Body image is a tricky thing for many women. Like looking into a funhouse mirror, the way they perceive their bodies can make them think they're thinner or more obese than they actually are. Researchers led by Temple University's Sharon Herring, MD, MPH, have found that this misperception is associated with excess weight gain during pregnancy – which can cause complications for both mother and baby.
In a study published on December 19 in the journal BMC Pregnancy and Childbirth, Herring and a team of researchers from the department of ambulatory care and prevention at Harvard Medical School and Harvard Pilgrim Health Care found that overweight and obese women who thought they weighed less than they actually did at the start of pregnancy had seven times the odds of gaining excessive weight during their pregnancy. In contrast, normal weight women who thought they weighed more than they actually did had twice to the odds of gaining excessive weight during their pregnancy.
The reasons for misperceived body weight aren't clear, but Herring and her team speculate that the high prevalence of obesity in the US might account for a skewed body image among the overweight or obese group so that they believe they are at a normal weight, and may be less likely to follow pregnancy weight gain guidelines as a result.
In normal weight women, the researchers speculate that the misperception may represent body dissatisfaction and a predisposition to disordered eating behaviors such as binge eating or bulimia, which could result in excessive gain.
"But it isn't clear yet whether these are the explanations," said Herring, an assistant professor of medicine and public health at Temple University's Center for Obesity Research and Education. "More work needs to be done to understand perceptions of weight among mothers at the start of pregnancy, and to determine if correcting misperception reduces the likelihood of excessive pregnancy weight gain."
The Institute of Medicine recommends that normal weight women gain 25-35 pounds during pregnancy, and overweight or obese women gain 15-25 pounds. Over 50 percent of mothers in Herring's study gained in excess of these recommendations, which Herring says can lead to higher rates of Caesarean sections, larger babies, and greater difficulty in losing weight after delivery.
The study looked at more than 1,500 women enrolled in Project Viva, a US birth cohort, who were normal weight, overweight or obese at the beginning of their pregnancies. Among normal weight women, 13 percent thought they were heavier than they truly were, while 14 percent of the overweight or obese group thought they were lighter than they really were. The remaining participants in each group all accurately assessed their weight status.
Overweight or obese mothers who underestimated their weight status tended to be younger, non-white, of lower income, less educated and single, and ate fewer fruits and vegetables than the normal weight group who accurately reported their weight. Normal weight women who underestimated their weight status, however, shared relatively similar characteristics to their accurate assessing counterparts.
While some of the mothers who accurately assessed their weight also gained an excessive amount, those who misperceived their weight were at greater risk of excessive gain.
Other authors on this study include Emily Oken MD, MPH, Jess Haines, PhD, MHSc, RD, Sheryl L. Rifas-Shiman, MPH, Ken P. Kleinman, ScD, and Matthew Gillman, MD, SM, of Harvard Medical School and Harvard Pilgrim Health Care; and Janet Rich-Edwards of Brigham and Women's Hospital in Boston, MA. This research was funded by grants from the National Institutes of Health (NIH), Harvard Medical School and the Harvard Pilgrim Health Care Foundation. Herring was additionally supported by an Institutional National Research Service Award from the NIH.
The research was carried out by a team of researchers led by Sharon Herring, MD, MPH, an Assistant Professor of Medicine and Public Health at Temple University. She said, "Compared to normal weight women who accurately assessed their pre-pregnancy weight status, the odds of gaining excessively during pregnancy were increased seven-fold among overweight and obese women who thought they weighed less than they really did. Normal weight women who thought they were overweight had twice the odds of excessive gestational weight gain."
The authors studied 1537 women enrolled in Project Viva, a US birth cohort, who were normal weight, overweight or obese at the beginning of their pregnancies. Underweight women were not included. Of the 1029 normal weight participants, 898 (87%) correctly reported that they were normal weight just prior to pregnancy, while 131 (13%) incorrectly thought they were overweight or obese. Of the remaining women who were overweight or obese, 438 (86%) accurately perceived their body weight status, while 70 (14%) under-assessed their size before pregnancy. Compared with normal weight women who accurately perceived their pre-pregnancy weight status, overweight or obese under-assessors were younger, more likely to be non-white, of lower income, less educated, and single. These women consumed fewer fruits and vegetables during their pregnancies, but did not differ from normal weight accurate assessors in amount of vigorous activity or fried food intake. Normal weight over-assessors, on the other hand, were relatively similar in all characteristics to their accurate assessor counterparts.
Although the reasons for misperceived body weight aren't completely understood, the authors speculate that the high prevalence of the obesity in the US may affect women's judgement about their respective weight status. By failing to recognize their overweight or obese status, these women may be less likely to follow pregnancy weight gain guidelines. Herring said, "As excessive gestational weight gain increases the risk of poor maternal and child outcomes, including higher rates of caesarean sections, larger babies, and greater difficulty losing weight after delivery, more work needs to be done to determine if correcting this misperception reduces the likelihood of excessive pregnancy weight gain."
Premature infants who need intensive care or surgery are less sensitive to thermal (hot and cold) sensations later in life, according to research conducted at UCL (University College London). The study, published in the journal Pain, suggests that pain and injury related to major medical interventions in early development may alter how children respond to painful stimuli much later in life.
In the study, 43 eleven-year-old children born at less than 26 weeks of gestation (14 weeks premature) who are being followed up by the EPICure study group, were tested for their responses to different sensations – temperature and light touch – using quantitative sensory testing. Compared to a group of children who had been born at full term, the premature children were less sensitive to temperature (cool, cold, warm and hot) but not to light touch, and this was most marked in those who had also undergone a surgical operation as a baby. The researchers also found a more marked decrease in sensitivity to temperature and to touch close to scars relating to major chest surgery, again suggesting that the severity of injury in early life influences the degree of sensory change. A questionnaire survey showed that the children's everyday pain experiences were similar, but there were some minor differences between the two groups in the way children coped with pain.
Dr Suellen Walker, UCL Institute of Child Health, says: "Our study shows that babies who are born premature and need intensive care or surgery develop long-term changes in their responses to hot and cold sensations. As the same nerve fibres transmit temperature and pain, changes in thermal sensitivity may also be associated with altered responses to pain in later life. In our laboratory studies, we have also shown that surgical incisions in early life reduce sensitivity to temperature and pressure, and alter pain responses to future surgery. These effects appear to be specific to early life, as seen in the premature children who were operated on as babies."
"The pain mechanisms in our bodies are plastic – that is, injury and nerve activity can alter them, but this is particularly true in early life when the nervous system is still developing. Our research aims to understand how responses to injury change, and how best to treat pain, at different stages of development. We are currently testing different types and doses of analgesics to prevent the long-term changes we have discovered, and this will help doctors to choose the most effective painkillers for preterm babies."
Professor Neil Marlow, UCL Elizabeth Garrett Anderson Institute for Women's Health, says: "The rate of preterm birth is rising, and improvements in intensive care mean that babies are surviving from very young gestational ages. Many of the procedures necessary to monitor and treat such babies are painful and even in the most premature babies, can trigger responses in pain-sensing areas of the brain. In some cases, major surgery may be needed to treat complications of prematurity or to correct congenital defects. It is therefore important for us to understand not only how these interventions at the earliest stages of development may affect the body's sensory functions later in life, but also how we can minimise exposure to painful stimuli."
The EPICure studies are funded by the Medical Research Council and are longitudinal studies of children following extremely preterm birth. More information may be obtained from www.epicure.ac.uk
Sexual abuse in childhood increases the risk of suicide in men by up to ten times, say researchers from the University of Bath. A recent study of Australian men has found that those who were sexually abused as children are more likely than women to contemplate taking their own lives.
Whilst gender and mental health problems are the most important risk factors for contemplating suicide, it is increasingly acknowledged that traumatic experiences such as childhood sexual abuse may be a significant risk factor.
Dr Patrick O'Leary and Professor Nick Gould from the University’s Department of Social & Policy Sciences conducted a series of surveys and face-to-face interviews with men in a study funded by the University of South Australia. The findings have been published online in the peer-reviewed British Journal of Social Work.
