Common Genetic Factors That Affect Autism Risk Have Been Identified

The first common genetic risk factor for autism spectrum disorder has been identified by a multi-center team of researchers that included Margaret Pericak-Vance, Ph.D., director of the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine.

Dr. Pericak-Vance and her collaborator Jonathan Haines, Ph.D. at Vanderbilt University Medical Center, joined the results of their study with those of Hakon Hakonarson, Ph.D., from Children’s Hospital of Philadelphia. The findings from the breakthrough study published online April 28 by the journal Nature may implicate a gene involved in forming the connections between brain cells. .

“Until now, no common genetic variant has been identified with such overwhelming evidence to support its role in autism spectrum disorders,” said Pericak-Vance, “The identification of a common variant for autism is a monumental achievement. Researchers have been looking for clues about the genetic architecture of autism for decades. Many thought that this day would never come, but we persisted.” .

The study included investigators from more than a dozen sites and participation of more than 10,000 subjects, including individuals with autism spectrum disorder, their family members and other volunteers from across the United States. .

“Each research team conducted a genome-wide association study of individuals with autism and controls, and found a significant association between autism and a region on chromosome 5 that is near two genes known as CDH9 and CDH10,” said Dr. Haines, lead investigator of the research team from Vanderbilt and director of the Vanderbilt Center for Human Genetics Research, “Both genes encode cadherins which are cell surface proteins thought to be important for establishing connections between cells in the developing brain and are candidate genes that may contribute to autism.” .

“Although no single gene is responsible for autism, cadherin is one of several proteins that affect the stability and maturation of nerve synapses in the brain, therefore this is an intriguing candidate for this region,” said John P. Hussman, Ph.D., one of the co-investigators in the research. “This discovery is important not only in its own right, but also because it offers important clues about specific biological processes we should investigate.” .

Since individuals with autism are so diverse, some researchers believed a common risk variant would never be found, but the advent of genome wide technology changed everything. “We’ve known that technology would evolve to where identification of the hardest to find genetic risk variants would be possible,” said Pericak-Vance. .

Haines added, “We also knew that the technology would require large numbers of patient participants as well as the tools and expertise to analyze data. We stayed invested and stayed on the cutting edge; it has paid off.” .

The study published in Nature reflects the collaborative efforts of research teams from the University of Miami Miller School of Medicine, Vanderbilt, Children’s Hospital of Philadelphia, the University of Washington in Seattle, and the University of California, Los Angeles. The institutions combined resources and datasets to achieve the genome-wide significant results. .

An independent publication in the Annals of Human Genetics details all the findings from the complete genome-wide study conducted by the University of Miami and Vanderbilt Medical Center on their independent datasets. Summary results from the candidate region on chromosome 5 were included in the Nature publication as they further support the overall finding. Deqiong Ma, M.D., Ph.D. is co-first author of both publications; other key authors on both publications are Michael L. Cuccaro, Ph.D., John R. Gilbert, Ph.D., and Daria Salyakina, Ph.D. from the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine. .

Autism is among a spectrum of disorders and is a neurodevelopmental disorder characterized by three primary areas of impairment: social interaction, communication, and restricted and repetitive patterns of interest or behavior. Recent prevalence studies suggest that autism spectrum disorders may affect as many as 1 in 150 children in the United States, making it one of the most common neurodevelopmental disorders. .

Funding for the autism research conducted at the Miami Institute for Human Genomics and the Center for Human Genetics Research at Vanderbilt University comes from the National Institutes of Health and specifically from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, from Autism Speaks, and from the Hussman Foundation. Dr. Pericak-Vance is the Dr. John T. Macdonald Professor of Human Genetics.

Miller School of Medicine – University of Miami

Teaching Autistic Children To Safely Cross The Road Using Virtual Reality

Recent research conducted at the University of Haifa found that children with autism improved their road safety skills after practicing with a unique virtual reality system. “Children with autism rarely have opportunities to experience or to learn to cope with day-to-day situations. Using virtual simulations such as the one used in this research enables them to acquire skills that will make it possible for them to become independent,” said Profs. Josman and Weiss, from the Department of Occupational Therapy at the University of Haifa.

