Spinal cord injury: as many as 500 000 people suffer each year

2 December 2013 | GENEVA - As many as 500 000 people suffer a spinal cord injury each year. People with spinal cord injuries are 2 to 5 times more likely to die prematurely, with worse survival rates in low- and middle-income countries. The new WHO report, "International perspectives on spinal cord injury", summarizes the best available evidence on the causes, prevention, care and lived experience of people with spinal cord injury.

Males are most at risk of spinal cord injury between the ages of 20-29 years and 70 years and older, while females are most at risk between the ages of 15-19 years and 60 years and older. Studies report male to female ratios of at least 2:1 among adults.

Causes: 90% traumatic

Up to 90% of spinal cord injury cases are due to traumatic causes such as road traffic crashes, falls and violence. Variations exist across regions. For example, road traffic accidents are the main contributor to spinal cord injury in the African Region (nearly 70% of cases) and the Western Pacific Region (55% of cases) and falls the leading cause in the South-East Asia and Eastern Mediterranean Regions (40% of cases). Non-traumatic spinal cord injury results from conditions such as tumours, spina bifida, and tuberculosis. A third of non-traumatic spinal cord injury is linked to tuberculosis in sub-Saharan Africa.

Consequences of spinal cord injury

Most people with spinal cord injury experience chronic pain, and an estimated 20-30% show clinically significant signs of depression. People with spinal cord injury also risk developing secondary conditions that can be debilitating and even life-threatening, such as deep vein thrombosis, urinary tract infections, pressure ulcers and respiratory complications.

Spinal cord injury is associated with lower rates of school enrollment and economic participation. Children with spinal cord injury are less likely than their peers to start school, and once enrolled, less likely to advance. Adults with spinal cord injury face similar barriers to socio-economic participation, with a global unemployment rate of more than 60%. Spinal cord injury carries substantial individual and societal costs.

Many of the consequences associated with spinal cord injury do not result from the condition itself, but from inadequate medical care and rehabilitation services, and from barriers in the physical, social and policy environments that exclude people with spinal cord injury from participation in their communities. Full Implementation of the Convention on the Rights of Persons with Disabilities is urgently required to address these gaps and barriers.

“Spinal cord injury is a medically complex and life-disrupting condition,” notes Dr Etienne Krug, Director of the Department of Violence and Injury Prevention and Disability, WHO. “However, spinal cord injury is preventable, survivable, and need not preclude good health and social inclusion.”

Essential health measures

Essential measures for improving the survival, health and participation of people with spinal cord injury include:

• timely, appropriate pre-hospital management: quick recognition of suspected spinal cord injury, rapid evaluation and initiation of injury management, including immobilization of the spine;
• acute care appropriate to the level and severity of injury, degree of instability and presence of neural compression;
• access to ongoing health care, health education and products such as catheters to reduce risk of secondary conditions and improve quality of life;
• access to skilled rehabilitation and mental health services to maximize functioning, independence, overall well-being and community integration;
• access to appropriate assistive devices that can enable people to perform everyday activities, reducing functional limitations and dependency; and
• specialized knowledge and skills among providers of medical care and rehabilitation services.

Essential social and economic measures

Essential measures to secure the right to education and economic participation include legislation, policy and programmes that promote:

• physically accessible homes, schools, workplaces, hospitals and transportation;
• inclusive education;
• elimination of discrimination in employment and educational settings;
• vocational rehabilitation to optimize the chance of employment;
• micro-finance and other forms of self-employment benefits to support alternative forms of economic self-sufficiency;
• access to social support payments that do not act as disincentive to return to work; and
• correct understanding of spinal cord injury and positive attitudes towards people living with it.

"International perspectives on spinal cord injury" was developed in association with the International Spinal Cord Society and Swiss Paraplegic Research, and launched on the occasion of the International Day of Persons with Disabilities on 3 December 2013.

For more information please contact:

Laura Sminkey
WHO Geneva
Telephone: +41 22 791 4547
Mobile: +41 79 249 3520
E-mail: sminkeyl@who.int

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Found a way around the two human proteins to get 'jumping genes' affect

Elusive 'jumping genes' law, researchers at Johns Hopkins Sydney Kimmel Comprehensive Cancer found one type of DNA to replicate two human proteins used to themselves and by using new methods to catch the Center (home), to move from place to place. Explore new frontiers as described in issue 11/21 of the cell, but they understand colonization of new areas of work to limit the risks posed by a bit of volatility like the DNA of the human genome, cell-driven jumping genes while an arms race.

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New technical precision, cancer improves ease of diagnosis.

UCLA (Jonsson Comprehensive Cancer Center home ）, Harvard University (Dana Farber Cancer Institute component) team from researchers has proven technology you can get cancer diagnosis a high degree of accuracy by measuring the physical properties of the fluid and individual cells. Using deformation cytometer and analyze the individual cell, technology can reduce the need for diagnostic procedure more cumbersome and costs associated with while improving the accuracy compared to current methods. More was published in the latest issue of the analysis of hydraulic oil samples from 100 patients pleural of first clinical research peer-reviewed journal journal Science translational medicine.

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Coping Tips for Winter Skin

Moisturize, cleanse (but don't overdo), expert says

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U.S. justices decline to hear another Obamacare challenge

By Lawrence Hurley

WASHINGTON (Reuters) - The U.S. Supreme Court on Monday declined to hear a broad new legal challenge to President Barack Obama's 2010 healthcare law.

The court rejected a petition filed by Liberty University, a Christian college in Virginia, which had raised various objections to the law, including to the key provision that requires individuals to obtain health insurance.

The justices upheld the constitutionality of a the individual mandate in a 5-4 ruling in June 2012.

Last week, the court agreed to hear two new cases in which employers have made religious objections to regulations implemented under Obamacare that require employers to provide health insurance that includes contraception for women. The case will be heard this term and decided by the end of June.

By rejecting the Liberty University case, the justices left intact a 4th U.S. Circuit Court of Appeals of a May 2013 decision that dismissed the claims made by the college and two individuals, Michele Waddell and Joanne Merrill.

The case is Liberty University v. Lew, U.S. Supreme Court, 13-306.

(Reporting by Lawrence Hurley; Editing by Howard Goller and Bill Trott)

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Quantitative approaches provide new perspective on development of antibiotic resistance

Nov. 28, 2013 — Using quantitative models of bacterial growth, a team of UC San Diego biophysicists has discovered the bizarre way by which antibiotic resistance allows bacteria to multiply in the presence of antibiotics, a growing health problem in hospitals and nursing homes across the United States.

Two months ago, the Centers for Disease Control and Prevention issued a sobering report estimating that antibiotic-resistant bacteria last year caused more than two million illnesses and approximately 23,000 deaths in the United States. Treating these infections, the report said, added $20 billion last year to our already overburdened health care system.

Many approaches are now being employed by public health officials to limit the spread of antibiotic resistance in bacteria -- such as limiting the use of antibiotics in livestock, controlling prescriptions of antibiotics and developing new drugs against bacteria already resistant to conventional drug treatments. But understanding how bacteria grow and evolve drug resistance could also help stop its spread by allowing scientists to target the process of evolution itself.

"Understanding how bacteria harboring antibiotic resistance grow in the presence of antibiotics is critical for predicting the spread and evolution of drug resistance," the UC San Diego scientists say in an article published in the November 29 issue of the journal Science.

In their study, the researchers found that the expression of antibiotic resistance genes in strains of the model bacterium E. coli depends on a complex relationship between the bacterial colony's growth status and the effectiveness of the resistance mechanism.

"In the course of developing complete resistance to a drug, a strain of bacteria often first acquires a mechanism with very limited efficacy," says Terry Hwa, a professor of physics and biology who headed the research effort. "While much effort has been spent elucidating individually how a drug inhibits bacterial growth and how a resistance mechanism neutralizes the action of a drug, little is known previously about how the two play off of each other during the critical phase where drug resistance evolves towards full strength."

