Friday, August 14, 2009

Mango Seeds May Protect Against Deadly Food Bacteria

Life in the fruit bowl is no longer the pits, thanks to a University of Alberta researcher. Christina Engels has found a way to turn the throwaway kernels in mangoes into a natural food preservative that could help prevent Listeriosis outbreaks like the one that killed 21 Canadians last year.

The findings can also apply to other fruit seeds like grapes, said Engels, who conducted the research to earn her master's degree from the Department of Agricultural, Food and Nutritional Science at the U of A. The research is published in the latest Journal of Agricultural and Food Chemistry.

Pure tannins, a plant component extracted from otherwise useless mango kernels by Engels, have proven inhibitory effects against various strains of bacteria including Listeria, a potentially deadly pathogen that infected some packaged meats and caused an outbreak of disease in Canada in 2008.

Engels' research focuses on a way to recycle wood-like mango kernels, which are usually thrown away or burned. "By processing the kernels for their tannins, businesses have a way to completely utilize all fruit parts and therefore increase their profit," she said. Currently, mangos are one of the main fruits marketed globally, ranked fifth in world production among the major fruit crops.

Baboon genes help fight parasites

Some baboons are born with an in-built resistance to a malaria-like disease, scientists have found. It is the first known example of a genetic variant in a non-human primate species that is correlated with a complex trait — in this case, resistance to a parasitic disease.

Like ancestral humans, baboons are large-bodied primates that roam the grasslands of East Africa. The research reveals that both groups have evolved similar solutions to fighting off malaria parasites that are common in that region.

"Our study suggests that looking at genetic differences between non-human primates may help us learn more about the possible solutions that evolution has come up with for us to cope with these sorts of things," says Jenny Tung, a graduate student at Duke University in Durham, North Carolina, who conducted the research with Gregory Wray, also of Duke, and Susan Alberts of Duke and the Institute of Primate Research at the National Museums of Kenya in Nairobi.

Mosquitoes against malaria?

Two malaria papers out this week in the New England Journal of Medicine have seen some press coverage. Undoubtedly the more concerning discusses the parasite’s increasing resistance to artemisinin-based drugs in Cambodia – see Nature’s news story.

The other, as Carlos Campbell of the PATH malaria vaccine initiative writes in an accompanying editorial, “reminds us that the whole malaria parasite is the most potent immunizing antigen identified to date”. In what AP describe as a “daring experiment” with “astounding” results, researchers found that ten people subjected to mosquito bites three times over three months whilst taking the drug chloroquine gained apparent immunity against malarial mosquito bites a month later.

It’s hard to see, however, that this finding adds much new to the vaccine-hunter’s arsenal.

It’s been known since the 1960s that sporozoites, cells that travel from the insect’s salivary gland to the bitten human’s liver can help provide immunity (which is why the first bout of malaria is usually the worst). This study has confirmed that. The difficulty is using this tactic to actually immunize patients – producing whole sporozoites for a real vaccine requires the breeding of many live mosquitoes and human blood to test on. As Campbell adds in his editorial, the carefully timed and controlled mosquito-inoculation approach, so far removed from the real world, “cannot be the basis for a human malaria vaccine”.

Right now, though, production of irradiated and weakened sporozoites – garnered from irradiated mosquitoes – is ongoing for injection in first-stage (safety) human trials at Maryland-based biotech company Sanaria (an effort that has taken over three decades). Meanwhile, in a PNAS paper last week which did not go through a rigorous peer review procedure, a collaboration of researchers reported that human trials would begin in early 2010 for another similar approach: this time weakening the sporozoite by snipping out two genes, rather than irradiating malaria.

Other malaria vaccine trials are based on using protein fragments, rather than the whole sporozoite to induce immunity. These include Glaxo’s RTS,S phase III trials which began a few months ago; while Dutch pharmaceutical company Crucell recently announced a collaboration with the PATH malaria vaccine initiative, to use adenoviruses to deliver a malaria antigen to the immune system.

New HIV came from gorillas

A new form of HIV from gorillas has been identified in a woman from Cameroon. The 62-year old woman, who is now living in Paris, appears to have a new human lineage of HIV virus type 1 and is the first definite human infection of HIV-1 from a non-chimpanzee ape source.

Jean-Christophe Plantier, of the University of Rouen in France, and his colleagues found the new virus to be highly similar to gorilla simian immunodeficiency virus but not to have undergone recombination with chimpanzee SIV. They propose the new lineage be labelled P as it is distinct from the currently known types M, O, and N.

“Our findings indicate that gorillas, in addition to chimpanzees, are likely sources of HIV-1,” write the authors in Nature Medicine. “The discovery of this novel HIV-1 lineage highlights the continuing need to watch closely for the emergence of new HIV variants, particularly in western central Africa, the origin of all existing HIV-1 groups.”

The current prevalence of the new HIV in humans is unknown. The researchers say that the woman detailed in the new paper currently shows no signs of AIDS and probably caught the virus from another person as she has not had contact with apes or bushmeat.

Paul Sharp, of the University of Edinburgh, believes the new strain probably transferred from chimpanzees to gorillas before arriving in humans. He also says it will probably not spread widely, which is fortunate as he adds, “the medical implication is that, because this virus is not very closely related to the other three HIV-1 groups, it is not detected by conventional test” (BBC).

An ‘aerial view’ of HIV

The complex shapes that the HIV genome twists itself into have been totally mapped by the first time by a team of US researchers. RNA viruses such as HIV like to fold themselves up and a proper picture of the shapes they form has been lacking, with researchers generally confining themselves to looking at small sections. In this week’s, Joseph Watts, of the University of North Carolina, and his colleagues set out to look at the bigger picture.

In the research paper, Hashim Al-Hashimi of the University of Michigan, Ann Arbor, notes that structural biologists usually “cut out” the motifs formed by RNA and then “zoom in to determine their three-dimensional structures in an attempt to further understand their function. … However, Watts et al. zoom out and provide an ‘aerial view’ of the secondary structure of the entire HIV-1 genome.”

What they produced is, in Wired’s words, “the cellular equivalent of a rough wiring diagram”. “What this may reveal is some of the proteins operating at a level below the structures, which may have all sorts of functions within the virus,” says David Robertson, of the University of Manchester (BBC). “More generally, if we can unpick the structures then we can compare the systems of different viruses and gain new understanding of how they work.” Study author Kevin Weeks says the technique used here with HIV could also be applied to other virus such as influenza and might open up new opportunities for drug treatmen.

New Drug-resistant TB Strains Could Become Widespread, Says New Study

The emergence of new forms of tuberculosis could swell the proportion of drug-resistant cases globally, a new study has found. The finding raises concern that although TB incidence is falling in many regions, the emergence of antibiotic resistance could see virtually untreatable strains of the disease become widespread. Australian researchers from the University of New South Wales and the University of Western Sydney have published the new finding in the latest issue of the Proceedings of the National Academy of Sciences.

