DNA clamp to grab cancer before it develops

Dec. 19, 2013 — As part of an international research project, a team of researchers has developed a DNA clamp that can detect mutations at the DNA level with greater efficiency than methods currently in use. Their work could facilitate rapid screening of those diseases that have a genetic basis, such as cancer, and provide new tools for more advanced nanotechnology. The results of this research is published this month in the journal ACS Nano.

Toward a new generation of screening tests

An increasing number of genetic mutations have been identified as risk factors for the development of cancer and many other diseases. Several research groups have attempted to develop rapid and inexpensive screening methods for detecting these mutations. "The results of our study have considerable implications in the area of diagnostics and therapeutics," says Professor Francesco Ricci, "because the DNA clamp can be adapted to provide a fluorescent signal in the presence of DNA sequences having mutations with high risk for certain types cancer. The advantage of our fluorescence clamp, compared to other detection methods, is that it allows distinguishing between mutant and non-mutant DNA with much greater efficiency. This information is critical because it tells patients which cancer(s) they are at risk for or have."

"Nature is a constant source of inspiration in the development of technologies," says Professor Alexis Vallee-Belisle. "For example, in addition to revolutionizing our understanding of how life works, the discovery of the DNA double helix by Watson, Crick and Franklin in 1953 also inspired the development of many diagnostic tests that use the strong affinity between two complementary DNA strands to detect mutations."

"However, it is also known that DNA can adopt many other architectures, including triple helices, which are obtained in DNA sequences rich in purine (A, G) and pyrimidine (T, C) bases," says the researcher Andrea Idili, first author of the study. "Inspired by these natural triple helices, we developed a DNA-based clamp to form a triple helix whose specificity is ten times greater than a double helix allows."

"Beyond the obvious applications in the diagnosis of genetic diseases, I believe this work will pave the way for new applications related in the area of DNA-based nanostructures and nanomachines," notes Professor Kevin Plaxco, University of California, Santa Barbara. "Such nanomachines could ultimately have a major impact on many aspects of healthcare in the future."

"The next step is to test the clamp on human samples, and if it is successful, it will begin the process of commercialization," concludes Professor Vallee-Belisle.

View the original article here

Mental health information at your fingertips – WHO launches the MiNDbank

10 December 2013 | GENEVA - MiNDbank, a new WHO database goes online today, presenting a wealth of information about mental health, substance abuse, disability, human rights and the different policies, strategies, laws and service standards being implemented in different countries. It also contains key international documents and information.

Launched on Human Rights Day, the platform is part of WHO’s QualityRights initiative, aiming to end human rights violations against people with mental health conditions.

“People with mental disabilities still face discrimination, violence and abuse in all countries,” says Dr Michelle Funk, from WHO’s Department of Mental Health and Substance Abuse. “The easy-to-use platform was established as a tool to facilitate debate, dialogue, advocacy and research on mental health, to improve care and to promote human rights across the globe.”

The care available in mental health facilities may often not only be of poor quality but can also hinder recovery. It can still be common in some countries for people to be locked away in small, prison-like cells with no human contact or to be chained to their beds, unable to move. The MiNDbank will help decision makers to address these issues, support reform efforts and ultimately improve the lives of people with mental health conditions in line with the Comprehensive Mental Health Action Plan 2013-2020, adopted by the World Health Assembly in May 2013.

The database, established with support from a broad range of partners, allows visitors to tap into the health information of WHO Member States and other partners. Users can review policies, laws and strategies and search for best practices and success stories in the field of mental health.

“If a government, for example, wishes to develop a new mental health policy in line with international human rights standards it can - on the new platform - quickly get an overview about the policies of other countries and benefit from their experiences and an array of international guidance tools and resources,“ explains Nathalie Drew, WHO Technical Officer working on mental health and human rights. So far, already more than 160 countries are sharing key mental health information through the MiNDbank and updates will be provided on a regular basis.

The WHO QualityRights initiative was launched in 2012, as part of the drive to raise human rights and quality standards in mental health and social care. The goal is to end human rights violations against people with mental health conditions and promote high-quality mental health services in the community.

For more information please contact:

Fadela Chaib
Communications Officer/Spokesperson
WHO
Telephone: +41 22 791 3228
Mobile: +41 79 475 5556
E-mail: chaibf@who.int

View the original article here

University of Colorado researchers found that arise from stem cells of muscle invasion and another muscle-invasive bladder cancer

Published today in the journal stem cells University of Colorado Cancer Center Research create a dangerous, invasive bladder cancer precursor cells shows that muscle with non-invasive bladder cancer to create progenitor cells.

View the original article here

Innovative screening strategy swiftly uncovers new drug candidates, new biology

Dec. 22, 2013 — Scientists at The Scripps Research Institute (TSRI) have demonstrated a drug-discovery strategy with a double payoff -- it enables the rapid selection of chemical compounds that have a desired effect on cells and also highlights how the compounds work.

To illustrate the power of the innovative technique, the TSRI researchers used it to identify a compound that shows promise for treating obesity-linked diabetes. At the same time, they were able to identify the fat-cell enzyme that the compound inhibits -- an enzyme that has not yet been a focus of diabetes drug development.

"This integrated strategy we've developed has the potential to accelerate the discovery of important biological pathways and may lead to faster development of new drugs for multiple diseases," said TSRI Associate Professor Enrique Saez.

Saez and his colleague Benjamin F. Cravatt, chair of TSRI's Department of Chemical Physiology, were the senior authors of the new study, which is reported December 22, 2013, in an advance online issue of Nature Chemical Biology.

Facilitating Drug Discovery

The new strategy has great potential to streamline drug discovery, a process whose importance to human health can hardly be overemphasized.

Typically, pharmaceutical scientists start the discovery process by "screening" large libraries of chemical compounds in search of one or a few that might treat disease. The dominant strategy of recent decades has been to screen compounds for a specific activity against a known target, for example, inhibiting the function of a certain enzyme thought to be critical for the disease in question. A key advantage of this "target-based" screening is that it uses biochemical tests that can be done relatively simply in a test-tube -- or rather, in a large array of tiny test tubes via automated, rapid screening systems that sort through hundreds of thousands of different compounds.

Target-based screening has enabled scientists to discover many useful new drugs, but some wonder whether this basic discovery strategy has already taken all the "low hanging fruit." In recent years, compounds selected with target-based in vitro tests have seemed to be failing increasingly often when tested in the more realistic biological environments of cells and animals.

An older strategy, "phenotypic" screening, avoids much of this problem by testing compounds for their ability to produce a desired effect directly on living cells. Unfortunately, such cell-based tests often leave open the question of how a useful compound works. "If you don't know what its relevant molecular target is, then developing that compound into a drug -- optimizing its potency, its selectivity, its half-life in the bloodstream and so on -- is going to be difficult," said Saez.

Identifying the molecular targets of compounds selected by phenotypic screens is typically burdensome and time-consuming. But in their new study, Saez, Cravatt and their colleagues were able to speed up the process dramatically. Indeed, their combined phenotypic screening and target-identification approach enabled them to quickly discover, characterize and carry out preclinical tests of a potential new drug for obesity-linked diabetes: a complex metabolic disorder that affects 347 million people worldwide.

A New Diabetes Drug Candidate, Plus Insights into the Disease

The strategy makes use of the increasing availability of special libraries of related compounds that act as inhibitors of entire enzyme classes. In this case, the researchers used a set of compounds, recently synthesized by Cravatt's laboratory, that tend to inhibit serine hydrolases -- a vast enzyme family whose members participate in most biological processes in mammals.

The scientists started with a phenotypic screen, testing their library of compounds for the ability to make young fat cells mature faster and store more fat. Better fat storage means that less fat leaks from fat cells into the liver, muscles and pancreas -- a process that frequently occurs with obesity, often interfering with insulin signaling enough to bring on diabetes.

The screen quickly yielded several compounds that had a strong effect in promoting fat-cell fat storage. The researchers then used a method called "activity-based profiling" to identify the fat-cell serine hydrolases that the compounds inhibited most strongly. One of the most potent compounds, WWL113, turned out to work principally by inhibiting Ces3, a serine hydrolase enzyme that scientists have not studied in the context of obesity or diabetes.

The researchers quickly demonstrated WWL113's effectiveness in two different mouse models of obesity-linked diabetes -- one in which the mice are genetically programmed to become obese and diabetic, and another in which normal mice are made obese and diabetic with a high-fat diet. "The treated animals showed resistance to weight gain -- they were not putting on as much weight as the controls," said Saez. "Their blood biochemistry also was getting normalized; their glucose, triglyceride and cholesterol levels were coming down towards normal levels."

In these mouse tests, WWL113 -- without any optimization for use as a drug -- performed about as well as the FDA-approved diabetes treatment rosiglitazone (Avandia). Notably, the new compound lacked one of the side effects that drugs in rosiglitazone's class have in mice: the toxic accumulation of lipids in the liver. "Our compound clears lipids from the diabetic mouse liver, whereas rosiglitazone has the opposite effect," said Saez.

To explore the relevance of these results to humans, the TSRI team worked with collaborating researchers in Australia to test fat samples from obese humans and diabetics. The tests confirmed that the human version of Ces3 also is unusually active in such patients. This suggests that an inhibitor may also work as a diabetes treatment in people.