They found that men who were sexually abused as children were up to ten times more likely to have suicidal tendencies; many of these men had not been clinically diagnosed as depressed.
Dr O;Leary said: “Childhood sexual abuse is an under-recognised problem in men - most of the studies exploring the link with suicide have been in women.
“Men are particularly vulnerable because they don’t like to talk to others about their problems. It’s difficult for anyone to come to terms with traumatic experiences such as childhood sexual abuse, but for men the stigma is worse because they don’t tend to confide in their friends as much.
“Many suffer feelings of failure and isolation and think that it is a sign of weakness to discuss their past abuse with others. Men also tend to visit their doctors less frequently, so those who are at risk of suicide often slip under the radar of the healthcare system.
“Men are particularly vulnerable to suicide and are three and a half times more likely than women to end their own lives, with more than 2,000 men dying as a result of suicide in the UK each year. However it is estimated that for every suicide, there are between 20 and 25 failed attempts.
“We carried out the study in Australia, which shares a similar ‘stiff upper lip’ culture that we see in the UK. We’re planning to do our next study in the UK to see if there are any differences.”
Dr O’Leary suggested that lives could be potentially saved if abuse victims are identified earlier.
He explained: “The abuse that these men have suffered as children often sees them attempting to cope by suppressing the experience through substance abuse, alcohol abuse and obsessive behaviour, with many ending up in the criminal justice system.
“Greater awareness in the healthcare and criminal justice systems will help identify those who are at risk and give them treatment before it is too late.”
A prototype of a therapeutic ultrasound device, developed by a Cornell graduate student, fits in the palm of a hand, is battery-powered and packs enough punch to stabilize a gunshot wound or deliver drugs to brain cancer patients. It is wired to a ceramic probe, called a transducer, and it creates sound waves so strong they instantly cause water to bubble, spray and turn into steam.
Tinkering in his Olin Hall lab, George K. Lewis, a third-year Ph.D. student in biomedical engineering and a National Science Foundation fellow, creates ultrasound devices that are smaller, more powerful and many times less expensive than today's models. Devices today can weigh 30 pounds and cost $20,000; his is pocket-sized and built with $100. He envisions a world where therapeutic ultrasound machines are found in every hospital and medical research lab.
"New research and applications are going to spin out, now that these systems will be so cheap, affordable and portable in nature," Lewis said.
The development of one of his portable devices is detailed in the journal Review of Scientific Instruments (79-114302), published online Nov. 11. Lewis, whose paper is co-authored by his adviser, William L. Olbricht, Cornell professor of chemical and biomolecular engineering, also presented his research in a talk at the November meeting of the Acoustical Society of America.
Ultrasound is commonly used as a nondestructive imaging technique in medical settings. Sound waves, inaudible to humans, can generate images through soft tissue, allowing, for instance, a pregnant woman to view images of her baby. But the higher-energy ultrasound that Lewis works with can treat such conditions as prostate tumors or kidney stones by breaking them up. His devices also can relieve arthritis pressure and even help treat brain cancer by pushing drugs quickly through the brain following surgery.
Lewis suggests that his technology could lead to such innovations as cell phone-size devices that military medics could carry to cauterize bleeding wounds, or dental machines to enable the body to instantly absorb locally injected anesthetic.
Lewis miniaturized the ultrasound device by increasing its efficiency. Traditional devices apply 500-volt signals across a transducer to convert the voltage to sound waves, but in the process, about half the energy is lost. In the laboratory, Lewis has devised a way to transfer 95 percent of the source energy to the transducer.
His new devices are currently being tested in a clinical setting at Weill Cornell Medical College. Under the direction of Jason Spector, M.D, director of Weill Cornell's Laboratory for Bioregenerative Medicine and Surgery and assistant professor of plastic surgery, Peter Henderson, M.D., the lab's chief research fellow, is using one of the devices in experiments that aim to minimize injury that occurs when tissues do not receive adequate blood flow.
Their lab is performing tests in animals to determine whether low doses of the chemical hydrogen sulfide, known to be toxic at high doses, might be able to minimize such injury by slowing cellular metabolism.
Doctors are hopeful that the ultrasound from Lewis' portable device will enable hydrogen sulfide to be targeted to specific parts of the body, allowing doctors to use less of it, and cutting down on toxicity risks, Henderson explained.
The medical doors that Lewis' device may one day open are groundbreaking, Henderson said.
"People are realizing that when harnessed appropriately, you can use ultrasound to treat things as opposed to just diagnose them," Henderson said. "It's a wide-open field right now, and George's device is going to play a huge role in catalyzing the discovery of new and better therapeutic applications."
MADISON -- When neurons started dying in Clive Svendsen's lab dishes, he couldn't have been more pleased.
The dying cells – the same type lost in patients with the devastating neurological disease spinal muscular atrophy – confirmed that the University of Wisconsin-Madison stem cell biologist had recreated the hallmarks of a genetic disorder in the lab, using stem cells derived from a patient. By allowing scientists the unparalleled opportunity to watch the course of a disease unfold in a lab dish, the work marks an enormous step forward in being able to study and develop new therapies for genetic diseases.
As reported this week in the journal Nature, Svendsen and colleagues at UW-Madison and the University of Missouri-Columbia created disease-specific stem cells by genetically reprogramming skin cells from a patient with spinal muscular atrophy, or SMA. In this inherited disease, the most common genetic cause of infant mortality, a mutation leads to the death of the nerves that control skeletal muscles, causing muscle weakness, paralysis, and ultimately death, usually by age two.
Genetic reprogramming of skin cells, first reported in late 2007 by UW-Madison stem cell biologists James Thomson and Junying Yu and a Japanese group led by Shinya Yamanaka, turns back the cells' developmental clock and returns them to an embryonic-like state from which they can become any of the body's 220 different cell types. The resulting induced pluripotent stem cells, known as iPS cells, harness the blank-slate developmental potential of embryonic stem cells without the embryo and have been heralded as a powerful potential way to study development and disease.
Just one year later, the new work is fulfilling that promise.
"When scientists study diseases in humans, they can normally only look at the tissues affected after death and then try to work out – how did that disease happen? It's a little like the police arriving at the scene of a road accident – the car's in the ditch, but they don't know how it got there or the cause of it," explains Svendsen, a professor of anatomy and neurology in the UW-Madison School of Medicine and Public Health and the Waisman Center, and co-director of the Stem Cell and Regenerative Medicine Center.
With iPS cells, he says, "Now you can replay the human disease over and over in the dish and ask what are the very early steps that began the process. It's an incredibly powerful new tool."
In the new study, the researchers created iPS cells from stored skin cells of a young SMA patient and his mother, who does not have the disease. The cells grew well in the lab, and the group developed a new method to efficiently drive them to make large numbers of motor neurons, the cells that control muscles and that are affected in SMA.
Initially, the motor neurons thrived in both samples. But after about a month, "the accident started happening," Svendsen says, and the motor neurons from the patient-derived cells began to disappear.
"The motor neurons we got started to die in culture, just like they do in the disease. This is the first validation of a human disease that we've modeled in a culture dish," he says.
They can now begin to dissect what kills the motor neurons and why these cells alone are targeted in the disease. Past studies to understand the effects of the SMA-causing mutation have often relied on the easy-to-obtain skin cells, which are not affected in SMA and offer limited insight into how and why motor neurons die, says UW-Madison researcher Allison Ebert, lead author on the new study.
"If we start to understand more of the mechanism of why the motor neurons specifically affected in the disease are dying, then potentially new therapies can be developed to intervene at particular times early in development," she explains. Current SMA treatment options are limited, and there is no cure.
Ebert points out that the patient-derived iPS cells can offer scientific advantages over other approaches, including embryonic stem cells, for studying disease. In effect, the researchers can watch the unfolding of an accident that has already occurred, and the known clinical outcome – the course and severity of the patient's disease – should help them understand how the changes they see in the cells fit into the bigger picture of the disease.
"The development of human-derived SMA motor neurons is an important step forward for the SMA field, especially as a variety of therapeutic avenues are being examined," agrees SMA expert Christian Lorson, a professor of veterinary pathobiology at MU and an author on the paper. "To be able to investigate therapeutic activity in these cells, whether it be novel drugs, viral vectors, oligonucleotides, or a better understanding of disease pathology, the iPS SMA motor neurons represent an excellent disease-related context."
