Monday, December 23, 2013

Can a Father's Diet Affect His Newborn's Health?

Can a Father's Diet Affect His Newborn's Health?
Fathers, like mothers, might need to watch their folic acid levels.
We've known for a long time that women who do not get enough folic acid in their diets from the very first weeks of pregnancy are at increased risk of having children with birth defects of the brain and spine, including spina bifida.

Now, however, comes the surprising news that low folic acid levels in fathers can also increase the risk. This isn't actually new; the link has been known for a while. But it's been hard to understand how this could work.
Mothers provide the environment for the developing fetus, including not only the roof over its head, so to speak, but the complex bath of chemicals in which it swims during pregnancy. It makes sense that altering that chemical soup—with a deficiency of folic acid, for example—would have consequences for the fetus. But the father's only direct connection with the fetus is a single tiny sperm cell. How could his diet have anything to do with the fetus?

In a new study in the journal Nature Communications, researchers at McGill University in Montreal say they've found a possible explanation. Diet can't alter the DNA in the sperm, but it can alter something else, leaving a telltale signature that can disrupt proceedings weeks later in the womb.

A man's diet, it turns out, alters the epigenetics of his sperm. The genes in the sperm carry all the hereditary characteristics that we're familiar with—eye color, height, and so forth. But the proper operation of those genes requires that they be turned on or off appropriately. Epigenetic markings are small molecules that can attach to genes and control whether or not they are turned on.

The McGill researchers now suggest that the link between fathers' folic acid levels and their children's risk of birth defects might be a consequence of diet altering these epigenetic markings in his sperm.

Does this mean men contemplating having children should take folic acid supplements? There’s no way yet to know. Researchers must do more work to establish with certainty what is going on, and at this point they have no way of predicting how much folic acid is enough to reduce the risk—if, indeed, further studies prove that the risk is real.

Nevertheless, the study is yet one more examples of how important fathers are in the lives of their children--often in ways, such as this, that no one could have predicted. This one came out too late for inclusion in my book Do Fathers Matter? What Science is Telling Us About the Parent We’ve Overlooked, (due out for Fathers Day, 2014), but you will see many similar studies there, including a more complete explanation of epigenetics and its role in many aspects of children’s health.

This is perhaps one of the most exciting new areas of research regarding fathers, and I’m following it closely and will be blogging on it here in the weeks and months to come.

CDC report shows danger at Camp Lejeune

The horror of Camp Lejeune, already one of the worst cases of drinking water contamination in American history, continues to grow. So does the shame of the U.S. Marine Corps.

Last week, the U.S. Centers for Disease Control and Prevention confirmed a long-suspected link between toxic chemicals in drinking water at the base and an increased risk of birth defects and childhood cancer.
The contamination stretches back decades, with exposure ending in 1987, when the Marine Corps closed the last of contaminated wells at the base.

Based on a survey of the parents of more than 12,000 children born at Lejeune between 1968 and 1985, the CDC concluded that pregnant women who drank tap water at the base were four times more likely to have babies with serious birth defects such as spina bifida. The study also found a slightly elevated risk for childhood cancers such as leukemia.

The study is limited in its findings. Researchers told The Associated Press that they were able to confirm only 52 cases of specific illnesses related to chemical exposure at Lejeune based on medical records. The cause can't be definitely shown for other birth defects and cancer diagnoses.

But the CDC study is the latest evidence of widespread health problems linked to leaks from a fuel depot at the base and a dry cleaner outside the base.

Although some of the contaminants were addressed in federal regulations dating to 1963, the Marine Corps repeatedly downplayed health problems at Lejeune over the years and didn't take action until 1985.

By that time, an estimated 1 million Marines and their families had been exposed.

Last year, President Barack Obama signed legislation expanding health care resources for those individuals. (Information on compensation claims for Lejeune veterans and their families can be found at the Department of Veterans Affairs website at

The compensation covers 15 health problems, including multiple forms of cancer. More than 80 men with connections to Lejeune have been diagnosed with a rare form of breast cancer.

For the Marine Corps and the VA, the mission remains much as it was before last week's news. They need to expedite claims and continue reaching out to veterans and their families and to any civilians who may have been exposed to carcinogens at the base.

Research also should continue on the extent of contamination. Among other things, the government needs to delve deeper into reports of problems related to storage of DDT and other insecticides in a building later used as a day care.

The government also must explore further when the contamination began. The legislation covers exposure beginning in 1957, but some research indicates at least one carcinogen may have been present as early as 1948.

Last week's CDC report was difficult but welcome news for Lejeune veterans and family members who've fought many years for answers.

The Marine Corps, the VA, the president and Congress need to continue working to address those concerns.

The loss of human life and the suffering cannot be reversed. But the Marine Corps can ensure it doesn't leave behind the men and women whose health was damaged at Lejeune.

Birth Defects Linked To Contaminated Marine Base Water

Birth Defects Linked To Contaminated Marine Base Water

By Sara Jerome
Contaminated water at a U.S. Marine Corps base in North Carolina may be a cause of neural tube defects (NTDs) in some children, according to a long-awaited study.

The study from the Centers for Disease Control found "associations between TCE and benzene in Camp Lejeune drinking water and NTDs," the report said.