According to Hwa, the interaction between drug and drug-resistance is complex because the degree of drug resistance expressed in a bacterium depends on its state of growth, which in turn depends on the efficacy of drug, with the latter depending on the expression of drug resistance itself. For a class of common drugs, the researchers realized that this chain of circular relations acted effectively to promote the efficacy of drug resistance for an intermediate range of drug doses.

The use of predictive quantitative models was instrumental in guiding the researchers to formulate critical experiments to dissect this complexity. In their experiments, E. coli cells possessing varying degrees of resistance to an antibiotic were grown in carefully controlled environments kept at different drug doses in "microfluidic" devices -- which permitted the researchers to manipulate tiny amounts of fluid and allowed them to continuously observe the individual cells. Hwa and his team found a range of drug doses for which genetically identical bacterial cells exhibited drastically different behaviors: while a substantial fraction of cells stopped growing despite carrying the resistance gene, other cells continued to grow at a high rate. This phenomenon, called "growth bistability," occurred as quantitatively predicted by the researchers' mathematical models, in terms of both the dependence on the drug dose, which is set by the environment, and on the degree of drug resistance a strain possesses, which is set by the genetic makeup of the strain and is subject to change during evolution.

"Exposing this behavior generates insight into the evolution of drug resistance," says Hwa. "With this model we can chart how resistance is picked up and evaluate quantitatively the efficacy of a drug." However, this model has only been established for one class of drugs and one class of drug-resistance mechanisms. Hwa believes it is important to establish such predictive models for all the common drugs in pathogenic bacterial species.

"My hope," he adds, "is to get the message out to drug companies and hospitals that there is an informative, quantitative way to look at the action of a drug on bacteria and at the consequences of using a drug on bacteria as they try to pick up resistance, and that this approach can be incorporated in both the design and evaluation of drug efficacy in clinically relevant settings."

Hwa says the principle of interaction between drug and drug-resistance is important to understand not only for the evolution of antibiotics, but also for the emergence of drug resistance in other diseases. A prominent example is the rapid emergence of cancer lines resistant to drug treatment, which underlies most failures in cancer drug therapies. While there are obviously numerous differences between the evolution of drug resistance in bacteria and in cancer, Hwa noted that the connection between the two was sufficient to motivate the Physical Science-Oncology program of the National Cancer Institute to co-sponsor this study.

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Mystery of neutron stars heats up: Previously unknown layers where rapid neutrino cooling occurs

Dec. 1, 2013 — Until now, scientists were pretty sure they knew how the surface of a neutron star -- a super dense star that forms when a large star explodes and its core collapses into itself -- can heat itself up.

However, research by a team of scientists led by a Michigan State University physicist has researchers rethinking that.

Scientists had long thought that nuclear reactions within the crust, the thick, solid, outermost layer of the star, contributed to the heating of the star's surface.

However, writing in the journal Nature, Hendrik Schatz and colleagues report results from theoretical calculations that identify previously unknown layers where nuclear reactions within the crust cause rapid neutrino cooling. Neutrinos are elementary particles created through radioactive decay that pass quickly through matter.

"These cooling layers are pretty shallow beneath the surface," said Schatz, a professor of physics and astronomy. "If heat from deeper within the star comes up, it hits this layer and never makes it to the surface."

Schatz said this discovery produces more questions than answers.

"This completely changes the way we think about the question of the star's hot surface," he said. "It's a big puzzle now."

On the sub-atomic level, the team found that the process is greatly affected by the shape of the reacting nuclei.

"Many nuclei are round, and that suppresses the neutrino cooling," said Sanjib Gupta, co-author and faculty member at IIT Ropar in India. "In this case, the nuclei are predicted by theorists to be 'deformed,' more football-shaped."

This study also points to the discovery potential of the Facility for Rare Isotope Beams. FRIB will be a new U.S. Department of Energy Office of Science national user facility built on the MSU campus. It is exactly these types of nuclei that researchers could examine in the facility.

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Programe for parents of preschoolers getting results

Nov. 29, 2013 — The results indicated that completion of the HOPE-20 program generated significant improvement in the children's mastery of preschool concepts and language skills, reduced the children's behavior problems, lowered the stress of their parents, and fostered the parents' sense of competence.

With sponsorship of Lo Ying Shek Chi Wai Foundation, the Department of Applied Social Sciences of The Hong Kong Polytechnic University (PolyU), and the Department of Social Work and Social Administration of The University of Hong Kong (HKU) have developed the HOPE-20 training program for parents of two-year-old children. This is one of the first locally-developed evidence-based parent education programs for such young children.

The study titled "The efficacy of the HOPE-20 program for parents of 2-year-old children" was jointly completed by Professor Cynthia Leung, Department of Applied Social Sciences, PolyU, and Dr Sandra Tsang JP, Associate Professor, Department of Social Work and Social Administration, HKU. The study evaluated the efficacy of the HOPE-20 program for parents of 2-year-old children, using a randomized controlled trial design. The results indicated that completion of the HOPE-20 program generated significant improvement in the children's mastery of preschool concepts and language skills, reduced the children's behavior problems, lowered the stress of their parents, and fostered the parents' sense of competence.

HOPE-20 is a parent education program conducted through 20 two-hour group sessions designed for parents of two-year-old children. The content included strategies to enhance parent-child relationship, promote child learning and language, and strategies to increase positive behavior and manage inappropriate behavior. Each session consisted of mini-lectures, discussion, and role play. Parents must complete five-minute daily activities with their children between sessions. The program was delivered by trained social workers in nursery schools.

The program was locally developed and fine-tuned after a pilot test. A randomized controlled trial was then conducted to evaluate the efficacy of the program. A total of 173 parents of two-year-old children from 18 nursery schools participated in the study and were randomly assigned into the intervention group, or the wait-list control group, which received the intervention only after the comparison study was completed. The intervention group included 110 participants from 10 nursery schools. At post-intervention, it was found that the children of the intervention group participants showed significant improvements in their mastery of preschool concepts and language skills. The intervention group participants reported fewer child behavior problems, lower parental stress and higher parenting sense of competence.

Professor Cynthia Leung says, "The results indicated that HOPE-20 was an effective universal parent training program, bringing benefits to both the parents and their children." Dr Sandra Tsang adds, "Though we ask parents to spend more time with their children, they do not necessarily know how to interact with their children. The HOPE-20 program provides a concrete and practical set of activities."

With policy support and close collaboration with social services centers, the team hopes nursery schools territory-wide will adopt this program to enhance the development of young children and the competence of their parents.

Sponsored by the Lo Ying Shek Chi Wai Foundation, the HOPE-20 project team is offering three training workshops for practitioners in the field, including psychologists, health professionals, social workers, and early childhood educators. Upon completion of the compulsory sessions, participants will be eligible to collect the program manual and relevant materials and deliver the HOPE-20 program in their work settings.

Dr Lo Ka Shui, Chairman of the Advisory Committee of the Foundation, says, "Although the design of this parental training program may have just ended, this is only the beginning of a long endeavor. We hope NGOs and district groups will continue to refine the parental training program and proactively incorporate parental training into their services. At the same time, we are advocating for the Government to increase its investment in this area, so as to make parental training a core component of early childhood development and facilitate the introduction of parental training to all nurseries in Hong Kong."

Ms Christine Fang BBS JP, Chief Executive of The Hong Kong Council of Social Service, adds, "Early intervention is the key to resolving many family issues. The HOPE-20 program provides an opportunity for social workers to get in closer touch with parents of young children and help them develop healthy parenting habits and attitudes."

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WHO and the Philippine Government launch mass vaccination campaign

22 November 2013 | MANILA, Philippines - WHO and the Philippine Department of Health have launched a vaccination campaign to prevent outbreaks of measles and polio among survivors of Typhoon Haiyan (Yolanda).

“Large numbers of non- or under-vaccinated children are at risk of contracting and spreading infectious diseases such as measles – particularly in congested areas where the homeless are now living,” says Dr Julie Hall, WHO Representative in the Philippines. “Measles can be deadly, especially in young children.”