While complex and late-hitting disorders like Alzheimer's and Parkinson's diseases will be harder to model with iPS cells, the researchers say the approach should pave the way for studies of other genetic disorders, such as Huntington's disease. "We have to find better ways to model complex human diseases that are difficult to reproduce in animals," Svendsen says. "iPS cells represent a promising new research tool to reach this goal."
He credits the UW-Madison Stem Cell and Regenerative Medicine Center with facilitating the work, especially by drawing on the expertise of Yu and Thomson, who pioneered the technique, to create the iPS cells used in this study. "This is an example of how the center is working to collaborate on campus and off campus to bring these kind of things to fruition," he says.
One part of the prenatal brain that may be particularly sensitive to alcohol's effects is white matter, nerve fibers through which information is exchanged between different areas of the central nervous system. A recent study has demonstrated that alcohol consumption during pregnancy can alter the microstructural integrity of developing fetal cerebral white matter in the frontal and occipital lobes of the brain. These anomalies may help to explain the executive dysfunction and visual processing deficits that are associated with gestational alcohol exposure.
Results will be published in the March issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"The brain's white matter is made up of nerve bundles that transfer information between brain regions," explained Susanna L. Fryer, a researcher at San Diego State University's Center for Behavioral Teratology and corresponding author for the study. "Optimal white-matter integrity is thought to support efficient cognition. So the finding that prenatal alcohol exposure is associated with altered white-matter integrity may help explain aspects of the cognitive and behavioral problems that individuals with fetal alcohol spectrum disorders (FASDs) commonly face."
"Several studies of FASD within the last three years have used a new magnetic resonance imaging (MRI) technique called Diffusion Tensor Imaging (DTI) to examine the brain's connective network – also known as white matter –in ways not previously possible," added Jeffrey R. Wozniak, assistant professor of psychiatry at the University of Minnesota.
DTI, like other MRI techniques, yields measures of biological tissue status at the microstructural level, allowing scientists to see more subtle forms of damage in the prenatally exposed brain. "Yet despite their sophistication, currently available MRI tools are still very crude instruments with limited sensitivity," said Wozniak. "Abnormalities observed with these tools may represent changes to tens or even hundreds of thousands of brain cells. The fact that these relatively crude measures can actually show clear evidence of abnormalities should serve to highlight that these are actually very large-scale changes that have damaging consequences for the individual."
Fryer and her colleagues used DTI to assess white-matter microstructure in 27 youth, ranging from eight to 18 years of age. The youth were divided into two groups: with (n=15) and without (n=12) histories of heavy prenatal alcohol exposure.
"The brains of individuals with FASDs showed evidence of altered nerve fiber integrity at a microstructural level, even though total brain size was statistically equivalent between alcohol-exposed and comparison participants," said Fryer. "Also, within the alcohol-exposed group, we generally found that white-matter microstructure did not differ based on whether youth met criteria for a diagnosis of fetal alcohol syndrome (FAS). In other words, similar brain alterations and behavioral problems can occur because of prenatal alcohol exposure, with or without the facial features and physical growth insufficiency required to diagnose FAS."
"While previous studies had shown evidence of white-matter abnormalities in FASD, especially in the corpus callosum, a major bundle of white-matter fibers connecting the right and left halves of the brain," added Wozniak, "this study also showed abnormalities in other brain regions."
Those other regions included white matter tracts in the frontal and occipital lobes of the brain.
"Among other functions, the frontal lobes are important for planning and regulating behavior at an executive level," said Fryer. "Individuals with FASDs may exhibit problems with executive functioning, which can lead to difficulty inhibiting inappropriate or maladaptive responses, impaired attention regulation, and poor judgment and decision making abilities. The occipital lobes are important for processing visual information, and disrupted white matter coherence in these regions may relate to altered visual-spatial abilities in individuals with FASDs."
"One of the most commonly asked questions of researchers in this area is 'What level of alcohol exposure is safe?,'" noted Wozniak. "Unfortunately, this question is impossible to answer for a variety of ethical and scientific reasons. Even more unfortunate is the fact that the public and some physicians conclude without scientific evidence that alcohol consumption during pregnancy is safe as long as it is not 'too much.'"
Conversely, he added, data from imaging studies of this type and from neuropsychological studies of mental skills suggests that FAS is only the tip of the iceberg. "As the technology improves, it seems clear that increasingly subtle forms of brain damage and cognitive deficits will become evident among those exposed to lower levels of alcohol, those who would not have previously been diagnosed with FAS. In other words, one cannot define a 'safe' level of alcohol exposure for the fetus."
"It is likely the cognitive and behavior problems will be the most devastating to affected individuals, and costly to society," Fryer added.
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Characterization of White Matter Microstructure in Fetal Alcohol Spectrum Disorders," were: Brian C. Schweinsburg of the Department of Psychiatry at the University of California, San Diego and the VA San Diego Healthcare System; Olivia A. Bjorkquist, Sarah N. Mattson and Edward P. Riley of the Department of Psychology, and the Center for Behavioral Teratology, at San Diego State University; Lawrence R. Frank of the VA San Diego Healthcare System, and the Department of Radiology at the University of California San Diego; and Andrea D. Spadoni of the San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.
Smoking during the first trimester of pregnancy is clearly linked with an increased risk of cleft lip in newborns. Genes that play a role in detoxification of cigarette smoke do not appear to be involved. This is shown in a new study published in the journal Epidemiology.
Oral clefts are one of the most common birth defects. Closure of the lip occurs about 5 weeks into pregnancy, followed by closure of the palate at week 9. If this does not happen, a cleft lip and/or cleft palate are the result, requiring surgery. The researchers wanted to see if smoking or exposure to passive smoking play a role in these defects and whether genes influence the oral cleft risk through the way toxic chemicals in cigarette smoke are processed.
The study is based on an extensive Norwegian case-control study on oral clefts with collaborating researchers from the Norwegian Institute of Public Health, University of Bergen, Rikshospital, Haukeland University Hospital and the National Institutes of Health in USA. Between 1996 and 2001, 676 babies born with oral clefts were referred for cleft surgery, and of these, 573 took part in the study. 763 babies born during the same period in Norway were randomly selected as controls.
DNA and questionnaires
Blood samples were taken from the children referred for surgery and their PKU test samples, routinely taken at birth, were also retrieved. Their mothers and fathers donated cheek swabs and blood samples. From the control group, cheek swabs were obtained from the mother, father (after November 1998) and child, plus the PKU test sample taken at birth. DNA was extracted from the samples.
Four weeks after birth, the mothers in both groups completed a questionnaire about medical conditions and environmental exposure. They were specifically asked about their smoking habits and exposure to passive smoking before pregnancy and during the first trimester. 42 % of case mothers and 32 % of control mothers said that they smoked in the first trimester.
There was little evidence of an effect of smoking on the risk of cleft palate alone. However, for cleft lip (with or without cleft palate), there was an increased risk, almost two-fold when the mother smoked over 10 cigarettes per day and a 1.6 fold risk from passive smoking (defined as being within 2 metres of a smoker for 2 hours a day). The researchers estimate that 19 % of cases of cleft lip in Norway may be due to maternal smoking in the first trimester.
Genetic Analysis
Using the DNA extracted from the babies and their parents, the researchers looked at the genes related to detoxification of chemicals in cigarette smoke (NAT1, NAT2, CYP1A1, GSTP1, GSTT1, GSTM1). These genes did not appear to affect the incidence of cleft lip, although there was an inconclusive link with NAT2 and cleft lip risk which was independent of smoking. The mechanism by which maternal smoking increases the risk of cleft lip remains unknown.
Reference
RT Lie, AJ Wilcox, J Taylor, HK Gjessing, OD Saugstad, F Aabyholm and H Vindenes. Maternal Smoking and Oral Clefts. Epidemiology 2008: 19 (4) 606-615
INDIANAPOLIS -- A national alcohol research group is concerned that the media's misinterpretation of a recent British research study could encourage pregnant women to be more at ease with temperate alcohol consumption.