Laboratory-based studies have suggested that antibiotic-resistant TB strains cause longer-lasting infections but with a lower transmission rate. Therefore, scientists have questioned whether drug-resistant TB strains are more likely than drug-sensitive strains to persist and spread – an important question for predicting the future impact of the disease.

One in three humans already carries the TB bacterium. Although it remains latent in most cases, the World Health Organisation (WHO) has estimated there were 9.27 million new cases of TB in 2007. There were 1.6 million TB-related deaths in 2005. Drug-resistant TB is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period or because the drug supply is unreliable.

A research team led by UNSW's Dr Mark Tanaka used epidemiological and molecular data from Mycobacterium tuberculosis strains isolated from Cuba, Estonia and Venezuela to estimate the rate of evolution of drug resistance and to compare the relative "reproductive fitness" of resistant and drug-sensitive strains. "We found that the overall fitness of drug-resistant strains is comparable to drug-sensitive strains," says Dr Tanaka of the Evolution and Ecology Research Centre. "This was especially so in Cuba and Estonia, where the there is a high prevalence of drug-resistant cases."

The finding may reflect an inconsistency in drug treatment programs in these countries. Indeed, Estonia now has one of the highest rates of multi-drug resistance in the world. The intermittent presence of drugs and the resulting transmission of resistant strains would have let drug-resistant strains collectively spend more time within untreated hosts, allowing them to evolve ways to become more infectious and out-compete the drug-sensitive strains.

The study also reveals that the contribution of transmission to the spread of drug resistance is very high – up to 99 per cent – compared with acquired resistance due to treatment failure. "Our results imply that drug resistant strains of TB are likely to become highly prevalent in the next few decades," says UNSW's Dr Fabio Luciani, the study's lead author. "They also suggest that limiting further transmission of TB might be an effective approach to reducing the impact of drug resistance."

"Mathematical and statistical methods can add a lot of value to empirical data by allowing us to account for the processes behind them," says research co-author, Dr Andrew Francis from the University of Western Sydney. "In this case, we use samples of TB genotypes, together with information about drug resistance, to make inferences and predictions that wouldn't have been possible just a few years ago."

Regular Yoga Practice Is Associated With Mindful Eating

Regular yoga practice is associated with mindful eating, and people who eat mindfully are less likely to be obese, according to a study led by researchers at Fred Hutchinson Cancer Research Center. The study was prompted by initial findings reported four years ago by Alan Kristal, Dr.P.H., and colleagues, who found that regular yoga practice may help prevent middle-age spread in normal-weight people and may promote weight loss in those who are overweight. At the time, the researchers suspected that the weight-loss effect had more to do with increased body awareness, specifically a sensitivity to hunger and satiety than the physical activity of yoga practice itself.

The follow-up study, published in the August issue of the Journal of the American Dietetic Association, confirms their initial hunch.

"In our earlier study, we found that middle-age people who practice yoga gained less weight over a 10-year period than those who did not. This was independent of physical activity and dietary patterns. We hypothesized that mindfulness – a skill learned either directly or indirectly through yoga – could affect eating behavior," said Kristal, associate head of the Cancer Prevention Program in the Public Health Sciences Division at the Hutchinson Center.

The researchers found that people who ate mindfully – those were aware of why they ate and stopped eating when full – weighed less than those who ate mindlessly, who ate when not hungry or in response to anxiety or depression. The researchers also found a strong association between yoga practice and mindful eating but found no association between other types of physical activity, such as walking or running, and mindful eating. "These findings fit with our hypothesis that yoga increases mindfulness in eating and leads to less weight gain over time, independent of the physical activity aspect of yoga practice," said Kristal, who is also a professor of epidemiology at the University of Washington School of Public Health.

To test whether yoga in fact increases mindfulness and mindful eating, Kristal and colleagues developed a Mindful Eating Questionnaire, a 28-item survey that measured a variety of factors:

  • disinhibition – eating even when full;
  • awareness – being aware of how food looks, tastes and smells;
  • external cues – eating in response to environmental cues, such as advertising;
  • emotional response – eating in response to sadness or stress; and
  • distraction – focusing on other things while eating.

Each question was graded on a scale of 1 to 4, in which higher scores signified more mindful eating. The questionnaire was administered to more than 300 people at Seattle-area yoga studios, fitness facilities and weight-loss programs, among other venues. More than 80 percent of the study participants were women, well-educated and Caucasian, with an average age of 42. Participants provided self-reported information on a number of factors, including weight, height, yoga practice, walking for exercise or transportation and other forms of moderate and strenuous exercise.

Higher scores on the mindfulness questionnaire overall (and on each of the categories within the questionnaire) was associated with a lower BMI, which suggests that mindful eating may play an important role in long-term weight maintenance, Kristal said."Mindful eating is a skill that augments the usual approaches to weight loss, such as dieting, counting calories and limiting portion sizes. Adding yoga practice to a standard weight-loss program may make it more effective," said Kristal, who himself scored high on the mindful-eating survey and has a BMI within the normal range.

Moving forward, Kristal and colleagues suggest that their Mindful Eating Questionnaire, the first tool of its kind to characterize and measure mindful eating, may be useful both in clinical practice and research to understand and promote healthy dietary behavior.

A screen for cancer killers

Method identifies drugs that target the cells behind cancer growth.

A new approach for identifying drugs that specifically attack cancer stem cells, the cellular culprits that are thought to start and maintain tumour growth, could change the way that drug companies and scientists search for therapies in the war against cancer.

"We now have a systematic method that had not been previously known that allows us to find agents that target cancer stem cells," says Piyush Gupta of the Massachusetts Institute of Technology and the Broad Institute in Cambridge, Massachusetts, and first author of the study, published online today in Cell. Applying the technique, Gupta and his colleagues discovered one of the first compounds that can selectively destroy cancer stem cells. The drug, an antibiotic commonly fed to pigs and chickens, reduces the proportion of breast cancer stem cells by more than 100-fold compared with a drug widely used in chemotherapy for breast cancer.

Although most cancer therapies wipe out the vast majority of tumour cells, they have not been able to eliminate the cause of the disease — the cancer stem cells — so the cancer often comes roaring back with a vengeance. Researchers have looked for drugs that preferentially target cancer stem cells, but these repeat-offender cells are so rare that screening for potential compounds has been nearly impossible. The study team, led by Robert Weinberg and Eric Lander, also from the Massachusetts Institute of Technology, exploited a trick, boosting the number of cancer-stem-cell-like cells to find a molecular missile that homes in on the real target.

