Image credit: Skin care on the back via Shutterstock

Use of sunscreen is about more than just preventing painful burns. A single sunburn during childhood nearly doubles the risk of melanoma — a particularly aggressive and serious type of skin cancer — in adulthood [2], and reports indicate that at least half of all children experience at least one sunburn by age 11 [3].

Sunlight is crucial to life on Earth. Without the sun’s radiant energy, the planet would be an uninhabitable chunk of ice. Visible light from the sun fuels photosynthesis, the process by which plants make sugar from the molecules carbon dioxide and water. This provides food for herbivores and omnivores, which in turn provide food for higher consumers.

In essence, the sun is the ultimate source of food energy on the planet. Even the sun’s damaging rays — those in the ultraviolet region of the light spectrum — serve important purposes with regard to health and wellness. For instance, humans make vitamin D when ultraviolet light hits the skin.

Ultraviolet light, however, falls into the category of ionizing radiation, which means that it (like x-rays and like gamma radiation, which comes from nuclear reactions) is capable of breaking chemical bonds in molecules. When ultraviolet light hits the skin, it penetrates a short distance. The light can then break chemical bonds in biological molecules, including skin proteins and genetic material, or DNA. The former leads to the visible signs of aging associated with excess sun exposure, such as wrinkles and sagging skin. The latter ultimately leads to skin cancer.

One of the body’s natural protection mechanisms against overexposure to ultraviolet light is increased production of melanin, which is a chemical that makes the skin darker in color and helps protect the cell from further damage to DNA. For this reason, some people consider a tan protective against the sun, or even healthy. Darkening of the skin in response to sunlight, however, while protective to some extent, is also indicative of damage to the skin cells. It’s a bit like the body’s way of closing the barn door after (some of) the cows get out, since it takes cellular damage to stimulate the cell to produce more of the protective chemical melanin. Unfortunately, tans are seen as attractive. According to the Pediatrics study, the percent of children reporting liking to have a tan increased from 54 to 67% percent between 2004 and 2007, which could at least partially explain the decreased use of sunscreen during that same period of time.

As part of an effort to educate children and their parents about the damaging effects of the sun, the American Cancer Society promotes the slogan “Slip! Slop! Slap! And Wrap!” In longer form, the slogan reads: “Slip on a shirt, slop on sunscreen, slap on a hat, and wrap on sunglasses.” The Pediatrics findings, however, suggest that this message may not be reaching preadolescent children. The authors recommend finding new ways of encouraging sun-safe behavior in this demographic.

References

1. Dusza et al. Prospective Study of Sunburn and Sun Behavior Patterns During Adolescence. Pediatrics 2012;129:309–317.
2. Dennis et al. Sunburns and risk of cutaneous melanoma: does age matter? A comprehensive meta-analysis. Ann Epidemiol. 2008 Aug;18(8):614-27.
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3. Cokkinides et al. Trends in sunburns, sun protection practices, and attitudes toward sun exposure protection and tanning among US adolescents, 1998-2004. Pediatrics. 2006 Sep;118(3):853-64.
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The campaign, launched in August 2011, features provocative television and outdoor advertisements around metro Atlanta seeking to raise public awareness of the childhood obesity crisis [1]. The hospital justifies the harsh nature of the ads by citing the many serious health issues associated with childhood obesity. These include heart disease, high blood pressure, and type 2 diabetes. Linda Matzigkeit, a senior vice president at Children’s Healthcare who leads the system’s wellness projects, told The Atlanta Journal-Constitution that the campaign’s harsh tone was necessary [2]:

We felt like we needed a very arresting, abrupt campaign that said: “Hey, Georgia! Wake up. This is a problem.”

The obesity epidemic in the United States isn’t limited to Georgia — or to children — but it’s more severe in the South than in other parts of the country. Further, while Americans are becoming fatter across age brackets, obesity in children is particularly problematic because it sets children up for a lifetime of health problems. According to the CDC, childhood obesity rates have been skyrocketing over the past two decades. In 1996, just over 20% of public school children in sixth grade were overweight. By 2003, this number had risen to 43%, half of whom were obese [3]. The report goes on to state that in the last five years, obesity rates have actually fallen a bit among school children, but that this trend is strongly associated with income and race. Minority children and those from poorest families have experienced the smallest drop in obesity.

Opponents of the Georgia ad campaign object to the ad’s negativity, claiming that they could impact the already low self-esteem of an overweight or obese child. However, proponents of the ads counter with the logic that a blow to the self-esteem is minor compared to the significant health consequences of childhood obesity. Children’s Healthcare of Atlanta explains that their targeted research shows children don’t see the ads as “bullying,” and want to be talked to directly about the problem.