Worst hit areas targetted

The campaign targets children in areas hardest hit by the disaster – starting with the evacuation centres in the city of Tacloban and at receiving centres in Cebu, where evacuated families are finding temporary shelter. Children under 5 years old are being vaccinated against polio and measles and given Vitamin A drops to boost their immune systems.

"Our system is shaken but not broken."

Enrique Ona, Philippine Secretary of Health

"Our system is shaken but not broken," said Philippine Secretary of Health, Enrique Ona. "With the support of partners, vaccinations have been re-launched at a vital time."

WHO worked with the Department of Health to finalize plans and procure all necessary vaccines and supplies to carry out the campaign and set up immunization stations. A team of 20 volunteer nurses is deploying to Tacloban this weekend to support local health-care workers.

WHO and partners procure vaccines and set up "cold chain"

WHO is working with partners to arrange for the delivery of vaccines using gas-powered and generator-powered fridges, freezers, vaccine-cases, cold boxes and ice packs for affected areas that have lost power. This “cold chain” is necessary to keep the vaccines from being spoiled. USAID has sent 6 solar-powered refrigerators to Tacloban.

Mass immunization and vitamin A supplementation are immediate health priorities following natural disasters in areas with inadequate coverage levels. Contagious diseases like measles spread quickly when people are living in unsanitary and overcrowded conditions.

As young children are most at risk, the initial phase of the campaign targets children 6 months to 5 years old in regions most severely affected by the disaster. The campaign will be extended to children up to 15 years old if resources allow.

For more information or interview requests, please contact:

Nyka Alexander (Manila)
Communications Officer
Telephone: +63 906 493 5097
E-mail: alexandern@wpro.who.int

Christy Feig
Director of Communications
Telephone: +41 79 251 7055
E-mail: feigc@who.int

Gregory Hartl
Coordinator, News and Social Media
Telephone: +41 79 203 6715
E-mail: hartlg@who.int

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Protien Cyclin D1 governs microRNA processing in breast cancer

Nov. 29, 2013 — Cyclin D1, a protein that helps push a replicating cell through the cell cycle also mediates the processing and generation of mature microRNA (miRNA), according to new research publishing November 29 in Nature Communications. The research suggests that a protein strongly implicated in human cancer also governs the non-protein-coding genome. The non-coding genome, previously referred to as junk DNA, makes up most of the human genome, and unlike the coding genome, varies greatly between species.

"In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. Dicer is a protein that converts inactive hairpin-structured microRNA precursors into their active single stranded form. "The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis."

Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome. These attenuating feedback loops between the non coding and coding genome may be a common theme in cancer and other biological processes.

In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA.

The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes.

In addition to the in vitro studies, the researchers also examined over 2,200 patient samples. They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. Luminal A subtype of breast cancer is the most common type and also has the best prognosis. The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. Indeed, lower levels of miRNAs have been observed in a number of human cancers.

"By linking the decrease in miRNA levels to Dicer, we show that a global decrease in miRNA processing may be important in the initiation and progression of certain cancers," says first author, Zuoren Yu, Ph.D., who holds a joint appointment at Jefferson's Kimmel Cancer Center and Tongji University School of Medicine in Shanghai, China.

Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis.

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Children in typhoon-hit Tacloban, Philippines, receive vaccines against measles, polio

26 November 2013 | Tacloban, Philippines - Children in Tacloban - the city hit hardest by Typhoon Haiyan - were today vaccinated against measles and polio in the first phase of a mass campaign by the Government of the Philippines with support from WHO, the United Nations Children's Fund (UNICEF) and other partners. They also received Vitamin A supplements to help improve their immunity against infections.

30 000 children targeted in first phase

Over 30?000 children are expected to be reached by the campaign which is taking place at fixed sites in evacuation centres and in communities using mobile health teams.

"It is virtually unprecedented that within two-and-a-half weeks of a disaster of this scale, with this level of devastation and these logistical challenges, that a mass vaccination campaign is already rolling out."

Dr Julie Hall, WHO Representative in the Philippines

The vaccination drive in Tacloban is the first phase of a campaign targeting children aged less than 5 years in all the typhoon-affected areas. Fifteen teams (10 foreign and 5 national) including volunteers from the Department of Health, the Philippines Red Cross and other non-governmental organisations, were in locations across Tacloban giving vaccines today. The first to receive them were children in 20 evacuation centres, such as San Jose Elementary School, where more than 300 families currently live in conditions that can heighten the risk of infectious diseases.

"The children of Tacloban need all the protection they can get right now," says Angela Kearney, UNICEF Coordinator for the Emergency Response in Tacloban. "Disease is a silent predator, but we know how to prevent it and we will do everything that we can."

WHO and UNICEF coordinate vaccine supply and establish cold chain

At the Government’s request, UNICEF purchased over US$ 2 million worth of vaccines to replenish in-country stocks now being used for the campaign. In addition, UNICEF and WHO are helping to re-establish the broken cold chain, which is critical in keeping vaccines at the right temperature.

"WHO and UNICEF staff hand-carried supplies from Manila to Tacloban, coordinated teams to give the vaccines and trained them on how to do it under these difficult circumstances. It is virtually unprecedented that within two-and-a-half weeks of a disaster of this scale, with this level of devastation and these logistical challenges, that a mass vaccination campaign is already rolling out," says Dr Julie Hall, WHO Representative in the Philippines.

During the campaign children being immunized are also screened for malnutrition by measuring their mid-upper arm circumference which will indicate if they are undernourished and require referral for treatment.

For further information, please contact:

Nyka Alexander
Communications Officer
WHO, Manila
Telephone: +63 906 493 5097
E-mail: alexandern@wpro.who.int

Gregory Hartl
Coordinator, News and Social Media
WHO, Geneva
Telephone: +41 79 203 6715
E-mail: hartlg@who.int

Zafrin Chowdhury
UNICEF, Tacloban
Telephone: + 63 917 867 8366
E-mail: zchowdhury@unicef.org

Kate Donovan
UNICEF, Tacloban
Telephone: + 1 212 303 7984,
Mobile: + 1 917 3781 2128
E-mail: kdonovan@unicef.org

Denise Shepherd-Johnson
UNICEF, Manila
Telephone: + 63 917 464 7028
E-mail: dshepherdjohnson@unicef.org

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High cholesterol fuels growth, spread of breast cancer

Nov. 28, 2013 — A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers at the Duke Cancer Institute report.

The researchers also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule.

Published in the Nov. 29, 2013, edition of the journal Science, the findings are early, using mouse models and tumor cells. But the research for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk.

"A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified," said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke. "What we have now found is a molecule -- not cholesterol itself, but an abundant metabolite of cholesterol -- called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer."

The hormone estrogen feeds an estimated 75 percent of all breast cancers. In a key earlier finding from McDonnell's lab, researchers determined that 27-hydroxycholesterol -- or 27HC -- behaved similarly to estrogen in animals.

For their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect.

Using mouse models that are highly predictive of what occurs in humans, McDonnell and colleagues demonstrated the direct involvement of 27HC in breast tumor growth, as well as the aggressiveness of the cancer to spread to other organs. They also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of 27HC was stopped.

The studies were substantiated using human breast cancer tissue. An additional finding in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. They also noted that 27HC could be made in other places in the body and transported to the tumor.

"The worse the tumors, the more they have of the enzyme," said lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke. Nelson said gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.

"This is a very significant finding," McDonnell said. "Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel."

McDonnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. Additionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.

The next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if 27HC plays a role in other cancers, McDonnell said.

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Drug drug strategy block a major driver of the cancer

Using a new strategy, researchers from the University of California at San (UCSF Helen Diller Family Comprehensive Cancer Center home ） to target the mutant RAS protein, small molecules have been successful without bind irreversibly normal form. Differentiate this function in cancer, targeted drug therapy every other molecular scientists. People grow up in the culture when you test your lung cancer cells molecule killed RAS driven cancer cells effectively.

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Large study links nut consumption is reduced mortality.

