Genome-wide screen of learning in zebrafish identifies enzyme important in neural circuit

Implications for understanding underlying molecular genetics of human neuropsychiatric disorders, according to Penn study

Researchers at the Perelman School of Medicine at the University of Pennsylvania describe the first set of genes important in learning in a zebrafish model in the journalNeuron this week. “Using an in-depth analysis of one of these genes, we have already revealed an important relevant signaling pathway,” says senior author Michael Granato, PhD, a professor of Cell and Developmental Biology. “The proteins in this pathway could provide new insights into the development of novel pharmacological targets.”Over the last 20 years, zebrafish have become great models for studying development and disease. Like humans, zebrafish are vertebrates and over 80 percent of human genes bearing disease descriptions are also present in zebrafish. As such, this animal model has become increasingly popular to study human diseases such as cardiovascular conditions or tumor formation.

Read the rest of the article at http://www.medicalnewstoday.com/releases/291338.php.

Childhood sleep disorders: how do they affect health and well-being?

Although around 25-40% of children and adolescents in the US experience some form of sleep disorder, such conditions are often overlooked, with a lack of realization of just how important a good night’s sleep is for a child’s present and later-life health. In line with National Sleep Awareness Week, we look at how sleep problems can affect the short- and long-term health of children and teenagers and what parents can do to reduce these risks.When you think of sleep disorders in children, the first types likely to spring to mind are night terrors, nightmares and sleepwalking. These fall into a class of sleep disorders known as parasomnias.It is estimated that up to 6.5% of children – particularly those aged 4-12 years – experience night terrors, defined as episodes of intense fear, screaming and flailing during sleep. Approximately 3% of preschool and school-aged children experience nightmares, while up to 15% of children aged 4-12 years sleepwalk.Perhaps less associated with children and adolescents isinsomnia and obstructive sleep apnea. In fact, insomnia, the inability to fall asleep or frequent awakening, is estimated to affect around 25% of children and teenagers. Obstructive sleep apnea – when an individual stops breathing for long periods during sleep – affects around 2-4% of children.

Read the rest of the article at http://www.medicalnewstoday.com/articles/290441.php.

NSAIDS linked to risk of bleeding in heart attack patients

Even short-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen increases the risk of bleeding in patients taking anti-clotting drugs after a heart attack, a study published in JAMA suggests.All patients who have had a myocardial infarction (MI) are recommended to take two antithrombotic drugs (aspirin and clopidogrel) as preventive treatment for up to a year after the heart attack, and to continue taking one of the anti-clotting pills thereafter.Risk of bleeding is known to be increased by then adding the use of NSAIDs, and some – ibuprofen, for example – have a counter effect to the preventive heart drugs, inhibiting the antithrombotic effects of aspirin.Guidelines from the American Heart Association, therefore, recommend against the use of NSAIDs in people with established heart disease.

Read the rest of the article at  http://www.medicalnewstoday.com/articles/289822.php.

New nanoparticle gene therapy strategy effectively treats deadly brain cancer in rats

Fast Facts

• Gene therapy may effectively treat glioma, a deadly form of brain cancer, but getting the right genes to cancer cells in the brain is difficult.
• For the first time, Johns Hopkins researchers used biodegradable nanoparticles to kill brain cancer cells in animals and lengthen their survival.
• The nanoparticles are filled with genes for an enzyme that turns a compound into a potent killer of cancer cells.

Despite improvements in the past few decades with surgery, chemotherapy and radiation therapy, a predictably curative treatment for glioma does not yet exist. New insights into specific gene mutations that arise in this often deadly form of brain cancer have pointed to the potential of gene therapy, but it’s very difficult to effectively deliver toxic or missing genes to cancer cells in the brain. Now, Johns Hopkins researchers report they have used nanoparticles to successfully deliver a new therapy to glioma cells in the brains of rats, prolonging their lives. A draft of the study appeared on the website of the journal ACS Nano.Previous research on mice found that nanoparticles carrying genes can be taken up by brain cancer cells, and the genes can then be turned on. However, this is the first time these biodegradable nanoparticles have effectively killed brain cancer cells and extended survival in animals.For their studies, the Johns Hopkins team designed and tested a variety of nanoparticles made from different polymers, or plastics. When they found a good candidate that could deliver genes to rat brain cancer cells, they filled the nanoparticles with DNA encoding an enzyme, herpes simplex virus type 1 thymidine kinase (HSVtk), which turns a compound with little effect into a potent therapy that kills brain cancer cells. When combined with the compound, called ganciclovir, these loaded nanoparticles were 100 percent effective at killing glioma cells grown in laboratory dishes.

