A new model developed by Wellcome Trust researchers to predict the persistence of stuttering could be used to screen all children at school age, new research suggests. Stuttering – also known as stammering – is thought to affect one in 20 children under the age of five, and onset generally occurs around the age of three. Around one child in 100 is likely to still be stuttering in their teenage years.
Screening for communication problems at key stages, including school entry, was suggested by the government in its Every Child Matters initiative, which was launched ten years ago.
Professor Peter Howell and colleagues from the Division of Psychology and Language Sciences at UCL (University College London) previously developed a model that allowed them to accurately predict which children at the age of eight would continue to stutter in their teenage years. In this new study, Professor Howell used the model to show that it is possible to screen children for stuttering when they enter primary school, around the age of five.
Professor Howell says: ‘For a screening tool to be used effectively, it needs to meet the rigorous standards for accurately identifying children who stutter separately from children who are fluent. We found that this method can do just that.
‘If we can identify children at risk of stuttering, then we can offer appropriate interventions to help them early on. Primary school is a key time in a child’s development and any help in tackling potential communication problems could make a big difference to the child’s life.’
Professor Howell developed the model working with 222 children who stutter and 103 fluent children, and he and his colleagues validated their findings in 272 children who stutter and 25 fluent children, all between ages five and 18. He used the Stuttering Severity Instrument Version 3 (SSI-3, a standardised test involving measurement of speech symptoms, their durations and physical symptoms accompanying stuttering such as tics), which they had previously been shown to be the only reliable tool for predicting persistence of stuttering.
He found that their model performs extremely well with five-year-olds. At this age, over 96 per cent of children who stutter and over 83 per cent of fluent children would be correctly identified. Although this would mean that some children who do not stutter would be incorrectly classified, Professor Howell and colleagues believe that some of these fluent children may suffer from other communication problems. Wellcome Trust

A new study reveals that primitive human stem cells are resistant to human cytomegalovirus (HCMV), one of the leading prenatal causes of intellectual disability, deafness and deformities worldwide. Researchers from the University of Pittsburgh School of Medicine found that as stem cells and other primitive cells mature into neurons, they become more susceptible to HCMV, which could allow them to find effective treatments for the virus and to prevent its potentially devastating consequences.

‘Previous studies have focused on other species and other cell types, but those studies did not evaluate what the cytomegalovirus does to human brain cells,’ said Vishwajit Nimgaonkar, M.D., Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine, and senior author of the report. ‘This study is the first of its kind, and the first to discover that primitive stem cells are actually resistant to HCMV.’

Access to cultured human neurons, necessary to understand the pathogenic effects of HCMV, has been limited by difficulties in growing the brain cells in the laboratory. Yet through human-induced pluripotent stem (iPS) cells, researchers were able to overcome this hurdle.

The study authors derived live iPS cells by reprogramming cells called fibroblasts obtained from human skin biopsies. The iPS cells were then induced to mature through several stages into neurons, the primary cells in the brain. The researchers were able to evaluate the patterns of damage caused by HCMV on all these cells.

The research findings suggest:
• Human iPS cells do not permit a full viral replication cycle, suggesting for the first time that these cells can resist CMV infection
• CMV infection distorts iPS cell differentiation into neurons, and that may be a mechanism by which infected babies develop impairments of brain maturation and intellectual ability
• iPS-derived mature neurons are more susceptible to CMV infection and once infected show effects including defective function that have been shown in other animal studies and in other human tissues, and the neurons die a few days after infection lab studies, possibly reflecting the impact of CMV on the human brain

‘The findings were quite surprising, but this is only the first in a series of studies on HCMV,’ added Nimgaonkar. ‘There is a lot of interest in what we can do to treat the infection, and current work is already underway to screen for new drugs that could be used to fight these viruses.’

Between 50 and 80 percent of people in the U.S. have been infected by HCMV by the time they reach 40. Infections are rarely serious, but the virus does not leave the body. CMV is also the most common congenital infection in the U.S., and occurs when a mother contracts CMV during pregnancy and passes the virus to her unborn child. According to the U.S. Centers for Disease Control and Prevention, one of every 150 children are born with CMV infection and one in five of them develop permanent problems, such as intellectual disability, vision and hearing loss, and seizures.

Pitt researchers are collaborating with the Drug Discovery Institute to further understand the cellular system and determine which agents are most effective against HCMV and similar viruses, and which treatments would be safe for human use. University of Pittsburgh