The independence of children with autism depends on their receiving treatment in natural settings. One of the main problems they face is their inability to learn how to safely cross the street, a necessary skill for independent living. While acquiring this skill could greatly improve these children’s independence, most of the methods for teaching street-crossing have been designed for use within the classroom, and they have been shown as insufficiently effective among autistic children.

The best way to teach children with autism skills is through repeated practice in natural settings, but the danger of learning to cross the street in a natural setting obviously prohibits this method. This is where virtual reality is very effective, as demonstrated by the research team which included Hadass Milika Ben-Chaim, then a student in the Occupational Therapy master’s program and Shula Friedrich, the principal of the Haifa Ofer School for Children with Autism as well as Profs. Josman and Weiss.

Six autistic children, ages 7-12, spent one month learning how to cross virtual streets, to wait for the virtual light at the crosswalk to change and to look left and right for virtual cars using a simulation programmed by Yuval Naveh. The children in the study showed substantial improvement throughout the learning process: at the beginning of the study, the average child was able to use the 2nd level of the software while by the end they mastered the 9th level, which is characterized by more vehicles traveling at a higher speed.

However, the research team was not looking to teach a virtual skill; they wanted to see if the children were able to transfer the skills they had mastered in a virtual environment to the real world. A local practice area with a street and crosswalk, complete with traffic signals, was used for this purpose. The children’s ability to cross the street safely was tested in this area evaluating, for example, whether they stopped to wait on the sidewalk or waited for a green light before crossing. The children were brought to the practice area before and after their virtual learning. Here too, the children exhibited an improvement in their skills, following the training on the virtual street, with three of the children showing considerable improvement.

One of the study participants, 16 years old, had participated in the past in a road safety program in the school, but he was not able to learn how to cross the street safely. Following learning the skill in a virtual environment, he learned how to stop on the sidewalk before stepping into the street, to look at the color of the traffic light, to cross only when the light was green and to cross without waiting too long.

“Previous studies have shown that autistic children respond well to computer learning. In this research we learned that their intelligence level or severity of their autism doesn’t affect their ability to understand the system and therefore this is an important way to improve their cognitive and social abilities,” summarized Profs. Josman and Weiss.

Source: Amir Gilat

University of Haifa

Getting Patients To Take Their Asthma Meds

Armed with the right information, physicians can play a stronger role in ensuring asthma patients don’t waver in taking drugs proven to prevent asthma attacks, according to researchers at Henry Ford Hospital in Detroit.

The study finds patients are more likely to routinely take inhaled corticosteroids (ICS) for asthma control when physicians kept close watch over their medication use and reviewed detailed electronic prescription information, including how often patients fill their prescriptions and the estimated number of days each prescription would last.

“Better inhaled corticosteroid adherence means better overall asthma control, and less hospitalization,” says lead study author L. Keoki Williams, M.D., MPH, Center for Health Services Research and Department of Internal Medicine at Henry Ford Hospital.

“Unfortunately, overall patient adherence to ICS medication is poor, accounting for an estimated 60 percent of asthma hospitalizations. So it’s important, as we move forward with health care reform, to look for more effective ways to make sure patients stay with their prescription regimens.”

The study – the first large-scale, controlled study to test the effectiveness of routinely providing patient medication adherence information to physicians – appears online in the Journal of Allergy and Clinical Immunology.

ICS, taken using an inhaler, help prevent and reduce airway swelling, and are considered the cornerstone therapy for controlling persistent asthma in patients, says Dr. Williams.

The Henry Ford scientific team set out to design an intervention that would provide physicians information on the most recent national asthma guidelines and methods for discussing medication non-adherence with their patients.

The intervention also offered physicians electronic access to patients’ medication prescription fill/refill information via Henry Ford’s ePrescribing application, part of its electronic medical record system that allows physicians to prescribe and review patient medications electronically.