References

1. Children’s Healthcare of Atlanta Launches Provocative Awareness Campaign to Combat Childhood Obesity. Children’s Healthcare of Atlanta. 2011 Aug 23.
2. Grim childhood obesity ads stir critics. Atlanta Journal-Constitution. 2012 Jan 1.
3. CDC. Obesity in K–8 Students — New York City, 2006–07 to 2010–11 School Years. MMWR Morb Mortal Wkly Rep. 2011 Dec 16;60:1673-8.
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Young girl pouring pills image via Shutterstock

“Up and Away and Out of Sight” encourages parents to follow some basic principles for keeping medications out of the hands of children:

• Keep prescription medications, over-the-counter medications, and vitamins out of reach of children, and in a place where the children can’t see the medications.

• Put medications away in an out-of-sight, out-of-reach place every time they’re used, even if another dose will be necessary in a few hours’ time.

• Listen for the “click” of a properly locked safety cap when closing medication.

• Teach children what medication is, and that they must not take it on their own. It’s important to avoid referring to medication as “candy” or a “treat.”

• Make sure visitors put their bags, purses, and anything else that contains medication out of reach of children.

• Call Poison Control in the case of a suspected or known medication overdose.

While many parents recognize that prescription medication can be dangerous in the case of an accidental ingestion or overdose, fewer realize that over-the-counter medication overdoses can have harmful or fatal consequences. For instance, acetaminophen — the ingredient in Tylenol — can lead to irreversible and catastrophic liver damage if too much is taken. Acetaminophen overdoses are particularly common in children, because the ingredient is present in many different over-the-counter medications, and parents or caregivers may not think to cross check all the medications they’re giving for a child’s symptoms. Further, parents or caregivers can unintentionally overdose a child in the event that they don’t communicate with one another about when a dose of medication was last given.

Until recently, acetaminophen was available in two different pediatric formulations: one for babies, and one for toddlers and older children. The infant formulation was administered by dropper, and was much more concentrated than the older child formulation, which was consequently administered in larger doses. A parent used to using the weaker formulation could inadvertently overdose a child by giving the same volume of the much stronger infant formulation. The FDA was originally planning to discuss the safety of Infant Tylenol, but several drugmakers — including Johnson & Johnson — preempted any formal action by announcing a decision to discontinue over-the-counter infant drops of medications that contain acetaminophen in May of 2011 [2]. This came amid a number of product recalls in 2011 as J&J was looking to restore brand confidence.

Because the FDA did not take formal action on the acetaminophen formulation issue, manufacturers are still free to make infant-strength acetaminophen formulations. Parents should therefore double-check the strength and dosage of acetaminophen — or any other medication — before administering it to children.

References

1. Many young children overdosing from medicines at home. U.S. Centers for Disease Control and Prevention press release. 2011 Dec 13.
2. OTC Industry Announces Voluntary Transition to One Concentration of Single-Ingredient Pediatric Liquid Acetaminophen Medicines. Consumer Healthcare Products Association. 2011 May 4

Researchers at the University of Toronto recently performed a meta-analysis of three Finnish studies and found that children who chewed gum — or took other products laden with xylitol, including lozenges or syrup — had about a 25% lower risk of developing an ear infection compared to controls. The study is published in the Cochrane Database of Systematic Reviews [1].

Acute ear infections are the most common bacterial infections suffered by children in the United States and are the leading reason for antibiotic prescriptions. Such extensive use of antibiotics is extremely expensive, costing almost $3.8 million USD annually, and may contribute to the rise of antibiotic resistance among pathogenic strains of bacteria. Thus alternate treatments are desirable. A research group at the University of Toronto recently compiled a number of studies evaluating a daily dose of xylitol for the prevention of acute middle ear infections in children without acute upper respiratory infections attending day care centers.

Their literature search, which included randomized controlled trials, quasi-randomized controlled trials, unpublished studies, technical reports, dissertations, and abstracts from annual meetings, turned up eighty-four potential studies. Of these, only four met their eligibility criteria. All four were randomized controlled trials performed with 3,103 Finnish children in day care and published between 1998 and 2007.

They found that among healthy children, 8-10 g per day of xylitol in any form — gum, lozenges, or syrup — reduced the incidence of acute ear infections by 25% compared to children in the control group. Gum was notably the best (in the studies, children chewed two pieces of gum five times a day after meals for at least five minutes). However, since peak incidence of ear infection occurs when children are between six months and one year old, when they are too young to chew gum, the finding that other delivery methods can also work are valuable.