Read the rest of the article at http://www.medicalnewstoday.com/releases/289033.php.

Research unlocks revolutionary new procedure for epilepsy diagnosis

Pioneering new research by the University of Exeter could revolutionise global diagnostic procedures for one of the most common forms of epilepsy.

Scientists from Exeter have investigated using mathematical modelling to assess susceptibility to idiopathic generalised epilepsy (IGE) by analysing electrical activity of the brain while the patient is in a resting state.

Current diagnosis practices typically observe electrical activities associated with seizures in a clinical environment.

The ground-breaking research has revealed differences in the way that distant regions of the brain connect with each other and how these differences may lead to the generation of seizures in people with idiopathic generalized epilepsies (IGE).

By using computer algorithms and mathematical models, the research team, led by Professor John Terry, was able to develop systems to analyse EEG recordings gathered while the patient is at rest, and reveal subtle differences in dynamic network properties that enhance susceptibility to seizures.

Professor Terry said: “Our research offers the fascinating possibility of a revolution in diagnosis for people with epilepsy.

“It would move us from diagnosis based on a qualitative assessment of easily observable features, to one based on quantitative features extracted from routine clinical recordings.

“Not only would this remove risk to people with epilepsy, but also greatly speed up the process, since only a few minutes of resting state data would need to be collected in each case.”

The pivotal research has been published in a recent series of papers, the most recent of which has been published online in the scientific journal Frontiers in Neurology.

In their first study, EEG recordings were used to build a picture of how different regions of the brain were connected, based upon the level of synchrony between them. The collaborative team of researchers from Exeter and Kings College, London, then used a suite of mathematical tools to characterise these large-scale resting brain networks, observing that in people with IGE these networks were relatively over-connected, in contrast to healthy controls.

They further observed a similar finding in first-degree relatives of this cohort of people with IGE; an intriguing finding which suggests that brain network alterations are an endophenotype of the condition – an inherited and necessary, but not sufficient, condition for epilepsy to occur.

In a second study the team sought to understand how these alterations in large-scale brain networks could heighten susceptibility to recurrent seizures and thus the condition epilepsy. The study revealed two intriguing findings – firstly, the level of communication between regions that would lead to their activity becoming synchronised was lower in the brain networks of people with IGE, suggesting a possible mechanism of seizure initiation; and further that altering the activity in specific left frontal brain regions of the computational model could more easily lead to synchronous activity throughout the whole network.

In their most recent study, researchers have introduced the concept of “Brain Network Ictogenecity” (or BNI) as a probabilistic measure for a given network to generate seizures. They found that the brain networks of people with IGE had a high BNI, whereas the brain networks of healthy controls had a low BNI.

Professor Terry said: “Our most recent analyses have revealed that the average connectedness of each brain region is key to creating an environment where seizures can thrive.

This feature appropriately discriminates between cohorts of people with idiopathic generalized epilepsies and healthy control subjects. The next critical state of our research is to validate in a prospective study the predictive power of these findings.”

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/286864.php

Link discovered between tooth loss and slowing mind and body

The memory and walking speeds of adults who have lost all of their teeth decline more rapidly than in those who still have some of their own teeth, finds new UCL research.

The study, published in the Journal of the American Geriatrics Society, looked at 3,166 adults aged 60 or over from the English Longitudinal Study of Ageing (ELSA) and compared their performance in tests of memory and walking speed. The results showed that the people with none of their own teeth performed approximately 10% worse in both memory and walking speed tests than the people with teeth.

The association between total tooth loss and memory was explained after the results were fully adjusted for a wide range of factors, such as sociodemographic characteristics, existing health problems, physical health, health behaviours, such as smoking and drinking, depression, relevant biomarkers, and particularly socioeconomic status. However, after adjusting for all possible factors, people without teeth still walked slightly slower than those with teeth.