The study enrolled 193 Henry Ford primary care physicians (family medicine, internal medicine, pediatrics). Eighty-eight were randomly assigned to the intervention group, while 105 were assigned to the control group (no intervention).

Physicians in the intervention group used ePrescribing to track medication fills and refills. The application also offered physicians the option to take it one step further: To review detailed adherence data, including estimates of the proportion of time that the patients took their medication.

Medication adherence for both groups was measured by using both electronic prescriptions and pharmacy claims for medication fills and refills.

Researchers found ICS adherence to be very similar among patients in the intervention group and those in the control group (21.3 percent vs. 23.3 percent).

But adherence was significantly higher in the intervention group (35 percent) when the patient’s physician elected to view detailed adherence information via the ePrescribing application.

Few physicians, however, in the intervention group accessed the detailed adherence information. “Going forward, one of the obstacles will be finding time for physicians to review and discuss this information with patients in their typically busy practices,” says Dr. Williams.

Funding: Henry Ford Hospital; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Disease; National Institutes of Health; and Strategic Program for Asthma Research of the American Asthma Association.

Krista Hopson
Henry Ford Health System

Diet, Obesity, And Asthma Linked

Australian researchers have identified a new protein in human airway epithelial cells that regulates allergic airway inflammation. This protein – adipocyte/macrophage fatty acid-binding protein aP2 – is known to regulate the uptake by fat cells of fatty acids and has been previously linked to insulin resistance in diabetes and the development of atherosclerosis. This new study suggests that in addition to its role in type 2 diabetes and hardening of the arteries, aP2 plays an essential role in allergic airway diseases such as asthma, and offers an additional intriguing link between the immune and metabolic systems. The study will appear online on July 13 in advance of print publication in the August issue of the Journal of Clinical Investigation.

The “hygiene hypothesis” currently dominates thinking in the medical field about the underlying causes of asthma. The hypothesis proposes that childhood infection and environmental factors such as diet and airborne pollution contribute to a predisposition to this condition. Michael Rolph and colleagues from The Garvan Institute of Medical Research, Sydney, now show for the first time that the protein aP2 is present in human epithelial cells lining the tubes that carry air from the windpipe to the lungs (bronchi), and that aP2 expression is significantly increased when these cells are stimulated with the molecules interleukin-4 and -13. This finding is very unexpected as aP2 has previously been considered to be a specific marker for fat cells. The group went on to show that mice lacking aP2 have a dramatic reduction in airway inflammation in a model of asthma. In addition, the infiltration into the airways of inflammatory molecules such as leukocytes and eosinophils was highly dependent on aP2 function in mice. The data emphasize the importance of lipids in the inflammatory response and contribute to the emerging theme that an overlap exists between the pathways that regulate inflammation and those that govern metabolism. Finally, the study suggests that blocking aP2 function may be a novel approach for the treatment of asthma and other inflammatory lung diseases.

TITLE: The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation


Michael S. Rolph
The Garvan Institute of Medical Research, Sydney, NSW, Australia.


Gokhan S. Hotamisligil
Harvard School of Public Health, Boston, Massachusetts, USA.
Email: ghotamishsph.harvard.

View the PDF of this article at: https://the-jci/article.php?id=24767

Contact: Brooke Grindlinger

Journal of Clinical Investigation

WFP Partners With UNRWA To Assist Palestinian Refugees In Lebanon

The United Nations World Food Programme (WFP) announced today that
it will provide technical assistance to support an emergency operation in
Lebanon mounted by the United Nations Relief and Works Agency for Palestine
Refugees in the Near East (UNRWA). The operation will assist people
displaced by the ongoing clashes in two of the largest Palestinian refugee
camps, al-Hilwah and Nahr al-Bared.

At the request of UNRWA, WFP has deployed three staff to provide help in
logistics, communications and coordination of assistance among partners.