Saez and his colleagues will next focus on using the new screening strategy to uncover more biological pathways that could yield new mechanisms to develop potential therapies.

Contributors to the study, "Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes," also included first author Eduardo Dominguez, then a postdoctoral fellow in the Saez Laboratory; as well as TSRI's Andrea Galmozzi, Jae Won Chang, Ku-Lung Hsu, Joanna Pawlak, Weiwei Li, Cristina Godio, Jason Thomas, David Partida, Sherry Niessen and Daniel K. Nomura; and Australian researchers Paul E. O'Brien and Matthew J. Watt of Monash University, and Aaron P. Russell of Deakin University.

The study was funded in part by the National Institutes for Health (DK081003, DK099810), the American Diabetes Association, The McDonald's Center for Type 2 Diabetes and Obesity, the National Health and Medical Research Council of Australia, the Hewitt Foundation for Medical Research and the Xunta de Galicia, Spain.

View the original article here

Statement on the death of Nelson Mandela

With the death of Nelson Mandela the world has lost a great and visionary leader – a global hero for whom a democratic and free society was “an ideal, which I hope to live for and to achieve. But if needs be, it is an ideal for which I am prepared to die".

Mandela’s commitment to overcome prejudice and hate inspired not only his determination to break down barriers between different races, but also to eliminate discrimination against those living with HIV, calling on people to give publicity to HIV/AIDS and no longer to hide it.

His belief in the power of truth and reconciliation, his capacity for hope, his unflagging dignity, and his faith in his fellow human beings, were and will continue to be an example to us all. Our thoughts are with his family – and all in South Africa and around the world whose lives were changed through his courage.

Share

Email Twitter Facebook Google Delicious LinkedIn

View the original article here

Shows promise for women with other drugs triple-negative breast cancer

In the nationwide survey of women with triple-negative breast cancer angiogenesis inhibitors led to rapid increase in number of carboplatin chemotherapy using drugs or with a standard chemotherapy drug Avastin off completely, the tumor shrank, adding investigators, reported at the San Antonio Breast Cancer Symposium 2013. In the study, cancer and leukemia Group B hosted by new Faber Cancer Institute, Brown University, University of Texas MD Anderson Cancer Center, UNC Lineberger comprehensive cancer include author from the Center. New York University, Washington University in St. Louis, hope comprehensive cancer center and Mount Sinai Medical Center.

View the original article here

Solar activity not a key cause of climate change, study shows

Dec. 22, 2013 — Climate change has not been strongly influenced by variations in heat from the sun, a new scientific study shows.

The findings overturn a widely held scientific view that lengthy periods of warm and cold weather in the past might have been caused by periodic fluctuations in solar activity.

Research examining the causes of climate change in the northern hemisphere over the past 1000 years has shown that until the year 1800, the key driver of periodic changes in climate was volcanic eruptions. These tend to prevent sunlight reaching Earth, causing cool, drier weather. Since 1900, greenhouse gases have been the primary cause of climate change.

The findings show that periods of low sun activity should not be expected to have a large impact on temperatures on Earth, and are expected to improve scientists' understanding and help climate forecasting.

Scientists at the University of Edinburgh carried out the study using records of past temperatures constructed with data from tree rings and other historical sources. They compared this data record with computer-based models of past climate, featuring both significant and minor changes in the sun.

They found that their model of weak changes in the sun gave the best correlation with temperature records, indicating that solar activity has had a minimal impact on temperature in the past millennium.

The study, published in Nature GeoScience, was supported by the Natural Environment Research Council.

Dr Andrew Schurer, of the University of Edinburgh's School of GeoSciences, said: "Until now, the influence of the sun on past climate has been poorly understood. We hope that our new discoveries will help improve our understanding of how temperatures have changed over the past few centuries, and improve predictions for how they might develop in future. Links between the sun and anomalously cold winters in the UK are still being explored."

View the original article here

Clues to how plants evolved to cope with cold

Dec. 22, 2013 — Researchers have found new clues to how plants evolved to withstand wintry weather. In a study to appear in the December 22 issue of the journal Nature, the team constructed an evolutionary tree of more than 32,000 species of flowering plants -- the largest time-scaled evolutionary tree to date. By combining their tree with freezing exposure records and leaf and stem data for thousands of species, the researchers were able to reconstruct how plants evolved to cope with cold as they spread across the globe. The results suggest that many plants acquired characteristics that helped them thrive in colder climates -- such as dying back to the roots in winter -- long before they first encountered freezing.

Fossil evidence and reconstructions of past climatic conditions suggest that early flowering plants lived in warm tropical environments, explained co-author Jeremy Beaulieu at the National Institute for Mathematical & Biological Synthesis (NIMBioS) at the University of Tennessee.

As plants spread to higher latitudes and elevations, they evolved in ways that helped them deal with cold conditions. Plants that live in the tundra, such as Arctic cinquefoil and three-toothed saxifrage, can withstand winter temperatures below minus 15 degrees Celsius.

Unlike animals, most plants can't move to escape the cold or generate heat to keep them warm. It's not so much the cold but the ice that poses problems for plants. For instance, freezing and thawing cause air bubbles to form in the plant's internal water transport system.

"Think about the air bubbles you see suspended in the ice cubes," said co-author Amy Zanne of the George Washington University. "If enough of these air bubbles come together as water thaws they can block the flow of water from the roots to the leaves and kill the plant."

The researchers identified three traits that help plants get around these problems.

Some plants, such as hickories and oaks, avoid freezing damage by dropping their leaves before the winter chill sets in -- effectively shutting off the flow of water between roots and leaves -- and growing new leaves and water transport cells when warmer weather returns.

Other plants, such as birches and poplars, also protect themselves by having narrower water transport cells, which makes the parts of the plant that deliver water less susceptible to blockage during freezing and thawing.

Still others die back to the ground in winter and re-sprout from their roots, or start growing as new plants from seeds when conditions are right.

To compile the plant trait data for their study, the researchers spent hundreds of hours scouring and merging multiple large plant databases containing tens of thousands of species, largely with the support of the National Evolutionary Synthesis Center in North Carolina and Macquarie University in Australia.

When they mapped their collected leaf and stem data onto their evolutionary tree for flowering plants, they found that many plants were well equipped for icy climates even before cold conditions hit.

Plants that die back to the ground in winter, for example, acquired the ability to die and come back when conditions improve long before they first experienced freezing. Similarly, species with narrow water transport cells acquired a finer circulatory system well before they confronted cold climates.

"This suggests that some other environmental pressure -- possibly drought -- caused these plants to evolve this way, and it happened to work really well for freezing tolerance too," said Zanne.

The only exceptions were plants that shed and replace their leaves seasonally -- these plant groups didn't gain the ability to drop their leaves during winter until after they encountered freezing, Beaulieu added.

As a next step, the researchers plan to use their evolutionary tree to find out how plants evolved to withstand other environmental stresses in addition to freezing, such as drought and heat.

View the original article here

World malaria report 2013 shows major progress in fight against malaria, calls for sustained financing

11 December 2013 | Geneva/Washington DC - Global efforts to control and eliminate malaria have saved an estimated 3.3 million lives since 2000, reducing malaria mortality rates by 45% globally and by 49% in Africa, according to the "World malaria report 2013" published by WHO.

An expansion of prevention and control measures has been mirrored by a consistent decline in malaria deaths and illness, despite an increase in the global population at risk of malaria between 2000 and 2012. Increased political commitment and expanded funding have helped to reduce incidence of malaria by 29% globally, and by 31% in Africa.

The large majority of the 3.3 million lives saved between 2000 and 2012 were in the 10 countries with the highest malaria burden, and among children aged less than 5 years – the group most affected by the disease. Over the same period, malaria mortality rates in children in Africa were reduced by an estimated 54%.

But more needs to be done.

“This remarkable progress is no cause for complacency: absolute numbers of malaria cases and deaths are not going down as fast as they could,” says Dr Margaret Chan, WHO Director-General. “The fact that so many people are infected and dying from mosquito bites is one of the greatest tragedies of the 21st century.”

In 2012, there were an estimated 207 million cases of malaria (uncertainty interval: 135 – 287 million), which caused approximately 627?000 malaria deaths (uncertainty interval 473?000 – 789?000). An estimated 3.4 billion people continue to be at risk of malaria, mostly in Africa and south-east Asia. Around 80% of malaria cases occur in Africa.

Long way from universal access to prevention and treatment

Malaria prevention suffered a setback after its strong build-up between 2005 and 2010. The new WHO report notes a slowdown in the expansion of interventions to control mosquitoes for the second successive year, particularly in providing access to insecticide-treated bed nets. This has been primarily due to lack of funds to procure bed nets in countries that have ongoing malaria transmission.

In sub-Saharan Africa, the proportion of the population with access to an insecticide-treated bed net remained well under 50% in 2013. Only 70 million new bed nets were delivered to malaria-endemic countries in 2012, below the 150 million minimum needed every year to ensure everyone at risk is protected. However, in 2013, about 136 million nets were delivered, and the pipeline for 2014 looks even stronger (approximately 200 million), suggesting that there is real chance for a turnaround.