Survey participants reported "35 NTDs, 42 oral clefts, and 29 childhood hematopoietic cancers," the study said. CDC "made extensive efforts to obtain medical information from health providers to confirm reported cases.  ATSDR was able to confirm 15 NTDs, 24 oral clefts, and 13 cancers."

The effects were observed "in children born from 1968 to 1985 whose mothers were exposed to contaminated drinking water in their residences at Camp Lejeune."

The study also observed "weaker associations" between "first trimester exposure to PCE, vinyl chloride, and 1,2- DCE," and childhood hematopoietic cancers such as leukemia.

According to the Associated Press, "a prior CDC study cited a February 1985 level for trichloroethylene of 18,900 parts per billion in one Lejeune drinking water well — nearly 4,000 times today's maximum allowed health limit of 5 ppb. Testing also found high levels of benzene, a fuel additive."

The contamination was caused by "a leaky on-base fuel depot and an off-base dry cleaner," the report said.
In the nearly 30 years since the contamination was first publicly disclosed, "military officials have repeatedly issued public statements downplaying health risks from drinking the tainted water prior to the closure of the most contaminated wells," the AP said.

The base kept using the wells for years even after tainted water was discovered, the AP reported. "The most highly contaminated wells were closed in 1984 and 1985, after a round of more extensive testing found dangerous concentrations of toxins associated with degreasing solvents and gasoline."

Lejeune spokeswoman Captain Maureen Krebs said in a statement published by Reuters that the Marine Corps has supported attempts to study the effects of the tainted water.

"These results provide additional information in support of ongoing efforts to provide comprehensive science-based answers to the health questions that have been raised," she said.

A law passed last year attempted to help those affected by the water. The law provides "medical care to former Marines and their dependents who were exposed to the contaminated wells between 1957 and 1987. The law covers 15 conditions including miscarriage, female infertility, leukemia, non-Hodgkin's lymphoma and several other forms of cancer," an editorial in Star News Online said.

People With Spinal Cord Injuries Prone To Premature Death: WHO Report

People With Spinal Cord Injuries Prone To Premature Death: WHO Report

12/3/2013 6:13 AM ET 
People with spinal cord injuries are two to five times more likely to die prematurely, with worse survival rates in low- and middle-income countries, says a new report by the World Health Organization (WHO).
As many as 500,000 people suffer a spinal cord injury each year, it is estimated. 

The report, titled "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.

The report 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, which falls on December 3.

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.

Up to 90 percent 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 accidents are the main contributor to spinal cord injury in the African Region (nearly 70 percent of cases) and the Western Pacific Region (55 percent of cases) and falls the leading cause in the South-East Asia and Eastern Mediterranean Regions (40 percent of cases). Non-traumatic spinal cord injury results from conditions such as tumors, spina bifida, and tuberculosis. A third of non-traumatic spinal cord injury is linked to tuberculosis in sub-Saharan Africa.

Most people with spinal cord injury experience chronic pain, and an estimated 20-30 percent 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 percent. 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 WHO's Department of Violence and Injury Prevention and Disability. "However, spinal cord injury is preventable, survivable, and need not preclude good health and social inclusion," according to him.
Essential measures for improving the survival, health and participation of people with spinal cord injury are detailed in the report. 

by RTT Staff Writer

Tuesday, August 13, 2013

Bone Marrow Cells Used in Bladder Regeneration


A new approach to bladder regeneration is capitalizing on the potential of two distinct cell populations harvested from a patient's healthy bone marrow, a new study reports.

The Northwestern Medicine® research, which will be published February 18 in the Proceedings of the National Academy of Sciences by lead author Arun K. Sharma, research assistant professor in urology at Northwestern University Feinberg School of Medicine and colleagues, is an alternative to contemporary tissue-engineering strategies. The bone marrow cells are being used to recreate the organ's smooth muscle, vasculature, and nerve tissue.

"We are manipulating a person's own disease-free cells for bladder tissue reformation," said Sharma, a member of the Institute for BioNanotechnology in Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago Research Center. "We have used the spina bifida patient population as a proof of concept model because those patients typically have bladder dysfunction. However, this regeneration approach could be used for people suffering from a variety of bladder issues where the bone marrow microenvironment is deemed normal."

In end-stage neurogenic bladder disease -- an illness often associated with spinal cord diseases like spina bifida -- the nerves which carry messages between the bladder and the brain do not work properly, causing an inability to pass urine. The most common surgical option, augmentation cystoplasty, involves placing a "patch" derived from an individual's bowel over a part of the diseased organ in order to increase its size. The current "gold standard," the procedure remains problematic because the bowel tissue introduces long-term complications like the development of electrolyte imbalance and bladder cancer.

Because Sharma's procedure does not use bowel tissue, it offers the benefits of augmentation without the association of long-term risks. His technique combines stem and progenitor cells from a patient's bone marrow with a synthetic scaffold created in the lab of Guillermo Ameer, ScD, professor of biomedical engineering at McCormick School of Engineering and Applied Science and of surgery at Feinberg. The scaffold takes the place of the traditional patch.

"We decided to use material that has the ability to be tailored to simulate mechanical properties of the bladder," said Sharma, director of pediatric urological regenerative medicine at Lurie Children's. "Using the elastomer created by Dr. Ameer and the bone marrow stem and progenitor cells, I believe that we have developed a technique that can potentially be used in lieu of current bladder augmentation procedures. However, further study is needed."