On Monday (4 June), UNRWA issued a flash appeal for US$12.6 million to
assist an estimated 27,000 people displaced from the Nahr al-Bared camp.
The agency estimates that most of the camp’s population has fled, seeking
shelter with relatives, in UNRWA schools or in the nearby Beddawi camp,
where living conditions are now seriously threatened as the population has
more than doubled – to 37,000. Those still remaining in Beddawi camp are
without adequate water and sanitation.

“We are concerned for the safety and welfare of thousands of refugees both
inside Beddawi camp as well as those who have fled to other areas; many
are still without power, medical help or supplies,” said Naila Sabra, WFP’s
Regional Director for the Middle East, Central Asia and Eastern Europe.
“WFP is working closely with UNRWA and the UN country team to reach those
in need,” she added.

Since fighting broke out in Nahr al-Bared camp near the northern city of
Tripoli on 20 May, thousands of civilians have fled the camp with only the
belongings they could carry. Clashes erupted earlier this week in a second
camp, al-Hilwah, near the southern city of Sidon.

Although WFP closed its office in Lebanon in October 2006 after concluding
a three-month emergency operation, it has maintained a national liaison
officer in Beirut who is monitoring the situation, liaising with UN and
other counterparts and participating in emergency preparedness activities,
including inter-agency contingency planning processes.

From late July to October 2006, WFP provided food assistance to over
810,000 Lebanese who were affected by the bombing of their country last

WFP is the world’s largest humanitarian agency: on average, each year, we
give food to 90 million poor people to meet their nutritional needs,
including 58 million hungry children, in 80 of the world’s poorest
countries. WFP — We Feed People.

Biologic Agents For The Treatment Of Rheumatoid Arthritis Are Used By Less Than 3% Of Patients On First-Line And Less Than 4% On Second-Line

Decision Resources, one of the
world’s leading research and advisory firms focusing on pharmaceutical and
healthcare issues, finds that although biologic agents used for the
treatment of rheumatoid arthritis are approved for first-line use, they are
actually used by less than 3% of patients on first-line treatment and less
than 4% on second-line treatment. According to the new report entitled
Treatment Algorithms in Rheumatoid Arthritis, this limited penetration is
due primarily to payer restrictions on reimbursement; patients must often
fail therapy on methotrexate before the high cost of biologics will be
reimbursed by health care plans. Therefore, substantial revenue opportunity
for conventional disease-modifying antirheumatic drugs (DMARDs) remains in
early lines of therapy.

Until January 1, 2006, when the Medicare Prescription Drug,
Improvement, and Modernization Act (MMA) went into effect,
Centocor/Schering-Plough/Tanabe Seiyaku’s Remicade held a reimbursement
advantage over other TNF-alpha inhibitors because, under previous Medicare
regulations, self-administered injectable drugs were not reimbursable.

“Despite Remicade’s advantage to Medicare subscribers, Amgen/Wyeth’s
Enbrel still managed to capture an equal percentage of first- and
second-line patient shares, and has greater use than Remicade in third-line
patient share,” said Dr. Madhuri Borde, analyst at Decision Resources.

Treatment Algorithms for Rheumatoid Arthritis allows pharmaceutical
organizations to quantify lines of therapy through primary research and
patient-level data. Users can:

Understand current treatment patterns and anticipate future market

Drive product growth through accurate knowledge of a product’s
positioning among the lines of therapy and why physicians use it at that

Target specific competitors that are preceding or following a product
and benefit from actionable analysis of the path to treatment and
physicians’ decision parameters.

Develop more sophisticated market-forecasting patient-flow models
based on unique, accurate information regarding the percentage of patients
receiving a product at specific stages in the line of therapy.

About Treatment Algorithms Insight Series

Decision Resources combines in-depth primary research with the most
extensive claims-based longitudinal patient-level data from PharMetrics(R)
to provide exceptional insight into physicians’ prescribing trends and the
factors that drive therapy product choice, from diagnosis through multiple
courses of treatment, for a specific disease.

For each disease examined, Decision Resources’ Treatment Algorithms
Insight Series provides:

Summary of U.S. medical practice based on interviews with leading
experts in the field.