The possibility of an inexpensive, convenient test for Alzheimer’s disease has been on the horizon for several years, but previous research leads have been hard to duplicate.
In a study, scientists have taken a step toward developing a blood test for Alzheimer’s, finding a group of markers that hold up in statistical analyses in three independent groups of patients.
‘Reliability and failure to replicate initial results have been the biggest challenge in this field,’ says lead author William Hu, MD, PhD, assistant professor of neurology at Emory University School of Medicine. ‘We demonstrate here that it is possible to show consistent findings.’
Hu and his collaborators at the University of Pennsylvania and Washington University, St. Louis, measured the levels of 190 proteins in the blood of 600 study participants at those institutions. Study participants included healthy volunteers and those who had been diagnosed with Alzheimer’s disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer’s disease, causes a slight but measurable decline in cognitive abilities.
A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer’s. When those markers were checked against data from 566 people participating in the multicenter Alzheimer’s Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide.
Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer’s. The analysis grouped together people with MCI, who are at high risk of developing Alzheimer’s, and full Alzheimer’s.
‘We were looking for a sensitive signal,’ says Hu. ‘MCI has been hypothesised to be an early phase of AD, and sensitive markers that capture the physiological changes in both MCI and AD would be most helpful clinically.’
‘The specificity of this panel still needs to be determined, since only a small number of patients with non-AD dementias were included,’ Hu says. ‘In addition, the differing proportions of patients with MCI in each group make it more difficult to identify MCI- or AD-specific changes.’
Neurologists currently diagnose Alzheimer’s disease based mainly on clinical symptoms. Additional information can come from PET brain imaging, which tends to be expensive, or analysis of a spinal tap, which can be painful.
‘Though a blood test to identify underlying Alzheimer’s disease is not quite ready for prime time given today’s technology, we now have identified ways to make sure that a test will be reliable,’ says Hu. ‘In the meantime, the combination of a clinical exam and cerebrospinal fluid analysis remains the best tool for diagnosis in someone with mild memory or cognitive troubles.’ EurekAlert

New research reveals a shared genetic susceptibility to epilepsy and migraine. Findings indicate that having a strong family history of seizure disorders increases the chance of having migraine with aura (MA).
Medical evidence has established that migraine and epilepsy often co-occur in patients; this co-occurrence is called ‘comorbidity.’ Previous studies have found that people with epilepsy are substantially more likely than the general population to have migraine headache. However, it is not clear whether that comorbidity results from a shared genetic cause.
‘Epilepsy and migraine are each individually influenced by genetic factors,’ explains lead author Dr. Melodie Winawer from Columbia University Medical Center in New York. ‘Our study is the first to confirm a shared genetic susceptibility to epilepsy and migraine in a large population of patients with common forms of epilepsy.’
For the present study, Dr. Winawer and colleagues analysed data collected from participants in the Epilepsy Phenome/Genome Project (EPGP)—a genetic study of epilepsy patients and families from 27 clinical centres in the U.S., Canada, Argentina, Australia, and New Zealand. The study examined one aspect of EPGP: sibling and parent-child pairs with focal epilepsy or generalised epilepsy of unknown cause. Most people with epilepsy have no family members affected with epilepsy. EPGP was designed to look at those rare families with more than one individual with epilepsy, in order to increase the chance of finding genetic causes of epilepsy.
Analysis of 730 participants with epilepsy from 501 families demonstrated that the prevalence of MA—when additional symptoms, such as blind spots or flashing lights, occur prior to the headache pain— was substantially increased when there were several individuals in the family with seizure disorders. EPGP study participants with epilepsy who had three or more additional close relatives with a seizure disorder were more than twice as likely to experience MA than patients from families with fewer individuals with seizures. In other words, the stronger the genetic effect on epilepsy in the family, the higher the rates of MA. This result provides evidence that a gene or genes exist that cause both epilepsy and migraine.
Identification of genetic contributions to the comorbidity of epilepsy with other disorders, like migraine, has implications for epilepsy patients. Prior research has shown that coexisting conditions impact the quality of life, treatment success, and mortality of epilepsy patients, with some experts suggesting that these comorbidities may have a greater impact on patients than the seizures themselves. In fact, comorbid conditions are emphasised in the National Institutes of Health Epilepsy Research Benchmarks and in a recent report on epilepsy from the Institute of Medicine.
‘Our study demonstrates a strong genetic basis for migraine and epilepsy, because the rate of migraine is increased only in people who have close (rather than distant) relatives with epilepsy and only when three or more family members are affected,’ concludes Dr. Winawer. ‘Further investigation of the genetics of groups of comorbid disorders and epilepsy will help to improve the diagnosis and treatment of these comorbidities, and enhance the quality of life for those with epilepsy.’ Columbia University Medical Center

Researchers Patricia A. Champion and Matthew Champion from the University of Notre Dame’s Eck Institute for Global Health have developed a method to directly detect bacterial protein secretion, which could provide new insights into a variety of diseases including tuberculosis.
The Champions point out that bacteria use a variety of secretion systems to transport proteins beyond their cell membranes in order to interact with their environment. For bacterial pathogens such as TB, these systems transport bacterial proteins that promote interaction with host cells, leading to virulent disease.
Previously, researchers have relied on methods that have fused enzymes or fluorescent markers to bacterial proteins to identify bacterial genes that are used to export bacterial proteins into host cells. However, these methods can’t be used in the analysis of all bacterial secretion systems, which has limited understanding of the mechanisms that bacteria use to interact with host cells.
The Champions developed a modified form of bacterial proteomics using a MALDI-TOF mass spectrometer, which directly detects the proteins from whole colonies by ionising them with a laser. This research revealed that the method was able to specifically monitor a specialised form of protein secretion, which is a major virulence determinant in both mycobacterial pathogens, such as TB, and Gram-positive pathogens, such as Bacillus and Staphylococcus species.
The Champions demonstrated that this new method is applicable to the study of other bacterial protein export systems that could not be effectively studied under previous methods. Their method could also help in the identification of compounds that can inhibit bacterial protein secretion.
The method’s importance can be seen in the fact that there are approximately 2 million fatal TB cases each year, mostly in the developing world. Also, antibiotic-resistant strains of TB are appearing increasingly. University of Notre Dame