Follow-up to landmark spina bifida study could influence future treatment


HOUSTON — Almost 10 years ago, the Management of Myelomeningocele (MOMS) study began comparing two approaches to treatment for a serious form of spina bifida: prenatal surgery versus the standard postnatal repair.

This breakthrough study, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and published by the New England Journal of Medicine in 2011, found that children whose spina bifida defects were repaired surgically before birth were more likely to walk without the assistance of orthotics or devices.  NICHD is one of the Institutes of the National Institutes of Health.

Now, a follow-up study, also funded by NICHD and informally known as MOMS2, is being conducted to determine whether prenatal repair done in the original study influenced the adaptive behavior of these children, now 5 to 9 years of age, compared with those who underwent postnatal repair.

One of the effects in question is the brain development of these children. Jenifer Juranek, Ph.D., a neuroimaging expert with the Texas Fetal Center and the Children’s Learning Institute at The University of Texas Health Science Center at Houston (UTHealth), is performing high-resolution magnetic resonance imaging (MRI) brain sequences on 177 of the children from the original study to investigate if those who underwent prenatal surgery experienced greater structural modification in their brains than those infants who underwent postnatal surgery.

The follow-up brain imaging protocol was set up by Juranek at each of the three original MOMS study sites: Vanderbilt University in Nashville, Tenn., The Children's Hospital of Philadelphia, and the University of California at San Francisco. Each follow-up image will be analyzed and quantified by Juranek for such key development indicators as brain volume, matter integrity, synaptic pruning (i.e., when excess connections between cells are eliminated) and myelination, which enables nerve cells to transmit information faster and allows for more complex brain processes.

“Researchers have demonstrated that many neurodevelopmental disorders like spina bifida may be linked to poorly-timed cellular events during brain development. These events lead to specific structural and functional brain development,” said Juranek. “With this follow-up study, researchers can evaluate the impact different intervention strategies have on brain structure, function and behavior.”

The results of the MOMS2 study could influence future surgical procedures for babies diagnosed with myelomeningocele, says KuoJen Tsao, M.D., associate professor of pediatric surgery at UTHealth Medical School and a co-director of the Texas Fetal Center.

“The MOMS study gave us data that goes two or three years out from surgery, but we know there is a lot of development beyond that,” said Tsao. “We know there are certain short-term outcomes, but there may be some long-term neurological effects we don’t know about. What’s most exciting about the MOMS2 study is they are going to follow these patients at school age.”

One common risk associated with myelomeningocele is the buildup of fluid inside the skull that leads to brain swelling. This swelling is repaired with shunts inserted into the brain to relieve pressure. The original MOMS study found that prenatal surgery reduced the need for shunts, which may improve long-term brain development.

“Once you put in a shunt you have risks,” said Juranek. “Getting into the center of brain isn’t easy. If you put in a shunt, you are likely to cut through gray and white matter, both of which are responsible for certain brain functions.”

Tsao added, “The important thing about the MOMS2 study is it will answer questions that we are asking now. That’s where Dr. Juranek’s work is very important.”

Other follow-up testing will look at other development factors such as attention, executive function and fine and gross motor skills.

Air pollutants linked to higher risk of birth defects, researchers find

 David Miklos


BY ERIN DIGITALE - Breathing traffic pollution in early pregnancy is linked to a higher risk for certain serious birth defects, according to new research from the Stanford University School of Medicine.
The finding comes from a study examining air quality and birth-defect data for women living in California’s San Joaquin Valley, one of the smoggiest regions of the country. “We found an association between specific traffic-related air pollutants and neural tube defects, which are malformations of the brain and spine,” said the study’s lead author, Amy Padula, PhD, a postdoctoral scholar in pediatrics. The research appears online today in the American Journal of Epidemiology.

“Birth defects affect one in every 33 babies, and about two-thirds of these defects are due to unknown causes,” said the paper’s senior author, Gary Shaw, PhD, professor of neonatal and developmental medicine. “When these babies are born, they bring into a family’s life an amazing number of questions, many of which we can’t answer.”

The scientists studied 806 women who had a pregnancy affected by a birth defect between 1997 and 2006, and 849 women who had healthy babies during the same period. The study examined two types of neural tube defects (spina bifida, a spinal-column malformation, and anencephaly, an underdeveloped or absent brain); cleft lip, with or without cleft palate; cleft palate only; and gastroschisis, in which the infant is born with some of his or her intestines outside the body.

All women studied resided in an area of California known for poor air quality — the San Joaquin Valley — during the first eight weeks of their pregnancies, a window of time when many birth defects develop. The researchers asked each woman for her home address during this period and scored subjects’ exposure to air pollutants using data collected by the Environmental Protection Agency as part of federally mandated air-quality monitoring. The pollutants assessed included carbon monoxide, nitrogen oxide, nitrogen dioxide, particulate matter and ozone, as well as local traffic density.

After controlling for factors such as race/ethnicity, maternal education and multivitamin use, women who breathed the highest levels of carbon monoxide were nearly twice as likely to have a baby with spina bifida or anencephaly as those with the lowest carbon monoxide exposure, the study found. Nitrogen oxide and nitrogen dioxide exposures were also linked to increased risk for these defects; women with the highest nitrogen oxide exposure had nearly three times the risk of having a pregnancy affected by anencephaly than those with the lowest exposure, for example. Further studies are needed to examine the combined effects of multiple pollutants.