However, despite the significant preventative effect in healthy children, xylitol did not reduce the occurrence of acute ear infections in those children who already had acute upper respiratory tract infections. And although xylitol has been known to cause stomach distress, no adverse affects were reported by any children included in these studies.

The authors warn that since they only analyzed a few studies, and those were peformed by the same research group with a very homogenous group of children, they had insufficient data to generate any kind of treatment guidelines, such as how much xylitol is necessary or sufficient to prevent acute ear infections. But since chewing any kind of gum has also been found to boost mental performance and enhance alertness [2,3], perhaps teachers will be more tolerant of it in the classroom.

Ear infection risk factors

Ear infections are more likely to occur in the fall and winter when colds and flu are prevalent. Additional factors that put children at higher risk for ear infection include:

• Age (children between the ages of 6 months and 2 years are more susceptible to ear infections because of the size and shape of the eustachian tubes)
• Air quality (exposure to tobacco smoke or high levels of air pollution can increase the risk of ear infection)
• Allergies can cause inflammation in the airways and may contribute to ear infections
• Bottle-fed babies may have a higher risk for ear infections than breastfed babies
• Day care (close and frequent exposure of children to other children can pose a risk for ear infections)
• Ethnicity (American Indians and Inuits of Alaska and Canada have an increased risk of ear infections)
• Family history (the risk of ear infections increases if another member of the family has had ear infections)

References

1. Azarpazhooh et al. Xylitol for preventing acute otitis media in children up to 12 years of age. Cochrane Database Syst Rev. 2011 Nov 9;11:CD007095.
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2. Smith A. Effects of chewing gum on cognitive function, mood and physiology in stressed and non-stressed volunteers. Nutr Neurosci. 2010 Feb;13(1):7-16.
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3. Johnson et al. Chewing gum moderates multi-task induced shifts in stress, mood, and alertness. A re-examination. Appetite. 2011 Apr;56(2):408-11. Epub 2011 Jan 11.
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Folic acid is one of the many vitamins pregnant women need to take in order to ensure normal fetal development. In fact, it may be the most critical prenatal supplement, both because many women don’t consume enough folic acid in food, and because deficiencies can lead to serious developmental problems, including neural tube defect, which is associated with spina bifida.

Researchers from the Norwegian Institute of Public Health, Oslo, and colleagues carried out a study to investigate whether a woman’s use of folic acid supplements was associated with a reduced risk of severe language delay among offspring at 3 years of age. The scientists tracked the use of folic acid supplements and other supplements in nearly 40,000 expectant women and followed up with them and their children at 3 years of age. They found that children of women who took other supplements — but no folic acid — were significantly more likely than children of women who took folic acid alone, or folic acid in combination with other supplements, to have severe language delay.

Folic acid is one of the B vitamins; specifically, it’s vitamin B9. In reality, there are several different forms of the vitamin, where folic acid is the form most commonly found in supplements. There are many different folic acid derivative chemicals, collectively called “folates,” which are found in foods and which are the forms used by the human body. Because they’re less stable than folic acid, however, they’re generally not used to produce supplements. Still the human body can use the folic acid in supplements to make physiologically active folates. Chemically-speaking, folates are coenzymes, and are critical participants in reactions in the body that involve amino acids and nucleic acids (biological molecules essential for life that include DNA and RNA).

While folic acid supplementation is recommended throughout pregnancy, it’s actually most critical in a pregnancy’s earliest days. The neural tube, a structure that eventually becomes the brain and spinal cord, develops during the third week post-conception (the fifth week of pregnancy). Because this crucial developmental step takes place so early, many women are not yet aware that they’re pregnant. Further, low folic acid status can be subclinical (that is to say, it’s possible to be somewhat deficient in folic acid without realizing it). Consequently, the American Academy of Pediatrics recommends that all women of childbearing years who could potentially become pregnant take 4 mg of folic acid daily [2].

While the importance of folic acid supplementation pre-conception and during early pregnancy has been known for some time, the Norwegian study is the first to scientifically evaluate whether folic acid supplementation continues to have an impact on neural development beyond the formation of the neural tube. The large size of the study and great significance of the results (the difference in outcomes between the groups was large) indicate that folic acid likely continues to play important developmental roles beyond the end of the fifth week of pregnancy. The researchers did not attempt to determine how long women needed to continue taking folic acid supplements in order for their children to reap the benefits; the women included in the “folic acid supplementation” group took folic acid supplements from at least four weeks prior to conception through at least eight weeks after conception, but they were not told to stop taking supplements after that time, and many may have continued to do so. As such, it’s wise to continue folic acid supplementation throughout pregnancy in order to maximize its potential benefits to fetal development.