Who ate nuts daily of the largest study of its kind, a handful were 20 percent less and were people who did not consume nuts so the Dana contains the report published in the New England Journal of medicine, say scientists from the Harvard School of Farber Cancer Institute, Brigham and women's Hospital and public health more than die by any cause over a period of 30 years is even better news. Regular nut-eaters found is thinner than people who did not eat the nuts, may find that eating more nuts will need to reduce the widespread concerns on obesity.

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Bolshoi performers say Russian dancer's guilt not proven

By Maria Tsvetkova

MOSCOW (Reuters) - Performers at Russia's Bolshoi Theatre made a last-minute plea for leniency on Monday for a dancer accused of ordering an acid attack on its artistic director, praising his "wonderful human qualities" and saying he was incapable of such an act.

A judge is due to pronounce a verdict on Tuesday in the month-long trial of former soloist Pavel Dmitrichenko that has shone a spotlight on bitter rivalries behind the scenes.

State prosecutors have asked for a nine-year prison term but he could still be jailed for up to 12 years if convicted over an attack that nearly blinded the Bolshoi ballet's artistic director, Sergei Filin.

The month-long trial of Dmitrichenko and two alleged accomplices has tainted the reputation of one of Russia's most prominent cultural symbols.

"In the open trial, the public has heard absolutely no evidence confirming his guilt," dozens of performers and other staff at the Bolshoi said in an open letter published on the website of the daily Izvestia newspaper.

Dancer Natalya Vyskubenko said it was signed by about 150 people.

EYESIGHT IMPAIRED

A masked assailant splashed acid in Filin's face when he was returning home late in the evening from the Bolshoi last January, leaving him writhing in pain. His eyesight remains impaired after more than 20 operations.

Dmitrichenko, 29, has acknowledged that he wanted Filin roughed up and had given co-defendant Yuri Zarutsky the go-ahead to hit him, but has pleaded not guilty to ordering an attack involving acid. Zarutsky has said the use of acid was his idea and that he had not told Dmitrichenko of his plan.

Citing what it called Dmitrichenko's "decency, flawless professionalism ... and wonderful human qualities," the letter said those who knew him found it "absolutely unacceptable (to say) he could have inspired and ordered a crime that was committed in such a savage way."

"The judge's decision in this case must be proportionate to the real guilt of each participant - or lack thereof," it said.

Prosecutors have asked the court to sentence Zarutsky to 10 years in prison and Andrei Lipatov, who is accused of driving Zarutsky to the scene, to six years.

The prosecution said Dmitrichenko was motivated by a conflict with Filin, 43. In court last week, prominent former Bolshoi dancer Nikolai Tsiskaridze told the court he had denied roles to both Dmitrichenko and his girlfriend, a ballerina.

Defense witnesses have attacked Filin's character, portraying him as an imperious hothead and Dmitrichenko as a champion of others who felt slighted by the artistic director, who has considerable power to make or break careers.

(Writing by Steve Gutterman)

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How to discover drugs, such as thalidomide to fight cancer

Causes of congenital defect of the 50 despite the tragic legacy of two years ago, thalidomide - new drugs derived from it - as an effective treatment for patients with multiple myeloma and other cancers. How it slows down the spread of cancer action, however the long description of the rebellious. In a new report, Dana Farber Cancer Institute scientists found that kill multiple myeloma cells by mechanisms different from the way their drug birth defects cause and says.

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Do black holes come in size medium?

Nov. 29, 2013 — Black holes can be petite, with masses only about 10 times that of our sun -- or monstrous, boasting the equivalent in mass up to 10 billion suns. Do black holes also come in size medium? NASA's Nuclear Spectroscopic Telescope Array, or NuSTAR, is busy scrutinizing a class of black holes that may fall into the proposed medium-sized category.

"Exactly how intermediate-sized black holes would form remains an open issue," said Dominic Walton of the California Institute of Technology, Pasadena. "Some theories suggest they could form in rich, dense clusters of stars through repeated mergers, but there are a lot of questions left to be answered."

The largest black holes, referred to as supermassive, dominate the hearts of galaxies. The immense gravity of these black holes drags material toward them, forcing the material to heat up and release powerful X-rays. Small black holes dot the rest of the galactic landscape. They form under the crush of collapsing, dying stars bigger than our sun.

Evidence for medium-sized black holes lying somewhere between these two extremes might come from objects called ultraluminous X-ray sources, or ULXs. These are pairs of objects in which a black hole ravenously feeds off a normal star. The feeding process is somewhat similar to what happens around supermassive black holes, but isn't as big and messy. In addition, ULXs are located throughout galaxies, not at the cores.

The bright glow of X-rays coming from ULXs is too great to be the product of typical small black holes. This and other evidence indicates the objects may be intermediate in mass, with 100 to 10,000 times the mass of our sun. Alternatively, an explanation may lie in some kind of exotic phenomenon involving extreme accretion, or "feeding," of a black hole.

NuSTAR is joining with other telescopes to take a closer look at ULXs. It's providing the first look at these objects in focused, high-energy X-rays, helping to get better estimates of their masses and other characteristics.

In a new paper from Walton and colleagues accepted for publication in the Astrophysical Journal, the astronomers report serendipitously finding a ULX that had gone largely unnoticed before. They studied the object, which lies in the Circinus spiral galaxy 13 million light-years away, not only with NuSTAR but also with the European Space Agency's XMM-Newton satellite. Archival data from NASA's Chandra, Swift and Spitzer space telescopes as well as Japan's Suzaku satellite, were also used for further studies. "We went to town on this object, looking at a range of epochs and wavelengths," said Walton.

The results indicate the black hole in question is about 100 times the mass of the sun, putting it right at the border between small and medium black holes.

In another accepted Astrophysical Journal paper, Matteo Bachetti of the Institut de Recherche en Astrophysique et Planetologie and colleagues looked at two ULXs in NGC 1313, a spiral galaxy known as the "Topsy Turvy galaxy," also about 13 million light-years way.

These are among the best-studied ULXs known. A single viewing with NuSTAR showed that the black holes didn't fit with models of medium-size black holes. As a result, the researchers now think both ULXs harbor small, stellar-mass black holes. One of the objects is estimated to be big for its size category, at 70 to 100 solar masses.

"It's possible that these objects are ultraluminous because they are accreting material at a high rate and not because of their size," said Bachetti. "If intermediate-mass black holes are out there, they are doing a good job of hiding from us."

NuSTAR is a Small Explorer mission led by Caltech and managed by NASA's Jet Propulsion Laboratory, Pasadena, Calif., for NASA's Science Mission Directorate in Washington. The spacecraft was built by Orbital Sciences Corporation, Dulles, Va. Its instrument was built by a consortium including Caltech; JPL; the University of California, Berkeley; Columbia University, New York; NASA's Goddard Space Flight Center, Greenbelt, Md.; the Danish Technical University in Denmark; Lawrence Livermore National Laboratory, Livermore, Calif.; ATK Aerospace Systems, Goleta, Calif., and with support from the Italian Space Agency (ASI) Science Data Center.

NuSTAR's mission operations center is at UC Berkeley, with the ASI providing its equatorial ground station located at Malindi, Kenya. The mission's outreach program is based at Sonoma State University, Rohnert Park, Calif. NASA's Explorer Program is managed by Goddard. JPL is managed by Caltech for NASA.

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Breastfeeding is life-saving for babies in Philippines typhoon emergency

28 November 2013 | Manila, Philippines - UNICEF and WHO today called on those involved in the response to the Philippines’ Typhoon Haiyan (Yolanda) disaster to promote and protect breastfeeding to avoid unnecessary illness and deaths of children.

Exclusive breastfeeding in first 6 months vital

The estimated 12 000 babies to be born in the worst-affected areas this month need to be exclusively breastfed, meaning that they get nothing but breast milk, which protects them from potentially deadly infections. Around one third of babies in the area born before the disaster who are less than 6 months old are already exclusively breastfed, and 9 out of 10 were at least partially breastfed before the emergency. The mothers who were doing at least some breastfeeding need to be supported to transition to exclusive breastfeeding.