The quality of earlier research linking air pollution and birth defects has been hampered by the difficulty of getting reliable data on women’s exposure to pollutants. The new study is the first to assess women’s pollutant exposures in early pregnancy, when birth defects are developing, rather than at birth.

Further studies are needed to confirm the results of the new research and to examine other pollutants, as well as other types of birth defects, the researchers said.

“If these associations are confirmed, this work offers an avenue for a potential intervention for reducing birth defects,” Padula said.

“In addition, for our colleagues who are bench scientists, this work gives them an opportunity to think about what pollution exposures might mean mechanistically,” Shaw said. “It could give them a better understanding of the details of human development.”

Suzan Carmichael
, PhD, associate professor of neonatal and developmental medicine, was another Stanford co-author. Scientists at the University of California-Berkeley and at Sonoma Technology Inc. in Sonoma, Calif., were also involved in the work.

The study was funded by grants from the National Institute for Environmental Health Science (grant ES018173), the U.S. Environmental Protection Agency and the Centers for Disease Control and Prevention.

Information about Stanford’s Department of Pediatrics, which also supported the work, is available at
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For more information, please visit the Office of Communication & Public Affairs site at

Prescriptions for valproate not decreasing despite birth defect-causing concerns


A recent study shows that prescriptions for the antiepileptic drug valproate have not decreased in recent years even though the drug is known to cause severe birth defects and brain damage.
A new study indicates that women without epilepsy are four times as likely to be prescribed this drug as are women with epilepsy.

Led by Godfrey P. Oakley, Jr. MD, research professor at Emory's Rollins School of Public Health, a research team analyzed data from the National Hospital and Ambulatory Medical Care Surveys from 1996 to 2007 to examine valproate prescriptions for adolescent girls and adult women aged 14-45 years. Findings from the study concluded that 83 percent of valproate prescriptions were written for women without epilepsy, with 74 percent of those prescribed for psychiatric, non-epilepsy diagnoses and the remaining valproate prescriptions used for conditions such as pain, migraine and other non-epilepsy conditions.

"We were surprised to find that there was no decrease in the number of valproate prescriptions prescribed to women of reproductive-age  despite the numerous, less harmful antiepileptic drugs available and the proven evidence of valproate's harmful effects during pregnancy," says Oakley who is also the director of Emory's Center for Spina Bifida Research, Prevention, and Policy.
The complete study is published in the June 3, 2013 edition of the Birth Defects Research Part A—Clinical and Molecular Teratology journal.

"We believe that sharply reducing the use of valproate for reproductive-age women is an important step in preventing birth defects," explains Oakley.

Genes Involved in Birth Defects May Also Lead to Mental Illness


Gene mutations that lead to major birth defects may also cause subtle disruptions in the brain that contribute to psychiatric disorders such as schizophrenia, autism, and bipolar disorder, according to new research by UC San Francisco scientists.

By Jeffrey Norris

Over the past several years, researchers in the laboratory of psychiatrist Benjamin Cheyette, MD, PhD, have shown that mutations in a gene called Dact1 cause cell signaling networks to go awry during embryonic development. Researchers observed that mice with Dact1 mutations were born with a range of severe malformations, including some reminiscent of spina bifida in humans.
This new study was designed to explore whether Dact1 mutations exert more nuanced effects in the brain that may lead to mental illness. In doing so, Cheyette, John Rubenstein, MD, PhD, and colleagues in UCSF’s Nina Ireland Laboratory of Developmental Neurobiology used a genetic technique in adult mice to selectively delete the Dact1 protein only in interneurons, a group of brain cells that regulates activity in the cerebral cortex, including cognitive and sensory processes. Poor function of interneurons has been implicated in a range of psychiatric conditions.

Brain cells called interneurons, which regulate activity in the cerebral cortex, were
shown by UCSF researchers to form more complex branching patterns in normal
mice (left) in comparison to mice in which the gene encoding the protein Dact1
was knocked out (right).
As reported in the June 24 online issue of PLOS ONE, researchers found that the genetically altered interneurons appeared relatively normal and had managed to find their proper position in the brain’s circuitry during development. But the cells had significantly fewer synapses, the sites where communication with neighboring neurons takes place. In additional observations not included in the new paper, the team also noted that the cells’ dendrites – fine extensions that normally form bushy arbors studded with synapses – were poorly developed and sparsely branched.

“When you delete this gene function after initial, early development – just eliminating it in neurons after they’ve formed – they migrate to the right place and their numbers are correct, but their morphology is a little off,” Cheyette said. “And that’s very much in line with the kinds of pathology that people have been able to identify in psychiatric illness.

"Neurological illnesses tend to be focal, with lesions that you can identify or pathology you can see on an imaging study," Cheyette explained. "Psychiatric illnesses? Not so much. The differences are really subtle and hard to see.”

Key Gene's Role in Development of Human Nervous System

The Dact1 protein is part of a fundamental biological system known as the Wnt (pronounced “wint”) signaling pathway. Interactions among proteins in the Wnt pathway orchestrate many processes essential to life in animals as diverse as fruit flies, mice and humans, including the proper development of the immensely complex human nervous system from a single fertilized egg cell.