Some media reports erroneously stated that the study by The University College London researchers revealed that light drinking by pregnant women could be beneficial to their babies. Other articles said light drinking during pregnancy would not affect the behavior or mental acuity of babies born to drinking mothers.
The Fetal Alcohol Spectrum Disorders Study Group, a subgroup of the Research Society on Alcoholism, says the conclusion of the study was not reported accurately. "Unfortunately, several media outlets misinterpreted this report to mean that drinking improved the children's outcome," the FASD Study Group said.
The published report looked at the drinking patterns of pregnant mothers of three-year-olds and assessed the behavior and cognitive skills of the children. The University College London researchers actually reported that the children born to women who drank lightly during pregnancy were not at increased risk compared with children of mothers who did not drink during pregnancy.
However, this result may be based on the higher socioeconomic status of the light drinking mothers and their children involved in this study. Higher socioeconomic status is well known to improve an infant's neurodevelopmental outcome. The study's authors, Dr. Yvonne Kelly at University College London and colleagues, suggested this explanation for their findings and the FASD Study Group agrees with that conclusion.
Many published reporters show that even moderate to light drinking can cause birth defects.
"Generally, the adverse effects of light drinking during pregnancy are subtle and may go undetected in children," said Feng Zhou, Ph.D., president of the FASD Study Group and a professor of anatomy, cell biology and neurobiology at the Indiana University School of Medicine. "Other alcohol research studies of moderate drinking during pregnancy have shown an adverse impact on multiple aspects of development through adolescence and young adulthood even when other important environmental factors are taken into account."
Dr. Zhou said the news reporters have been carried in various European and American publications and on news web sites.
"The media reports are alarming for a number of reasons but it is particularly disturbing at this time of year when holiday parties may make alcohol consumption more accessible and appealing to pregnant women who have read the erroneous reports," he said.
The consensus of public health providers and alcohol researchers is that even light drinking can interfere with biological processes critical in the development of the fetal brain, said Dr. Zhou and other Study Group officers, Cynthia J.M. Kane, Ph.D., vice president and professor of neurobiology and developmental sciences, University of Arkansas for Medical Sciences, and Susan Smith, Ph.D., secretary and treasurer, and professor of nutritional science at the University of Wisconsin- Madison.
Measurement of the human face from 3D facial images may help to diagnose patients with fetal alcohol spectrum disorders (FASD), even across ethnically disparate populations. Fetal alcohol syndrome (FAS) is the most extreme expression of alcohol's adverse effects on the developing fetus, and is part of the wider fetal alcohol spectrum disorders (FASD). While clinicians agree that effective management of FAS-related problems depends on a timely and reliable diagnosis, clearly identifying accompanying facial features has been challenging. It now appears that computerized craniofacial anthropometry - measurement of the human face from 3D facial images - may help to diagnose patients with FAS, even across ethnically disparate populations.
Results are published in the October issue of Alcoholism: Clinical & Experimental Research.
"Craniofacial anthropometry is the precise measurement of the head and face," said Elizabeth S. Moore, research scientist at St. Vincent Hospital and corresponding author for the study. "It has mostly been used as a descriptive tool and has helped clinicians in the description, diagnosis, and surgical treatment of abnormal skeletal and facial patterns. It is especially useful in medical genetics because many of the syndromes present at birth - such as Apert, Down, and Soto - involve the head and face, so it can assist clinicians to objectively describe what they are seeing."
"The identification of individuals with FAS, and even more so the early identification, has remained a challenge over the years," added Kenneth R. Warren, associate director for Basic Research at the National Institute on Alcohol Abuse and Alcoholism. "First, there is no genetic marker for FAS. The second problem arises from the subtle nature of the facial dysmorphic features, as all the features in FAS are also seen in the normal population. No one of these features alone - flat philtrum, thin upper lip, small palpebral fissures, etc. - would appear abnormal to any physician." What is unique about FAS, he said, is the presence of all of these features as a cluster, along with a head circumference below the 10th percentile.
As part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), researchers recruited 276 subjects from four sites - Cape Town, South Africa; Helsinki, Finland; Buffalo, New York; and San Diego, California - and obtained 3D facial images and detailed dysmorphology evaluations to classify subjects as either FAS (43 per cent) or 'control' subjects (57 per cent). Most (54 per cent or 149) of the participants were female; their ages ranged from 2.75 to 21.17 years of age. Study authors then used computerized anthropometry to identify facial features among the wide age range and disparate ethnicities of the study populations.
"One key finding of this study is that [a] reduced length of the eye opening is found across children of different ethnicities," said Moore. "This means [that] a 'shortening' of the eye from the inside corner to the outer corner may reflect reductions in the size of the eye globe and/or boney orbit. It was also found that in each of the ethnic populations, unique facial features were identified which distinguished individuals with alcohol exposure from controls. This latter finding suggests that FAS differs across the various ethnic groups, making it potentially more difficult to identify individuals who were prenatally exposed to alcohol."
"The results related to the size of the eye orbit emphasize that impairment in the development of the eye is a common teratogenic action of alcohol," said Warren. "The size of the eye orbit is a function of the size of the eye."
"We hope that future research will find out why there are overlapping measurements, why do the eye measurements always show up, and why there are some measurements unique to specific ethnic groups," said Moore. "We may find that the eyes are consistently affected in all populations, regardless of ethnicity because of the areas of the brain that are damaged or because alcohol always affects the cells that will form the eye. Or, the eye-consistent measurements could be secondary to the way alcohol affects facial and brain development." Moore's group, CIFASD, has just received funding for the next five years to continue with this work, expanding in the United States and South Africa, as well as into the Ukraine.
Both Moore and Warren were eager to see the study results help with early identification of and intervention for FAS children.
"One possible outcome could be the ability to submit a photograph of an individual suspected of being affected by FAS to a 'facial recognition' program that has been 'trained' to identify subtle but diagnostic features associated with such exposures," said Moore.
"Given the subtle nature of FAS deficits, accurate diagnoses have depended upon evaluations by a sub-specialty of paediatricians known as dysmorphologists at a very small number of academic hospitals," added Warren. "The use of craniofacial anthropometry offers the potential to both improve and make even more objective the diagnosis of FAS; and extends the availability of diagnostic capability to a much broader range of clinicians. In addition, craniofacial anthropometry - particularly if coupled with MRI non-invasive imaging - could help to determine the specific nature of the underlying brain-structural deficits in FAS."
"It is important to remember that the effects of alcohol are along a continuum," said Moore. "The same amount of alcohol can produce different results due to numerous environmental and genetic factors. Our research is trying to offer more insights into how and why alcohol affects humans, and how what a clinician sees relates to the brain and behavior. By better understanding the specific regions of the face which are affected, and more importantly, by linking this information to studies of how brain and behavior are affected, a better picture should emerge of how alcohol damages the developing baby. Perhaps it may even be possible to prevent fetal damage by using certain substances that block alcohol's actions. At the very least, we hope that improved detection could lead to earlier intervention for at-risk children and, through this, better chances for improving the lives of such children."
Diabetes and high levels of blood sugar may be linked to abnormalities in a person's body clock and sleep patterns, according to a genome-wide association study published today in the journal Nature Genetics.
The research suggests that diabetes and higher than normal blood sugar levels could partly be tackled by treating sleep problems, say the researchers, from Imperial College London, the French National Research Institute CNRS, Lille University, McGill University in Canada, Steno Diabetes Centre in Denmark and other international institutions.
People with high blood sugar levels and diabetes have a greatly increased risk of developing a range of conditions, including cardiovascular diseases.
The new study shows that a mutation called rs1387153, near a gene called MTNR1B, is associated with having an increased average blood sugar level and around a 20 percent elevated risk of developing type 2 diabetes.
MTNR1B forms part of a signalling pathway that controls the action of the hormone melatonin. This hormone regulates the body's circadian rhythm - the internal clock that controls sleeping and eating patterns – by responding to daylight and darkness.
The discovery of the rs1387153 mutation provides evidence that high blood sugar and diabetes could be directly linked to an impaired circadian rhythm.