By silencing a specific gene in breast cancer cells, the researchers coaxed them to convert from epithelial cells, which make up most of the human body, into mesenchymal cells, which have many stem-cell-like characteristics. They then used these cells — which have the same molecular signatures as cancer stem cells and are equally drug resistant — to screen around 16,000 chemicals. They found 32 contenders, then whittled the list down to one drug: salinomycin, an antibiotic often found in animal feed.

Better Sleep Is Associated With Improved Academic Success

Getting more high-quality sleep is associated with better academic performance, according to a research abstract that will be presented on Wednesday, June 10, at SLEEP 2009, the 23rd Annual Meeting of the Associated Professional Sleep Societies. The positive relationship is especially relevant to performance in math. Results indicate that higher math scores were related to greater sleep quality, less awakenings and increased sleep efficiency. Higher English and history scores were associated with less difficulty awakening. Increased sleep-onset latency over the weekend was associated with worse academic performance.

According to principal investigator Jennifer C. Cousins, PhD, postdoctoral fellow at the University of Pittsburgh Medical Center, it was surprising that although more and better sleep produced overall improvements, different types of sleep measures were related to different types of functioning.

"Sleep deficits cause problems for adolescents, but students differ in their personal resources and in how chaotic their sleep-wake schedules are," said Cousins. "The more regular and predictable their sleep is, the better they are likely to do when confronted with short-term sleep deficits. Therefore, participants with better sleep overall may be affected differently in a sleep condition compared to those who have a more varying sleep/wake schedule."

The study involved data from 56 adolescents (34 female) between the ages of 14 and 18 years who had complaints of daytime sleepiness and or insufficient sleep at night. Participants reported their subject grades and overall academic standing. Sleep was measured objectively with actigraphy and subjectively through sleep diaries. Higher math scores were related to less night awakenings, less time spent in bed, higher sleep efficiency and great sleep quality; there was also a trend for decreased sleep onset latency (SOL). Higher scores in English were associated with less nighttime awakenings. Increased SOL during the weekends was related to worse academic performance.

According to Cousins, poor sleep and poor sleep habits are associated with substance use, emotional problems, cognitive problems and a general decline in daily functioning. Sleep education may be a preventative tool to help increase awareness of the importance of sleep and of the negative consequences of poor sleep. Authors of the study state that results provide overwhelming evidence of the importance of sleep during a period of development that is critical in adolescents and highlight the importance of the development of sleep intervention programs for students in order to improve existing problems with sleep and daily functioning.

Child DNA donors should have their say

Biobanks should revamp how they handle DNA from healthy children, says an international team of bioethics experts. Children whose parents have signed them up for long-term studies should not have their genetic data distributed or made public until the donors consent at an older age, says the team, which publishes its recommendations today in Science.

"Children should be able to decide, when they're mature enough, about their full or fuller involvement," says Bartha Maria Knoppers, director of the Centre of Genomics and Policy at McGill University in Montreal, Canada, and an author of the paper. If implemented, the recommendation could help protect young participants' privacy, but critics say that it is arbitrary and will hamper research into children's health.

Many large biobank projects, including the US National Children's Study and the Norwegian Mother and Child Cohort Study, are now routinely collecting biological samples from healthy newborns and children. These young participants present a unique ethical challenge. They are too young to give informed consent, so authorization is needed from parents or guardians. But they will eventually become adults who may not wish to share their DNA.

David Gurwitz, director of the National Laboratory for the Genetics of Israeli Populations at Tel-Aviv University in Israel, and lead author of the study, says that the recommendations are needed to safeguard child donors from the risks associated with revealing personal genetic data. "Don't rush into distributing the DNA samples to external researchers, because DNA is a strong, unique identifier," he says. To avoid delays in paediatric research, in-house research facilities should be built so that analyses can continue without samples leaving the biobank until adult consent is obtained, Gurwitz adds.

Going To Bed Late May Affect The Health, Academic Performance Of College Students

College students who go to bed late are more likely to have poor quality sleep, which may affect their mental health and academic performance, according to new research.

The study, conducted by Jung Kim, PhD, of Pohang University of Science in Technology in South Korea, was based on a survey of 399 college students in Korea.

"The present study shows that the greater one stayed up at night, the more maladjusted in college life, in terms of global mental health, sleep quality and academic performance," said Kim. "It seems important to give relevant information and helpful guidance on good sleep habits to students from the beginning of college life."

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.

Experts recommend that adults get between seven and eight hours of sleep each night to maintain good health and optimum performance. An abstract of this research was presented June 13 at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies.


Timeline: Swine flu

A chronology of the H1N1 outbreak.

A new strain of swine flu - influenza A (H1N1) - is spreading around the globe. This timeline will be continually updated with key dates, drawing on authoritative information from the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC) and other sources. For more on the situation see the Nature News swine flu special, and read updates on The Great Beyond blog.

3 August 2009 : India confirms first death from H1N1, the victim being a 14-year old girl in the city of Pune.

29 July 2009 : Researchers from the US Centers for Disease Control and Prevention warn that pregnant women "might be at increased risk for complications from pandemic H1N1" in a research paper in The Lancet (more on this story).

The UK moves its swine flu response from 'containment' to 'treatment'. "Our national focus should be on treating the increasing numbers affected by swine flu," says health minister Andy Burnham. In the US there are or have been cases in all 50 states, including 17 deaths, according to the CDC. MedImmune, a biotechnology firm in Gaithersburg, Maryland, wins a $90 million contract from the federal government to begin developing a live attenuated vaccine for H1N1. "This virus may have given us a grace period, but we do not know how long this grace period will last," said Margaret Chan, WHO director-general. "No one can say whether this is just the calm before the storm."

Mexico has reported 48 deaths and the United States three. Worldwide, 30 countries have officially reported 4694 cases. A modeling study in Science suggests that the virus spreads at a rate comparable to that of previous influenza pandemics. The latest WHO figures say the virus has now spread to 21 countries. Mexico has reported 590 cases and 25 deaths while the United States has reported 286 cases and one death.

However, the Texas Department of State Health Services has confirmed a second person has died in the United States. The DSHS says a woman with "chronic underlying health conditions" died earlier this week.

The following countries have reported cases but no deaths: Austria, Canada, China (Hong Kong Special Administrative Region), Costa Rica, Colombia, Denmark, El Salvador, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Portugal, Republic of Korea, Spain, Switzerland and the United Kingdom.

Canadian authorities announce that H1N1 has been detected in a swine herd in Alberta. The pigs likely caught the virus from a Canadian who had recently visited Mexico, making this the first known case of human-to-animal transmission.

The WHO raises pandemic alert level to 4 having confirmed human-to-human transmission able to cause 'community-level outbreaks'. "Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion," says the organisation.

First Human Gene Implicated In Regulating Length Of Human Sleep

Scientists have discovered the first gene involved in regulating the optimal length of human sleep, offering a window into a key aspect of slumber, an enigmatic phenomenon that is critical to human physical and mental health.While most Americans obtain less than eight hours of sleep a night (the average on non-work days is 7.4 hours), and some may feel they succeed with less when engaged in exhilarating work, domestic life or recreation, scientific evidence indicates that, over time, the body suffers from this regimen, the researchers say.

