes for a good vehicle to express the antibodies because it is inexpensive and it can produce a lot," said Erica Ollmann Saphire, a professor at The Scripps Research Institute and a prominent researcher in viral hemorrhagic fever diseases like Ebola. "It is grown in a greenhouse and you can manufacture kilograms of the materials. It is much less expensive than cell culture."

In the standard method of genetic engineering, DNA is slipped into bacteria, and the microbes produce a protein that can be used to combat a disease.

A competing approach called molecular "pharming" uses a plant instead of bacteria. In the case of the Ebola treatment, Mapp uses the common tobacco plant, Nicotiana benthanmianas.

The process is very similar. A gene is inserted into a virus that is then used to infect the tobacco plant. The virus acts like a micro-Trojan Horse, ferrying the engineered DNA into the plant.

Cells infected with the virus and the gene it is carrying produce the target protein. The tobacco leaves are then harvested and processed to extract the protein, which is purified.

ZMapp's protein is a monoclonal antibody, which resembles ordinary disease-fighting antibodies but has a highly specific affinity for particular cells, including viruses such as Ebola. It attaches itself to the virus cells and inactivates them.

 

APPROVAL PROCESS

The drug so far has only been produced in very small quantities, but interest in it is stoking debate over whether it should be made more widely available to the hundreds of people stricken with Ebola in Africa while it remains untested.

“We want to have a huge impact on the Ebola outbreak,” Mapp CEO Kevin Whaley said in an interview at company headquarters in San Diego. "We would love to play a bigger role.”

Whaley said he was not aware of any significant safety issues with the serum. He would not discuss whether the company has been contacted about providing the drug overseas.

But he did note the novel manufacturing process carries its own risk, and would have to be cleared by the U.S. Food and Drug Administration as part of the approval process.

The FDA would, for example, have to be satisfied that the plant extraction process had not led to contamination of the resulting drug.

The tobacco plant grows quickly, said Reynolds spokesman David Howard, and "it takes only about a week (after the genes are introduced) before you can begin extracting the protein."

He declined to say how much medication each plant can yield or whether Kentucky Bioprocessing is in a position to produce ZMapp in significant quantities.

Scripps' Saphire said it can still take anywhere from one to three months to produce the ZMapp serum for wider use given the complexities of the process.

 

PENTAGON FUNDING

In 2007, Kentucky Bioprocessing entered into an agreement with Mapp Biopharmaceutical and the Biodesign Institute of Arizona State University to refine the tobacco-plant approach. The approach attracted funding support from the Pentagon's Defense Advanced Research Projects Agency (DARPA).

For all the hope, however, the plant technique has delivered few commercial products. In 2012 the FDA okayed a drug for the rare genetic disorder Gaucher disease from Israel's Protalix BioTherapeutics and Pfizer. Called Elelyso, it is made in carrot cells, and is the only such drug to reach the market.

Other companies have fallen far short, though it is not clear if the technique was to blame. Calgary-based SemBioSys Genetics Inc, which used safflowers to produce an experimental diabetes drug, folded in 2012 before it finished clinical trials.

Even Kentucky Bioprocessing, which at one point was developing monoclonal antibodies against HIV (the virus that causes AIDS), C. difficile bacterial infection, and the human papillomavirus, has dropped the last two projects, Howard said.

Last year Mitsubishi Tanabe Pharma Corp acquired a majority share of Quebec City-based Medicago, which is developing influenza and other vaccines using the tobacco-plant technology. The other 40 percent is owned by tobacco giant Philip Morris International.

 

 

(Reporting by Sharon Begley, Toni Clarke and Deena Beasley; Editing by Michele Gershberg and Martin Howell)

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