Professor Philippe Froguel, the corresponding author of the research from the Department of Genomic Medicine at Imperial College London, said: "There is already some research to suggest there are links between sleep problems and conditions such as obesity and depression, both of which are associated with diabetes. For example, we know that obese children tend to sleep badly and that people become more obese if they are not having enough sleep. Our new study demonstrates that abnormalities in the circadian rhythm may partly be causing diabetes and high blood sugar levels. We hope it will ultimately provide new options for treating people."
In healthy people, blood sugar levels are kept under control by insulin, which the pancreas releases in varying amounts at different periods during a 24-hour natural cycle. The researchers suggest that when there is a genetic abnormality that affects melatonin levels and sleep patterns, this may also disturb the levels of insulin in the blood, preventing the body from maintaining control of blood sugar levels.
Insulin is normally secreted in peaks during the daytime, in order to allow blood sugar from meals to be processed properly, and at lower levels at night. In contrast, melatonin levels are low during the daytime and high at night.
The new study is part of a series of discoveries about the genetics of diabetes made by Professor Froguel and his colleagues. In May 2008 they identified a genetic mutation that can raise the amount of sugar in a person's blood to harmful levels and in February 2007 they identified the key genes associated with a risk of developing type-2 diabetes in the first study to map the genes of any disease in such detail.
The new study shows that identifying which people have high numbers of genetic mutations can reveal who is at most risk of developing high blood sugar levels. On average, the more genetic mutations associated with high blood sugar levels people had, the higher their blood sugar level.
For example, people with five genetic mutations had an average fasting blood sugar level of 5.4, whereas people with one mutation had an average level of 5.12.
Forty three percent of those carrying six or more mutations had levels of fasting blood glucose of 5.6 mmol/l or more. This level is defined as being 'impaired' by the American Diabetes Association, meaning that such people have a very high risk of developing diabetes in the future.
Professor Froguel added: "We have been developing quite a clear picture of the key genes involved with high blood sugar and diabetes and this allows us to better understand them and suggest new avenues for treatment. We are also nearing the stage when we can develop tests that can identify the people at most risk of developing high blood sugar and diabetes later in their lives, so we can intervene to improve their health before they reach that point."
For the new study, the team analysed the genetic makeup of 2,151 non-diabetic French people (comprising 715 lean adults, 614 lean children, 247 obese adults and 575 obese children) and identified the rs1387153 mutation as being associated with high blood sugar levels. They confirmed their findings by looking at the genetic makeup of more than 16,000 non-diabetic people from different groups in France, Denmark and Finland.
The team then determined that the presence of the rs1387153 increased the risk of type 2 diabetes by comparing the genetic makeup of 6,332 French and Danish diabetic subjects with that of a group of 9,132 French and Danish people with normal blood sugar levels. The researchers found the same links between rs1387153 and a risk of diabetes in all the European populations they studied.
If you need another reason to quit smoking, consider that it may diminish your chances of being a parent or grandparent. Scientists at the University of Rochester Medical Center have found that women exposed to second hand smoke, either as adults or children, were significantly more likely to face fertility problems and suffer miscarriages.
An epidemiologic analysis of more than 4,800 non-smoking women showed those who were exposed to second hand smoke six or more hours per day as children and adults faced a 68 percent greater chance of having difficulty getting pregnant and suffering one or more miscarriages. The study is published online in Tobacco Control and is one of the first publications to demonstrate the lasting effects of second hand smoke exposure on women during childbearing years.
"These statistics are breathtaking and certainly points to yet another danger of second hand smoke exposure," said Luke J. Peppone, Ph.D., research assistant professor at Rochester's James P. Wilmot Cancer Center.
In the study, four out of five women reported exposure to second hand smoke during their lifetime. Half of the women grew up in a home with smoking parents and nearly two-thirds of them were exposed to some second hand smoking at the time of the survey.
More than 40 percent of these women had difficulty getting pregnant (infertility lasting more than a year) or suffered miscarriages, some repeatedly.
"We all know that cigarettes and second hand smoke are dangerous. Breathing the smoke has lasting effects, especially for women when they're ready for children," said Peppone, who analyzed information in the Patient Epidemiology Data System, a well-studied cohort that has yielded information on a variety of cancers.
Peppone analyzed surveys collected from 4,804 women who visited Roswell Park Cancer Institute for health screenings or cancer care from 1982-1998. The 16-page survey focused on lifestyle, habits, family and personal health history, and occupational and environmental exposures. Each participant in this study reported that they had never smoked, and had been pregnant at least once or tried to become pregnant.
Participants reported whether one or both of their parents smoked and if they lived with or worked with smokers as adults. They also estimated the amount of time they were exposed to second hand smoke.
Peppone acknowledges that the data is based upon self-reporting and that is not perfect. However, he said "Women, especially mothers, have extremely accurate recall. Mothers can easily recall details like how long they breastfed, what vitamins they took during prenatal care, and childhood activities."
Many of the women in the study grew up in the 1940s and 1950s, long before the surgeon general issued the first warning about the dangers of cigarette smoking in 1964. Since then, millions of dollars were spent to study the dangers of cigarette smoking. Tobacco use contributes to more than nearly 90 percent of all deadly lung cancers and 30 percent of all cancer deaths in the U.S., and a host of other health problems
Since the mid-1960s, smoking bans and government-funded, anti-smoking campaigns have encouraged smokers to quit and discouraged others from starting using a number of passive and aggressive techniques. Smoking rates have declined, however people continue to use tobacco and suffer the health risks.
Medical students frequently suffer from depression, especially during their internship years. New research published in the open access journal BMC Medical Education reveals the extent of the problem and features a detailed analysis of the symptoms and sufferers.
Sergio Baldassin, from the ABC Regional Medical School, Brazil, led a team of researchers who carried out a study on 481 medical students in the private medical school near the São Paulo state capital. He said, "We used cluster analyses to better describe the characteristics of depressive symptoms - affective, cognitive, and somatic. This is the first study to directly evaluate, in a cross-sectional design, the characteristics of depressive symptoms by applying such clusters".
Affective symptoms represent the core symptoms of a depressive mood, based on students' reported levels of sadness, dissatisfaction, episodes of crying, irritability and social withdrawal. The cognitive cluster assessed pessimism, sense of failure or guilt, expectation of punishment, dislike of self, suicidal ideation, indecisiveness and change in body image. Finally, the somatic cluster assessed the presence of slowness, insomnia, fatigue, loss of weight and loss of sexual interest. Baldassin said, "There was a high prevalence towards depressive symptoms among medical students, particularly females, mainly involving the somatic and affective clusters. Of the students in our study, 38% had at least 10 of a possible 63 symptoms of depression".
The authors' cluster analysis found that the reasons for most students' depression scores were in the affective cluster, and that the problem was at its worst in the internship years. Cognitive cluster symptoms were also highest in this year, probably due to feelings of fear and insecurity about entry into the hospital environment. According to Baldassin, "Frequently pre-internship students fear they 'know nothing', and are insecure about the physical examination of other people". Likewise, somatic cluster scores were highest during internship, reflecting sleepless nights on call, devoid of friend and family support.
Having a parent who is a doctor was found to reduce the depression risk.
The authors conclude, "The increased depression scores during the internship period of medical school are associated with a decrease in student health, and this is probably the period when professors and educators should try to be most aware of suicidal thoughts and risk in their students".
Comprehensive Assessments of 113 Families During Mother-Father-Infant Assessments
St. Petersburg, FL -- A new study in the journal Family Process shows that infants appear to be active participants in complex interactional sequences with their parents far earlier than previously thought. Researchers documented the capacity of three-month old infants to share attention with two partners simultaneously.
Triangular capacities were defined as the frequency of babies’ rapid multi-shift gaze transitions between parents, as the infants shifted their gaze back-and-forth between the two adults during a well-established family interaction paradigm. The babies did the same thing in a more stressful procedure in which the two adults challenged them by posing motionless faces following a period of free play.
Early patterns of coordinated infant eye gaze were seen as early as three months, and were linked to signs of better coparental coordination and adjustment within the family.