"Short term and chronic disruptions in the length of optimal sleep can have serious consequences on cognition, mood and physical health, including cancer and endocrine function," says the senior author of the study, Ying-Hui Fu, PhD, UCSF professor of neurology. However, teasing out this impact can be challenging, she says, given access to such stimuli as coffee and chocolate.

The finding, she says, offers an opportunity to unravel the regulatory mechanism of sleep. While the mutation may be rare, it could offer a probe more generally into the regulatory mechanisms of sleep quality and quantity. Understanding these mechanisms could lead to interventions to alleviate pathologies associated with sleep disturbance.

Sleep remains a relatively inscrutable biological phenomenon. Scientists know that it is regulated in large part by two processes: 1) circadian rhythms -- genetic, biochemical and physiological mechanisms that wax and wane during a 24 hour period to regulate the timing of sleep, 2) and homeostasis – unknown mechanisms that ensure that the body acquires over time the necessary amount of sleep, nudging it toward sleep when it has been deprived, prompting it out of sleep when it has received enough. This regulation of sleep intensity is measured in non rapid eye movement sleep and REM sleep. Interactions between the circadian rhythms and homeostatic mechanisms influence the timing, duration and quality of sleep and wakefulness.

But "the details in the process are really completely unknown," says Fu.

In the current study, the team identified a small extended family in which a mother and her adult daughter had life-long shorter daily sleep requirements than most individuals. Fu's lab then studied blood samples from these women and their extended family. They identified a mutation in a gene known as hDEC2, which is a transcription factor that represses expression of certain other genes and is implicated in the regulation of circadian rhythms.

Next, the team genetically engineered mice and fruit flies to express the mutated human gene, and Ying He, PhD, a postdoctoral fellow in the Fu lab, studied its impact on their behavior and sleep patterns. Mice slept less, as seen in the extent of their scampering about in the dark (mouse preference) over the course of 24 hours and in electroencephalography (EEG) and electromyography (EMG) measurements indicating reduced nonREM and REM sleep. While lacking a Lilliputian size EEG to monitor the fruit flies, He studied the miniscule creatures' activity and sleep patterns by tracking the frequency of their movements through infrared light.

Next, the team compared the response of the genetically engineered mice and normal mice to the consequence of six hours of sleep deprivation. The engineered mice needed to compensate for their lost sleep to a much lesser extent – as seen in nonREM and REM measures – than their normal counterparts.

"These changes in sleep homeostasis in the mutant mice could provide an explanation for why human subjects with the mutation are able to live unaffected by shorter amounts of sleep throughout their lives," says Fu.

The next step, she says, is determining the DEC2's precise role. "We know the gene encodes a protein that is a transcriptional repressor and we know it makes the repressor's activity weaker. But we don't know if the weaker repressor is directly related to the shorter amount of sleep, because proteins can have many functions. It could be the protein functions as part of a larger transcriptional machinery, not necessarily as a repressor."

"The mouse model also provides an opportunity to investigate whether there are other behaviors or physiological conditions associated with a short sleep syndrome," says Fu. She suspects there will be.

Tuesday, August 11, 2009

Chemists Discover Twisted Molecules That Pick Their Targets

New York University chemists have discovered how to make molecules with a twist—the molecules fold in to twisted helical shapes that can accelerate selected chemical reactions. The research, reported in the latest issue of the Proceedings of the National Academy of Sciences (PNAS), could yield valuable methods for making pharmaceuticals and other chemicals that require precise assembly of complex structures.

The NYU team performs studies in "biomimetic chemistry." This research pursues synthetic molecules with structures and functions resembling molecules found in nature. Many biological molecules, such as proteins and DNA, can fold themselves into ordered helices and bundles. Within the past decade, scientists have successfully synthesized molecular chains that can also fold into various shapes. Although these "foldamers" resemble biochemical forms, finding mimics of biochemical functions has been more elusive. Now, the NYU chemists are able to create folded molecules that can perform a complex function. In this case, the new molecules are catalysts—substances that speed up the rate of chemical transformations.

The PNAS paper describes how to embed a catalytic chemical group within a larger twisted architecture. The researchers' hypothesis was that the arrangement of the surrounding twist would help determine how contacts could be made between the catalyst and surrounding molecules. To test the functionality of their foldamer, they combined it with a pair of mirror-image molecules—those with identical composition, but whose atoms are distributed in opposing spatial locations, much like left-handed and right-handed gloves—to determine if it could correctly interact with one of the pair in order to form a new chemical. The ability of the foldamer to do so was evidence of its precision.

"Our molecules are particularly interesting in that they are 'selective'—they will recognize one type of target molecule and catalyze its chemical conversion," explained NYU Chemistry Professor Kent Kirshenbaum, one of the study's authors. "This is especially important for making complex chemical structures, so we think this may be eventually useful for the synthesis of new drugs."

"Molecules used in pharmaceuticals have to be manufactured in an extremely specific manner," he added. "The difference in resulting chemicals between two mirror-image molecules could be enormous, so it is crucial that a catalyst correctly make a distinction between similar structures. Once we learn the rules to connect different molecular folds to desired functions, there should be many new tricks and new tasks we can teach our molecules to perform."

Young Early Stage Ovarian Cancer Patients Can Preserve Fertility

A new study finds that young women with early-stage ovarian cancer can preserve future fertility by keeping at least one ovary or the uterus without increasing the risk of dying from the disease.

The study is published in the September 15, 2009 issue of Cancer, a peer-reviewed journal of the American Cancer Society. Most cases of ovarian cancer are diagnosed at later stages and in older women. However, up to 17 percent of ovarian tumors occur in women 40 years of age or younger, many of whom have early stage disease. Surgery for ovarian cancer usually involves complete removal of the uterus (hysterectomy) and ovaries, which not only results in the loss of fertility, but also subjects young women to the long-term consequences of estrogen deprivation.

Researchers led by Jason Wright, M.D., of Columbia University College of Physicians and Surgeons in New York City conducted a study to examine the safety of fertility-conserving surgery in premenopausal women with ovarian cancer. This type of surgery conserves at least one ovary or the uterus.

The investigators analyzed data from women 50 years of age or younger who were diagnosed with early stage (stage I) ovarian cancer between 1988 and 2004 and who were registered in the National Cancer Institute's Surveillance, Epidemiology and End Results database, a population-based cancer registry that includes approximately 26 percent of the US population. Patients who had both of their ovaries removed were compared with those who had only the cancerous ovary removed. A second analysis examined uterine conservation vs hysterectomy.