References

1. Roth et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011 Oct 12;306(14):1566-73.
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2. Folic acid for the prevention of neural tube defects. American Academy of Pediatrics. Committee on Genetics. Pediatrics. 1999 Aug;104(2 Pt 1):325-7.
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The children in the study who appeared to have difficulty grasping the fundamental concept of exact numerical quantities — that the printed numeral 3, for example, represents three dots on a page — went on to be diagnosed with math learning disability by fifth grade.

Other early factors correlated with a math learning disability were difficulty recalling answers to single-digit addition problems, distractibility in class, and difficulty understanding that more complex math problems can be broken down into smaller problems that can be solved individually.

Although the math learning disabled children did make limited progress in subsequent grades, by fifth grade they had not caught up to their typically achieving peers in the ability to recall number facts or in their ease of adding sets of dots and numerals together. The authors note that the math disabled students did catch up in other areas, such as the use of counting to solve problems.

The study was not designed to prove cause and effect, so the researchers do not know whether the factors they identified caused the children’s math learning disability or were linked to other, unidentified factors.

Kathy Mann Koepke, Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the study, said:

The search for factors underlying difficulty learning mathematics is extremely important. Once we identify such factors, the hope is that we can modify them through appropriate teaching methods to help people who have difficulty learning and using math.

Dr. Mann Koepke directs the NICHD’s Mathematics and Science Cognition and Learning Development and Disorders program. She said:

Math skills are important for higher education and for entry into many higher paying technical fields. Math skills have many health implications. For example, many American adults lack even the basic math skills necessary to estimate the appropriate number of calories in their diets or to calculate the time intervals at which to take their medications.

The study was conducted by Mary K. Hoard, Ph.D., Lara Nugent, Drew H. Bailey and David C. Geary, Ph.D., all of the University of Missouri, Columbia. Their findings appear in the Journal of Educational Psychology [1].

The researchers’ analysis was based on a battery of tests they gave one to three times each year to 177 students at 12 Columbia, Missouri, public schools. The testing process took place from kindergarten through fifth grade. The researchers measured several factors:

1. math achievement
2. reading ability
3. intelligence and general cognitive ability
4. paying attention in class
5. working memory, the ability to hold one idea or concept in mind while switching between tasks
6. an understanding of numbers and their relation to each other
7. understanding of the number line
8. aptitude for solving simple and complex addition problems

The researchers classified the students into three groups based on their early achievement and the subsequent progress they made in math from kindergarten to fifth grade. One group — referred to as typically achieving students — had average scores in kindergarten and developed their skills at an average rate during their early school years (132 students). Low-achieving students had an average score in kindergarten and made inconsistent and slow progress (29 students). Students with a low initial score and consistently slow progress were described as learning disabled with regard to math (16 students).

After their analysis, the researchers found that differences between groups in kindergarten scores were correlated with the result of one test in particular. For this test, students were asked to look at a series of rectangles, resembling dominoes, on a computer screen. Each domino was each divided into two or three areas; some areas contained one to nine dots, and others a written numeral. Students were asked to quickly circle any dominos in which the number of dots, together with the numeral, matched the target number and to not circle those that did not match.

The researchers found that the difference in scores from this test was linked to the overall gap in math scores between typically achieving and math learning disabled groups.

Dr. Geary said:

Our findings suggest that children who generally struggle with math — the low achievers — may have a poor sense of numbers, but they can narrow the achievement gap in part because most of them can memorize new math facts and, thus, learn some aspects of math as quickly as their typically achieving peers.

He added that, in contrast to the low achievers, students with a math learning disability not only have a poor concept of numbers, but also have difficulty memorizing math facts.

Clarifying the factors that contribute to a math learning disability may lead to the development of teaching methods that help students overcome difficulties with number concepts and skills, Dr. Mann-Koepke said. It is important to identify potential difficulties early, when chances for successfully overcoming them are greatest.

Other NICHD-funded investigators have also identified basic risk factors for math learning disability. These researchers have shown that math skills are linked to the approximate number system, a person’s intuitive ability to estimate quantities or identify the approximate number in a set. One study of grade school children showed that this ability is impaired in children with a math learning disability. A related study showed that difficulty with estimating such quantities is apparent in children as young as 3 and is correlated with later poor math performance in school. Researchers do not yet know if the ability to distinguish between small, exact quantities is related to the approximate number system.

