3D model of blood flow predicts heart attacks

The EPFL Laboratory of Multiscale Modeling of Materials, in Switzerland, has developed a flowing 3D model of the cardiovascular system that should allow for predictions of certain heart diseases before they become dangerous.

The supercomputer Cadmos, installed at the Ecole Polytechnique Fédérale de Lausanne (EPFL) in August of 2009, has bared one of its first fruits: the Laboratory of Multiscale Modeling of Materials has recently developed a computer program that accurately models the complex system of blood flow in the heart for individuals at an unheard of precision of ten millionths of a metre or ten microns. These individual- specific models, which take up to six hours using a supercomputer, will allow for a detailed study of the cardiovascular system and lead to early predictions of heart conditions such as arteriosclerosis, that often leads to heart attacks. Plans are in the works to develop the program for individual PCs for clinical applications within the next two to three years.

“When studying the blood flow in arteries, one has to take into account a vast number of different fluid interactions that happen on different time scales and of different sizes,” explained Simone Melchionna, who heads the project.

Based on a detailed heart scan, the simulation juggles over a billion different variables in order to represent a fluid containing ten-million red blood cells. Using another supercomputer based in Juelich, Germany, the research team has achieved even greater precision with their program that allows for the visualisation of the interaction of plasma, red blood cells and even micro-particles.

“We can evaluate all of the elements and how they interact with each other; move, stagnate and whirl and turn over each other,” Melchionna said.

This precision will allow for the detection of the first signs of arteriosclerosis when the plaques begin to form on the artery’s walls and disturb blood flow. Early detection of the forces leading to arteriosclerosis is one element in the strategy developed by EPFL and the universities of Geneva and Lausanne to rationalise the investment in a supercomputer of 16,000 microprocessors – the equivalent of 8,000 PCs.

HIV risk higher during pregnancy

Findings from a new study reveal that a man's risk of contracting HIV from an infected female partner doubles during pregnancy. Other studies have indicated that women are more susceptible to HIV infection during pregnancy, but this is the first to show that men are also at greater risk.

The findings were presented in May at the International Microbicides Conference in Pittsburgh in the US. Researchers from the Partners in Prevention HSV/HIV Transmission Study Team followed 3,210 discordant couples [in which one partner was HIV-infected and the other not] in seven African countries over a two-year period, to better understand the factors contributing to HIV risk.

They found that 28% of the 61 women who became infected with HIV during the study period acquired the virus while they were pregnant, and 21% of the 57 men who became infected did so while their partner was pregnant.

Analysis of the results found that pregnancy increased HIV risk for both sexes, but other factors such as sexual behaviour played a role in the case of some women. In the men, the link between pregnancy and heightened HIV risk was clearer even when the researchers took into account whether or not they were circumcised or had had unprotected sex.

One of the study investigators, Dr Nelly Mugo, of the University of Nairobi and Kenyatta National Hospital in Nairobi, and the University of Washington in Seattle, speculated that biological changes occurring during pregnancy might explain the increase in female-tomale HIV transmission.

Further research is needed to confirm this, but the finding emphasizes the need for men to join their partners in being tested for HIV during antenatal visits.

New hope in combating drug-resistant bacteria

Researchers at the Universities of Bonn, Utrecht, Aalborg and of the Danish company Novozymes, a multinational bioinnovation company, have found the mechanism by which plectasin, an antimicrobial peptide, kills bacteria that can cause severe infections in humans.

Peptide antibiotics such as plectasin have retained antibiotic activity throughout evolution. The new knowledge shows that plectasin and other related peptides from invertebrates such as flies and mussels, targets the ‘bacterial Achilles heel’. Basically it binds and sequesters a precursor used in the cell-wall biosynthesis. As the bacteria cannot live without the cell-wall it is simply destroyed.

Experiments with plectasin show that it is very difficult for bacteria to develop resistance towards it. Bacteria truly resistant to Vancomycin, the current antibiotic of choice in combating resistant bacteria, are still sensitive towards plectasin, making it a promising new alternative to resistant infections.