For their first analysis, the researchers identified 1,186 ovarian cancer patients. While most had both ovaries removed, about one in three (36 percent) had one ovary conserved. They found those in whom one ovary was saved had similar survival for up to at least five years.

To examine the effect of uterine preservation, the investigators studied a total of 2,911 women. While most of the women underwent hysterectomy, about one in four (23 percent) had uterine preservation. Uterine preservation also had no effect on survival. Women who were younger, who were diagnosed in more recent years, and who resided in the eastern or western United States were more likely to undergo ovarian or uterine conservation.

These results are promising for the many young women who are diagnosed with ovarian cancer each year. An estimated 21,650 women in the United States were diagnosed with the disease in 2008. "Given the potential reproductive and nonreproductive benefits of ovarian and uterine preservation, the benefits of conservative surgical management should be considered in young women with ovarian cancer," the authors concluded.

Light-treatment Device To Improve Sleep Quality In The Elderly

Sleep disturbances increase as we age. Some studies report more than half of seniors 65 years of age or older suffer from chronic sleep disturbances. Researchers have long believed that the sleep disturbances common among the elderly often result from a disruption of the body’s circadian rhythms — biological cycles that repeat approximately every 24 hours.

In recent years, scientists at Rensselaer Polytechnic Institute’s Lighting Research Center and elsewhere have demonstrated that blue light is the most effective at stimulating the circadian system when combined with the appropriate light intensity, spatial distribution, timing, and duration. A team at the Lighting Research Center (LRC) has tested a goggle-like device designed to deliver blue light directly to the eyes to improve sleep quality in older adults.

“Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day,” said Mariana Figueiro, Ph.D., Lighting Research Center Light and Health Program director and principal investigator on the project. “Light stimulus travels through the retina, the light-sensitive nerve tissue lining the back wall of the eye, to reach the master clock in the brain. However, a combination of age-related changes in the eye and a more sedentary lifestyle may reduce the amount of light stimulus reaching an older person’s retina, therefore reducing the amount of light for the circadian system.”

As we age, the lens in the eye thickens and the pupil shrinks, reducing the amount of light passing through to the retina. Making matters worse, in some cases, such as with persons with Alzheimer’s disease, the circadian system may require a stronger light stimulus due to deteriorating neural processes in the brain. These physical and neural changes can lead to muted signals to the circadian system. Factor in environmental influences, such as an indoor lifestyle with less access to daylight, and you have a perfect scenario for the development of irregular sleep-activity patterns, according to Figueiro.

The research team explains that a marked increase in daytime lighting levels can counteract the age-dependent losses in retinal light exposure by providing a stronger signal to the circadian system. However, the color and intensity of commercially available lighting systems, like those used in senior residences, assisted-living facilities, and nursing homes, are designed for visual effectiveness and minimal energy use and not necessarily efficacious for generating light to stimulate the older circadian system.

Commercially-available “white” light sources advertised to treat circadian-related sleep disorders are usually very bright light and can cause glare and compromise compliance.

In this project, the light-treatment prototype tested by Figueiro’s team was developed by Topbulb.com, LLC, based on prior LRC light and health research. The device offers an alternative approach using specially designed goggles that deliver blue light spectrally tuned for optimum circadian response.

“The goal of this phase of the development project was to create a device in a smaller form factor or envelope that allowed for social inclusion and end-user mobility, while still delivering the required dose of light,” said Topbulb.com Senior Developer Philip H. Bonello, Ph.D.

The device was worn by eleven subjects between the ages of 51 and 80 years of age. Each subject was exposed to two levels of blue light (about 50 lux and 10 lux) from the personal light-treatment device for 90 minutes on two separate nights. Blood and saliva samples were collected at prescribed times to assess levels of nocturnal melatonin, a hormone used as a marker for the circadian clock, with high levels at night when a person is in a dark environment and low levels during the day.

After only one hour of light exposure, the light-induced nocturnal melatonin suppression level was about 35 percent for the low light level and about 60 percent for the high light level. In addition, the higher level of blue light suppressed nocturnal melatonin more quickly, to a greater extent over the course of the 90-minute exposure period, and was maintained after 60 minutes.

“The study suggests that the light goggles might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders. The next steps are to conduct field studies where we will be testing the effectiveness of this personal light-treatment device on those suffering from circadian-related sleep disorders, while also verifying the acceptance of the a device among the test groups,” said Figueiro.

Contrary To Previous Findings, Smoking Is Detrimental Rather Than Beneficial To Patients With Alzheimer's, UCI Study Shows

UCI researchers have determined that chronic nicotine exposure worsens some Alzheimer’s-related brain abnormalities, contradicting the common belief that nicotine can actually be used to treat the disease.

In the latest online edition of the Proceedings of the National Academy of Sciences, the researchers report that chronic nicotine exposure increases neurofibrillary tangles – the bundles of fibers that are one of the two neuropathological hallmarks of the disease, the other being clump-like plaques. Previous animal studies had suggested that nicotine reduces the number of these plaques; however, this possible benefit is outweighed by the increase in tangles.

The paper also will appear in the Feb. 22 print edition of PNAS.

Alzheimer’s disease is a slow, progressive disease and the most common cause of dementia among the elderly in the United States, affecting 4.5-5 million adults – 10 times more than those affected by Parkinson’s disease. The disease is marked by the accumulation of two distinct brain lesions – beta-amyloid plaques and neurofibrillary tangles – which accumulate in specific brain regions critical to learning and memory.

“In earlier work, we showed that plaques can induce tangles,” said Salvatore Oddo, graduate student in the School of Biological Sciences’ Department of Neurobiology and Behavior, and the first author of the paper. “But that is only one way in which tangles can form. There are other pathways, independent of plaques, that can lead to the formation of tangles. One of these, our work shows, is nicotine. It increases tangles independent of plaques, and, therefore, should not be used as a treatment for Alzheimer’s disease.”

To determine whether nicotine has a preventative effect on both lesions of Alzheimer’s disease, the researchers administered the drug in the drinking water of 20 mice that were genetically engineered to develop both the plaques and the tangles of Alzheimer’s disease. The researchers found that chronic nicotine exposure increased the tangles while having no significant effect on the plaques.

“In contrast to previous reports that nicotine has some marginally positive effects, our latest findings suggest that chronic nicotine exposure may actually be detrimental, enhancing certain Alzheimer’s disease brain pathologies,” said Frank LaFerla, principal investigator of the research project, associate professor of neurobiology and behavior, and co-director of the UCI Institute for Brain Aging and Dementia. “But these previous studies drew their conclusions after focusing only on plaque formation. Our paper stresses the importance of investigating Alzheimer’s disease therapies in animal models that involve both types of pathologies – plaques and tangles – as it is possible for a compound to positively affect one lesion while worsening the other.”