Qualitative diagnosis/referral/treatment algorithm for the United

— Drug usage by lines of therapy (1st, 2nd, 3rd line).

— Discussion of key freeform combinations by lines of therapy.

— Product share (class and specific compound level) within each line of
therapy (1st, 2nd, 3rd line).

— Progression of therapy from key 1st line products.

— Pathway to key therapies from previous therapies.

— Qualitative analysis of 2-year forecast incorporating upcoming
launches, changes in reimbursement, etc.

About Decision Resources

Decision Resources, Inc., (DecisionResources) is a world leader
in healthcare market research publications, advisory services, and
consulting designed to help clients shape strategy, allocate resources, and
master their chosen markets.

All company, brand, or product names contained in this document may be
trademarks or registered trademarks of their respective holders.

Decision Resources

View drug information on Enbrel; Remicade.

A ”Yes/No” Blood Test For Alzheimer’s?

For every person with Alzheimer’s disease, there are many more-loved ones, healthcare providers, social workers, volunteers, and advocates-whose lives are directly or indirectly touched by this illness. Because the causes of the disease are unknown and there is currently no cure, Alzheimer’s poses enormous challenges for physicians and researchers. Therefore, early, definitive detection may ultimately be as important as treatment or a final cure.

Currently, the gold standard of Alzheimer’s detection is a “probable diagnosis” that involves analyzing the symptoms of the disease, followed by ruling out other possible causes. Patients are usually evaluated by the “Mini Mental State Examination” (MMSE), family/medical history, and possibly brain scans. The status quo for the detection of the disease, however, may soon change thanks to a new blood serum test for neurodegenerative diseases, called NuroPro.

“Proteins, or biomarkers, in the blood hold the key to the diagnosis of many illnesses, including neurodegenerative diseases,” said Dr. Ira Goldknopf, a recognized pioneer and leader in proteomics, and the Director of Proteomics at Power3 Medical. “By monitoring the concentration of several proteins in blood serum, researchers have shown that the NuroPro test can accurately detect and distinguish between Alzheimer’s disease, Lou Gehrig’s disease, and Parkinson’s disease.”

Some may argue that without a cure, early diagnosis is futile and may do more harm than good. There are a number of treatments, however, that can slow the progress of the disease and ease its detrimental effects. Some medicines may help control behavioral symptoms of Alzheimer’s such as sleeplessness, agitation, wandering, anxiety, and depression. Treating these symptoms often makes patients more comfortable and makes their care easier for caregivers.

“Early detection of Alzheimer’s will allow physicians to intervene at an early stage to delay disease progression,” said Dr. Goldknopf. “Tests such as these have the potential to allow patients to outlive their debilitating symptoms.”

Definitive detection may also help researchers develop better Alzheimer’s treatments. In the near future, drug makers may utilize the biomarker profiles developed by Power3 Medical to help halt the disease. Drug makers and physicians may someday also use NuroPro to monitor the progression or regression of the disease while the patient is undergoing treatment, minimizing the trial-and-error potential in drug therapy and providing for a more targeted, individually tailored approach.


New Effort To Save Lives Of Mothers And Newborns In Bangladesh Gains Support From UK, EC And UN Agencies

The United Kingdom, the European Commission (EC) and three United Nations agencies are assisting Bangladesh in a major new effort to save lives and improve the health and well-being of mothers and newborns.

Agreements signed last week launched a five-year project intended to dramatically increase the use of quality health services. With support worth $31.2 million from the UK Department for International Development (DFID) and the EC, the project will be jointly implemented, starting next month, by the Government, UNFPA, the United Nations Population Fund, the UN Children’s Fund (UNICEF) and the World Health Organization (WHO).

Despite significant recent progress, far too many Bangladeshi women still give birth without skilled assistance or access to lifesaving emergency services. As a consequence, maternal and neonatal deaths remain high, respectively estimated at 320 and 4,100 per 100,000 live births.