Source: NIH News

References

1. Geary et al. Mathematical cognition deficits in children with learning disabilities and persistent low achievement: A five year prospective study. Journal of Educational Psychology. In press.

Poland points out that the current anti-vaccination movement, which is by no means unique in history, looks particularly unfavorably upon the measles, mumps, and rubella (MMR) vaccine. This is largely due to a since-retracted study published in the Lancet journal by Andrew Wakefield [2], which suggested a causal link between the MMR vaccine and autism. In his commentary, Poland emphasizes that there are more than 20 well-conducted studies that show no link between MMR and autism, and that scientific societies unilaterally agree that there is no reason to suspect such a link. Nevertheless, fear of autism and other serious adverse reactions to vaccines is having a significant impact upon public health in the United States. Indeed, just this week, inaccurate statements about the HPV vaccine causing mental retardation made the headlines.

As more and more children are withheld from vaccination, the risk of contracting the disease for which they were to be immunized increases. Last year, researchers determined that children whose parents refused the chickenpox vaccine have an 8-fold increased risk of catching the virus compared to fully immunized children.

One of the arguments used by opponents of vaccination is that the diseases for which children are routinely vaccinated aren’t serious, but the adverse reactions associated with vaccines are. U.S. Centers for Disease Control and Prevention (CDC) data, however, demonstrate otherwise. Measles is incredibly communicable — prior to the advent of vaccination, almost 100% of the U.S. population got the disease — and isn’t as innocuous as opponents of vaccination claim. As many as 20% of measles cases in the U.S. result in hospitalization, and six percent of total cases result in pneumonia, which is the major cause of measles-related death. Approximately three of every 1000 individuals infected with measles die.

Reactions to the MMR vaccine, on the other hand, are largely innocuous by comparison. While as many as one in six people vaccinated will experience a fever, these vaccine-related fevers are mild, short-lived, and have no lasting effects. Other mild reactions to the vaccine include a rash (about 5% of those vaccinated) and swelling of lymph nodes. Seizures as a result of the vaccine are considered a more serious consequence, but are very rare, at one in 3000 doses (or one ninth the risk of death from measles infection). Serious reactions include allergy, which happens in less than one in 1,000,000 vaccinations, and debilitating seizures or brain damage, which happen too rarely to quantify and, in fact, are so rare that there’s no way to be sure these events are the result of the vaccination at all. By the numbers, a given individual is many times more likely to die of the measles than to have even a moderate reaction to the vaccine.

The importance of the MMR vaccine, however, doesn’t end with self-interest and personal safety. Vaccines work in two ways: they help to protect the vaccinated individual from infection, and they reduce the likelihood that the disease in question can spread through a population by helping to produce herd immunity.

Because measles is so contagious, 96% of the population must be vaccinated to secure herd immunity, explains Poland. As anti-vaccination sentiment continues to spread, the United States is losing herd immunity, as evidenced by the measles cases reported in the early part of 2011 [3]. In the first six months of this year alone, there have been three times as many measles cases reported as normally seen in an entire year in the U.S. Particularly at risk are babies too young to be vaccinated, as the first dose of MMR isn’t given until an infant is 12 months of age. To leave a vaccine-eligible individual unvaccinated doesn’t just threaten that individual; it threatens the entire community — especially the community’s most vulnerable individuals.

Interestingly enough, anti-vaccine sentiment isn’t new in a historical context. Anti-vaccination movements have gained popularity periodically since the very first laws requiring vaccination, including the Vaccination Act of 1853 that required inoculation of children in the United Kingdom. Public health officials and researchers have noticed that anti-vaccination movements often follow a pattern in which a researcher attempts to explain an otherwise poorly-understood medical phenomenon by tying it to vaccination. While these anti-vaccination studies are generally poorly conducted and irreproducible, they nevertheless ignite fear in the public when they’re reported, and lead to a reduction in vaccination rates. The disease for which vaccination rates have decreased then experiences a resurgence, which results in many avoidable deaths, until such time as the public regains confidence in the vaccine. Examples of epidemics produced as a result of this repeating pattern include the smallpox epidemic in Stockholm in 1873 [4], the pertussis epidemic in the 1970s in the U.K. [5], and the Netherlands measles epidemic of 1999 [6].

Poland suggests that vaccine denialist propaganda does a public disservice, and recommends that it may be time to consider legislating vaccinations for the public good, and to protect vulnerable members of the population. He notes that while anti-vaccination movements call for more research, continued investigation into vaccine safety — particularly with regard to the well-established MMR vaccine — represents a misallocation of limited research dollars, because of the incredible scientific consensus regarding vaccine safety.