The infant-family linkages were found by James McHale, Elisabeth Fivaz-Depeursinge, Susan Dickstein, Janet Robertson and Matthew Daley, who evaluated comprehensive assessments of emergent co-parenting alliances completed in the homes of 113 families, and charted infants’ eye gaze patterns during two different mother-father-infant assessments. The investigation was sponsored by the National Institute of Child Health and Development.
“The evidence from our study can embolden practitioners to consider inclusion of babies in therapeutic enactments, drawing attention to their patterns of attention and their role in ongoing family trilogues. Parents' focus can be drawn both to their infant's sensitivity to their ongoing relationship and to the significance of their cooperation as coparents.”
Researchers are calling for more studies into the practice of forcing psychiatric patients to take medication, after a research review showed that there have been very few rigorous investigations of the procedure.
The review, published in the latest Journal of Advanced Nursing, suggests that patients receiving coerced medication (CM) are more likely to be in their thirties with a diagnosis of schizophrenia, bipolar disorder or another psychotic disorder.
CM is used more often in the UK than in other countries where other forms of restraint are more common.
Most of the patients featured in the studies that were reviewed had been admitted to psychiatric care on an involuntary basis.
"It is clear from our review that there is little clinical evidence on the use of CM and more research is needed to examine all aspects of this contentious practice" says Manuela Jarrett, a registered mental health nurse from the Health Service and Population Research Department at the Institute of Psychiatry in London.
Jarrett, who co-authored the paper with Professor Len Bowers and Dr Alan Simpson from City University London, carried out a detailed analysis of 14 papers from seven countries, published between 1987 and 2004. These studies included interviews with 543 patients and 263 staff and analysis of 1,165 forms and records from the UK, USA, Sweden, Finland, Germany, Canada and Denmark.
"Legislation for involuntary psychiatric treatment exists in all European Union member states and in other western countries, where an increased risk to self and others provides the ethical and legal grounds for detaining and treating psychiatric patients without their consent" she says. "The fact that there is legislation in different countries suggests recognition of the seriousness and ethical uncertainty of such procedures.
"Perceived risk to others emerged as an important factor in the decision by staff to give a patient CM. But although half the researchers interviewed patients about their views on receiving CM, they didn't ask them whether they perceived themselves to be a risk to their self or others at the time when CM was administered.
"The studies showed that patients experienced a range of negative feelings when they received CM, including fear, embarrassment, anger and helplessness. Despite this, many said that they retrospectively agreed with the practice."
Research papers included in the review showed a notable lack of detailed exploration into the events leading up to the CM incidents and a complete absence of investigation into alternatives.
"This may reflect variations in the way conflict is managed in inpatients settings in different countries" suggests Jarrett. "CM is more likely to be used in the UK than in other countries, in which other forms of restraint such as seclusion or physical restraint are employed. Previous research by Professor Bowers showed that in some countries, such as the Netherlands, injecting someone against their will is seen as a serious violation of the body, yet the use of mechanical restraints is acceptable."
Jarrett and colleagues conclude that their review has highlighted a lack of clinical evidence on which to base CM, pointing out that the practice may discourage people from seeking help from, and engaging with, mental health services.
"Earlier and more effective interventions might be useful in minimising the use of CM, while better training in skills such as de-escalation strategies might also be valuable in avoiding coercion" says Jarrett.
The authors also feel that more research is needed into the use of CM.
"While there has been a lot of research into the pharmacological effectiveness of particular medications for quick and effective sedation, the reasons for the compulsory administration of powerful sedative and neuroleptic drugs have not been scrutinised closely or frequently. And there is little evidence that alternatives have been explored.
"The staff views reported in the literature and small number of studies available suggests that CM is a 'taken for granted' practice in inpatient psychiatry. We feel that this is unacceptable and more needs to be done to establish sound clinical evidence and viable alternatives to this contentious approach."
DURHAM, NC -- Fertility patients who are done having children feel responsible for the stored, frozen embryos left over from their treatment, yet more than half are against implanting the embryos in anyone else, according to a new study by researchers at Duke University Medical Center.
"This really turns our moral presumptions on their heads," says Anne Drapkin Lyerly, MD, an obstetrician/gynecologist and bioethicist at Duke, and lead investigator of the findings that appear online in Fertility & Sterility.
"Parents care very much about what happens to their embryos, but that doesn't mean they want them to become children. Our study shows that many feel they have to do what they can to prevent their embryo from becoming a child."
The survey of more than 1,000 fertility patients is the largest and only multi-site study to shed important light on the state of the nation's 500,000 frozen embryos currently in storage. It reveals previously unexplored concerns that patients have about their embryos, and it comes at a time when several states and even the federal government are attempting to enact legislation that would either assert an embryo is a person, allow abandoned embryos to be adopted by another couple, or allow unused embryos to become "wards of the state."
What to do with those unused embryos has also become a sticking point for providers, since they are held responsible for safe storage or disposition of apparently abandoned embryos.
Fresh embryos are used in more than 80% of fertility treatment cycles, but most patients also choose to freeze some embryos that were created but not implanted, to use as a possible backup. This means that extra embryos often remain after treatment is completed. Previous studies have found that when childbearing is complete, as many as 70 percent of patients put off for five years -- or more -- the decision of what to do with those frozen embryos, even while they continue to pay annual storage fees. In Lyerly's study, 20 percent of the patients who had completed childbearing indicated they were likely to freeze their embryos "forever."
The lack of acceptable options fuels patients' reluctance to make a decision. "Either the options they prefer aren't available or they are unacceptable," explains Lyerly.
In the survey, the researchers presented four embryo disposition options: thawing and discarding; reproductive donation; indefinite freezing; and donation for research. The majority were unlikely to choose any of these options except for one: research donation.
In a previous paper published in Science, Lyerly reported that 60 percent would be likely to donate unused embryos for stem cell research, an option not readily available. But even if federal policies on funding stem cell research change, Lyerly says that doesn't solve patients' conundrum.
"For many of these patients, the need to make a decision about disposing these embryos is not discussed up front. Understandably, fertility patients have hard times thinking about destroying their embryos when they are emotionally and financially invested in trying to make a baby," she says.
The conundrum arises when reproductive goals change without a renewed discussion about what to do with the embryos that have been stored. "Many centers don't make available all the options for disposition," Lyerly says. "Even in places where embryo research is not conducted, it's possible that embryos can be transferred to another center, yet this might not be discussed."
Two methods that were considered somewhat acceptable by about 20 percent of the fertility patients were placement of embryos in a woman's body at an infertile time, and the idea of a ritual disposal ceremony. Yet, Lyerly says these alternatives are rarely offered to patients even though "these may be the answers to many patients' desires as they allow the embryos to pass in a way that seems most respectful to them."
By bringing fertility patients' concerns to the forefront, Lyerly hopes the next step will be the development of clinical guidelines and ongoing informed consent processes for patients at various stages of fertility treatment. She also hopes it will encourage more detailed disclosure about the available disposition options and facilitate broad availability of disposition decisions that are morally acceptable to the majority of fertility patients.
Many specialized cells, such as in the skin, intestinal mucosa or blood, have a lifespan of only a few days. For these tissues to function, a steady replenishment of specialized cells is indispensable. This is the task of so-called "adult" stem cells also known as tissue stem cells.
Stem cells have two main characteristics: First, they are able to differentiate into all the different cell types that make up their respective tissue – a property called pluripotency. Second, they need to renew themselves in order to be able to supply new specialized tissue cells throughout life. These processes have best been studied in mouse bone marrow.
Up to now, scientists have assumed that adult stem cells have a low division rate. According to theory, they thus protect their DNA from mutations, which happen particularly during cell division and can lead to transformation into tumor stem cells. However, the actual number of divisions of a blood stem cell throughout an organism's lifespan has remained unknown.
Professor Dr. Andreas Trumpp and Dr. Anne Wilson have now discovered a group of stem cells in mouse bone marrow that remain in a kind of dormancy almost throughout life. Trumpp, who has been head of the Cell Biology Division at DKFZ since summer 2008, had carried out these studies at the Ecole Polytechnique Fédérale in Lausanne, Switzerland, jointly with colleagues at the Ludwig Institute for Cancer Research located in the same city.