Benjamin Cheyette, MD, PhD
One way the Wnt pathway manages this task is by maintaining the “polarity” of cells during development, said Cheyette, “a process of sequestering, increasing the concentration of one set of proteins on one side of the cell and a different set of proteins on the other side of the cell.” Polarity is particularly important as precursor cells transform into nerve cells, Cheyette said, because neurons are “the most polarized cells in the body,” with specialized input and output zones that must wind up in the proper spots if the cells are to function normally.
Cheyette said his group is now conducting behavioral experiments with the mice analyzed in the new PLOS ONE paper and with genetically related mouse lines to test whether these mice have behavioral abnormalities in sociability, sensory perception, anxiety or motivation that resemble symptoms in major psychiatric disorders.

John Rubenstein, MD, PhD
He also hopes to collaborate with UCSF colleagues on follow-up experiments to determine whether the activity of neurons lacking Dact1 is impaired in addition to the structural flaws identified in the new study and prior published work from his lab.

Meanwhile, as-yet-unpublished findings from human genetics research conducted by Cheyette’s group suggest that individuals with autism are significantly more likely than healthy comparison subjects to carry mutations in a Wnt pathway gene called WNT1.

“Just because a gene plays an important role in the embryo doesn’t mean it isn’t also important in the brain later, and might be involved in psychiatric pathology,” said Cheyette. “When these genes are mutated, someone may look fine, develop fine and have no obvious medical problems at birth, but they may also develop autism in childhood or have a psychotic break in adulthood and develop schizophrenia.”

Rubenstein is the Nina Ireland Distinguished Professor in Child Psychiatry.
Additional study authors include postdoctoral scholars Xiaoyong Yang, PhD, Daniel Vogt, PhD, and Amelia Stanco, PhD, and graduate student and first author Annie Arguello. Yang and Stanco are supported by a postdoctoral training grant (T32) led by Judy Ford, PhD, to the UCSF Department of Psychiatry from the National Institute of Mental Health.

Arguello conducted this research while obtaining her PhD in the UCSF doctoral program in Biomedical Sciences (BMS), and was supported by the Initiative to Maximize Student Development Program of the National Institute of General Medicine, as well as by BMS, the UCSF Department of Psychiatry, and the Center for Neurobiology and Psychiatry led by Sam Barondes, MD, Jeanne and Sanford Robertson Endowed Chair in Neurobiology and Psychiatry.

New treatment may work with folic acid to prevent neural tube defects like spina bifida


Researchers at the UCL Institute of Child Health (ICH) are investigating a new treatment that could work alongside folic acid to boost its effectiveness and prevent a greater proportion of neural tube defects – such as spina bifida – in early pregnancy.

A new study published in the journal Brain shows that the new treatment, when tested in mice, reduced the incidence of neural tube defects (NTDs) by 85 per cent. This new approach was also successful in preventing some kinds of NTDs that are currently unresponsive to folic acid.
Researchers at the ICH, which is the research partner of Great Ormond Street Hospital for Children NHS Foundation Trust, believe the findings could make way for future trials in patients, to investigate whether the same level of prevention can be achieved for human NTDs.
NTDs such as spina bifida and anencephaly are still among the most common birth defects worldwide, affecting about 1 in 1,000 pregnancies with much higher rates in some countries.
Folic acid supplements taken in the very early stages of human pregnancy, when an embryo’s central nervous system is still developing, currently prevent a proportion of NTDs (20-80 per cent depending on geographic region). Folic acid works by helping the embryo’s neural tube to close normally, which is an essential step of development (failure of this process results in NTDs). However, a significant number of NTDs are unresponsive to folic acid supplements.
This nucleotide treatment could boost the effects of folic acid and offer expectant mothers an even more reliable safeguard against relatively common defects like spina bifida.
Professor Nicholas Green, Institute of Child Health
One reason why folic acid might not always be effective is that a ‘genetic blockage’ can occur in the way folic acid is handled, or metabolised, in cells. In such cases, even if folic acid is taken early in pregnancy it is blocked from having the desired effect on the embryo. The new treatment being tested at the ICH involves supplementing with ‘nucleotides’, which are needed to make DNA as cells divide in the growing embryo. Nucleotides can bypass the blockage in the way folic acid is handled, ensuring the growth of crucial cells in the embryo.

NTDs are likely to have many possible causes and the ICH team considers that the most effective way to reduce the risk of NTDs is to use a combination of different treatments. In previous studies they found that a particular vitamin, inositol, has a protective effect and this is being tested in a clinical trial.

Similar studies are now proposed for the ‘nucleotide’ treatment, and researchers envisage that a single tablet could eventually be developed for women planning a baby, which would contain folic acid and the new protective compounds.

Commenting on the new research, Nicholas Greene, Professor of Developmental Neurobiology at the ICH, said: “We are still in the early stages of this research, but we hope that these promising results in mice can eventually be replicated with human NTDs. If it is found to be effective, this nucleotide treatment could boost the effects of folic acid and offer expectant mothers an even more reliable safeguard against relatively common defects like spina bifida.”

Professor Greene added: “While we continue our research into this new treatment, it’s important to emphasise that folic acid supplements remain the most effective prevention against NTDs currently available for women who are planning a baby. While we are greatly encouraged by these new findings, I would strongly urge women to continue taking folic acid in its current form until we reach a point where additional supplements might become available.”