References

1. Poland. MMR Vaccine and Autism: Vaccine Nihilism and Postmodern Science. Mayo Clin Proc. 2011 Sep;86(9):869-71.
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2. Wakefield et al. Ileal-lymphoid-nodular hy- perplasia, non-specific colitis, and pervasive developmental disorder in children [retracted in: Lancet. 2010;375(9713):445]. Lancet. 1998;351(1903):637-641.
3. Centers for Disease Control and Prevention (CDC). Measles: United States, January–May 20, 2011. MMWR Morb Mortal Wkly Rep. 2011 May 27;60(20):666-8.
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4. Nelson et al. The right to die? Anti-vaccination activity and the 1874 smallpox epidemic in Stockholm. Soc Hist Med. 1992 Dec;5(3):369-88.
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5. Gangarosa et al. Impact of anti-vaccine movements on pertussis control: the untold story. Lancet. 1998 Jan 31;351(9099):356-61.
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6. Centers for Disease Control and Prevention. Measles outbreak–Netherlands, April 1999-January 2000. MMWR Morb Mortal Wkly Rep. 2000 Apr 14;49(14):299-303.
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Neurofibromatosis (NF) is a genetically-inherited disorder that causes tumors to grow on nerve tissue. There are three main types of NF tumors: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. NF1 is the most frequent of the three tumor types affecting one in every 3,000 people. The severity of symptoms range from benign ‘cafe au lait’ patches on the skin, to small dermal tumors on the surface of the skin, to larger “plexiform” neurofibromas that are associated with deep nerve structures, to malignant tumors of the nerve sheath.

Previous studies have shown that loss of the gene neurofibromin (Nf1) during mouse embryo development causes defects in bone and cartilage development [2-3]. One of the observed changes was an increase in the expression of the transcription factor SRY-BOX 9 (SOX9), which regulates cartilage differentiation and was recently found to be highly expressed in NF1-related tumors supporting cell survival [4]. German researchers hypothesized that some of the cartilage specific genes regulated by SOX9 might prove to be relevant biomarkers of NF1 tumors. They tested this hypothesis by analyzing expression of the SOX9 target gene melanoma-inhibitory activity (MIA) in tumor and serum samples from NF1 patients.

In a mouse Nf1 model, Mia was expressed at higher levels than in control mice. In humans, MIA was expressed in all tumors from NF1 patients. MIA serum level was determined in 42 NF1 patients and in 22 healthy individuals. Linear regression analysis revealed an association between total internal tumor load and the number of subcutaneous tumors (i.e. tumors under the skin).

Serum levels were significantly higher in NF1 patients than in healthy controls. MIA serum levels were significantly higher in NF1 patients with plexiform neurofibromas and with high tumor load than in patients without such tumors. Notably, MIA serum levels correlated significantly with internal tumor burden. The data indicate that elevated MIA serum level may be indicative of an increased internal tumor load.

Since there was an observed association between total internal tumor load and the number of plexiform tumors, a larger study will be necessary to reveal the relative contributions of internal, subcutaneous and possibly also cutaneous tumors to elevated MIA levels. Provided that the correlation can be confirmed in a larger cohort of NF1 patients, MIA could be a valuable biomarker for internal tumor load.

References

1. Kolanczyk et al. MIA is a potential biomarker for tumor load in neurofibromatosis type 1. BMC Med. 2011 Jul 4;9(1):82. [Epub ahead of print]
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2. Kolanczyk et al. Multiple roles for neurofibromin in skeletal development and growth. Hum Mol Genet 2007, 16:874- 886.
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3. Elefteriou et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab 2006, 4:441-451.
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4. Miller et al. Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med 2009, 1:236-248.
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Diagnoses of Attention Deficit Hyperactivity Disorder (ADHD), like those of food allergies, have risen dramatically in children over the last few generations. And again like food allergies, the cause is unclear. However, a team of researchers in England recently identified a genetic link for the disorder [1]. The study, published in The Lancet, found that children with ADHD were more likely to have small segments of their DNA duplicated or missing than other children that don’t have the disorder.

ADHD is one of the most common mental health disorders in childhood, affecting approximately 2% of children [2]. It is characterized by intense motor restlessness, problems with concentration and radical impulsivity. While it’s known that ADHD is highly heritable, there hasn’t been an identification of specific susceptibility genes until this study. Researchers compared the genomes of children with ADHD to healthy controls and found chromosomal duplications and deletions in the ADHD group.