In line with the national health strategy and effort to achieve Millennium Development Goals 4 and 5, the new project aims to improve community health practices and to strengthen, diversify and increase demand for public services, with a focus on reaching the poor and excluded. The goal is to reduce maternal deaths by 15 per cent and neonatal deaths by 25 per cent, saving some 885 mothers and 24,000 newborns during the life of the project.

Starting in four districts and eventually expanding to 20, the initiative will test innovative ways to address deadly delays in seeking and receiving obstetric care, including voucher schemes for poor households.

On 7 June, representatives of the three participating United Nations agencies signed a memorandum of understanding, and the representatives of UNFPA and DFID signed a funding agreement. Senior officials from Bangladesh’s Ministry of Health and Family Welfare witnessed the signing.


Alzheimer’s Disease May Be Easily Misdiagnosed

New research shows that Alzheimer’s disease and other dementing illnesses may be easily misdiagnosed in the elderly, according to early results of a study of people in Hawaii who had their brains autopsied after death. The research is being released today and will be presented as part of a plenary session at the American Academy of Neurology’s 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

“Diagnosing specific dementias in people who are very old is complex, but with the large increase in dementia cases expected within the next 10 years in the United States, it will be increasingly important to correctly recognize, diagnose, prevent and treat age-related cognitive decline,” said study author Lon White, MD, MPH, with the Kuakini Medical System in Honolulu.

For the study, researchers autopsied the brains of 426 Japanese-American men who were residents of Hawaii, and who died at an average age of 87 years. Of those, 211 had been diagnosed with a dementia when they were alive, most commonly attributed to Alzheimer’s disease.

The study found that about half of those diagnosed with Alzheimer’s disease did not have sufficient numbers of the brain lesions characterizing that condition to support the diagnosis. Most of those in whom the diagnosis of Alzheimer’s disease was not confirmed had one or a combination of other brain lesions sufficient to explain the dementia. These included microinfarcts, Lewy bodies, hippocampal sclerosis or generalized brain atrophy.

However, diagnoses of Lewy body dementia and vascular dementia were more accurate. Misdiagnoses increased with older age. They also reflected non-specific manifestations of dementia, a very high prevalence of mixed brain lesions, and the ambiguity of most neuroimaging measures.

“Larger studies are needed to confirm these findings and provide insight as to how we may more accurately diagnose and prevent Alzheimer’s disease and other principal dementing disease processes in the elderly,” said White.

The study was supported by the National Institute on Aging and the Department of Veterans Affairs.

This research will be presented as part of the Contemporary and Clinical Issues and Case Studies Plenary Session on Wednesday, April 13, 2011, at the 2011 American Academy of Neurology’s Annual Meeting in Honolulu.

Source: American Academy of Neurology (AAN)

Asthma Management Chart Updated, Australia

The National Asthma Council Australia has released an updated version of the popular
‘Managing Your Asthma’ wall chart, which is designed to help health professionals discuss
asthma medications with patients.

The new wall chart features up-to-date colour photographs of 43 different asthma
medications available in Australia today.

Each product is shown next to its current packaging for at-a-glance recognition and is
grouped according to its classification. Relievers, non-steroidal preventers, corticosteroid
preventers, symptom controllers and combination medications, as well as inhalers used in
COPD, are all highlighted.

The original version of the chart was produced by the Townsville Division of General Practice
which has collaborated with the National Asthma Council in the subsequent versions. In 2005
and again in 2006, an unrestricted educational grant from Merck Sharp & Dohme has
enabled the National Asthma Council to update and reissue the Chart, making it available
nationally, at no cost.

The latest version of the chart features an expanded collection of products and vastly
superior photography to ensure the product colours on the chart exactly match the real thing.

Distribution of the updated ‘Managing Your Asthma’ wall chart will commence this month. It
will be particularly relevant to general practitioners, pharmacists, thoracic physicians, asthma
educators, allergists and practice nurses.

National Asthma Council Australia Limited
1 Palmerston Crescent
South Melbourne, Vic 3205