These links between older adults in England losing all natural teeth and having poorer memory and worse physical function 10 years later were more evident in adults aged 60 to 74 years than in those aged 75 and older.

“Tooth loss could be used as an early marker of mental and physical decline in older age, particularly among 60-74 year-olds,” says lead author Dr Georgios Tsakos (UCL Epidemiology & Public Health). “We find that common causes of tooth loss and mental and physical decline are often linked to socioeconomic status, highlighting the importance of broader social determinants such as education and wealth to improve the oral and general health of the poorest members of society.

“Regardless of what is behind the link between tooth loss and decline in function, recognising excessive tooth loss presents an opportunity for early identification of adults at higher risk of faster mental and physical decline later in their life. There are many factors likely to influence this decline, such as lifestyle and psychosocial factors, which are amenable to change.”

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/287280.php

 

 

 

Capacity to balance on one leg reflects brain health

Struggle to balance on one leg? It is a simple act that reduces many to wobbling and windmilling, but there may be a place for it in medicine. According to new research, an inability to balance on one leg for 20 seconds or longer could signal brain damage in otherwise healthy individuals.

 

The study, published in Stroke, reports an association between a lack of balancing skills and an increased risk for small blood vessel damage and reduced cognitive function in people who appear otherwise asymptomatic.

“Our study found that the ability to balance on one leg is an important test for brain health,” said lead study author Yasuharu Tabara, from the Kyoto University Graduate School of Medicine in Kyoto, Japan.

The ability to stand on one leg has previously been recommended as a predictor of certain health outcomes. In a study published in the BMJ earlier this year, researchers found an association between the amount of time people at the age of 53 were able to balance on one leg and all cause mortality rates.

Small vessel disease damages arteries by making them less flexible, interfering with the flow of blood. The incidence of this disease often increases with age.

Cerebral blood vessel disease is believed to indicate an elevated risk of future symptomatic stroke. In previous studies, subclinical (asymptomatic) brain damage has been indicated by loss of motor co-ordination and cognitive impairment.

Brain lesions and balancing

The researchers asked participants to stand on one leg for up to 60 seconds (if possible) with both eyes open. This examination was carried out twice, with the best recorded time from each participant used within the study analysis. A total of 841 women and 546 men, with an average age of 67, participated in the study.

Afterward, the brains of the participants were examined using magnetic resonance imaging (MRI) to evaluate any cerebral small vessel disease damage. Cognitive impairment was also measured by the researchers, using computer-based questionnaires.

Cerebral small vessel disease was associated with being unable to balance on one leg for more than 20 seconds. In particular, the researchers noted an association with small subclinical infarctions – obstruction of blood supply to tissue leading to tissue death – such as lacunar infarctions and microbleeds.

The following numbers of participants had trouble balancing on one leg:

• 34.5% of participants with more than two lacunar infarction lesions
• 16% of participants with one lacunar infarction lesion
• 30% of participants with more than two microbleed lesions
• 15.3% of participants with one microbleed lesion.

Inability to stand on one leg for particularly long was also independently associated with lower cognitive functioning scores.

Participants found to have cerebral small vessel disease were, on average, older with higher blood pressure and thicker carotid arteries than participants without damage to their brains. Once the researchers adjusted their findings for these factors, participants with more subclinical infarctions were found to have shorter times for standing on one leg.

Potentially a ‘consequence of the presence of brain abnormalities’

The researchers write that previous studies have consistently found evidence supporting a relationship between postural instability and changes within the brain, but few have extended this connection to lacunar infarction or microbleeds.

A major limitation of the study is that the researchers did not assess the participants’ histories of falling or potential physical fitness issues, including abnormalities in their gaits, which could have had major implications for their findings.

The authors state that additional long-term studies will be required in order to verify these findings and fully assess the significance of postural instability.

“One-leg standing time is a simple measure of postural instability and might be a consequence of the presence of brain abnormalities,” concludes Tabara. “Individuals showing poor balance on one leg should receive increased attention, as this may indicate an increased risk for brain disease and cognitive decline.”

Earlier this month, Medical News Today reported on a study finding that people with lower levels of oxygen in their blood were more likely to develop subclinical infarctions.