In theory, we each have two copies of every gene: one on the chromosome from our mother and the other on the chromosome from our father. In reality, however, this isn’t necessarily the case. The Human Genome Project revealed that Copy Number Variations (CNVs) — the presence of more or less than two copies of a region of DNA due to its duplication or deletion — is quite widespread in humans. CNVs have been shown to be associated with a number of human maladies, including cancer, susceptibility or resistance to HIV infection, and notably, neurodevelopmental disorders and intellectual disabilities.

The genomes of 366 white British children (316 boys and 50 girls) with ADHD between the ages of 5 and 17 were included in the study, which took place between 2001 and 2009. Children with neurological disorders like schizophrenia, Tourette’s syndrome, autistic spectrum disorders or epilepsy were excluded from the study. These disorders are known to have higher rates of CNVs and researchers did not want to bias the study; they wanted to be sure that any extra CNVs they saw were due solely to ADHD. Control genomes came from 1,047 British men and women born during one week in 1958. The study was then repeated with an Icelandic population — 825 patients with ADHD and 35, 243 controls — to independently confirm the results.

The scientists looked for large CNVs spanning at least 500 kilobases of DNA as these are the easiest to detect accurately and are known to be associated with neurodevelopmental disorders. Children with ADHD exhibited twice as many large CNVs as controls, both deletions and duplications. The excess was most apparent in, but not limited to, children who had intellectual disabilities (IQ lower than 70) along with ADHD. There were some CNVs in the ADHD children that overlapped with regions of the genome implicated in autism spectrum disorders. Six duplications observed in patients with ADHD span a region of the genome known to be involved in schizophrenia. No duplications of this region were found in controls; however, a deletion was observed in one control individual.

This region is located on the short arm of chromosome 16 and contains seven genes. One of them — nuclear distribution gene E homologue 1 (NDE1) — is particularly interesting because it plays a role in neurodevelopment and interacts with disrupted in schizophrenia 1 (DISC1), a gene implicated in schizophrenia and other major psychiatric disorders that encodes a protein also involved in neurodevelopment. Duplications in this region have also been detected in patients with autistic spectrum disorders and intellectual disabilities. Although ADHD is currently thought to be completely separate from schizophrenia and autism, there is some overlap in terms of clinical symptoms and cognitive deficits. These recent findings suggest there is a shared biological basis to these disorders.

The researchers note that they do not intend for children to be screened for these CNVs as a means of diagnosing ADHD — there are rigorous clinical assessments for that. Rather, they set out to demonstrate that ADHD clearly is a genetic disease and that the brains of children with ADHD are different from those without it.

Dr. Anita Thapar, Professor of Child and Adolescent Psychiatry at Cardiff University School of Medicine who led the study, said [3]:

We hope that these findings will help overcome the stigma associated with ADHD. Too often, people dismiss ADHD as being down to bad parenting or poor diet. As a clinician, it was clear to me that this was unlikely to be the case. Now we can say with confidence that ADHD is a genetic disease and that the brains of children with this condition develop differently to those of other children.

References

1. Williams et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet. 2010 Oct 23;376(9750):1401-8. Epub 2010 Sep 29.View abstract
2. Franke et al. Genome-wide association studies in ADHD. Hum Genet. 2009 Jul;126(1):13-50. Epub 2009 Apr 22.View abstract
3. ADHD’s genetic link. Cardiff University News Centre. 2010 Sep 30.

Celiac disease is a genetic digestive disorder triggered by consumption of the protein gluten, which is found in bread, pasta, cookies, pizza crust and many other foods containing wheat, barley or rye. Researchers now report that there is a factor independent of diet that contributes to oxidative stress in celiac disease patients; children with celiac disease have higher than normal levels of two oxidative DNA damage biomarkers, regardless of what they eat [1].

Celiac disease is an autoimmune disease in which the consumption of gluten — a protein found in all forms of wheat, including spelt, kamut, semolina and triticale, as well as in barley and rye — induces an inflammatory reaction that destroys the gut. It occurs in almost 1% of the population, although in the United States as many as 97% of cases remain undiagnosed. Most autoimmune diseases are thought to be caused by an interaction between a genetic predisposition and an environmental trigger, but celiac disease is the only one for which the environmental trigger is known: gluten.