There was no such setback for malaria diagnostic testing, which has continued to expand in recent years. Between 2010 and 2012, the proportion of people with suspected malaria who received a diagnostic test in the public sector increased from 44% to 64% globally.

Access to WHO-recommended artemisinin-based combination therapies (ACTs) has also increased, with the number of treatment courses delivered to countries rising from 76 million in 2006 to 331 million in 2012.

Despite this progress, millions of people continue to lack access to diagnosis and quality-assured treatment, particularly in countries with weak health systems. The roll-out of preventive therapies – recommended for infants, children under 5 and pregnant women – has also been slow in recent years.

“To win the fight against malaria we must get the means to prevent and treat the disease to every family who needs it,” says Raymond G Chambers, the United Nations Secretary General’s Special Envoy for Financing the Health MDGs and for Malaria. "Our collective efforts are not only ending the needless suffering of millions, but are helping families thrive and adding billions of dollars to economies that nations can use in other ways.”

Global funding gap

International funding for malaria control increased from less than US$ 100 million in 2000 to almost US$ 2 billion in 2012. Domestic funding stood at around US$ 0.5 billion in the same year, bringing the total international and domestic funding committed to malaria control to US$ 2.5 billion in 2012 – less than half the US$ 5.1 billion needed each year to achieve universal access to interventions.

Without adequate and predictable funding, the progress against malaria is also threatened by emerging parasite resistance to artemisinin, the core component of ACTs, and mosquito resistance to insecticides. Artemisinin resistance has been detected in four countries in south-east Asia, and insecticide resistance has been found in at least 64 countries.

“The remarkable gains against malaria are still fragile,” says Dr Robert Newman, Director of the WHO Global Malaria Programme. “In the next 10-15 years, the world will need innovative tools and technologies, as well as new strategic approaches to sustain and accelerate progress.”

WHO is currently developing a global technical strategy for malaria control and elimination for the 2016-2025 period, as well as a global plan to control and eliminate Plasmodium vivax malaria. Prevalent primarily in Asia and South America, P. vivax malaria is less likely than P. falciparum to result in severe malaria or death, but it generally responds more slowly to control efforts. Globally, about 9% of the estimated malaria cases are due to P. vivax, although the proportion outside the African continent is 50%.

"The vote of confidence shown by donors last week at the replenishment conference for the Global Fund to Fight AIDS, Tuberculosis and Malaria is testimony to the success of global partnership. But we must fill the annual gap of US$ 2.6 billion to achieve universal coverage and prevent malaria deaths," said Fatoumata Nafo-Traore, Executive Director of the Roll Back Malaria Partnership. "This is our historic opportunity to defeat malaria."

Notes for editors:

The "World malaria report 2013" summarizes information received from 102 countries that had on-going malaria transmission during the 2000-2012 period, and other sources, and updates the analyses presented in 2012.

The report contains revised estimates of the number of malaria cases and deaths, which integrate new and updated under-5 mortality estimates produced by the United Nations Inter-agency Group for Child Mortality Estimation, as well as new data from the Child Health Epidemiology Reference Group.

For more information, please contact:

In Geneva
Fadela Chaib
WHO Communications Officer/Spokesperson
Telephone: +41 22 791 3228
Mobile: +41 79 475 5556
E-mail: chaibf@who.int

In Washington DC
Phil Coticelli
Telephone: +1 301 801 5801
E-mail: phil@coticelligroup.com

View the original article here

Obamacare's signup deadline on Monday has its exceptions

By Susan Cornwell and Roberta Rampton

WASHINGTON (Reuters) - For most Americans who don't have health insurance, Monday is the deadline to sign up for coverage starting on January 1 under President Barack Obama's healthcare law.

For others, it's not a deadline.

There is a "hardship" exception for some that permits them not to sign up any kind of health insurance at all without facing a penalty - the hardship being problems they've encountered with Obamacare and its malfunctioning website HealthCare.gov.

There will also be a "good faith exception" for others, according to a senior Obama administration official.

"We'll have a special enrollment period," the official said last week, for "all those who make a good faith effort to get enrolled by the deadline" but fail to do so.

The official did not say how the government would determine whether or not the effort was made in good faith.

Still others may simply get a break from insurance companies, which the administration has urged to be flexible with people who miss the deadline.

Such is the uncertain state of "Obamacare" as it approaches what was originally supposed to be a defining moment - a signup deadline that would provide the first real test of the viability of the healthcare program brought into law by the Affordable Care Act.

Adding to the confusion is the fact that the original deadline for obtaining medical coverage was December 15. That was extended to December 23 after the federal government's website, HealthCare.gov, proved dysfunctional and sometimes non-functional.

The administration has reserved the right to change the deadline again "should exceptional circumstances pose barriers to consumers" enrolling on or before Monday.

Obama said on Friday that one million people had enrolled for new insurance plans under the law through HealthCare.gov, which serves 36 states, and 14 state-run marketplaces.

Many more enrollments are a major priority for Obama's signature healthcare reform, which officials are still hoping will help millions of uninsured and under-insured Americans finally to obtain medical coverage by the end of March.

GAPS IN COVERAGE?

It is not known how many consumers may have no insurance coverage during periods of 2014 because they failed to sign up on HealthCare.gov by Monday.

Some of the 14 states running their own healthcare exchanges have extended their sign-up deadlines past December 23.

On Thursday, the administration announced that if people's old insurance plans were canceled because of new standards under the law, they can claim a "hardship" exemption to the requirement that all Americans must have coverage by March 31 or face penalties that start at $95.

So some of these people may not sign up.

The Obama administration says it is trying to be flexible, but some Republican critics of the law say the frequent delays and changes have muddied the waters and confused people.

"With no clarity as to when people should sign up and who they should pay and when, it's a virtual certainty that many consumers will find themselves uncovered for a period of time through no fault of their own," Senator Orrin Hatch, a Utah Republican, said last week.

Administration officials said on Friday there are fewer than 500,000 people who have received cancellation notices from their insurance companies and have not yet found alternatives. Some were "auto-enrolled" in other plans by their insurance companies, the officials said.

The pace of sign-ups has picked up since October and November when technical problems crippled the HealthCare.gov website. Anyone who tried the website in October and November and became stuck has been getting attention from the administration.

Officials sent more than two million emails to people who could not advance through the website. They have also made more than 600,000 phone calls to consumers and mailed notices to hundreds of thousands of people, officials said.

"We are confident that we are doing everything we can so that individuals know what their options are to get coverage, whether it is at the marketplace or seeking it through the private insurers," said the senior official.

(Reporting By Susan Cornwell. Editing by Fred Barbash and Christopher Wilson)

View the original article here

Some plants may not adapt quickly to future climate change

Dec. 22, 2013 — Using the largest dated evolutionary tree of flowering plants ever assembled, a new study suggests how plants developed traits to withstand low temperatures, with implications that human-induced climate change may pose a bigger threat than initially thought to plants and global agriculture.

The study appearing Sunday (Dec. 22) in the journal Nature and co-authored by University of Florida scientists shows many angiosperms, or flowering plants, evolved mechanisms to cope with freezing temperatures as they radiated into nearly every climate during pre-historic times. Researchers found the plants likely acquired many of these adaptive traits prior to their movement into colder regions. The study also suggests some modern angiosperms, including most flowering plants, trees and agricultural crops, may not have the traits needed to rapidly respond to human-induced climate change, said study co-author Pam Soltis, a distinguished professor and curator of molecular systematics and evolutionary genetics at the Florida Museum on the UF campus.

"Only some plants were able to make the adjustments to survive in cold climates," said Soltis, who also is a member of the UF Genetics Institute. "In fact, some had traits used for other purposes that they co-opted for cold tolerance. The results have implications for plant response to climate change -- some plant lineages, including many crops, will not have the underlying genetic attributes that will allow for rapid responses to climate change."

Early flowering plants are thought to have been woody -- meaning they maintain a prominent stem above ground across years and changing weather conditions, such as a maple tree -- and restricted to warm, wet, tropical environments. But they have since put down roots in colder climates, dominating large swaths of the globe where freezing occurs. How they managed this expansion has long vexed researchers searching for plants' equivalent to the winter parka.

"Until now, we haven't had a compelling narrative about how leaf and stem traits have evolved to tolerate cold temperatures," said lead author Amy Zanne, assistant professor of biology in George Washington University's Columbian College of Arts and Sciences who earned her doctorate at UF. "Our research gives us this insight, showing us the 'whens,' 'hows' and 'whys' behind plant species' trait evolution and movements around the globe."

Zanne continued: "Freezing is a challenge for plants. Their living tissues can be damaged. It's like a plant's equivalent to frostbite. Their water-conducting pipes can also be blocked by air bubbles as water freezes and thaws. So over time, if plants moved into colder climates, they've had to figure out how to get around these problems."

Identifying evolutionary adaptations to these problems and likely paths to them required the team to build two sets of data. Researchers first created a database of 49,064 species, recording whether each maintains a stem aboveground over time, loses or keeps its leaves, has been exposed to freezing, and the width of its water-carrying pathways. Researchers combined the information with a dated evolutionary tree of 32,223 plant species and modeled the evolution of species' traits and climate over time, which identified the order of evolutionary events.