Starting with mild memory problems and ending with severe brain damage, Alzheimer’s usually begins after the age of 60, the risk increasing with age. If no effective therapies are developed, by 2050 it is estimated that 13 million Americans will have the disease. In the United States, five percent of the population over age 65 and one-third of the population over age 85 are afflicted by it. It is the third most expensive disease to treat and is the third leading cause of death, trailing cancer and coronary heart disease.

Besides LaFerla and Oddo, co-authors of the PNAS paper are Antonella Caccamo, Kim Green, Kevin Liang, and Levina Tran, all of whom are researchers in the Department of Neurobiology and Behavior; and Yiling Chen and Frances M. Leslie in the School of Medicine’s Department of Pharmacology. The study was funded by grants from the National Institute on Aging, the Alzheimer’s Association and the National Institute on Drug Abuse.

About the University of California, Irvine: The University of California, Irvine is a top-ranked public university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion.

Optics Of Alzheimer’s Disease

One of the hallmarks of Alzheimer’s disease is the formation of plaques made of protein aggregates in the brain tissue. There is still considerable debate among scientists as to whether these plaques are the cause of the neuronal death that occurs in Alzheimer’s or just a by-product of the disease, however.

In the last decade, autopsies have revealed that people with the worst dementia often don’t have the worst plaques, and clots and hemorrhages in small blood vessels have also been implicated in the disease.

New optical techniques may allow the link between altered blood flow and Alzheimer’s disease to be studied further by enabling scientists to directly look at the effect of clots in the brain’s microvasculature on the development of Alzheimer’s. Chris Schaffer and his colleagues at Cornell University use tightly focused femtosecond lasers to introduce clots in the microvasculature in the brains of rodents. The laser cuts open the cells lining the blood vessels, triggering natural clotting mechanisms and leading to the formation of an occlusion. The clotting process, as well as the subsequent changes in the brain, can be followed with fluorescence microscopy.

Schaffer and his colleagues are looking at whether putting tiny clots in the microvasculature can exacerbate Alzheimer’s disease. Using transgenic mice that are predisposed to developing early-onset Alzheimer’s disease, they have already shown that clotting a microvessel triggers the formation of new protein plaques. Next they plan to systematically study the effect of these clots on the cognitive decline of the Alzheimer’s mice.

Medical research is a cornerstone of Frontiers in Optics 2008 (FiO), the 92nd Annual Meeting of the Optical Society (OSA), being held Oct. 19-23 at the Riverside Convention Center in Rochester, N.Y. FiO 2008 will take place alongside Laser Science XXIV, the annual meeting of the American Physical Society’s Division of Laser Science. The presentation FTuE4, “Femtosecond Laser-Induced Microvascular Clots Trigger Alzheimer's Disease Pathology.”

First Mouse To Develop Disease As Teenager, Just Like Humans

First Mouse Model to Develop Disease as a Teenager

Penzes discovered the kalirin effect after he created the mouse model, which was the first to have a low level of kalirin and the first to develop symptoms of schizophrenia as an adolescent (two months old in mouse time). This mimics the delayed onset of the disease in humans. In normal development, the brain ramps up the production of kalirin as it begins to mature in adolescence.

New Direction for Treatment

"This discovery opens a new direction for treating the devastating cognitive symptoms of schizophrenia," Penzes said. "There is currently no treatment for that. It suggests that if you can stimulate and amplify the activity of the protein kalirin that remains in the brain, perhaps we can help the symptoms."

Currently the only drug treatment for schizophrenia is an antipsychotic. "The drugs address the hallucinations and calm down the patient, but they don't improve their working memory (the ability of the brain to temporarily store and manage information required for complex mental tasks such as learning and reasoning) or their ability to think or their social behavior," Penzes said. "So you end up with patients who still can't integrate into society. Many attempt suicide."

Similarities Between Human and Mouse Brains

A few years ago in postmortem examinations of schizophrenic human brains, other scientists had found fewer connections between the brain cells in the frontal cortex and lower levels of kalirin. But the scientists couldn't show whether one condition led to the other.

With the new mouse model, Penzes was able to demonstrate that the low level of kalirin resulted in fewer dendritic spines in the frontal cortex of the brain, the part of the brain responsible for problem solving, planning and reasoning. Other areas of the brain had a normal number of the dendritic spines. Human brains and mouse brains share many similarities in the way they function, Penzes said.

The new schizophrenic mouse model also exhibits more schizophrenic symptoms than other models, making these mice especially good for drug testing and development, Penzes said. The mice with low amounts of kalirin had a poor working memory, were antisocial and hyperactive.

Penzes said future studies would aim at enhancing the function of kalirin in the brain in an effort to correct the cognitive symptoms of schizophrenia.

Traffic Jam In Brain Causes Schizophrenia Symptoms

Schizophrenia waits silently until a seemingly normal child becomes a teenager or young adult. Then it swoops down and derails a young life.

Scientists have not understood what causes the severe mental disorder, which affects up to 1 percent of the population and results in hallucinations, memory loss and social withdrawal.

But new research from the Northwestern University Feinberg School of Medicine has revealed how schizophrenia works in the brain and provided a fresh opportunity for treatment. In a new, genetically engineered mouse model, scientists have discovered the disease symptoms are triggered by a low level of a brain protein necessary for neurons to talk to one another.

A Traffic Jam in Brain

In human and mouse brains, kalirin is the brain protein needed to build the dense network of highways, called dendritic spines, which allow information to flow from one neuron to another. Northwestern scientists have found that without adequate kalirin, the frontal cortex of the brain of a person with schizophrenia only has a few narrow roads. The information from neurons gets jammed up like rush hour traffic on an interstate highway squeezed to a single lane.

"Without enough pathways, the information takes much longer to travel between neurons and much of it will never arrive," said Peter Penzes, assistant professor of physiology at the Feinberg School. He is senior author of a paper reporting the findings published in a recent issue of the Proceedings of the National Academy of Science. Michael Cahill, a Feinberg doctoral student in neuroscience, is the lead author.

First Mouse Model to Develop Disease as a Teenager

Penzes discovered the kalirin effect after he created the mouse model, which was the first to have a low level of kalirin and the first to develop symptoms of schizophrenia as an adolescent (two months old in mouse time). This mimics the delayed onset of the disease in humans. In normal development, the brain ramps up the production of kalirin as it begins to mature in adolescence.

New Direction for Treatment

"This discovery opens a new direction for treating the devastating cognitive symptoms of schizophrenia," Penzes said. "There is currently no treatment for that. It suggests that if you can stimulate and amplify the activity of the protein kalirin that remains in the brain, perhaps we can help the symptoms."

Currently the only drug treatment for schizophrenia is an antipsychotic. "The drugs address the hallucinations and calm down the patient, but they don't improve their working memory (the ability of the brain to temporarily store and manage information required for complex mental tasks such as learning and reasoning) or their ability to think or their social behavior," Penzes said. "So you end up with patients who still can't integrate into society. Many attempt suicide."