Normal intestine vs celiac disease

The inner surface of our small intestine is folded up and down into fingerlike projections, called villi or villus, to increase the surface area available for absorbing nutrients. In people with celiac disease, the presence of gluten causes inflammation that flattens these villi so that nutrients cannot be absorbed. This explains the highly varied clinical symptoms that can be suffered by patients with celiac: anemia because of the lack of iron, brittle bones because of the lack of calcium, gastrointestinal distress and failure to thrive. Fortunately, complete elimination of gluten from the diet, while quite onerous, can halt the inflammation and reverse any damage it has caused.

Increased production of the proinflammatory cytokines interferon gamma (IFNG) and Tumor Necrosis Factor alpha (TNF) have been observed in patients with active celiac disease. These cytokines can produce a large amount of reactive oxygen species, which oxidatively damage DNA. Oxidatively damaged DNA may be used as a marker for predicting later cancer development. Two recent studies have shown an increased risk of cancer for patients with celiac disease, especially for B- and T-cell lymphoma, a type of cancer involving lymphocytes (cells of the immune system) [2-3]. In the present study, scientists aimed to quantify the level of oxidatively damaged DNA in children with celiac disease [1]. None of the children had histories of cancer or any chronic inflammatory disease.

Oxidative DNA damage in children with celiac disease

To determine if celiac disease enhances oxidative DNA damage — and, by extension, if this is the means by which celiac increases cancer risk — researchers looked at three groups of children. One consisted of children with celiac disease, confirmed by villous atrophy observed after an endoscopy and who continued to eat gluten; another of children also with histologically confirmed celiac disease who had maintained a gluten-free diet for an average of 10 years; and a group of healthy controls. The scientists measured the level of oxidatively damaged DNA in leukocytes as well as the level of the antioxidants vitamin A, vitamin C and vitamin E, and uric acid in the blood. Antioxidant vitamins and uric acid are free radical scavengers that can decrease oxidative stress. Researchers also measured the levels of 8-oxodG (7,8-dihydro-8-oxo-2′-deoxyguanosine) and 8-oxoGua (7,8-dihydro-8-oxoguanine) excreted in the urine. These are the most widely studied biomarkers (i.e. a molecular signature) of oxidative DNA damage and, as they are found in urine rather than blood, they are easier to attain from children.

Scientists found that all of the markers for oxidative DNA damage were higher in celiac patients than in controls. Only the level of urinary 8-oxoGua was reduced by a gluten-free diet; the level of 8-oxodG, both in blood and in urine, was higher in celiac patients regardless of diet. Likewise, antioxidant parameters were lower in celiac patients than in healthy controls. Vitamins A and E were higher in those children who conformed to the gluten-free diet but vitamin C and uric acid were reduced equally in all celiacs, regardless of what they ate.

The level of 8-oxodG in DNA is one of the most important parameters we have for assessing oxidative damage. It is a mutated form of guanine, one of the molecules that comprises DNA, that is generated by oxidative stress. Thus, its concentration reflects the amount of oxidative DNA damage a given cell has undergone but can also reveal insights into how well the cell can repair its damaged DNA. Since patients with celiac disease had increased levels of 8-oxodG in both blood and urine, the data suggests that the DNA damage repair pathway may be compromised. A study of people with celiac disease who developed adenocarcinoma found that this was indeed the case, and the DNA repair mechanism may play a role in the prevention of the mutagenic effect of 8-oxodG [2].

The (relatively) good news out of all this for patients with celiac disease is the level of vitamin A, the strongest of the antioxidant vitamins, while reduced in children who ate gluten, was statistically the same in those celiacs adhering to their gluten-free diet as it was in healthy controls. This result suggest that consumption of a gluten-free diet helps to mitigate oxidative DNA damage in celiac patients. The authors note that in addition to strictly adhering to their gluten free diet, people with celiac disease should consider vitamin A and E supplements to reduce their cancer risk.

For more information on celiac disease, visit the Celiac Disease Center at the University of Chicago and the MedlinePlus page on Celiac Disease.

References

1. Szaflarska-Poplawska et al. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1960-5.
   View abstract
2. Freeman HJ. Malignancy in adult celiac disease. World J Gastroenterol. 2009 Apr 7;15(13):1581-3.
   View abstract
3. Gao et al. Increased risk for non-Hodgkin lymphoma in individuals with celiac disease and a potential familial association. Gastroenterology. 2009 Jan;136(1):91-8. Epub 2008 Sep 25.
   View abstract
4. Boiteux et al. Repair of 8-oxoguanine in Saccharomyces cerevisiae: interplay of DNA repair and replication mechanisms. Free Radic Biol Med. 2002 Jun 15;32(12):1244-53.
   View abstract