"We can determine the relative order of events without a dated tree, but the dated tree allows us to say exactly when something happened, so that we can correlate the events with geological events, like big changes in Earth's temperature," Soltis said.

Using this "timetree," researchers identified three repeated evolutionary shifts they believe flowering plants made to fight the cold. Plants either dropped their leaves seasonally, shutting down the pathways that would normally carry water between roots and leaves; developed thinner water-conducting pathways, allowing them to keep their leaves while reducing the risk of air bubbles developing during freezing and thawing; or avoided the cold seasons altogether as herbs, losing aboveground stems and leaves and retreating as seeds, or storing organs underground, such as tulips or potatoes.

"Angiosperms were not successful until they got the adaptation to drop their leaves," said study co-author Doug Soltis, a Florida Museum distinguished professor with appointments in UF's biology department and the UF Genetics Institute. "Sometimes the trait evolves for some other purpose, and then the organism is able to adapt and use it for something new."

Researchers found that woody plants most often became herbs or developed thinner pathways before moving into freezing climates, while plants that dropped their leaves usually did so after moving into freezing climates. But the changes did not occur rapidly, Pam Soltis said.

"Some of these changes were probably not as simple as we once thought," she said. "Adjusting to big shifts in their environments is probably not easy for plants to do."

The researchers plan to use the findings to explore other aspects of plants' evolutionary history, including examining how they respond to environmental changes other than freezing temperatures.

"The onset of freezing temperatures did not affect the entire world, but only certain habitats became colder," Pam Soltis said. "Certain lineages could not move into the cold, but were able to persist unaffected by the cold in warmer areas. With climate change that is human-induced, all habitats will be affected over a short period of time, and plants and other organisms will have to adapt quickly if they are to survive."

View the original article here

New combination therapy may improve outcomes for women with triple-negative breast cancer.

I-spy 2 trial, innovative multidrug resistance, phase II trial cancer led to a positive result in the first drugs to complete testing in breast cancer trial. Using the standard chemotherapy for women with triple-negative breast cancer improved outcomes I spy carboplatin combination chemotherapy and molecular targeted drugs veliparib 2 from trial (UCSF Helen Diller family comprehensive cancer led by researchers from the Center) in and results will be announced in 2013, according to the San Antonio Breast Cancer Symposium held 12/10-14.

View the original article here

Found that prophylactic mastectomy of Angelina Jolie, awareness occurred, without knowledge of the risk of breast cancer.

Were Angelina Jolie, preventive double mastectomy surgery, at the University of Maryland School of public health new research reveals Jolie and I's talk about awareness, even though most Americans are not when she published 5/2013 about the risks of breast cancer answer questions correctly heightened awareness about breast cancer.

View the original article here

U.S. Cancer Death Rates Continue to Decline: Report

But researchers added that people with other health problems have lower odds of survival

View the original article here

‘Biggest Loser' trainer says fitness a mental and physical process

By Dorene Internicola

NEW YORK (Reuters) - As celebrity trainer Dolvett Quince challenges and prods obese, unfit contestants to slim down and shape up on the weight-loss TV show "The Biggest Loser" he also uses survivor skills acquired during his childhood to boost their self esteem.

The Los Angeles-based trainer said getting fit is a mental as well as a physical challenge. He can identify with the struggles of his outsized team because as an adopted child he was mentally and physically abused and has experienced his share of self doubt.

"I walked into an environment where education was low and discipline was high," said Quince, 40, who was born in Stamford, Connecticut. "I understand what it's like to feel defeated and because I faced my own demons I can empower others."

Quince said fitness for people who are 100 pounds (45kg) or more overweight, involves a lot more than pushups.

"Health is a four-point component: emotional, physical spiritual and mental," said Quince, whose best-selling book, "The 3-1-2-1 Diet: Eat and Cheat Your Way to Weight Loss - Up to 10 Pounds in 21 Days," was published last month.

The fitness coach, who began his career at the YMCA where his clients included the elderly, mothers, teenagers and children, tries to chip away at people's personal doubts and past disappointments.

"People become extremely vulnerable as their bodies fatigue and they're going through transformations. It's in that vulnerability that the concrete cracks and some light pushes in," he said in a phone interview.

Karate, yoga, hiking and basketball are included in his fitness regime. At the gym he suggests combining cardio training, usually running on a treadmill, with strength training to systematically target different muscle groups.

"Doing intervals keeps your body guessing," he explained.

Lauve Metcalfe, a wellness coach and past president of the International Association for Worksite Health Promotion, believes shows like "The Biggest Loser" can raise public awareness about the importance of fitness.

But she has concerns about the rapid weight loss, often 10 pounds a week or more, expected of contestants.

"A pound and a half per week is a healthier goal," said Metcalfe, who is based in Tucson, Arizona. "And the aspect of every week getting on that scale, and the shame if you haven't met (the goal), is a negative,"

Quince attributes his success in helping people get in shape to his refusal to take no for an answer.

"I think people don't necessarily truly love working out," he said. "I think it's more like, ‘Man, must we work out? Can't we just have a drink?"

His job, he added, is to instill belief as well as to motivate people to move.

(Editing by Andrew Hay)

View the original article here

Points better than the new model of drug resistance in breast cancer treatment

In model of human breast cancer tumors metastatic carcinoma transplanted in mice, from the Washington University School of medicine Alvin j. Siteman Cancer Center (home) and provides insights into how to attack breast cancer unresponsive to medications used to treat them in the St. Louis and San Antonio Breast Cancer Symposium according to survey released 12/12.

View the original article here

2nd opinion planned for teen declared brain dead

OAKLAND, Calif. (AP) — The family of a Northern California girl on life support after being declared brain dead was expected to appear with hospital officials in court Monday to announce the name of the independent physician it has chosen to provide a second opinion on the girl's condition.

Jahi McMath's family obtained an order Friday from Superior Court Judge Evelio Grillo to keep doctors at Children's Hospital Oakland from removing Jahi from a ventilator.

Grillo ordered the family to meet with doctors to select a neurologist to evaluate the 13-year-old.

In its court memorandum, the hospital said it has no duty to maintain life support because Jahi's condition is irreversible.

"Ms. McMath is dead," the hospital said in the memo. "Children's is under no legal obligation to provide medical or other intervention for a deceased person."

The family says the girl bled profusely after a routine tonsillectomy. She then went into cardiac arrest before being declared brain dead Dec. 12.

The teen's mother, Nailah Winkfield, over the weekend pleaded for prayers for her daughter.

"Despite what they say, she is alive. I can touch her, she is warm. She responds to my touch," Winkfield said in an open letter Saturday. "Given time I know (God) will spark her brain awake."

Children's Hospital responded in a statement that while it sympathizes with Winkfield's wishes, it would be unfair to give false hope.

Winkfield said her daughter bled profusely and went into cardiac arrest after undergoing a "simple procedure" to remove her tonsil to help with her sleep apnea.

The hospital's statement contends the surgery was complicated, and that the facility is committed to fully investigating what caused "this catastrophic outcome."

The family's attorney, Christopher Dolan, told Grillo the family wanted independent tests because it does not believe the hospital's physicians are sufficiently independent.

The hospital said in documents presented to the court Friday that a staff neurologist and Jahi's attending physician conducted separated exams, both of which determined that Jahi's entire brain, including her brain stem, stopped functioning.

Copyright c 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

View the original article here

Pakistani army launches offensive near Afghan border

By Maria Golovnina

ISLAMABAD (Reuters) - Residents of Pakistan's ethnic Pashtun region of North Waziristan accused government troops on Monday of killing dozens of civilians during a military operation against Taliban insurgents.

The operation started just after a December 18 suicide bomb attack on a checkpoint in North Waziristan, a stronghold for al Qaeda-linked Taliban militants on Pakistan's mountainous border with Afghanistan.

Speculation that the army might launch a major offensive in the frontier tribal areas has been building as the government's attempts to engage the Pakistani Taliban in peace talks have floundered in recent months.

Military officials said more than 30 militants, most of them ethnic Uzbeks, had been killed in the operation.

"Security forces exercised utmost restraint to avoid any collateral damage," the army said in a statement.

"The Pakistan military spokesman reiterated that the military action against the terrorists in North Waziristan on December 19 was in response to an attempt by terrorists to ambush a military convoy.

"The intelligence-based sting military operation later was specifically targeted against foreign terrorists holed up in a nearby compound."

Foreign militants from various places including central Asia have long been known to be based in the region.

The army in its statement did not say anything about residents' accusations of civilian casualties. The military's media wing could not be immediately reached for comment.

Pakistani authorities imposed a curfew and residents said many people had fled from their homes after days of shelling and raids by helicopter gunships in the Mir Ali region of North Waziristan following the suicide attack.

Resident Muhammed Tayyab said he lost three of his children and his wife in the shelling.

"On the first day of the attack an artillery shell hit the room where my kids and wife were sleeping," Tayyab told Reuters by telephone. "The government has put them to sleep forever."

"WHERE IS SAFE?"

Residents put the civilian death toll at several dozen.