The groundbreaking results have been published in the 28 May issue of Science. “When we originally identified plectasin we knew that it was a breakthrough for research into antimicrobial peptides,” said Per Falholt, Novozymes’ executive vice president for Research & Development. “This new knowledge confirms it. We now know why it is almost impossible for bacteria to provoke resistance against plectasin.”

Until now it has been anticipated that plectasin like other peptides acts on and disintegrate the membrane making the bacteria collapse. Hans-Henrik Kristensen, one of the scientists behind the new discovery said they set out to determine how exactly plectasin kills the bacteria because several observations suggested that it would be different.

“What we know now is that plectasin acts by directly binding the bacterial cellwall precursor. This explains the specificity of plectasin and the observation that much larger doses of plectasin compared to other membrane-active peptides can be safely administered,” he said.

Plectasin acts on bacterial infections that have developed resistance to conventional antibiotics. It even targets severe diseases like pneumonia, endocarditic, meningitis and blood poisoning caused by bacteria-like Streptococcus and Staphylococcus which are resistant to all existing antibiotics. This will make it an effective new weapon for doctors, who are currently powerless in the face of these infections.

Novozymes identified Plectasin in 2002, but it was not until 2005 when Nature magazine published an article about the peptide that it became well-known to the global scientific community. In 2008 Novozymes granted Sanofi-aventis an exclusive worldwide license for the development, registration and commercialisation of plectasin.

Paediatric brain MRI anomalies – what to tell patients?

Paediatricians whose patients undergo routine brain MRIs need a plan to deal with unexpected-but-benign findings unrelated to the original disease which prompted the need for an MRI, according to researchers at Johns Hopkins Children's Center in the US.

“Doctors need to figure out what, if anything, they want to share with patients about such findings because they seldom require urgent follow-up,” says senior investigator John Strouse, MD, PhD, a haematologist at Hopkins Children’s.

In a report published online 14 June in the journal Pediatrics, Strouse and team describe the results of what they believe is the largest study to date of the frequency and type of unexpected brain findings in children who get MRI tests for reasons unrelated to these benign anomalies.

The most common reasons for MRI testing in children are seizures and headaches or as a prerequisite for enrolling in certain studies. The patients in the Hopkins study, all of whom had sickle cell disease and were predominantly African- American, had brain MRIs before enrolling in a research study about their condition. The investigators emphasise that none of the brain anomalies discovered in the study were related to the patients’ underlying condition, meaning the findings may apply to healthy children in general.

Of the 953 children, ages 5 to 14, in the study, 63 (6.6%) had a total of 68 abnormal brain findings. None of the children required emergency treatment or follow-up, and only six children (0.6%) needed urgent follow-ups. The urgent findings involved changes suggestive of slowgrowing tumours and a structural defect called Chiari malformation type 1, in which brain tissue extends into the spinal canal. None of the six children with urgent findings had any clinical symptoms suggestive of the anomalies.

Because stumbling upon such unexpected findings – especially ones of unclear clinical importance – can lead to more, often unnecessary, tests and fear, the Hopkins study highlights the need for paediatricians to prepare for such discussions, Strouse says. And in the absence of guidelines on how to deal with such findings, many paediatricians, Strouse adds, feel so unprepared that they may forego the discussion altogether and simply refer the patient to a neurologist or a neurosurgeon for consultation.

“Helpful as it is, imaging technology can open a Pandora's box, sometimes showing us things we didn’t expect to see and are not sure how to interpret,” says lead investigator Lori Jordan, MD, PhD, a paediatric neurologist at Hopkins Children's.

Polypill for heart disease to be tested in international trial

Researchers will be exploring whether a new, very low cost, one-a-day combined ‘polypill’ could reduce the risk of heart attacks, strokes and other cardiovascular problems across the world, in a major new international trial that launched in May.

Cardiovascular disease is the world's biggest killer and the leading cause of loss of healthy life years.

The new ‘Red Heart Pill’ contains lowdose aspirin, a statin and two blood pressure- lowering medicines in a single polypill. It is expected to be substantially cheaper than existing medications to combat cardiovascular problems.

Researchers are now recruiting volunteers who are at high risk of heart attack or stroke, or who have already had such a cardiovascular event, for a two-year trial of the Red Heart Pill.