Written by James McIntosh

http://www.medicalnewstoday.com/articles/287201.php

 

 

Parkinson’s drugs likely safe for the heart, larger studies needed

Non-ergot derived dopamine agonists used to treat Parkinson’s disease may be safe for the heart, according to preliminary research presented at EuroEcho-Imaging 2014 by Dr Hilal Erken Pamukcu, cardiologist at Ankara Diskapi Education and Research Hospital in Turkey.

EuroEcho-Imaging is the annual meeting of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC), and was held 3-6 December in Vienna, Austria.

Dr Erken Pamukcu said: “Parkinson’s disease is a neurological disorder that occurs in nearly 1% of the world’s population over 60 years of age and in 4% of people over 80 years of age. Various drug treatments are available. Ergot derived dopamine agonists were often used in the past but today their usage is not preferred by most neurologists worldwide because they caused fibrotic heart valve disease and fibrosis in other tissues.”

She continued: “Today, non-ergot derived dopamine agonists are widely used in daily clinical practice but recent studies have suggested that the non-ergot derived dopamine agonist pramipexole increases the risk of heart failure. In September 2012 the US Food and Drug Administration (FDA) informed the public about a possible increased risk of heart failure with pramipexole but the studies were inconclusive and the review is ongoing.”

The current study was designed to investigate whether the use of pramipexole and ropinirole, both non-ergot derived dopamine agonists, was associated with heart failure. Heart failure was deemed to occur if patients had asymptomatic myocardial dysfunction and deterioration of myocardial systolic function. These were assessed by examining left ventricular function using two-dimensional strain echocardiography.

The same measurements were made in patients taking levodopa, a drug commonly used in Parkinson’s disease that does not have any adverse cardiac effects. Dr Erken Pamukcu explained: “We could not create a control group of Parkinson’s disease patients who were not taking any drugs because most of these patients take one or more drugs. We therefore used patients taking only levodopa as a control group.”

The study included 55 patients with Parkinson’s disease, of which 24 were taking levodopa alone, 18 were using levodopa and pramipexole and 13 were using levodopa and ropinirole. The mean age of the study population was 63 years. There were no significant differences between groups in age, sex or presence of hypertension.

The researchers did not find any significant differences between groups in the global and segmental longitudinal strain length and strain rate values.

Dr Erken Pamukcu said: “Our measurements of left ventricular function produced similar values in all three treatment groups. We did not detect any evidence of asymptomatic myocardial dysfunction or deterioration of systolic function in patients taking pramipexole or ropinirole.”

She continued: “As we did not show any statistically significant myocardial dysfunction in the groups taking pramipexole or ropinirole, our study suggests that these drugs do not cause heart damage. Our conclusion from this small, preliminary study is that non-ergot derived dopamine agonists are safe for the heart.”

Dr Erken Pamukcu concluded: “We believe this is the first study to assess left ventricular function using two-dimensional strain echocardiography in Parkinson’s disease patients taking non-ergot dopamine agonists. This may be a new approach to study the cardiac effects of these drugs. Larger studies are needed to confirm our results.”

http://www.medicalnewstoday.com/releases/286498.php

 

 

Specialized ambulance increases thrombolysis for stroke patients in ‘golden hour’

A specialized ambulance staffed with a neurologist and equipped with a computed tomographic scanner helped increase the percentage of patients with stroke who received thrombolysis to break down blood clots within the so-called ‘golden hour,’ the 60 minutes from time of symptom onset to treatment when treatment may be most effective, according to a study published online by JAMA Neurology.

The time to treatment with tissue plasminogen activator (tPA) to break down blood clots is crucial to how patients fare after acute ischemic stroke. But when prehospital times are added to hospital delays the onset to treatment (OTT) within 60 minutes seems out of reach for most patients. An approach to shorten the OTT is prehospital thrombolysis in a specialized ambulance, according to background information in the study.

Martin Ebinger, M.D., of the Charité-Universitätsmedizin Berlin, Germany, and co-authors examined the achievable rate of golden hour thrombolysis in prehospital care and the effect it had on how patients fared. The authors used data from a study conducted in Berlin where weeks were randomized according to the availability of a stroke emergency mobile unit (STEMO) from May 2011 through January 2013.