The new research has been funded by the Wellcome Trust, Medical Research Council and Newlife Foundation for Disabled Children, who also co-sponsored the establishment of the Newlife Birth Defects Research Centre at the UCL Institute of Child Health.

Monday, July 22, 2013

NKX2-8 Gene Mutation Linked To Spina Bifida

NKX2-8 Gene Mutation Linked To Spina Bifida

Neural tube defects affect more than 300,000 babies born around the world each year, according to the U.S. Centers for Disease Control and Prevention. Neural tube defects, including anencephaly and spina bifida, are caused by the incomplete closure or development of the spine and skull.

Using dogs as a model, researchers recently found that a gene related to neural tube defects in man's best friend may be an important risk factor for human neural tube defects. The cause of neural tube defects is poorly understood but has long been thought to be associated with genetic, nutritional and environmental factors.

Dogs provide an excellent biomedical model because they receive medical care comparable to what humans receive, share in a home environment and develop naturally occurring diseases that are similar to those found in humans. More specifically, several conditions associated with neural-tube defects are known to occur naturally in dogs. The DNA samples used in the study were taken from household pets, rather than laboratory animals.

The researchers carried out genome mapping in four Weimaraner dogs affected by spinal dysraphism, a naturally occurring spinal-cord disorder, and in 96 such dogs that had no neural tube defects. Spinal dysraphism, previously reported in the Weimaraner breed, causes symptoms that include impaired motor coordination or partial paralysis in the legs, abnormal gait, a crouched stance and abnormal leg or paw reflexes.

Analysis of a specific region on canine chromosome eight led the researchers to a mutation in a gene called NKX2-8, one of a group of genes known as "homeobox genes," known to be involved with regulating patterns of anatomical development in the embryo.

The researchers determined that the NKX2-8 mutation occurred in the Weimaraner breed with a frequency of 1.4 percent — 14 mutations in every 1,000 dogs.

Additionally, they tested nearly 500 other dogs from six different breeds that had been reported to be clinically affected by neural tube defects, but did not find copies of the NKX2-8 gene mutation among the non-Weimaraner dogs.

"The data indicate that this mutation does not appear as a benign mutation in some breeds, while causing defects in other breeds," said   Noa Safra, lead author on the study and a postdoctoral fellow in the laboratory of Professor Danika Bannasch in the UC Davis School of Veterinary Medicine. "Our results suggest that the NKX2-8 mutation is a 'private' mutation in Weimaraners that is not shared with other breeds."

The researchers say that identification of such a breed-specific gene may help veterinarians diagnose spinal dysraphism in dogs and enable Weimaraner breeders to use DNA screening to select against the mutation when developing their breeding plans.

In an effort to investigate a potential role for the NKX2-8 mutation in cases of neural tube defects in people, the researchers also sequenced 149 unrelated samples from human patients with spina bifida. They found six cases in which the patients carried mutations of the NKX2-8 gene but stress that further studies are needed to confirm whether these mutations are responsible for the diagnosed neural tube defects.

Citation: Noa Safra, Alexander G. Bassuk, Polly J. Ferguson, Miriam Aguilar, Rochelle L. Coulson, Nicholas Thomas, Peta L. Hitchens, Peter J. Dickinson, Karen M. Vernau, Zena T. Wolf, Danika L. Bannasch, 'Genome-Wide Association Mapping in Dogs Enables Identification of the Homeobox Gene, NKX2-8, as a Genetic Component of Neural Tube Defects in Humans', PLoS Genet 9(7): e1003646. doi:10.1371/journal.pgen.1003646

Wednesday, January 23, 2013

Pennridge powerlifting team muscles its way into the record books

Pennridge powerlifting team muscles its way into the record books

Sunday, January 06, 2013

Coach Steve Pattison, or “CP” for short, recruits Pennridge students for his powerlifting team by walking up to them in the school hallway and asking, “Hi, how are you? How much do you weigh?”

Unmoved by the brazen question, about 35 students and parents have joined CP in his gym in Perkasie for intense one- to two-hour lifting sessions four times a week. And whatever he’s doing, it’s working because the Pennridge powerlifting team has beaten not just school, state and regional records, but 26 world records. Going up against about 40 other countries, the team beat others and its own past world records in bench, squat, dead-lift and total — the best of all three — at the world championships in Las Vegas in 2012.

“Coming from a town like Perkasie, what these guys have accomplished really is unheard of,” CP said. “It’s just not done.”

The team is on its own for finances, which can add up to large amounts quickly. This year the team had to pay its way to Las Vegas, and two years ago team members paid their way to the Czech Republic.

Though the team does have some tall, brawny characters, the majority of them look like normal Pennridge students until they flex.

“It’s not necessarily a body builder strength,” CP said. “Your body does get bigger, harder, firmer but it’s more power. That’s what it’s all about.”

Danielle Tasher, a Pennridge student who weighs 97 pounds, can dead-lift 230 pounds, but no one would guess it with her petite frame.

Johnny Hess, a 92-pound member of the team with bright blue eyes, broad shoulders and a constant smile, can bench 135 pounds. What makes Hess even more impressive is that the 16-year-old sophomore can bench that much while paralyzed from the waist down, a result of spina bifida, a birth defect.

CP said usually your legs are your base of everything, your drive for power.