The scientists labeled the genetic material of all mouse blood cells and subsequently investigated how long this label is retained. With each division, the genetic material is apportioned to the daughter cells and, thus, the labeling dilutes. During these studies, the investigators discovered the dormant stem cells which divide only about five times throughout the life of a mouse. Translated to humans, this would correspond to only one cell division in 18 years. Most of the time, these cells, which constitute no more than about 15 percent of the whole stem cell population, remain in a kind of dormancy with very low metabolism. In contrast, stem cells of the larger group, the "active" stem cells, divide continuously about once a month.
However, in an emergency such as an injury of the bone marrow or if the messenger substance G-CSF is released, the dormant cell population awakes. Once awakened, it shows the highest potential for self-renewal ever to be observed in stem cells. If transplanted into irradiated mice, these cells replace the destroyed bone marrow and restore the whole hematopoietic system. It is possible to isolate new dormant stem cells from the transplanted animals and these cells are able to replace bone marrow again – this can be done several times in a row. The situation is different with "active" stem cells, where bone marrow replacement can successfully be carried out only once.
"We believe that the sleeping stem cells play almost no role in a healthy organism," Trumpp explains. "The body keeps its most potent stem cells as a secret reserve for emergencies and hides them in caves in the bone marrow, also called niches. If the bone marrow is damaged, they immediately start dividing daily, because new blood cells are needed quickly." Once the original cell count is restored and the bone marrow is repaired, these stem cells go back to deep sleep. The larger population of "active" stem cells, however, keeps up the physiological balance of blood cells in the normal healthy state.
Andreas Trumpp expects that these results may give valuable impetus to our understanding of cancer stem cells: "Cancer stem cells, too, probably remain in a dormant state most of the time – we think that this is one of the reasons why they are resistant to many kinds of chemotherapy that target rapidly growing cells. If we were able to wake up these sleepers before a patient receives treatment, it might be possible to also eliminate cancer stem cells for the first time and, thus, to treat the disease much more effectively by destroying the supply basis."
In a second article*, Dr. Elisa Laurenti from Trumpp's team shows that the two cancer genes c-Myc and N-Myc play a vital role in the functioning of stem cells. The two genes provide the blueprints for what are called transcription factors, which in turn regulate the activity of other genes and are overactive particularly in cancer cells. If both c-Myc and N-Myc are switched off at the same time in mice, the animals quickly start suffering from a general lack of blood cells and quickly die.
The two genes are not only responsible for survival of nearly all blood cells, but they also jointly control the two prime characteristics of stem cells – the capability of self-renewal and the potential to produce differentiated blood cells. This result is not only relevant for our understanding of stem cells, but it also explains the damage that can be caused by overactive Myc genes. Trumpp explains: "In tumors, too, c-Myc and N-Myc are presumably responsible for the self-renewal of cancer stem cells and, thus, for uncontrolled growth."
WASHINGTON -- Stem cells derived from bone marrow may serve as a novel therapeutic option to treat a disease called epidermolysis bullosa (EB), a disorder characterized by extraordinarily fragile skin, according to a study prepublished online in Blood, the official journal of the American Society of Hematology.
Epidermolysis bullosa is a disorder characterized by extraordinarily fragile skin and blistering on touch, akin to third degree burns. While the disease is often lethal in the neonatal period, more severe forms of the disease, such as recessive dystrophic EB (referred to as RDEB), can lead to years of painful blistering and mutilating scarring. The condition is caused by significantly reduced collagen type 7 protein (col7) production, a key component of the anchoring fibrils that connect the cutaneous membranes to the dermis of the skin and mucosal tissues in the gastrointestinal tract. A lack of these fibrils means the dermal-epidermal connection is very sensitive, and any action, which can include simple functions such as walking or eating, and the touch of clothing, creates friction between the skin layers that creates blisters and painful sores.
Children with RDEB, who are often referred to as “butterfly children” because their skin is said to be as sensitive as butterfly wings, develop painful skin and mucosal blistering, mutilating scarring, alopecia (hair loss), and other erosions shortly after birth. As a result of the extreme fragility of the skin and the chronic trauma of friction, RDEB patients often develop squamous cell carcinomas (a form of skin cancer). There is currently no cure for the disease, and palliative care includes complex bandaging, surgical removal of damaged tissue, and nutritional support.
“We have been looking into stem cells as viable treatment options for correction of conditions such as epidermolysis bullosa, because they can produce extracellular matrix proteins,” said Jakub Tolar, MD, PhD, of the University of Minnesota and lead author of the study. “In this condition, the skin, the largest organ in the body, can significantly benefit from a renewable source of healthy cells that can help improve the connection between the dermis and epidermis and strengthen the skin against everyday stresses.”
In this study, researchers worked with a mouse model of RDEB-infused bone marrow cells to determine if they would increase production of the col7 protein and formation of anchoring fibrils, and improve survival in the mouse recipients. The research team used bone marrow cells enriched for hematopoietic (stem cells that can develop into most blood cell types) and progenitor cells to increase the concentration of cells with the capacity to produce col7. The team tested these cells against non-enriched stem cells to determine their benefit to the treated mice.
Results of the study found that when injected into mice with RDEB, these specially selected marrow-derived stem cells diminished the disease process. They traveled to the diseased skin areas, increased protein and anchoring fibrils, prevented blister formation and extended survival. In contrast to other marrow cells, the selected cells extended the median survival time versus untreated or non-enriched marrow-treated recipients (10.0 versus 5.6 versus 6.0 days, respectively). Three of the 20 mice treated with the enriched cells benefited enough from the treatment to survive longer than the treatment period (untreated RDEB mice usually die within two weeks). Importantly, each survivor demonstrated marked improvement of new blister formation (blisters develop consistently in the areas of trauma, including footpads due to walking or in the oral cavity due to eating) with some evidence of old blisters healing.
“Our data provide the first evidence that a selected population of marrow cells can connect the epidermis and dermis in a mouse model of the disease and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders. These results provide proof of principle of bone marrow transfer to repair the basement membrane defect in RDEB, and they warrant a clinical trial to assess the safety and efficacy of treatment of human RDEB by means of hematopoietic cell transplantation,” said Dr. Tolar.
Research suggests that the systemic infusion of wild-type bone marrow cells could provide benefit to other human disorders of the extracellular matrix. Efforts are underway to identify the requirements of bone marrow-derived stem cells capable of efficiently homing to wounded skin and producing an array of extracellular matrix proteins. As the principal advantage of systemic therapy is its potential to target not only the skin but also the mucosa of the mouth and gastrointestinal tract, the clinical testing of efficacy of human bone marrow for the treatment of human RDEB is underway to determine whether it is of more substantial benefit than local protein, gene, or cellular therapies currently being investigated by other researchers.
An estimated 50 in 1 million live births are diagnosed with EB. The disorder occurs in every racial and ethnic group throughout the world and affects both sexes.
CHAMPAIGN, Ill. -- With up to half of a person’s body mass consisting of skeletal muscle, chronic inflammation of those muscles – which include those found in the limbs – can result in significant physical impairment.
According to University of Illinois kinesiology and community health professor Kimberly Huey, past research has demonstrated that the antioxidant properties of Vitamin E may be associated with reduced expression of certain pro-inflammatory cytokines, in vitro, in various types of cells. Cytokines are regulatory proteins that function as intercellular communicators that assist the immune system in generating a response.
To consider whether the administration of Vitamin E, in vivo, might have similar effects on skeletal and cardiac muscle, Huey and a team of Illinois researchers put Vitamin E to the test in mice. The team included study designer Rodney Johnson, a U. of I. professor of animal sciences, whose previous work has suggested a possible link, in mice, between short-term Vitamin E supplementation and reduced inflammation in the brain.
The study represents the first time researchers have looked at in vivo effects of Vitamin E administration on local inflammatory responses in skeletal and cardiac muscle.
In this study, the researchers investigated the effects of prior administration of Vitamin E in mice that were then injected with a low dose of E. coli lipopolysaccharide (LPS) to induce acute systemic inflammation. The effects were compared with those found in placebo control groups.