"From the first day of the attack until now 70 civilians have been killed," said a tribal elder in Mir Ali who declined to be identified for fear of state reprisals.

"Some truck drivers and hotel and shop keepers were shot directly, and dozens were killed by gunships, mortars, and artillery shelling on the civilian population."

Reports from North Waziristan are hard to verify independently because journalists and observers are not allowed to work on the ground in the heavily militarized region.

The Pashtun lands along the Afghan border have never been brought under the full control of any government.

Taliban commander Hafiz Gul Bahadur said insurgents would respond by launching a full-scale counter-offensive on army positions if attacks against civilians did not stop on Monday.

Residents said bodies were left in the open in the villages of Mosaki and Hasukhel as terrified villagers fled the area.

"We are moving our families to keep them safe but the army's mortars and shells are following us," said Asad Sher of Mir Ali. "Please tell us where is safe. The army is demolishing our homes and bazaars."

Malik Gul Salehjan, another man, said: "My children are asking me for bread but I am not able to give them anything because there is nothing in my house."

A North Waziristan administration official said tribal elders and army representatives convened a jirga, or meeting, on Monday to try to find a negotiated end to hostilities.

(Additional reporting by Jibran Ahmad in Peshawar; Editing by Robert Birsel)

View the original article here

Personalized for the most deadly type of brain tumor vaccine shows promise

History showed itself from the patients with treatment of patients with recurrent glioblastoma made an experimental vaccine (GBM) resection tumor survival rates improve, alone, received the standard care patients compared to this vaccine has been published in the journal of neuro-oncology, accompanied by an editorial to emphasize the importance of the trial phase 2 according to the analysis of the test. Phase 2 trials, Northwestern Feinberg School and the Robert H. Lurie Comprehensive Cancer Center enrolled 41 conducted by adult recurrent tumor cases 2007-2011, from the researchers.

View the original article here

Change elevated circulating tumor cell metastasis BC before patients not beneficial chemotherapy.

Women with metastatic breast cancer, after first line chemotherapy in the amount of their blood circulating tumor cell (Ctc) were higher in the immediately switch to another chemotherapy did not improve overall survival or phase III clinical trials, 2013 at the San Antonio Breast Cancer Symposium University of Michigan comprehensive cancer time to progress, according to results announced by researchers in the Center, held 10-14 December.

View the original article here

China investigates after vaccine suspected in seven deaths

BEIJING (Reuters) - Chinese health authorities are investigating after seven infants died following inoculation with a hepatitis B vaccine, state media reported on Monday.

China has been beset by a series of product safety scandals over the past few years.

At least six children died in 2008 after drinking milk contaminated by the industrial chemical melamine, and there have also been reports of children dying or becoming seriously ill from faulty encephalitis, hepatitis B and rabies vaccines.

State news agency Xinhua said that of the seven deaths from the hepatitis B vaccine in the latest case, four were in the southern province of Guangdong. The other cases were in the provinces of Hunan and Sichuan.

The official China Daily said that all hospitals using the vaccine, made by Shenzhen-based BioKangtai, had been ordered to take it off their shelves while the Health Ministry investigates the company's products and the deaths.

The company said in a statement last week, carried by state media, said that it rigorously followed safety rules but that they were testing the batches suspected of causing the deaths.

The topic has been widely discussed on China's popular Twitter-like microblogging service Sina Weibo, with many people worried about the safety of China's vaccines and calling on the government to make more information public.

"Why was this allowed onto the market? The government needs to come clean about this," wrote one Weibo user.

Many Chinese people are suspicious that the government tries to cover up bad news about health problems, despite assurances of transparency. In 2003, the government initially tried to cover-up the outbreak of the SARS virus.

(Reporting by Ben Blanchard and Hui Li; Editing by Robert Birsel)

View the original article here

Cerebral sensory development: Genetic programming versus environmental stimuli

Dec. 22, 2013 — Hiroshi Kawasaki and colleagues at Kanazawa University, Tokyo University, Tokyo Institute of Technology and Kumamoto University in Japan have identified how sensory map development is regulated in mice pups at birth, and the molecular signalling responsible.

The part of the brain associated with the sense of touch -- the somatosensory cerebral cortex -- has attracted numerous studies aimed at determining the influence of extrinsic environmental and intrinsic genetic factors in sensory development. Understanding the role of these factors in sensory map formation and development may provide insights into the mechanisms behind other circuits in the central nervous system.

Now Hiroshi Kawasaki and colleagues at Kanazawa University, Tokyo University, Tokyo Institute of Technology and Kumamoto University in Japan have identified how sensory map development is regulated in mice pups at birth, and the molecular signalling responsible.

Rodents have a sensory map in the primary somatosensory cerebral cortex, characterized by cell clusters called barrels filled with patches of nerve fibre. Inputs from the part of the brain that link to the rodent's whiskers terminate at these barrels. The barrel distribution pattern is the same as the distribution of the whiskers on the snout and forms soon after birth.

The researchers induced preterm birth in mice and quantitatively compared the degree of development of whisker-related barrel pattern formation with mice born after the full term of pregnancy. At set periods after conception, barrel formation was significantly more advanced in the mice born preterm. Further experiments ruled out the role of maternal hormones prior to birth and identified the critical effect of serotonin reductions during the days after birth.

"Interestingly, the regulatory mechanisms described here were also found to regulate eye-specific segregation in the visual system, raising the possibility that they are utilized in various brain regions," the researchers suggest. They add that further investigation of the range of roles of serotonin and the underlying mechanisms will be interesting for future research.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is based on materials provided by Organization of Frontier Science and Innovation, Kanazawa University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Tomohisa Toda, Daigo Homma, Hirofumi Tokuoka, Itaru Hayakawa, Yukihiko Sugimoto, Hiroshi Ichinose, Hiroshi Kawasaki. Birth Regulates the Initiation of Sensory Map Formation through Serotonin Signaling. Developmental Cell, 2013; 27 (1): 32 DOI: 10.1016/j.devcel.2013.09.002

Note: If no author is given, the source is cited instead.

View the original article here

Malaria drug target raises hopes for new treatments

Dec. 22, 2013 — Scientists have taken an important step towards new malaria treatments by identifying a way to stop malaria parasites from multiplying.

In a study published in Nature Chemistry, they show that blocking the activity of an enzyme called NMT in the most common malaria parasite prevents mice from showing symptoms and extends their lifespan. The team are working to design molecules that target NMT more potently, and hope to start clinical trials of potential treatments within four years.

A recent study estimated that 1.2 million people died from malaria in 2010. Although a variety of antimalarial drugs are available, some strains of the parasite are resistant to treatment. These strains are becoming more common, with treatment failures reported across multiple frontline drugs. If acute illness is cured, the parasite can remain dormant in the blood and return to cause illness later. Malaria vaccines have been researched intensively, but none have been introduced into clinical practice.

The new study shows that NMT is involved in a wide range of essential processes in the parasite cell, including the production of proteins that enable malaria to be transmitted between humans and mosquitoes, and proteins that enable malaria to cause long-term infection.

The researchers have tested a handful of molecules that block the activity of NMT in the parasite living inside human red blood cells, and in mice, but further refinement will be needed before a treatment is ready to be tested in humans.

Dr Ed Tate, from the Department of Chemistry at Imperial College London, who led the project, said: "The drug situation for malaria is becoming very serious. Resistance is emerging fast and it's going to be a huge problem in the future.

"Finding an enzyme that can be targeted effectively in malaria can be a big challenge. Here, we've shown not only why NMT is essential for a wide range of important processes in the parasite, but also that we can design molecules that stop it from working during infection. It has so many functions that we think blocking it could be effective at preventing long-term disease and transmission, in addition to treating acute malaria. We expect it to work not just on Plasmodium falciparum, the most common malaria parasite, but the other species as well.

"We need to do some more work in the lab to find the best candidate molecule to take into clinical trials, but hopefully we'll be ready to do that within a few years."

The discovery is the culmination of a five-year project by a consortium of researchers from Imperial College London, the MRC National Institute for Medical Research, the University of Nottingham, the University of York, and Pfizer, funded by the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council.

View the original article here

Among the patients with CLL trigger Ibrutinib and rituximab 95% response rate

University of Texas MD Anderson Cancer from the Center researchers United States blood of no. 55 times tournament report targeted therapy ibrutinib and antibody rituximab treatment of chronic lymphocytic leukemia patients meet the phase II clinical trials in high-risk almost everything.

View the original article here

Tesaro nausea drug effective in late-stage trials

(Reuters) - Tesaro Inc said its experimental drug for treating chemotherapy-induced nausea and vomiting was found effective in two late-stage studies.

The trials tested the drug, rolapitant, in cancer patients receiving chemotherapy that can induce vomiting.

The patients either received a combination of two drugs to reduce the side effects of chemotherapy or rolapitant plus the two-drug combo.

Tesaro said it continued to enroll patients in a third late-stage trial of the drug, and was preparing for a marketing approval application by mid-2014.