Wednesday, August 5, 2009

Early Pregnancy Loss: Incidence

Introduction

For both the physician and the patient, early pregnancy loss is a frustrating and heart-wrenching experience. Early pregnancy loss is unfortunately the most common complication of human gestation, occurring in at least 75% of all women trying to conceive. Most of these losses are unrecognized and occur before or with the next expected menses. Of those that are recognized, 15-20% are spontaneous abortions (SABs) or ectopic pregnancies diagnosed after the pregnancy is clinically recognized. Approximately 5% of couples trying to conceive have 2 consecutive miscarriages, and approximately 1% of couples have 3 or more consecutive losses.

Early pregnancy loss is defined as the termination of pregnancy before 20 weeks' gestation or with a fetal weight of <500>

Table 1: Terms Used to Describe Pregnancy Loss

Table
Term Definition
Chemical pregnancy loss Loss of a biochemically evident pregnancy
Early pregnancy loss Abortion of the first trimester, loss of a histologically recognized pregnancy, or a loss based on ultrasonographic findings
SAB Pregnancy loss before 20 weeks' gestation, as based on last menstrual period
Habitual or recurrent abortion 3 or more consecutive SABs
Stillbirth Pregnancy loss after 20 weeks' gestation (Neonatal loss is the death of a liveborn fetus.)
Term Definition
Chemical pregnancy loss Loss of a biochemically evident pregnancy
Early pregnancy loss Abortion of the first trimester, loss of a histologically recognized pregnancy, or a loss based on ultrasonographic findings
SAB Pregnancy loss before 20 weeks' gestation, as based on last menstrual period
Habitual or recurrent abortion 3 or more consecutive SABs
Stillbirth Pregnancy loss after 20 weeks' gestation (Neonatal loss is the death of a liveborn fetus.)

Incidence

The incidence of spontaneous miscarriage is10-15%, whereas the rate of recurrent miscarriage is 3-5%.

Most studies demonstrate a spontaneous miscarriage rate of 10-15%. However, the true rate of early pregnancy loss is close to 50% because of the high number of chemical pregnancies that are not recognized in the 2-4 weeks after conception. Most of these pregnancy failures are due to gamete failure (eg, sperm or oocyte dysfunction). In a classic study by Wilcox et al in 1988, 221 women were followed up during 707 total menstrual cycles. A total of 198 pregnancies were achieved. Of these, 43 (22%) were lost before the onset of menses, and another 20 (10%) were clinically recognized losses.

The likelihood for an SAB increases with each successive abortion. Data from various studies indicate that, after 1 SAB, the baseline risk of a couple having another SAB is approximately 15%. However, if 2 SABs occur, the subsequent risk increases to approximately 30%. The rate is higher for women who have not had at least 1 liveborn infant. Several groups have estimated that the risk of pregnancy loss after 3 successive abortions is 30-45%. Therefore, controversy exists regarding how many pregnancy losses should occur before a diagnostic evaluation is considered. One could argue that the diagnostic evaluation should be performed after 2 losses rather than 3 because diagnostic yields after 2 versus 3 miscarriages are identical.

Early Pregnancy Loss: Etiology

The etiology of early pregnancy loss is varied and often controversial. More than 1 etiologic factor is often present. The most common causes of recurrent miscarriages are as follows:

  • Genetic causes
    • Mendelian disorders
    • Genetic translocations
    • Multifactorial disorders
    • Chromosomal inversions
    • Sex-chromosome aneuploidies
  • Autoimmune causes
    • Immunologic causes
    • Alloimmune causes
  • Anatomic causes
    • Uterine müllerian anomaly
      • Uterine septum (the anomaly most common associated with pregnancy loss)
      • Hemiuterus (unicornuate uterus)
      • Bicornuate uterus
    • Diethylstilbestrol-linked condition
    • Acquired defects (eg, Asherman syndrome)
    • Incompetent cervix
    • Leiomyomas
    • Uterine polyps
  • Infectious causes
  • Environmental causes
    • Smoking
    • Excessive alcohol consumption
  • Endocrine factors
    • Diabetes mellitus
    • Antithyroid antibodies
    • Luteal-phase deficiency
  • Hematologic disorders

The gestational age at the time of the SAB can provide clues about the cause. For instance, nearly 70% of SABs in the first 12 weeks are due to chromosomal anomalies. However, losses due to antiphospholipid syndrome (APS) and cervical incompetence tend to occur after the first trimester.

Early Pregnancy Loss: Anatomic Causes

Anatomic uterine defects are known to cause obstetric complications, including recurrent pregnancy loss, preterm labor and delivery, and malpresentation. Therefore, a uterine malformation should be considered in any woman with recurrent pregnancy loss. However, not all women with abnormal uteri have obstetric complications. Impaired vascularization and fetal growth restriction due to uterine distortion are 2 commonly discussed reasons for pregnancy loss.

The incidence of uterine anomalies is estimated to be 1 per 200-600 women, depending on the method used for diagnosis. When manual exploration is preformed at the time of delivery, uterine anomalies are found in approximately 3% of women. However, in women with a history of pregnancy loss, uterine abnormalities are present in approximately 27%.

Uterine müllerian anomalies

The most common uterine defects include septate, bicornuate, and didelphic uteri. The unicornuate uterus is least common. Bicornuate and unicornuate uteri are frequently associated with second-trimester loss and preterm delivery. The highest rate of reproductive losses are found in bicornuate uteri (47%) compared with unicornuate uteri (17%). Malpresentation and fetal growth restriction are other complications that women with unicornuate uteri face. Women with unicornuate and didelphys uteri have the highest rate of abnormal deliveries, while women with uterine septa have a 26% risk of reproductive loss.

In addition to müllerian anomalies, other anatomic causes of recurrent pregnancy loss to consider for include diethylstilbestrol exposure related-anomalies, Asherman syndrome, incompetent cervix, leiomyomas, and uterine polyps.

Controversies exist among these listed uterine anatomic abnormalities as causes for pregnancy loss. They are suggested but not scientifically proven potential causes.

Management

Imaging studies of choice include hysteroscopy, hysterosalpingography (HSG), and vaginal ultrasonography. Findings may be confirmed with MRI. For instance, a banana-shaped cavity with a single fallopian tube is the most common finding in a unicornuate uterus. Prophylactic cervical cerclage should be considered in patients with a unicornuate uterus. Some authors support expectant management in these patients, with serial assessments of cervical lengths by using digital and ultrasonographic examinations.

Surgical correction of uterine anatomic abnormalities has not been shown to benefit pregnancy outcomes in a prospective controlled trial. However, data from uncontrolled retrospective reviews have suggested that resection of the uterine septum increases delivery rates (70-85% in 1 study).