Study results indicate there were 3,213 emergency calls for suspected stroke during weeks when STEMO was available and 2,969 calls during control weeks when STEMO was not available. Overall, 200 of 614 patients with stroke (32.6 percent) received thrombolysis when the STEMO was deployed and 330 of 1,497 patients (22 percent) received thrombolysis in conventional care. Median OTT was 24.5 minutes shorter after STEMO deployment compared with conventional care. In all ischemic strokes, the rate of golden hour thrombolysis increased from 16 of 1,497 patients (1.1 percent) during conventional care to 62 of 614 (10.1 percent) after STEMO deployment. The median OTT was 50 minutes in golden hour thrombolysis vs. 105 minutes in all other thrombolysis. Patients with golden hour thrombolysis had no higher risks for seven- or 90-day mortality compared with patients with longer OTT and were more likely to be discharged home.

“The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour. Golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes,” study notes.

Editorial: Prehospital Thrombolysis for Stroke, ‘Golden Hour’ Has Arrived

In a related editorial, Steven Warach, M.D., Ph.D., of the University of Texas Southwestern Medical Center, Austin, writes: “There is no doubt that, in Berlin, STEMO significantly shortened the time to thrombolytic treatment, which may translate to clinical benefits. Let there also be no doubt that the mobile stroke unit is here to stay and is starting to disseminate into prehospital stroke care. Many questions need to be answered in order to determine the appropriate niche where the benefit justifies the intensive use of resources that this approach requires. It is the duty of the early adopters to resist the temptation to uncritically embrace this approach as a certain good and to address these issues through rigorous clinical investigations.”

http://www.medicalnewstoday.com/releases/285558.php

 

 

Could a high-fat diet help slow brain aging?

Brain aging can be delayed in mice if they are placed on a high-fat diet, according to a study conducted by the Center for Healthy Aging at the University of Copenhagen in Denmark and the National Institute of Health.

It is normal for defects to appear in the nervous system as people age. Among these, the brain loses some of its intellectual capacity, and the risk of Parkinson’s and Alzheimer’s disease increases.

Although human cells have a system for repairing damage to DNA, this repair function breaks down as we age.

This damage to DNA has been linked with Alzheimer’s and Cockayne syndrome – a premature aging disorder that results in death by the age of 10-12.

The new study uses a mouse model of Cockayne syndrome to investigate these defects to the DNA repair system.

Lead author Prof. Vilhelm Bohr – from the Center for Healthy Aging, University of Copenhagen and the National Institute of Health – describes the team’s findings:

“The study is good news for children with Cockayne syndrome, because we do not currently have an effective treatment. Our study suggests that a high-fat diet can postpone [the] aging processes.”

“A diet high in fat also seems to postpone the aging of the brain. The findings, therefore, potentially imply that patients with Alzheimer’s and Parkinson’s disease in the long term may benefit from the new knowledge,” he adds.

Boosting brain energy with medium-chain fatty acids

Fast facts about Cockayne syndrome

• Symptoms of Cockayne syndrome include dwarfism, mental retardation and hearing and vision impairments
• Cockayne syndrome is linked to a defect in the CSB protein – the main component of the DNA repair system
• Without functioning CBS, protein synthesis fails in cells, which has been described as “the most dramatic of imaginable consequences for an organism.”

The researchers explain that sugar and “ketones” are sources of energy that our brains require a constant supply of. When blood sugar is low, ketones are produced by the body breaking down fat.

The researchers found that the mice with Cockayne syndrome benefited from having an extra supply of similar brain fuel, provided here in the form of medium-chain fatty acids from coconut oil.

Although the researchers did not provide Medical News Today with data on the extent of the improvement in the mice with Cockayne syndrome, Morten Scheibye-Knudsen, from the National Institute of Health, further explains the results.

“In cells from children with Cockayne syndrome,” he says, “we have previously demonstrated that aging is a result of the cell repair mechanism being constantly active.”

“It eats into the resources and causes the cell to age very quickly,” Scheibye-Knudsen adds. “We therefore hope that a diet with a high content of coconut oil or similar fats will have a beneficial effect, because the brain cells are given extra fuel and thus the strength to repair the damage.”

Written by David McNamee

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