The research team examined the impact the Vitamin E or placebo treatment had on the mRNA and protein levels of three cytokines – interleukin (IL-6), tumor necrosis factor-alpha (TNF-alpha) and IL-1beta.
“The mice were administered Vitamin E for three days prior to giving them what amounts to a minor systemic bacterial infection,” Huey said. “One thing we did – in addition to (looking at) the cytokines – was to look, in the muscle, at the amount of oxidized proteins.
“Oxidation can be detrimental, and in muscle has been associated with reduced muscle strength,” Huey said.
Among the team’s major findings, in terms of function, Huey said, was that “there was a significant reduction in the amount of LPS-induced oxidized proteins with Vitamin E compared to placebo.”
“So that’s a good thing,” she said. “Potentially, if you reduce the oxidized proteins, that may correlate to increased muscle strength.”
Additionally, the researchers’ experiments yielded a significant decrease in two cytokines – IL-6 and IL-1beta – with Vitamin E, compared with the placebo.
That finding translates to somewhat mixed reviews.
“It’s hard to say functionally what those cytokine changes might mean,” Huey said. “IL-1beta is primarily a pro-inflammatory cytokine, so that could be a good thing – especially in terms of cardiac function.”
However, she said, “IL-6 can have both pro- or anti-inflammatory actions.” She said that the literature has yielded some evidence pointing to the detrimental effects of chronic increases in IL-6. But the effects of acute increases in IL-6 in skeletal muscles – which occur during exercise – may be another story.
“Whether there’s a difference between exercise-induced increases versus inflammation-induced increases in IL-6 is still highly debatable,” she said.
Nonetheless, Huey said, the larger take-home message of the study, published in the December issue of the journal Experimental Physiology, is that Vitamin E “may be beneficial in individuals with chronic inflammation, such as the elderly or patients with type II diabetes or chronic heart failure.”
While the Illinois research team’s work provides a foundation for future investigations that could ultimately have positive outcomes for people afflicted with chronic skeletal or cardiac muscle inflammation, Huey cautioned that it is still far too soon to speculate on results in humans.
“This is clearly an animal model so whether it would translate to humans still requires a lot more research,” she said. “Vitamin E is a supplement that is already approved, and these results may suggest an additional benefit of taking Vitamin E beyond what’s already been shown.”
In addition to Huey and Johnson, other members of the research team included undergraduate student Gabriel Fiscus, graduate student Ben Meador and former graduate student Amy Richwine.
Researchers find a novel mechanism for a healthier heart
Results from the European study IMMIDIET show that moderate wine intake is associated with higher levels of omega-3 fatty acids considered as protective against coronary heart disease
Moderate alcohol intake is associated with higher levels of omega-3 fatty acids in plasma and red blood cells. This is the major finding of the European study IMMIDIET that will be published in the January issue of the American Journal of Clinical Nutrition, an official publication of the American Society for Nutrition and is already available on line (www.ajcn.org ). The study suggests that wine does better than other alcoholic drinks. This effect could be ascribed to compounds other than alcohol itself, representing a key to understand the mechanism lying behind the heart protection observed in moderate wine drinkers.
The IMMIDIET study examined 1,604 citizens from three geographical areas: south-west London in England, Limburg in Belgium and Abruzzo in Italy. Thanks to a close cooperation with General Practitioners of these areas, all participants underwent a comprehensive medical examination, including a one year recall food frequency questionnaire to assess their dietary intake, alcohol consumption included.
Omega-3 fatty acids, mainly derived from fish, are considered as protective against coronary heart disease and sudden cardiac death, thus their high blood concentration is definitely good for our health.
Now European researchers found that moderate alcohol drinking acts like a 'trigger', boosting the amount of omega-3 fatty acids in our body.
"Several studies have shown that moderate alcohol consumption, including wine, is associated with protection against coronary heart disease and ischemic stroke - says Romina di Giuseppe, lead author of the study, from the Research Laboratories at Catholic University of Campobasso - Although the mechanisms are not completely defined, there was some evidence that alcohol intake might influence the metabolism of essential polyunsaturated fatty acids, as omega-3. That is exactly what we found in our population study. People drinking moderate amounts of alcohol, one drink a day for women and two for men, had higher concentration of omega-3 fatty acids in plasma and red blood cells independently of their fish intake".
However important these results appear to be, the best is yet to come. Researchers from Catholic University of Campobasso, in Italy, and from University of Grenoble, in France, turned their attention on the variety of alcoholic beverages consumed in order to see whether the high levels of omega-3 fatty acids detected might be ascribed to alcohol itself or to other substances.
"From our previous studies we know that association between wine drinking and increased concentration of omega-3 fatty acids have been observed – says Michel de Lorgeril, from the University of Grenoble, partner of the IMMIDIET project and co-leader of the study - Nevertheless, it was not possible to separate the effects of wine from those of beer or spirits. Our study of 3 populations with different dietary habits and different consumption of alcoholic beverages types allowed us to explore this aspect.".
"Analysis carried out on different alcoholic beverages –argues Licia Iacoviello coordinator of the IMMIDIET study at Catholic University of Campobasso - showed that the association between alcohol and omega-3 fatty acids was present in both wine drinkers and beer or spirits drinkers. However, the association was stronger between wine drinking and omega-3 fatty acids levels. This suggests that components of wine other than alcohol is associated with omega-3 fatty acids concentration. We may guess this effect can be ascribed to polyphenols".
Polyphenols are naturally occurring compounds contained in a different variety of food and beverages, such as wine. Due to their strong antioxidant activity, they are able to reduce oxidation processes caused by free radicals.
"We consider these data to be a major finding - de Lorgeril concludes - opening a new window in the field of cardiovascular prevention. Beyond the alcohol issue, our results raise crucial questions regarding the effects of polyphenols on lipids (both in blood and cell membranes) and possibly of lipids on polyphenols".
The IMMIDIET study
Funded by the European Union under Key Action 1: Food, Nutrition and Health QLK1-CT-2000-00100, IMMIDIET aims to acquire fundamental knowledge in the field of cardiovascular disease, especially regarding the interaction between genetics and lifestyle.
At the core of the study there is an important episode of Italian migration: Belgium, a country that became the new home for thousands of Italians, mostly from the Abruzzo region, who came to work in the mines. Many of those emigrants didn't come back to Italy but remained in their new country. Some of them married a Belgian partner. Their genes remained the same, of course, but how much "Italy" is still there in their diet? And how much did they transmit it to their spouses? Moreover, how many Italian emigrants assimilate dietary habits of the country in which they were guests? In this framework, the role of genetic factors and lifestyle can be assessed to explore new ways in prevention of cardiovascular diseases.
To carry on the research, married couples have been recruited in three European areas: South-East London in England, Limburg in Belgium and Abruzzo in Italy. In the first phase of the study the couples involved were formed by people from the same area, Italians married with Italians (in the Abruzzo region), Belgians married with Belgians (in the Limburg area) and English married with English (in the South-East part of London)".
The second phase of IMMIDIET recruited mixed Italian–Belgian couples to understand if, acquiring dietary habits from Abruzzo, the Belgian partner changed his own risk regarding heart diseases.
###
IMMIDIET PARTNERS
Scientific coordinator:
Licia Iacoviello
Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, "John Paul II" Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso - Italy
Participants:
Jozef Arnout
Center for Molecular and Vascular Biology, Katholieke Universiteit, Leuven - Belgium
Frank Buntinx
Department of General Practice, Katholieke Universiteit, Leuven - Belgium
Francesco P. Cappuccio
Clinical Sciences Research Institute, University of Warwick Medical School, Coventry – United Kingdom
Pieter C. Dagnelie
Department of Epidemiology, NUTRIM Subdivision of Nutritional Epidemiology, Maastricht University - The Netherlands
Michel de Lorgeril
Nutrition Vieillissement et Maladies Cardiovasculaires, UFR de Medecine, La Tronche, Grenoble - France
Vittorio Krogh
Nutritional Epidemiology Unit, National Cancer Institute, Milan - Italy
Alfonso Siani
Unit of Epidemiology and Population Genetics, Institute of Food Sciences CNR, Avellino - Italy