(Reporting by Esha Dey in Bangalore; Editing by Saumyadeb Chakrabarty)

View the original article here

New Test May Help Predict Survival From Ovarian Cancer

Method was used to count special type of immune cells in tumors from 30 women in study

View the original article here

Many Lung Cancer Tumors May Prove Harmless, Study Finds

Research suggests CT scan screening might lead to needless worry, treatment in these cases

View the original article here

New compound could reverse loss of muscle mass in cancer, other diseases

Dec. 19, 2013 — A new antibody could dramatically boost strength and muscle mass in patients with cancer, chronic obstructive pulmonary disease (COPD), sporadic inclusion body myositis, and in elderly patients with sarcopenia according to research published ahead of print in the journal Molecular and Cellular Biology.

"Age-related loss of muscle mass is a major contributing factor to falls, broken bones, and the loss of mobility," says co-corresponding author David Glass of Novartis, Cambridge, MA, one of the compound's developers, along with first author Estelle Trifilieff, also of Novartis. "This study illustrates that we may have a powerful tool to prevent muscle wasting and promote growth."

The new compound (BYM338) acts to prevent muscle wasting by blocking a receptor that engages a cellular signaling system that exists to put the brakes on muscle development when appropriate. But sometimes those brakes are activated inappropriately, or are stuck on.

"Our goal was to release the brakes," says Glass.

A variety of signals can activate the receptor. Prior to development of BYM338, compounds developed to block these molecules were blunt instruments, either trapping all incoming signals (which stimulated muscle growth but also caused harmful side effects) or blocking just a single receptor activator (providing only tepid growth stimulation.) BYM338 was designed to be in the Goldilocks zone (just right.)

In the study the compound boosted muscle mass 25 to 50 percent and increased strength in animal models. Those gains were significantly superior to those of compounds that blocked a single receptor activator. Clinical trials are currently underway.

The conditions BYM338 is designed to treat are losses of skeletal muscle and fat, which are not reversed by simply eating more, and are known as cachexias when associated with certain chronic illnesses. Cancer cachexia develops in a majority of patients with advanced malignancy, and can interfere with the ability to undergo chemotherapy, says Glass. COPD afflicts an estimated 65 million people worldwide, and is predicted to become the third leading cause of death by 2020. As many as a quarter of COPD patients suffer from cachexia, which can worsen already dire respiratory difficulties.

Sarcopenia -- age-related loss of muscle and physical function -- afflicts 5-13% of 60-70 year olds, rising to 11-50% in individuals over 80 years old. These individuals become especially vulnerable to falling. Among older adults, falls are the leading cause of both fatal and non-fatal injuries, according to the Centers for Disease Control and Prevention.

Preliminary data on the antibody was promising enough to have it designated a breakthrough therapy by the US Food and Drug Administration for sporadic inclusion body myositis, a rare muscle wasting disease with no approved therapies.

"We need to be able to help people maintain productive and meaningful lives, and muscle function is a major part of the equation," says Glass. "It could be the difference between independent living and having to move into a nursing home."

View the original article here

Over 23 million children to be vaccinated in mass polio immunization campaign across Middle East

9 December 2013 | CAIRO, AMMAN - The largest-ever immunization response in the Middle East is under way this week, aiming to vaccinate more than 23 million children against polio in Syria and neighbouring countries over the coming weeks.

The campaign is a crucial part of the response to an outbreak of the virus-borne disease in Syria, where 17 cases have so far been confirmed, and to the detection of the virus in environmental samples in other parts of the Middle East.

In order to stop the outbreak and prevent further spread, organizers aim to vaccinate, repeatedly over the next few months, all children under the age of 5, whether they are living at home or displaced by conflict. Depending on the area, vaccination will be offered at fixed sites at populous locations or by going from house to house. The activities are carried out by national and local health authorities supported by UNICEF, WHO, the Syrian Arab Red Crescent and other partners.

Inside Syria, the campaign aims to reach 2.2 million children, including those who live in contested areas and those who were missed in an earlier campaign. Many children in Syria remain inaccessible, particularly those trapped in sealed off areas or living in areas where conflict is ongoing.

Despite the gaps in coverage, initial information suggests that vaccine is getting to more areas of Syria than has so far been the case for health interventions delivered as part of the larger ongoing humanitarian effort. In parallel with the vaccination effort, work is going on to bolster systems for verifying coverage data in upcoming campaigns inside the war-torn country.

“All Syrian children should be protected from disease,” noted Dr. Ala Alwan, Regional Director, WHO Eastern Mediterranean Region. “To eradicate polio, we need to eradicate any reason for failing to reach children. We appeal to all parties of the conflict in Syria to cooperate and facilitate pauses in hostilities over the coming 6 months to allow vaccination campaigns to reach all children.”

“As if children in Syria had not suffered enough, they now have to contend with yet another threat to their health and well-being,” said Maria Calivis, UNICEF Regional Director for the Middle East and North Africa. “The current polio vaccination efforts are a huge undertaking by many partners, but we can only halt the spread of the virus if we reach those children who have remained out of reach."

Over the coming months, UNICEF is planning to deliver 10 million doses of polio vaccine to Syria. The first shipment of 2 million vaccines arrived in Damascus on Friday 29 November.

The total cost to UNICEF and WHO of supporting the seven-country polio response from November through April is US$ 39 million, based on a strategic plan developed for the Middle East.

Note to editors

As of 26 November, 17 children have been paralyzed by polio in Syria: 15 of these children are in the contested governorate of Deir Ez Zour, 1 is in Aleppo and another in Douma, near Damascus. Prior to this outbreak, no polio cases have been recorded in Syria since 1999. The risk of spread to countries in the region and beyond is considered high, and health authorities from 21 countries have declared a public health emergency. Further polio immunization campaigns will be repeated across the region. In Syria, they will be carried out at monthly intervals until April 2014.

Genetically-related polioviruses, which originated in Pakistan, have also been detected in sewage samples in Egypt in December 2012, and in Israel and the West Bank and Gaza Strip earlier in 2013.

Inside Syria and for the past 2 years, immunization activities have been significantly constrained by ongoing conflict. Cold chain equipment in many districts has been lost and many mobile health teams have not been able to perform regular visits. This has led to missing out on vaccinating between 500?000–700?000 children in these areas.

For more information, please contact:

Rana Sidani
WHO Regional Office in Cairo
Telephone: +20 109 975 6506
E-mail: sidanir@who.int

Sona Bari
WHO Geneva
Telephone: +41 79 475 5511
E-mail: baris@who.int

Simon Ingram
UNICEF Regional Office for the Middle East and North Africa in Amman
Telephone: +962 79 590 4740
E-mail: singram@unicef.org

Najwa Mekki
UNICEF Regional Office for the Middle East and North Africa in Amman
Telephone: +962 79 573 2745
E-mail: nmekki@unicef.org

View the original article here

Researchers find potential new treatment approach for pancreatic cancer

Dec. 20, 2013 — Scientists from The University of Manchester -- part of Manchester Cancer Research Centre believe they have discovered a new way to make chemotherapy treatment more effective for pancreatic cancer patients.

Pancreatic cancer is an aggressive cancer with poor prognosis and limited treatment options and is highly resistant to chemotherapy and radiotherapy.

But researchers believe they have found an effective strategy for selectively killing pancreatic cancer while sparing healthy cells which could make treatment more effective.

Dr Jason Bruce, from the Physiological Systems and Disease Research Group, who led the research, said: "Pancreatic cancer is one of the most aggressive and deadly cancers. Most patients develop symptoms after the tumour has spread to other organs. To make things worse, pancreatic cancer is highly resistant to chemotherapy and radiotherapy. Clearly a radical new approach to treatment is urgently required. We wanted to understand how the switch in energy supply in cancer cells might help them survive."

The research, published in The Journal of Biological Chemistry this month, found pancreatic cancer cells may have their own specialised energy supply that maintains calcium levels and keeps cancer cells alive.

Maintaining a low concentration of calcium within cells is vital to their survival and this is achieved by calcium pumps on the plasma membrane.

This calcium pump, known as PMCA, is fuelled using ATP -- the key energy currency for many cellular processes.

All cells generate energy from nutrients using two major biochemical energy "factories," mitochondria and glycolysis. Mitochondria generate approximately 90% of the cells' energy in normal healthy cells. However, in pancreatic cancer cells there is a shift towards glycolysis as the major energy source. It is thought that the calcium pump may have its own supply of glycolytic ATP, and it is this fuel supply that gives cancer cells a survival advantage over normal cells.

Scientists used cells taken from human tumours and looked at the effect of blocking each of these two energy sources in turn.

Their study, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), National Institute of Health Research (NIHR) Biomedical Research Centre and AstraZeneca, shows that blocking mitochondrial metabolism had no effect. However, when they blocked glycolysis, they saw a reduced supply of ATP which inhibited the calcium pump, resulting in a toxic calcium overload and ultimately cell death.

Dr Bruce added: "It looks like glycolysis is the key process in providing ATP fuel for the calcium pump in pancreatic cancer cells. Although an important strategy for cell survival, it may also be their major weakness.

"Designing drugs to cut off this supply to the calcium pumps might be an effective strategy for selectively killing cancer cells while sparing normal cells within the pancreas."