“The uncontrolled distribution and use of infant formula in emergency situations like this – where there are serious water and sanitation challenges and other disease risks – is extremely dangerous. Supporting breastfeeding is one of the most important things we can do to protect babies in areas of the Philippines hit by the typhoon,” said Dr Julie Hall, WHO Representative in the Philippines.

"Supporting breastfeeding is one of the most important things we can do to protect babies in areas of the Philippines hit by the typhoon."

Dr Julie Hall, WHO Representative in the Philippines

UNICEF and WHO prioritise the protection, promotion and support of breastfeeding as a life-saving measure for babies everywhere, and especially in emergencies.

“With the right support – from a health worker, a counsellor or another mother – a woman who is already doing some breastfeeding can increase her milk production within days just by feeding her baby more frequently,” said Tomoo Hozumi, UNICEF Representative in the Philippines.

Babies under 6 months the most vulnerable in emergency situations

During emergency situations, disease and death rates among babies and children are higher than for any other age group; and the younger the child, the higher the risk, leaving babies under 6 months most vulnerable. Babies who drink formula made with water that is contaminated with germs or given with an unsterile bottle or teat, can become very sick with diarrhoea and die within a matter of hours.

Feeding babies with formula in emergencies must only be considered as a last resort, when other safer options – such as helping non-breastfeeding mothers to reinitiate breastfeeding, finding a wet nurse or pasteurized breast milk from a breast milk bank – have first been fully explored.

Only a relatively small number of infants under 6 months affected by this disaster – estimated to number around 6 600 – are not breastfed at all. These babies should be urgently identified, their feeding situation assessed, and be provided with skilled support and the safest feeding option.

UNICEF and WHO strongly urge all who are involved in funding, planning and implementing the emergency response in the Philippines to avoid unnecessary illness and death by protecting, promoting, and supporting breastfeeding. Community leaders are called upon to monitor and report any donations that may undermine breastfeeding.

For further information, please contact:

Liv Lawe-Davies
Communications Officer
WHO, Manila
Telephone: +63 915 896 6345
E-mail: lawedavieso@who.int

Gregory Hartl
Coordinator, News and Social Media
WHO, Geneva
Telephone: +41 79 203 6715
E-mail: hartlg@who.int

Zafrin Chowdhury
UNICEF, Tacloban
Telephone: + 63 917 867 8366
E-mail: zchowdhury@unicef.org

Kate Donovan
UNICEF, Tacloban
Telephone: + 1 212 303 7984,
Mobile: + 1 917 3781 2128
E-mail: kdonovan@unicef.org

Denise Shepherd-Johnson
UNICEF, Manila
Telephone: + 63 917 464 7028
E-mail: dshepherdjohnson@unicef.org

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Protien Cyclin D1 governs microRNA processing in breast cancer

Nov. 29, 2013 — Cyclin D1, a protein that helps push a replicating cell through the cell cycle also mediates the processing and generation of mature microRNA (miRNA), according to new research publishing November 29 in Nature Communications. The research suggests that a protein strongly implicated in human cancer also governs the non-protein-coding genome. The non-coding genome, previously referred to as junk DNA, makes up most of the human genome, and unlike the coding genome, varies greatly between species.

"In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. Dicer is a protein that converts inactive hairpin-structured microRNA precursors into their active single stranded form. "The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis."

Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome. These attenuating feedback loops between the non coding and coding genome may be a common theme in cancer and other biological processes.

In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA.

The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes.

In addition to the in vitro studies, the researchers also examined over 2,200 patient samples. They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. Luminal A subtype of breast cancer is the most common type and also has the best prognosis. The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. Indeed, lower levels of miRNAs have been observed in a number of human cancers.

"By linking the decrease in miRNA levels to Dicer, we show that a global decrease in miRNA processing may be important in the initiation and progression of certain cancers," says first author, Zuoren Yu, Ph.D., who holds a joint appointment at Jefferson's Kimmel Cancer Center and Tongji University School of Medicine in Shanghai, China.

Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis.

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Biogen says FDA extending review of hemophilia drug

(Reuters) - Biogen Idec Inc on Monday said the U.S. Food and Drug Administration will extend by three months its deadline for reviewing the company's experimental long-acting medicine for hemophilia.

Biogen, which is developing the drug in partnership with Swedish Orphan Biovitrum AB, said it had provided the FDA additional information related to validation of a manufacturing step for the medicine, called Alprolix.

It is the first member of a new class of drugs for Hemophilia B, a rare inherited disorder in which the ability of a person's blood to clot is impaired.

Biogen last summer said the drug, in a late-stage trial, had consistently controlled bleeding during and after 14 major surgeries in 12 patients with the condition.

The company has described the drug as the first major treatment advance for hemophilia B in 15 years.

Biogen in January said it had asked the FDA to approve Alprolix.

(Reporting by Ransdell Pierson; Editing by Gerald E. McCormick)

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Messy children make better learners: Toddlers learn words for nonsolids better when getting messy in a highchair

Dec. 2, 2013 — Attention, parents: The messier your child gets while playing with food in the high chair, the more he or she is learning.

Researchers at the University of Iowa studied how 16-month-old children learn words for nonsolid objects, from oatmeal to glue. Previous research has shown that toddlers learn more readily about solid objects because they can easily identify them due to their unchanging size and shape. But oozy, gooey, runny stuff? Not so much.

New research shows that changes if you put toddlers in a setting they know well, such as shoving stuff in their mouths. In those instances, word learning increases, because children at that age are "used to seeing nonsolid things in this context, when they're eating," says Larissa Samuelson, associate professor in psychology at the UI who has worked for years on how children learn to associate words with objects. "And, if you expose them to these things when they're in a highchair, they do better. They're familiar with the setting and that helps them remember and use what they already know about nonsolids."

In a paper published in the journal Developmental Science, Samuelson and her team at the UI tested their idea by exposing 16-month-olds to 14 nonsolid objects, mostly food and drinks such as applesauce, pudding, juice, and soup. They presented the items and gave them made-up words, such as "dax" or "kiv." A minute later, they asked the children to identify the same food in different sizes or shapes. The task required the youngsters to go beyond relying simply on shape and size and to explore what the substances were made of to make the correct identification and word choice.

Not surprisingly, many children gleefully dove into this task by poking, prodding, touching, feeling, eating -- and yes, throwing -- the nonsolids in order to understand what they were and make the correct association with the hypothetical names. The toddlers who interacted the most with the foods -- parents, interpret as you want -- were more likely to correctly identify them by their texture and name them, the study determined. For example, imagine you were a 16-month-old gazing at a cup of milk and a cup of glue. How would you tell the difference by simply looking?

"It's the material that makes many nonsolids," Samuelson notes, "and how children name them."

The setting matters, too, it seems. Children in a high chair were more apt to identify and name the food than those in other venues, such as seated at a table, the researchers found.

"It turns out that being in a high chair makes it more likely you'll get messy, because kids know they can get messy there," says Samuelson, the senior author on the paper. The authors say the exercise shows how children's behavior, environment (or setting) and exploration help them acquire an early vocabulary -- learning that is linked to better later cognitive development and functioning.

"It may look like your child is playing in the high chair, throwing things on the ground, and they may be doing that, but they are getting information out of (those actions)," Samuelson contends. "And, it turns out, they can use that information later. That's what the high chair did. Playing with these foods there actually helped these children in the lab, and they learned the names better."

"It's not about words you know, but words you're going to learn," Samuelson adds. Lynn Perry, who helped design the study and analyze the data as part of her doctoral studies at the UI, is the first author on the paper. Johanna Burdinie, who was an UI undergraduate during the project, is a contributing author.

The National Institutes of Health (grant number: R01 HD045713) funded the research. Burdinie was funded by a fellowship from the Iowa Center for Research for Undergraduates.

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Comet ISON may have survived

Dec. 1, 2013 — Continuing a history of surprising behavior, material from Comet ISON appeared on the other side of the sun on the evening on Nov. 28, 2013, despite not having been seen in observations during its closest approach to the sun.