The trial – called UMPIRE (Use of a Multidrug Pill In Reducing cardiovascular Events) has been launched in London in the UK and at other centres in Ireland, the Netherlands and (pending regulatory approval) in India.

Related trials began earlier in the year in New Zealand and Australia and plans for further trials are also underway in Brazil, Canada, China and South Africa. Collectively these parallel trials will include around 7,000 participants in ten countries and can thereby evaluate the potential of the polypill treatment strategy to prevent cardiovascular events.

The researchers behind the trial will be investigating whether patients are more likely to stick with a preventive treatment regime using a single, one-a-day polypill, rather than multiple tablets. The researchers will also be exploring whether the Red Heart Pill is effective at reducing blood pressure and lowering cholesterol.

If the treatment strategy is effective, the researchers plan to establish how the polypill could be made available to people on low incomes in countries like India, where 80% of health care is paid out of pocket and the majority of people do not currently have access to cardiovascular drugs.

It is expected that the Red Heart Pill could be made available in low-income countries at a substantially lower cost than separate medications, providing a cost-effective approach that could potentially save millions of lives across the world.

Professor Simon Thom, the co- Principal Investigator on the study from the National Heart and Lung Institute at Imperial College London, said: “Polypills are being used successfully to treat other diseases like tuberculosis and HIV, but we don't yet know whether they could be effective in those with cardiovascular problems. The UMPIRE trial aims to test whether the polypill does help people take their cardiovascular medicines in the long term and whether there are any unintended problems with this approach.”

Sickle cell disease may affect brain function

Sickle cell disease may affect brain function in adults who have few or mild complications of the inherited blood disease, according to results of the first study to examine cognitive functioning in adults with sickle cell disease. The multicentre study, funded by the US National Heart, Lung, and Blood Institute (NHLBI), compared brain function scores and imaging tests in adult patients with few sickle cell complications with results in similar adults who did not have the blood disease.

Researchers report that the brain function scores in sickle cell patients were, on average, in the normal range. However, twice as many patients as healthy adults (33% versus 15%) scored below normal levels. Those who were more likely to score lower were older and had the lowest levels of haemoglobin, compared to sickle cell participants who scored higher. Findings from brain magnetic resonance imaging scans did not explain differences in scores.

Results of the research are published in the 12 May issue of the Journal of the American Medical Association.

“This study suggests that some adult patients who have sickle cell disease may develop cognitive problems, such as having difficulty organising their thoughts, making decisions, or learning, even if they do not have severe complications such as stroke related to sickle cell disease,” said NHLBI Acting Director Susan B. Shurin, MD. “Such challenges can tremendously affect a patient’s quality of life, and we need to address these concerns as part of an overall approach to effectively managing sickle cell disease.”

Elliott P. Vichinsky, MD, of the Children’s Hospital & Research Center Oakland, principal investigator of the study and the lead author of the paper, said: “We need to study whether existing therapies, such as blood transfusions, can help maintain brain function, or perhaps even reverse any loss of function. These effects were found in patients who have clinically mild sickle cell disease, which raises the question of whether therapies should be given to all patients to help prevent these problems from developing.”

Researchers develop test to identify ‘best’ sperm

Researchers at Yale School of Medicine have discovered a method to select sperm with the highest DNA integrity in a bid to improve male fertility. The method is comparable to that of the egg’s natural selection abilities, according to the study published in the June/July issue of the Journal of Andrology.

“Our results could help address the fact that approximately 40 percent of infertility cases can be traced to male infertility,” said the senior author of the study, Gabor Huszar, M.D., director of the Sperm Physiology Lab and senior research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale.

Huszar said that past semen analysis focused on sperm concentration and motility. It was assumed that if a man had a high sperm count and active sperm, that he was fertile. But there was no information on the sperm’s fertility or its ability to attach to its mark, the female gamete. In an ideal case, the egg naturally selects the optimal sperm, but during in-vitro fertilisation treatment of men who had only a few sperm, clinicians did not know whether they were injecting the correct sperm into the egg for fertilisation. “We have now found a biochemical marker of sperm fertility so that we can select sperm with high genetic integrity,” Huszar said.

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