Maggie Blanks, CEO of the national charity, the Pancreatic Cancer Research Fund said: "These findings will certainly of great interest to the pancreatic cancer research community and we'd be keen to see how this approach progresses. Finding weaknesses that can be exploited in this highly aggressive cancer is paramount, so we want to congratulate the Manchester team for their discovery."

View the original article here

Advances in nanotechnology's fight against cancer

Dec. 19, 2013 — As cancer maintains its standing as the second leading cause of death in the U.S., researchers have continued their quest for safer and more effective treatments. Among the most promising advances has been the rise of nanomedicine, the application of tiny materials and devices whose sizes are measured in the billionths of a meter to detect, diagnose and treat disease.

A new research review co-authored by a UCLA professor provides one of the most comprehensive assessments to date of research on nanomedicine-based approaches to treating cancer and offers insight into how researchers can best position nanomedicine-based cancer treatments for FDA approval.

The article, by Dean Ho, professor of oral biology and medicine at the UCLA School of Dentistry, and Edward Chow, assistant professor at the Cancer Science Institute of Singapore and the National University of Singapore, was published online by the peer-reviewed journal Science Translational Medicine. Ho and Chow describe the paths that nanotechnology-enabled therapies could take -- and the regulatory and funding obstacles they could encounter -- as they progress through safety and efficacy studies.

"Manufacturing, safety and toxicity studies that will be accepted by the Food and Drug Administration before clinical studies are just some of the considerations that continue to be addressed by the nanomedicine field," said Chow, the paper's co-corresponding author.

Compared with other available therapies, nanomedicine has proven to be especially promising in fighting cancer. In preclinical trials, nanomaterials have produced safer and more effective imaging and drug delivery, and they have enabled researchers to precisely target tumors while sparing patients' healthy tissue. In addition, nanotechnology has significantly improved the sensitivity of magnetic resonance imaging, making hard-to-find cancers easier to detect.

"A broad spectrum of innovative vehicles is being developed by the cancer nanomedicine community for targeted drug delivery and imaging systems," said Dr. Ho, the paper's corresponding author and co-director of the Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the UCLA School of Dentistry. "It is important to address regulatory issues, overcome manufacturing challenges and outline a strategy for implementing nanomedicine therapies -- both individually and in combination -- to help achieve widespread acceptance for the clinical use of cancer nanomedicine."

Ho's team previously pioneered the development of a nanodiamond-doxorubicin compound named NDX. In preclinical studies conducted with Chow, NDX was found to be safer and more effective than unmodified doxorubicin, a clinical standard, for treating breast, liver and other cancer models.

Ho and Chow's new report features multiple studies in which the use of nanoparticles was translated from the preclinical to the clinical stage. In several of the highlighted studies, nanotechnology-modified drugs showed improvements over conventional, drug-only approaches because of their ability to overcome drug resistance (which occurs when tumors reject the drug and stop responding to treatment), to more effective tumor reduction, among other advantages.

The authors also describe how algorithm-based methods that rapidly determine the best drug combinations, and computation-based methods that draw information from databases of drug interactions and side effects, to help rationally design drug combinations could potentially be paired with nanomedicine to deliver multiple nano-therapies together to further improve the potency and safety of cancer treatments.

"This research review by Dr. Ho and his colleagues lays the groundwork for nanomedicine to become a widely accepted cancer therapy," said Dr. No-Hee Park, dean of the UCLA School of Dentistry. "This blueprint for navigating the process from bench research to mainstream clinical use is invaluable to the nanotechnology community."

Dr. Ho, also a professor of bioengineering and a member of the Jonsson Comprehensive Cancer Center and California NanoSystems Institute, noted that nanomedicine regulation is still in its early stages, but the clinical use of existing nanoparticle drugs, such as the protein-modified breast cancer drug Abraxane, is a promising start.

"The FDA's approval of Abraxane provides a strong foundation for the continued acceleration of new cancer nanomedicine therapies and imaging solutions in the fight against cancer," Ho said.

View the original article here

UN humanitarian chiefs strongly condemn attacks on medical personnel and facilities by all parties to the Syria conflict

6 December 2013 | New York/Geneva - We strongly condemn attacks on health and any other civilian facilities in Syria and are deeply concerned by the serious implications for patients, health personnel and provision of critical medical supplies.

This brutal conflict continues to result in substantial damage to health facilities across the country. Over 60% of public hospitals have been damaged or are out of service, while a similar proportion of ambulances have been stolen or badly damaged. At a time when hospitals are overwhelmed with patients, it is vital that these facilities be protected and medical staff be allowed to provide urgent medical, surgical and obstetric care to patients without any risk.

Health facilities must be respected and protected in all circumstances - they should not be used for military purposes. Attacks against health facilities can be considered a war crime under international law.

All parties must respect their obligations under international humanitarian law to protect civilians, health facilities and health professionals during conflict and to permit the supply of vital humanitarian aid, such as medicines, vaccines and medical equipment to reach the most needy communities. It is of the interest of both parties in the conflict and of all Syrian people to preserve the neutrality and the functionality of health infrastructure.

Despite the insecurity and serious access challenges the United Nations and partners have helped vaccinate more than 3.3 million children against measles and polio in recent weeks. Over 8000 women have received reproductive and maternal health services, while medical supplies and training have been provided to ensure that hundreds of thousands of people with chronic health problems are treated.

We and our humanitarian partners continue to call for a halt to the violence and for all those with influence over the parties to urge immediate compliance with international law. And we ask that all our partners increase our common efforts to draw attention to these inhumane acts and to protect innocent women, men and children.

For further information, please contact:

WHO Geneva
Gregory Hartl
Telephone: +41 22 791 4458
E-mail: hartlg@who.int

OCHA New York
Amanda Pitt
Telephone: +1 917 442 1810,
E-mail: pitta@un.org

OCHA New York
Clare Doyle
Telephone: +1 646 288 6331
E-mail: doylecm@un.org

UNICEF New York
Rita Ann Wallace
Telephone: +1 212 326 7586
Mobile: +1 917 213 4034
E-mail: rwallace@unicef.org

UNICEF New York
Kent Page
Telephone: +1 212 326 7605
Mobile: +1 917 302 1735
E-mail: kpage@unicef.org

View the original article here

H. pylori vaccine shows promise in mouse studies

Dec. 19, 2013 — Researchers from Southern Medical University in Guangdong, Guangzhou, China, have developed an oral vaccine against Helicobacter pylori, the bacteria responsible for peptic ulcers and some forms of gastric cancer, and have successfully tested it in mice. The research is published ahead of print in the journal Clinical and Vaccine Immunology.

The investigators constructed a live recombinant bacterial vaccine, expressing the H. pylori antigen, adhesin Hp0410, in the food-grade bacterium, Lactobacillus acidophilus. They then used it to orally vaccinate the mice.

The vaccine elicited specific anti-Hp0410 IgG antibodies in serum, and showed "a significant increase" in the level of protection against gastric Helicobacter infection, according to the report. When assayed, following challenge with H. pylori, immunized mice had significantly lower bacterial loads than non-immunized mice.

H. pylori is a class 1 human carcinogen, according to the World Health Organization. It causes gastritis, peptic ulcers, stomach cancer, and mucosa-associated lymphoid tissue lymphoma. Antibiotic therapy is complex, unsuccessful in some patients (particularly in developing countries) and relapse is common. A vaccine against H. pylori could circumvent these difficulties.

L. acidophilus, a bacterium which is common in yogurt cultures, has distinct advantages as an oral vaccine antigen delivery vehicle. It is safe and nontoxic. It resists the stomach's acidity and tolerates bile, all of which aids in enabling it to survive in the gastrointestinal (GI) tract for more than 72 hours. Additionally, it adheres to, and elicits an immune response from the GI tract mucosa.

The current first-line treatment option for H. pylori infection includes two antibiotics and a proton pump inhibitor, but is ineffective in roughly 20 percent of patients.

"The high cost of treatment, noncompliance, and antibiotic resistance are the most important reasons," says first author Fan Hongying.

Roughly 15-30 percent of patients relapse quickly, she says, noting that after treatment, H. pylori may be resupplied to the stomach from a reservoir in the mouth. A vaccine would circumvent these problems.

"Our results collectively indicate that adhesin Hp0410 is a promising candidate vaccine antigen and recombinant Lactobacillus acidophilus expressing Hp0410 is likely to constitute an effective, low-cost live bacterial vaccine against H. pylori," says Hongying.

View the original article here

Pain medication will be used in the removal of the prostate has been linked to cancer

Use the anesthetic management of patients with prostate cancer, to surgical methods and control pain, prostate gland cancer affecting their long-term cancers result when removing, guided by a Mayo Clinic study has found. Suppress the ability of the immune system to fight cancer cells after opioid, usually specified when, after painkillers. To radical prostate removal except before in research reduce opioids patients need surgery after the spinal or epidural associated complement and painkillers combined with General anesthesia, found this lower risk of cancer recurrence is suggested. Survey results will be published online in the British Journal of anaesthesia.

View the original article here

Rebuilding shattered health system an urgent priority in next phase of Typhoon Haiyan response

6 December 2013 | Manila, Philippines - One month after Typhoon Haiyan hit the Philippines, WHO identifies as top priorities expanding essential health services, reviving clinics and hospitals, preventing disease and scaling up mental health services as the relief effort shifts from emergency to early recovery programmes.