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Lack of Key Enzyme in the Metabolism of Folic Acid Leads to Birth Defects

Lack of Key Enzyme in the Metabolism of Folic Acid Leads to Birth Defects

Jan. 17, 2013 — Researchers at The University of Texas at Austin have discovered that the lack of a critical enzyme in the folic acid metabolic pathway leads to neural tube birth defects in developing embryos.

It has been known for several decades that folic acid supplementation dramatically reduces the incidence of neural tube defects, such as spina bifida and anencephaly, which are among the most common birth defects. In some populations, folic acid supplementation has decreased neural tube defects by as much as 70 percent.
However, scientists still do not fully understand how folic acid decreases neural tube defects, or why folic acid supplementation does not eliminate birth defects in all pregnancies.

"Now, we've found that mutation of a key folic acid enzyme causes neural tube defects in mice," said Dean Appling, professor of biochemistry in the College of Natural Sciences. "This is the clearest mechanistic link yet between folic acid and birth defects."

Appling and his colleagues published their research in the Jan. 8 issue of Proceedings of the National Academy of Sciences (PNAS).

The scientists made the discovery using mice that lack a gene for a folic acid enzyme called Mthfd1l, which is required for cells to produce a metabolite called formate. Embryos need formate to develop normally.
"This work reveals that one of the ways that folic acid prevents birth defects is by ensuring the production of formate in the developing embryo," said Appling, "and it may explain those 30 percent of neural tube defects that cannot be prevented by folic acid supplementation."

Appling said that the mice provide researchers with a strong model system that they can use to further understand folic acid and its role in birth defects in humans. In fact, humans share the same gene for the folic acid enzyme with the mouse and all other mammals. Indeed, it has recently been discovered that point mutations in that human gene increase the risk of birth defects.

Appling said that he and his colleagues would like to use the mouse system to begin looking for nutrients that could be delivered to pregnant mothers to prevent those neural tube defects that cannot be prevented by folic acid.

Ultimately, women could someday be screened for the gene that produces the enzyme. If they are deficient, steps could be taken to improve their chances for developing embryos free of neural tube defects through further nutrient supplementation.

Folic acid was discovered at The University of Texas at Austin in the 1940s by biochemists Esmond Snell and Herschel Mitchell. The U.S. has fortified all enriched cereal grain products with folic acid since 1996 to ensure that women of childbearing age receive adequate quantities of the vitamin.

Postdoctoral researcher Jessica Momb and graduate student Jordan Lewandowski were largely responsible for this research. Co-authors include graduate student Joshua Bryant, researcher Rebecca Fitch, researcher Deborah Surman, and Steven Vokes, assistant professor of biology.

Going for gold is Rachel's Rio dream for 2016

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Rachel Coady was courtside to watch Australia collect silver at last year's Paralympic Games, but when the Gliders go for gold in Rio in 2016 she wants to be in the game.

By then Coady hopes Canberra has a national league wheelchair basketball team to call its own.
The Australian women's wheelchair basketball team has been on the podium at the past four Paralympics, and has been in camp in Canberra this week to begin a four-year campaign towards Rio.

The Gliders have finished with three silver and one bronze from the past four Paralympics, but coach David Gould said he was determined to stack Australia's depth for a shot at gold in 2016.
The Gliders lost the Paralympic final to Germany in London and have already started plotting redemption in Rio.

''The idea of this camp is to start off our four-year journey to Rio, with that in mind we decided to bring in a lot of developing players,'' Gould said.

''We want to make our squad a lot deeper so as it comes up to the world championships and Rio Paralympics we've got some really tough decisions to make for the team.

''A few of the younger girls probably didn't handle the pressure in London because it was their first Paralympic final, but that's the idea behind trying to develop our squad even further now, to give as many of these girls as much international competition as possible.''

Coady, a silver medallist with Australia's Under 25 world championships team in 2011, was one of the development players invited to this week's camp in Canberra.

It was a rare privilege for the 24-year-old to train at home. There is no Canberra team in the Women's National Wheelchair Basketball League, comprising five teams across Sydney, Melbourne, Brisbane and Perth.

Teams are made up of athletes with varying disabilities, players given a classification from 1 to 4.5, points decreasing as the severity of the disability increases.

Coady, born with spina bifida, is classified as a 1 and commutes to Sydney to train and play with the Sydney University Flames.

''I go to Sydney twice a month for training, then come back here and try to do my best,'' she said. ''It'd be great to get a Canberra team, we're trying to find more players. But it could take a couple of years.''

Coady travelled much further to watch the Gliders at the Paralympics. ''I went to London with my mum to watch all the girls' games … it's great to go and support.''

Surgery establishes penile sensation in men with spina bifida

Surgery establishes penile sensation in men with spina bifida

December 28, 2012
By Chris Mc Cann, UW Health Sciences/uw Medicine
A procedure to establish feeling in the penis for men with spina bifida was performed for the first time in the United States in Seattle.

Tony Avellino, UW professor of neurological surgery, and Thomas Lendvay, a UW associate professor of pediatric urology who practices at Seattle Children’s Hospital, led the surgical team.

“This is truly an innovative procedure for either spina bifida patients or patients with lower-level spinal-cord injury who have sensation in the groin but not the penis,” said Avellino.