As ISON appeared to dim and fizzle in several observatories and later could not be seen at all by NASA's Solar Dynamics Observatory or by ground based solar observatories, many scientists believed it had disintegrated completely. However, a streak of bright material streaming away from the sun appeared in the European Space Agency and NASA's Solar and Heliospheric Observatory later in the evening. The question remains whether it is merely debris from the comet, or if some portion of the comet's nucleus survived, but late-night analysis from scientists with NASA's Comet ISON Observing Campaign suggest that there is at least a small nucleus intact.

Throughout the year that researchers have watched Comet ISON -- and especially during its final approach to the sun -- the comet brightened and dimmed in unexpected ways. Such brightness changes usually occur in response to material boiling off the comet, and different material will do so at different temperatures thus providing clues as to what the comet is made of. Analyzing this pattern will help scientists understand the composition of ISON, which contains material assembled during the very formation of the solar system some 4.5 billion years ago.

For more information on Comet ISON: www.nasa.gov/ison

To download recent ISON imagery: http://svs.gsfc.nasa.gov/Gallery/CometISON.html

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B cells can provide a potential treatment of RNA has changed a bit.

California College San Diego medical Moores Comprehensive Cancer Center (home) of researchers successfully different kinds of white blood cells, and designed to provide a bit of a non-coding RNA or microRNA (miRNA)-it plays a central role in the immune response of the body – is targeting the T lymphocytes. Achieved in the mouse study published in this week National Science Academy Journal online early Edition are probably used for genetic recombination miRNA therapeutic purposes, the first step of the prominent vaccine and cancer treatment.

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Translate the new findings to enhance treatment of patients with malignant melanoma cancer researchers.

From translational researchers at UCLA's Jonsson Comprehensive Cancer Center (number of days), published results of a study provide insightful journal Cancer found BRAF inhibitor resistance two key areas critical to tumor how two back-to-back: focus and use to learn how to be resistant to melanoma tumor cells inhibitor with cell signal transduction pathway BRAF-mutant, evolve and limited development cell BRAF inhibitor drug resistance is how black keys.

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Cyclin D1 is the dominating microRNAs in breast cancer treatment.

Cells to replicate through the help push, cyclin D1 protein cell cycle is also brokering process mature microRNA (miRNA), Thomas Jefferson University's Kimmel Cancer generation published according to a new study from the Center for natural communication 11/29. Research is protein is strongly involved in human cancer protein coding dominated non-genome also suggests. Different species make up most of the formerly called junk DNA is unlike the genome the human genome coding and non-coding genome.

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Admit intestinal microorganisms based on NIH mouse determines the results of cancer treatment.

National cancer are in the population of microorganisms that live in symbiotic Gut microflora, intestinal as required according to the mouse study by scientists at the Institute (NCI) ideal response to cancer treatment.

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Scientists achieve most detailed picture ever of key part of hepatitis C virus

Nov. 28, 2013 — Scientists at The Scripps Research Institute (TSRI) have determined the most detailed picture yet of a crucial part of the hepatitis C virus, which the virus uses to infect liver cells. The new data reveal unexpected structural features of this protein and should greatly speed efforts to make an effective hepatitis C vaccine.

The findings, which appear in the November 29, 2013 issue of the journal Science, focus on a protein known as E2 envelope glycoprotein.

"We're excited by this development," said Ian A. Wilson, the Hansen Professor of Structural Biology at TSRI and a senior author of the new research with TSRI Assistant Professors Mansun Law and Andrew B. Ward. "It has been very hard to get a high resolution structure of E2 and it took years of painstaking work to finally accomplish that."

Any successful hepatitis C vaccine is likely to target the E2 protein. Scientists already have isolated rare antibodies from patients that can bind E2 in ways that neutralize a broad range of viral strains.

"It took our team six years to crack this very difficult scientific problem, but we didn't give up," said Law. "Now that we can visualize the structural details of these binding sites, we can design vaccine molecules that mimic them."

A Silent Killer

There has long been an urgent need for an effective vaccine against hepatitis C virus. Once confined to isolated geographical regions, the virus spread globally during the 20th century, chiefly via blood transfusions, unsterilized medical instruments and re-used hypodermic needles. Although hospitals have screened blood products for hepatitis C virus (HCV) since the early 1990s, as many as 200 million people currently are thought to harbor the virus. These include more than 3 million people in the United States, where the virus is responsible for more deaths each year than HIV.

HCV was able to spread so widely because it typically causes few or no symptoms when it infects someone. In many cases it establishes a long-term infection of the liver, damaging it slowly for decades -- until liver cirrhosis and/or cancer develop. "It's known as a 'silent killer'," said Law. Expensive and risky liver transplantation is often the only way to save a patient's life. Some antiviral drugs are useful in treating and even curing chronic HCV infection, but the more effective ones are extremely expensive -- and most HCV-positive people don't even know that they're infected and need treatment.

An HCV vaccine could put an end to the global pandemic by preventing new infections. "It could be given to people when they're young and healthy, and they'd never have to worry about developing HCV-related liver diseases," said Ward.

However, like HIV and some other viruses, HCV uses several effective countermeasures to evade the immune system. These include fast-mutating regions on the E2 protein, which ensure that antibodies to one HCV strain typically are ineffective against other strains. The E2 protein also coats itself with relatively antibody-proof sugar molecules.

To defeat these viral countermeasures, scientists have wanted to "see" the high-resolution atomic structure of HCV, particularly E2 and its CD81 receptor binding site, which does not vary much from strain to strain. In recent years, Law's laboratory and others have isolated antibodies that manage to grab hold of this relatively conserved region of E2, thereby blocking the infectivity of a large fraction of HCV strains. In principle, a vaccine that prompts the body to make similar antibodies would effectively and cheaply immunize people against most of their risk of HCV infection.

Unruly E2

But precisely mimicking these antibody-binding sites in a vaccine means first determining their high-resolution structures, which has been difficult even to attempt. "Usually if you try to express the E2 protein in cultured cells, you either can't express it in useful quantities or you can but it aggregates and becomes a big mess," said Leopold Kong, a research associate in the Wilson laboratory who was the study's lead author.

Over the past several years, Kong and his colleagues have run dozens of experiments to find the right way to modify E2 -- enough that the protein doesn't aggregate so readily and also so that the antibody-binding sites are maintained. This would enable the protein to be soluble and pure enough to grow crystals to determine its structure by the technique known as X-ray crystallography. "It was a Herculean effort," said Ward. "This is one of the most difficult and unstable viral envelope proteins around."

In the end, the team succeeded, using a slightly altered version of E2 -- the E2 core -- with some of its glycans (sugar molecules) and outer variable and stalk segments removed. The scientists were then able to obtain the high-resolution structure of the protein while it was bound to a known broadly neutralizing antibody developed at TSRI. The scientists then followed up by imaging a more complete version of E2 using electron microscopy to extend the structural model.

When finally revealed, E2's structure surprised the researchers. "It had been thought that HCV's E2 belongs to a family of viral fusion proteins called class 2 fusion proteins, which includes envelope proteins for West Nile and dengue viruses, for example," said Kong. "But we showed that E2 is structurally distinct and probably works differently than what had been widely assumed."

Based on the new structural data, Law and colleagues at TSRI are already designing and testing novel antibody-stimulating components of a future HCV vaccine. "Having the E2 structure has certainly helped us," said Law.

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Adolescents falling through gaps in HIV services

25 November 2013 | Geneva - More than 2 million adolescents between the ages of 10 and 19 years are living with HIV, and many do not receive the care and support that they need to stay in good health and prevent transmission. In addition, millions more adolescents are at risk of infection.

The failure to support effective and acceptable HIV services for adolescents has resulted in a 50% increase in reported AIDS-related deaths in this group compared with the 30% decline seen in the general population from 2005 to 2012.