The typhoon, one of the strongest ever recorded, tore through the central Philippines on 8 November, sweeping away villages, killing over 5700 people, wreaking havoc on the lives of more than 11 million others and damaging the majority of medical facilities.

From the outset of the disaster, WHO has been working side-by-side with the Philippines Department of Health to assess and address the life-saving needs of survivors and coordinate the emergency health response.

“Our immediate goal was to help plug critical gaps in medical services and to get the right experts and supplies into the right places swiftly and efficiently,” says Dr Julie Hall, WHO Representative in the Philippines.

One month into the crisis, 181 medical teams (65 foreign, 116 local) are delivering critical care in affected areas. WHO has coordinated the distribution of more than 72 tonnes of medicines and supplies to support the relief effort. A mass campaign to vaccinate children under 5 against measles and polio is underway in storm-hit communities and evacuation centres. WHO and partners have also worked with the government to reactivate disease monitoring and reporting to ensure cases of infectious diseases are quickly identified and responded to.

The risk of infectious diseases remains high, particularly in the crowded and unsanitary environments where hundreds of thousands of homeless people are now sheltering. Infectious diseases like measles, water-borne diseases such as typhoid fever and vector-borne diseases like dengue, can thrive in such conditions.

However, the primary reasons people in affected areas are seeking medical care right now are acute respiratory infections, fever, diarrhoea, high blood pressure, skin diseases, new injuries from clearing debris and follow-up care for injuries and wounds sustained in the typhoon.

The medical teams are also tending to on-going health needs, including maternal and child health care. An average of 865 women give birth every day in affected areas, of whom an estimated 15% will experience complications, some of them life-threatening.

With many foreign medical teams preparing to leave within the next month or two and others arriving, WHO is working with the Department of Health to ensure a smooth transition. Dr Hall says it is critically important that gaps in services do not emerge and that international attention and support to the health sector does not wane.

“We must ensure that essential health services are not interrupted and that in the months to come, the Philippine Government as well as humanitarian aid organizations and other key partners have adequate resources to restore health services across the affected regions,” says Dr Hall.

At the one-month mark in the crisis, priorities for the health sector include:

• Extending and expanding treatment: Providing free primary and emergency health care as Philippine medical services are re-established. Special attention is required for obstetric and neonatal care and treatment of chronic diseases and infections like tuberculosis.
• Preventing disease: Strengthening disease surveillance and response systems to inform health care needs and prevent the spread of disease. Other essential preventive measures include increasing coverage with recommended vaccines, pre-positioning supplies for possible outbreaks and improving waste management and water supply.
• Restoring health infrastructure and systems: Supporting the Philippine Government as it repairs and rebuilds medical facilities and restores the drug supply and routine health programmes. Health authorities are still tallying total costs, but say they need an initial P 1.4 billion (around US$ 32 million) for basic repairs and replacement of equipment and medicines.
• Integrating healthcare with other key services: Linking health care with social support programmes, especially mental health assistance. WHO and the Department of Health have trained Filipino health professionals who will in turn train field workers to deliver psychological first aid to typhoon survivors.

“Rebuilding the health system is going to be part and parcel of rebuilding lives and livelihoods in central Philippines,” says Hall. “Given the scale of this disaster, it’s going to take a healthy population to fuel the region’s recovery.”

For more information, interviews, or to arrange field visits, please contact:

Paulo Lyra in Manila
Mobile: +63 915 896 6345,
E-mail: lyrapaul@who.int

Aphaluck Bhatiasevi in Tacloban
mobile: +63 917 490 9757 and +63 947 170 7512,
E-mail: bhatiaseviap@who.int

Melissa Winkler in Geneva
Mobile: +41 79 445 2518
E-mail: winklerm@who.int

View the original article here

Huntsman Cancer Center researcher k-RAS gene mutation proves explores why so life-threatening cancer.

Work on how to overturn the usual mechanisms of cell death called found primarily in anticipation of the worst cancer k-RAS gene mutation and cell.

View the original article here

Key drug receptor: Atom-level simulation of a G protein-coupled receptor could lead to improved drug design

Dec. 20, 2013 — The successful atom-level simulation of a G protein-coupled receptor could lead to improved drug design, blazing the path for specialized scientific projects on cloud computer systems.

Roughly 40 percent of all medications act on cells' G protein-coupled receptors (GPCRs). One of these receptors, beta 2 adrenergic receptor site (B₂AR), naturally transforms between two base configurations; knowing the precise location of each of approximately 4,000 atoms is crucial for ensuring a snug fit between it and the drug.

Now, researchers at Stanford and Google have conducted an unprecedented, atom-scale simulation of the receptor site's transformation, a feat that could have significant impact on drug design.

This is the first scientific project to be completed using Google Exacycle's cloud computing platform, which allows scientists to crunch big data on Google's servers during periods of low network demand.

The study was published online in Nature Chemistry on Dec. 15.

As a type of GPCR, the B₂AR is a molecule that sits within the membrane of most cells. Various molecules in the body interact with the receptor's exterior, like two hands shaking, to trigger an action inside the cell.

"GPCRs are the gateway between the outside of the cell and the inside," said co-author Vijay Pande, a professor of chemistry and, by courtesy, of structural biology and computer science at Stanford. "They're so important for biology, and they're a natural, existing signaling pathway for drugs to tap into."

Roughly half of all known drugs -- including pharmaceuticals as well as natural molecules such as caffeine -- target some GPCR, and many new medications are being designed with these receptor sites in mind. The 2012 Nobel Prize in Chemistry was co-awarded to Brian Kobilka, a professor at the Stanford University School of Medicine, for his role in discovering and understanding GPCRs.

Traditionally, maps that detail each atom of GPCR, and other receptors, are created through a technique called X-ray crystallography. The technique is industry standard, but it can only visualize a molecule in its resting state; receptors naturally change configurations, and their intermediate forms might also have medical potential.

When developing a drug, scientists will often run a computer program, known as a docking program, that predicts how well the atomic structure of a proposed drug will fit into the known receptor.

In the case of GPCRs, for example, the X-ray crystallography techniques have detailed teceptors' "on" and "off" configurations; many medications have been specifically designed to fit into these sites. Scientists expect, however, that other fruitful configurations exist. Many drugs engage with GPCR sites, even though computational models suggest that they don't fit either of the two defined reaction site configurations.

Computer simulations of a GPCR's shape as it morphs from "on" to "off" could create a thicker catalog of reaction site profiles, Pande said, and provide scientists a better jumping-off point for computational drug design and more discoveries.

A cloud-based attack

To simulate the GPCR alternatives at the same atom-level accuracy of X-ray crystallography, however, would take too long using traditional computing methods.

"The computational burden of a model that is faithful to atomic details is very high," Pande said. "A very fast computer processor can compute a billionth of a second of this reaction in one computer day. So if you want to simulate a full reaction on a millisecond time scale, it's going to take millions of days."

Instead, Pande and his colleagues tapped the power of Google's Exacycle cloud computing system, which harnesses a distributed network of computers to process data in parallel.

The B₂AR simulation consists of almost 60,000 atoms. Each Exacycle system simulated tens of thousands of random trajectories that these atoms could take as the protein shifted its shape, generating about 250,000 molecular structures per simulated system.

The researchers then wrote algorithms to identify the most consistently generated configurations and to sift through that group for the states that are the most likely to actually exist given real-world constraints.

In total, the researchers simulated 2.5 milliseconds -- a virtual eternity in chemical reaction time, the authors said -- of the receptor shifting from "on" to "off," capturing every viable configuration of atoms in between. These intermediate structures can then be experimentally confirmed, Pande said, but even before that happens, they can guide more efficient drug design. In particular, the authors have shown that different classes of drugs are preferred by different intermediate GPCR states.

"There is some tension right now between doing this type of work with specialized hardware or with general commodity hardware, as we have done," Pande said. "Cloud resources are much more accessible to the general scientific community, and I think that we've shown here that, with the right method and algorithms, you can do the same quality of work."

The next "ridiculous" challenge

The work grew out of a key project from Simbios, the NIH Center for Biomedical Computation at Stanford, a decade-old collaboration between a broad group of bioengineering, chemistry, biology and computer science faculty from Stanford and the Stanford School of Medicine.

"This work really represents a capstone to the molecular types of calculations that a diverse group of people can tackle, and it's a challenge that I thought was really pushing the limits," Pande said. "Ten years ago I would have said this is ridiculous; even five years ago it felt a little bit out of reach.

"But we brought together people who are really at the top of their game, and being around people like that really pushes you to be the best that you can."

Asked to project the next insane step in this research, something that might take another 10 years to unfold, Pande said he'd really like to develop similar atomistic simulations of processes at the scale of an entire cell.

A key challenge of battling a disease like cancer, he said, is that the tumor cells are using normal proteins to conduct abnormal processes. Deciphering how the cells and proteins behave (or, rather, misbehave) at the molecular scale, he said, could help scientists design drugs that target specific molecular pathways to battle cancer.

"We will need to push the boundaries of both computers and algorithms," Pande said, " but the conceptual steps are there."

View the original article here