Lendvay noted that, “Based on the positive results of the first two patients, this new procedure has the potential to greatly improve the quality of life in our spina bifida adult and adolescent patients.”
People with spinal bifida were born with an incomplete closure of their backbone, often because the neural tube didn’t form correctly during early embryonic development. Even when the spine is surgically closed after birth, the spinal cord in the affected section may not work properly in conducting nerve impulses. The patient may have a combination of nerve function and loss. They may have paralysis or numbness in only some parts of their body, for example.

The new operation is known as “Tomax” (for TO MAX-imize sensation, sexuality and quality of life). The procedure entails transferring a branch of the nerve supplying sensation from the thigh skin to the main skin sensation nerve to the penis. The successful completion of the procedure allows men with spinal cord impairment to feel sensation in a previously insensitive penis and improve sexual health.

Max Overgoor from the University of Utrecht in The Netherlands had performed 18 successful operations when David Shurtleff, UW professor of pediatrics, invited him to Seattle to observe the first U.S. operation of this nature.
Lendvay and Avellino performed the procedure at Seattle Children’s Hospital in March 2009. Their first U.S. patient was a 19-year-old college student. At a recent follow-up appointment, the young man reported having erogenous penile skin sensation and enhanced sexuality over the course of  the past 18 months.
He said: “Before the surgery, I had no sensation at all. I found that sex was very frustrating and unsatisfying. Today, I have very good sensation. … I feel like a gained a body part that I was previously missing.”
Avellino and Lendvay performed two procedures (at Harborview Medical Center and UW Medical Center) on another patient who also experienced erogenous sensation where he had never before felt anything. This man reported, “It continues to improve my quality of life and makes me feel like I have a much more normal and complete body.”

Avellino said the success of this pioneering procedure is due to a truly multidisciplinary effort. “We can do innovative things here because we have experts from different specialties collaborating as a team. Pediatricians, spina bifida specialists, urologists and neurosurgeons — all working together.”
Lendvay added, “We are planning to collaborate with our Rehabilitation Medicine colleagues to expand this surgical opportunity to patients with traumatic spinal cord injury.  We also hope to explore the role such surgery may have in female patients with spinal cord lesions.”

In October, Lendvay presented one of the surgical videos at the American Academy of Pediatrics meeting in New Orleans during the “Innovative Procedures in Pediatric Urology” panel. Avellino and Lendvay have submitted a video of the most recent procedure to the American Urological Association annual meeting, which will be held May 4–8, 2013, in San Diego, Calif.

For more information about the procedure, read Overgoor’s article in the Journal of Urology, “Increased Sexual Health After Restored Genital Sensation in Male Patients with Spina Bifida or a Spinal Cord Injury: the TOMAX Procedure.”


American College of Obstetricians and Gynecologists recommends counseling for prenatal spina bifida surgery

American College of Obstetricians and Gynecologists recommends counseling for prenatal spina bifida surgery

Published On: 1/21/2013 2:48:37 PM

IMNG Medical News

Breaking News

Certain pregnant women who are carrying a fetus with severe spina bifida should be counseled about the potential benefits and risks of maternal-fetal surgery, according to the American College of Obstetricians and Gynecologists.

The ACOG Committee on Obstetric Practice recently recommended counseling about maternal-fetal surgery for myelomeningocele, the most severe form of spina bifida, following promising results from the procedure in an 8-year randomized controlled trial (Obstet. Gynecol. 2013;121:218-9).

In the Management of Myelomeningocele Study (MOMS), prenatal repair before 26 weeks of gestation reduced the need for a shunt at 12 months and also decreased the rate of hindbrain herniation by one-third at 12 months of age. The procedure also doubled the rate of independent walking and produced higher levels of functioning than were expected based on anatomic levels (N. Engl. J. Med. 2011;364:993-1004).

But the study, which was sponsored by the National Institutes of Health, also found significant maternal and fetal risks. For example, the surgery was associated with high rates of preterm birth, fetal bradycardia, oligohydramnios, placental abruption, pulmonary edema, maternal transfusion at delivery, and an increased incidence of uterine thinning.

ACOG cautions that the MOMS trial used stringent inclusion criteria and rigorous requirements for the experience of the surgeons involved. As a result, outcomes from the trial should be considered a "best-case scenario," the committee members wrote. They urged physicians to use the same inclusion criteria as the researchers when considering which women to counsel about the maternal-fetal surgery. The criteria were a singleton pregnancy, myelomeningocele with the upper boundary between T-1 and S-1, evidence of hindbrain herniation, gestational age between 19.0 and 25.9 weeks, and a normal karyotype. The major exclusion criteria included a fetal anomaly unrelated to the myelomeningocele; severe kyphosis; risk of preterm birth; a maternal body mass index of 35 kg/m2 or more; and contraindications to surgery, including previous hysterotomy in the active uterine segment.

Women should also be counseled about the implications of the surgery for future pregnancies, the ACOG committee recommended.

"It is a highly technical procedure with potential for significant morbidity and possibly mortality, even in the best and most experienced hands," they wrote. "Maternal-fetal surgery for myelomeningocele should only be offered at facilities with the expertise, multidisciplinary teams, services, and facilities to provide the intensive care required for these patients."

The study authors declared that they received funding from the National Institutes of Health. One of the authors reported receiving funding from Vanderbilt University in Nashville, Tenn.