Addressing the specific needs of adolescents

The WHO recommendations "HIV and adolescents: Guidance for HIV testing and counselling and care for adolescents living with HIV" are the first to address the specific needs of adolescents both for those living with HIV as well as those who are at risk of infection. They are being released in advance of World AIDS Day 2013 (1 December).

“Adolescents face difficult and often confusing emotional and social pressures as they grow from children into adults,” says Dr Gottfried Hirnschall, Director of WHO HIV/AIDS Department. “Adolescents need health services and support, tailored to their needs. They are less likely than adults to be tested for HIV and often need more support than adults to help them maintain care and to stick to treatment.”

“Adolescents need health services and support, tailored to their needs. They are less likely than adults to be tested for HIV and often need more support than adults to help them maintain care and to stick to treatment.”

Dr Gottfried Hirnschall, Director of WHO HIV/AIDS Department

Across sub-Saharan Africa, many who were infected at birth are becoming adolescents. In addition to the many changes associated with adolescence, they also face the challenges of living with a chronic infection: disclosing the news to friends and family and preventing transmission to sexual partners.

“Adolescent girls, young men who have sex with men, those who inject drugs or are subject to sexual coercion and abuse are at highest risk. They face many barriers, including harsh laws, inequalities, stigma and discrimination which prevent them from accessing services that could test, prevent, and treat HIV,” says Craig McClure, Chief of HIV programmes for UNICEF. “About one-seventh of all new HIV infections occur during adolescence. Unless the barriers are removed, the dream of an AIDS-free generation will never be realized.”

Making it easier to know HIV status

Furthermore, many young people do not know their HIV status. For example, in sub-Saharan Africa, it is estimated that only 10% of young men and 15% of young women (15-24 years) know their HIV status and, in other regions, although data is scarce, access to HIV testing and counseling by vulnerable adolescents is consistently reported as being very low.

WHO recommends governments review their laws to make it easier for adolescents to obtain HIV testing without needing consent from their parents. The guidelines also suggest ways that health services can improve the quality of care and social support for adolescents. And they highlight the value of involving this age group to create an adolescent-centered approach to the services that work for people of their age.

Better equipping adolescents

“Young people need to be better equipped to manage their HIV infection and take ownership of their health care,” says Dr Elizabeth Mason, Director of WHO Maternal, Newborn, Child and Adolescent Health Department. “We have seen for example in Zimbabwe that, by developing adolescent friendly services, it is possible to achieve good treatment outcomes among adolescents. We urge others to be inspired by these examples.”

To help health workers put these recommendations into practice WHO has developed a new online tool which will be launched in January 2014. It uses practical examples from country programmes that are working closely with adolescents on HIV issues.

Note to editors

The guidelines provide recommendations and expert suggestions – mainly for policy-makers and national programme managers – on prioritizing, planning and providing HIV testing, counselling and care services for adolescents. Designed to be used with the recent WHO consolidated Antiretroviral guidelines, these new guidelines provide complimentary recommendations and guidance to support better provision of services to help adolescents remain in care and adhere to treatment.

The guidelines were developed based on scientific evidence, community consultations with adolescents and health workers, field experience of health workers and expert opinion. WHO led the development of these guidelines in collaboration with the United Nations Children’s Fund (UNICEF), the Global Network of People Living with HIV (GNP+), the United Nations Educational, Scientific and Cultural Organization (UNESCO), and the United Nations Population Fund (UNFPA).

For more information please contact:

Mr Glenn Thomas
Communications Officer, WHO
Telephone: +41 22 791 3983
Mobile: +41 79 509 0677
E-mail: thomasg@who.int

Rita Ann Wallace
UNICEF Media
Telephone: +1 212 326 7586
E-mail: rwallace@unicef.org

Iman Morooka
UNICEF Strategic Communications
Telephone: +1 212 326 7211
E-mail: imorooka@unicef.org

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Target for anti-cancer drug has extensive features than what its name suggests.

Drugs that inhibit the activity of the enzyme called histone deacetylase （ Hdac) widely in cancer and the market already two other diseases to treat has been developed. Perelman medical researcher, University of Pennsylvania (Abramson Cancer Center to house), so this suggests re-evaluation of the molecular targets of the justification for this kind of drug, when abolished the enzymatic activity in the mouse indicates major HDAC function a beneficial effect of the HDAC Inhibitors may not be actually HDAC activity inhibits.

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New Hampshire hospital worker to be sentenced for spreading hepatitis

(Reuters) - A former New Hampshire hospital technician who infected patients as old as 80 with hepatitis after injecting himself with stolen painkillers will learn on Monday how much of his life will be spent in prison.

The technician, David Kwiatkowski, 34, in August admitted to leaving dirty syringes for hospital use despite knowing that he was infected with hepatitis C. He pleaded guilty to obtaining controlled substances by fraud and tampering with a consumer product.

Kwiatkowski has asked U.S. District Judge Joseph Laplante to sentence him to 30 years in federal prison.

Prosecutors have requested a 40-year sentence, saying that he knowingly put patients in eight states in danger over about a decade of work as a traveling hospital technician.

Kwiatkowski admitted to injecting himself with pre-filled syringes of the painkiller fentanyl, which he would steal from hospital supply cabinets. He filled the empty syringes with saline solution, causing the syringes to become tainted by his infected blood. Hospital staff then injected patients with the needles, not realizing they had been tampered with.

"The defendant continued this reckless conduct with full knowledge that he had hepatitis C and that he was, by his own admission, 'going to kill a lot of people out of this,'" prosecutors argued in their sentencing memo, filed in U.S. district court in Concord, New Hampshire, where Kwiatkowski will be sentenced.

Kwiatkowski's crimes were discovered when several patients at Exeter Hospital in Exeter, New Hampshire, were infected with the disease. That prompted a review of all patients Kwiatkowski had worked with in his years in the field, in what prosecutors described as a "national public health crisis."

His attorneys argued for a shorter, 30-year-sentence, noting that Kwiatkowski confessed early in the legal process against him, sparing the state the expense of the trial.

"While Kwiatkowski initially denied involvement in the offense, he confessed to the crime before his first court appearance, when he admitted that he knew that he was infected with hepatitis C and did not try to blame anyone else for his conduct," his attorneys wrote in a court filing.

(Reporting by Scott Malone; Editing by Steve Orlofsky)

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Methylation signaling controls cancer growth

Nov. 28, 2013 — A study led by researchers at Boston University School of Medicine (BUSM) demonstrates a new mechanism involving a signaling protein and its receptor that may block the formation of new blood vessels and cancer growth. The findings are published in the December issue of Science Signaling.

Angiogenesis creates new blood vessels in a process that can lead to the onset and progression of several diseases such as cancer and age-related macular degeneration.

Vascular endothelial growth factor (VEGF) is a signaling protein produced by damaged cells, which binds to one of its receptors VEGFR-2, located on the surface of blood vessel cells. Once VEGF is bound to its receptor, it is activated and sends a biochemical signal to the inside of the blood vessel cell to initiate angiogenesis. There are currently multiple Federal Drug Administration-approved medications that target this process. However these medications are limited by insufficient efficacy and the development of resistance.

The researchers demonstrated that a biochemical process called methylation, which can regulate gene expression, also affects VEGFR-2, and this can lead to angiogenesis. Using multiple methods, the researchers were able to interfere with the methylation process of VEGFR-2 and subsequently block angiogenesis and tumor growth.

"The study points to the methylation of VEGFR-2 as an exciting, yet unexplored drug target for cancer and ocular angiogenesis, ushering in a new paradigm in anti-angiogenesis therapy," said Nader Rahimi, PhD, associate professor of pathology, BUSM, who served as the study's senior investigator.

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Shire agrees to supply Adderall XR generic to Sandoz

LONDON (Reuters) - Pharmaceutical company Shire said on Monday it had agreed to supply an authorized generic version of Adderall XR, its drug to treat hyperactivity, to Sandoz.

Adderall, an amphetamine, is available in instant release and extended release formulations. Shire now only produces the extended version, for which it retains patent rights, and sales of the drug have been falling since a generic version became available in 2009.

However, the drug still generated sales of $81.4 million for Shire in the third quarter of the year.

Under the agreement, Sandoz, the generic arm of Novartis, will exclusively sell the authorized generic version of Adderall XR supplied by Shire from July 1, 2016 in the United States, Shire said, adding it would receive a royalty on sales.

(Reporting by Paul Sandle; editing by Kate Holton)

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WHO issues new guidance for treating children with severe acute malnutrition

27 November 2013 | GENEVA - WHO today released new treatment guidelines for the almost 20 million children under-five worldwide who have severe acute malnutrition.

Severe acute malnutrition is when children suffer severe wasting that may or may not be accompanied by swelling of the body from fluid retention. It occurs when infants and children do not have adequate energy, protein and micronutrients in their diet, combined with other health problems such as recurrent infections. It is diagnosed when the circumference of the upper arm is less than 115 mm or when the weight for height of a child is severely reduced.

Children with severe acute malnutrition are among the most vulnerable people in the world. They are very thin: most of their fat and muscle has been used by their bodies to stay alive.

Main recommendations

The updated WHO guidelines recommend that children with severe acute malnutrition who do not have health complications that require hospitalization, receive special, high-energy food and antibiotics to treat infection. This allows them to recover at home with their families. They also give guidance on how to treat them for HIV and, if necessary make recommendations on how to treat severely malnourished infants under six months.

“The guidelines are critical because many national health plans currently overlook children with severe acute malnutrition... If these children don’t get the right medical and nutritional care, very often they die,”

Dr Francesco Branca, Director, WHO Department of Nutrition for Health and Development

“The guidelines are critical because many national health plans currently overlook children with severe acute malnutrition. This can be fatal. If these children don’t get the right medical and nutritional care, very often they die,” says Dr Francesco Branca, Director of WHO’s Department of Nutrition for Health and Development.

New guidelines reflect new opportunities and technologies

The new guidelines supersede those issued by WHO in 1999 which recommended that all severely malnourished children be hospitalized, given fortified formula milk and appropriate treatment including antibiotics. The guidelines have been updated to reflect new opportunities and technologies that allow severely malnourished children who have an appetite and no evident medical complications to be effectively treated at home with specially-formulated foods that provide energy and nutrients and antibiotic medicines.

“It’s generally better for children and better for their families if they’re treated as outpatients,” says Dr Elizabeth Mason, Director of WHO’s Department of Maternal, Newborn, Child and Adolescent Health. “It can be easier for families who need to continue providing and caring for other children, and it allows vulnerable, malnourished children to stay home and avoid the risk of getting hospital infections.”

The proactive use of antibiotics is important because the immune system of a child who is severely malnourished can virtually shut down. This lack of immune response means both that the body cannot fight off infection and that tests may not detect infection, even when one is present. Evidence shows that giving a broad spectrum antibiotic such as amoxicillin enables the child’s body to fight off common infections like pneumonia and urinary tract infections which can be fatal to this group of children.

However, the new recommendation is specifically for children with severe acute malnutrition—not those who are simply undernourished. Widespread use of antibiotics among children who do not need them would increase the risk of infections becoming resistant to lifesaving antibiotics—a situation that would harm the health and survival of all children.

Severely malnourished children with HIV

Another new aspect of the guidelines relates to the treatment of severely malnourished children with HIV. The 1999 guidelines did not recommend HIV testing of children with severe acute malnutrition. At that time, there was poor availability and little experience of treating children with antiretroviral drugs. Circumstances today are very different. We now know that antiretrovirals significantly increase survival of children with HIV, and access to these drugs is improving. The new guidelines recommend that children with severe acute malnutrition in countries where HIV is common be routinely tested for the virus, and those who are positive should start on antiretroviral drugs as well as special foods and antibiotics to treat their severe malnutrition.

Infants under 6 months with severe acute malnutrition

The other group whose needs are addressed for the first time in these guidelines are infants under 6 months with severe acute malnutrition. WHO recommends that all babies under 6 months are exclusively breastfed for optimal nutrition and protection against infections. This is particularly important for babies who are severely malnourished. Health services should give special support to mothers of these infants to breastfeed as well as treating the child with antibiotics. If there is no realistic prospect of a severely malnourished baby being breastfed, the family may need breast milk from another woman, e.g. a family member, a neighbour, a wet nurse or a milk bank. If this is not possible, they will need infant formula and support to prepare and use it safely.

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

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Untreated cancer pain a 'scandal of global proportions,' survey shows

Nov. 27, 2013 — A ground-breaking international collaborative survey, published today in Annals of Oncology, shows that more than half of the world's population live in countries where regulations that aim to stem drug misuse leave cancer patients without access to opioid medicines for managing cancer pain.

The results from the Global Opioid Policy Initiative (GOPI) project show that more than 4 billion people live in countries where regulations leave cancer patients suffering excruciating pain. National governments must take urgent action to improve access to these medicines, says the European Society for Medical Oncology, leader of a group of 22 partners that have launched the first global survey to evaluate the availability and accessibility of opioids for cancer pain management.

"The GOPI study has uncovered a pandemic of over-regulation in much of the developing world that is making it catastrophically difficult to provide basic medication to relieve strong cancer pain," says Nathan Cherny, Chair of the ESMO Palliative Care Working Group and lead author of the report, from Shaare Zedek Medical Center, Jerusalem, Israel. "Most of the world's population lacks the necessary access to opioids for cancer pain management and palliative care, as well as acute, post-operative, obstetric and chronic pain."

"When one considers that effective treatments are cheap and available, untreated cancer pain and its horrendous consequences for patients and their families is a scandal of global proportions," Cherny says.

The study conducted in Africa, Asia, Latin America & the Caribbean and the Middle East assessed the availability of the seven opioid medications considered to be essential for the relief of cancer pain by the WHO Model List of Essential Medicines [3] and the International Association for Hospice and Palliative Care [4]. Those essential medications include codeine, oral oxycodone, transdermal fentanyl, immediate and slow release oral morphine, as well as injectable morphine, and oral methadone.

While there are problems with the supply of these medicines in many countries, the main problem is over-regulation that makes it difficult for healthcare professionals to prescribe and administer them for legitimate medical use, the authors say.

"This is a tragedy born out of good intentions," says Cherny. "When opioids are over-regulated, the precautionary measures to prevent abuse and diversion are excessive and impair the ability of healthcare systems to relieve real suffering. The GOPI study has uncovered over-regulation in much of the developing world."

"The next step is for international and local organizations working alongside governments and regulators to thoughtfully address the problems," adds study co-author James Cleary, Director of the Pain and Policy Studies Group and Founding Director of the Palliative Medicine at the UW Carbone Cancer Center, Madison, Wisconsin, USA.

"Regulatory reform must be partnered with education of healthcare providers in the safe and responsible use of opioid medication, education of the public to destigmatize opioid analgesics and improved infrastructure for supply and distribution," he says.

There are already concrete examples of countries reforming their policies to improve access to opioid medicines, the study authors say, among them the Ukraine, which previously had a limited opioid formulary. "Concerted efforts supported by the Open Society Institute, reports from Human Rights Watch, together with the investment in local clinical champions through programs such as the Pain and Policy Studies Group's (PPSG) International Pain Policy Fellowship (IPPF) Program, have led to the government approving the manufacture and distribution of immediate release oral morphine in the Ukraine with concurrent changes in policy," Cleary says.

"The ongoing initiatives to reform regulations, improve accessibility and promote the education of clinicians and consumers in the effective use of opioid medications for the relief of cancer pain will require vision, determination and the same spirit of cooperation between organizations that made this study successful. The challenges are great, but no greater than our resolution to the task of making pain relief for cancer patients a reality irrespective of geography. Governments should look at the GOPI survey data for their country and take concrete actions to reduce the barriers," Cherny concludes.

The "Global Opioid Policy Initiative project to evaluate the availability and accessibility of opioids for cancer pain management" is published as a Supplement of Annals of Oncology; free access available here: http://annonc.oxfordjournals.org/content/24/suppl_11.toc.

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