Emory Scientists Find New Prostate Cancer Suppressor Gene

ATLANTA -- A gene named ATBF1 may contribute to the development of prostate cancer through acquired mutations and/or loss of expression, according to research at Emory University School of Medicine and its Winship Cancer Institute. The findings were published in the online edition of Nature Genetics on March 6. The Emory research team was led by Jin-Tang Dong, PhD, associate professor in the Winship Cancer Institute. Lead author was postdoctoral fellow Xiaodong Sun, PhD.

Although previous research has suggested that a section of chromosome 16 harbors a tumor suppressor gene in several types of human cancers, the particular gene responsible has not previously been identified. By studying the genes within the section of chromosome 16, the Emory scientists found that ATBF1 was a strong candidate for an important tumor suppressor gene because its function is frequently lost in prostate cancer through gene mutations and/or loss of expression. In addition, ATBF1 was found to inhibit cell growth in culture dishes. A tumor suppressor gene is a gene whose loss of function contributes to the development of cancer.

ATBF1 is a transcription factor (regulator of gene expression) that functions to regulate the expression of other genes. If its function is impaired by mutations or loss of expression, a cell could lose the control of cancer genes. The Myb oncogene, for example, is normally inhibited by ATBF1, but it can be activated if ATBF1 is lost.

"Sporadic cancers often are the result of multiple genetic alterations that accumulate over time," said Dr. Dong, "but only a small number of genes have been shown to undergo these frequent mutations. Because ATBF1 inhibits cell proliferation, frequent acquired mutations that inhibit the gene, such as the ones we found, could lead to a lack of growth control in prostate cancer. Because gene deletion in chromosome 16 is common in many types of cancer, including lung, head and neck, nasopharynx, stomach, breast, and ovary, ATBF1 could be involved in the development of these cancers as well."

###

The research was supported by grants from the National Cancer Institute, the Department of Defense Prostate Cancer Research Program and the Georgia Cancer Coalition.

Mammography

Mammography is the process of using low-dose X-rays (usually around 0.7 mSv) to examine the human breast.


It is used to look for different types of tumors and cysts.

Mammography has been proven to reduce mortality from breast cancer.

No other imaging technique has been shown to reduce risk, but self-breast examination (SBE) and physician examination are essential parts of regular breast care.

In some countries routine (annual to five-yearly) mammography of older women is encouraged as a screening method to diagnose early breast cancer.

Like all x-rays, mammograms use doses of ionizing radiation to create the image.

Radiologists then analyze the image for any abnormal growths.

It is normal to use longer wavelength X-rays (typically Mo-K) than those used for radiography of bones. At this time, mammography along with physical breast examination is still the modality of choice for screening for early breast cancer..

Pregnancy

Pregnancy is the carrying of one or more embryos or fetuses by female mammals, including humans, inside their bodies. In a pregnancy, there can be multiple gestations (for example, in the case of twins, or triplets).

Human pregnancy is the most studied of all mammalian pregnancies. Human pregnancy lasts approximately 9 months between the time of the last menstrual cycle and childbirth (38 weeks from fertilisation). A pregnancy is considered to have reached term between 37 and 43 weeks from the beginning of the last menstruation. Babies born before the 37 week mark are considered premature, while babies born after the 43 week mark are considered post-mature.

Perinatal period

Perinatal defines the period occurring "around the time of birth", specifically from 22 completed weeks (154 days) of gestation (the time when birth weight is normally 500 g) to 7 completed days after birth. Legal regulations in different countries include gestation age beginning from 16 to 22 weeks (5 months) before birth.

Postnatal period

The postnatal period begins immediately after the birth of a child and then extends for about six weeks. During this period the mother's body returns to prepregnancy conditions as far as uterus size and hormone levels are concerned.

Childbirth

Childbirth is the process whereby an infant is born. It is considered by many to be the beginning of the infant's life, and age is defined relative to this event in most cultures. A woman is considered to be in labour when she begins experiencing regular uterine contractions, accompanied by changes of her cervix — primarily effacement and dilation. While childbirth is widely experienced as painful, some women do report painless labours, while others find that concentrating on the birth helps to quicken labour and lessen the sensations. Most births are successful vaginal births, but sometimes complications arise and a woman may undergo a cesarean section. During the time immediately after birth, both the mother and the baby are hormonally cued to bond, the mother through the release of oxytocin, a hormone also released during breastfeeding.

Stem Cell 'Daughters' Lead To Breast Cancer

Walter and Eliza Hall Institute scientists have found that a population of breast cells called luminal progenitor cells are likely to be responsible for breast cancers that develop in women carrying mutations in the gene BRCA1.

BRCA1 gene mutations are found in 10-20 per cent of women with hereditary breast cancer. Women with BRCA1 mutations often develop 'basal-like' breast cancer, which is a particularly aggressive form of the disease.

A team led by Associate Professors Jane Visvader and Geoff Lindeman from the institute's Victorian Breast Cancer Research Consortium Laboratory have discovered that luminal progenitor cells – the 'daughters' of breast stem cells – are the likely source of basal-like breast tumours. Their finding, published in today's issue of the international journal Nature Medicine, represents a major shift in the way scientists think breast cancer develops.

Dr Visvader said it had been thought in recent years that breast stem cells gave rise to BRCA1 tumours. "However, research carried out at the institute by Drs Elgene Lim and François Vaillant has shown that breast tissue from women with BRCA1 mutations has unexpectedly high numbers of luminal progenitor cells," she said.

"Further, our gene expression studies have revealed that BRCA1 breast tissue and basal breast tumors are more similar to normal luminal progenitor cells than any other cell type in the breast. This places the spotlight on errant luminal progenitors, rather than breast stem cells."

Dr Lindeman, who also heads the Familial Cancer Centre at the Royal Melbourne Hospital, said that now the importance of luminal progenitor cells in breast cancer was known it opened the way for the development of new drugs or therapies to treat breast cancer, one of the biggest causes of premature death in women.

"BRCA1 women have approximately a 65 per cent lifetime chance of developing breast cancer. Following surgery, treatment options available to these women are often limited to chemotherapy and radiotherapy, so identifying new treatment and prevention strategies is a priority for us," he said.

Luminal progenitor cells in women with BRCA1 mutations have 'forgotten' how to behave, Dr Lindeman said. "Usually, luminal progenitor cells multiply rapidly in the presence of certain growth factors. In BRCA1 women these cells don't even require growth factors to proliferate – they misbehave from the outset. "We also know that the BRCA1 gene is required for normal DNA repair. There may therefore be a triple whammy effect – faulty growth control, faulty DNA repair and expanded luminal progenitor cell numbers –ultimately resulting in breast cancer in some BRCA1 mutation carriers."

Dr Visvader said in the long-term, breast biopsies might be able to reveal misbehaving luminal progenitor cells. What's more, certain 'markers' might one day help guide diagnosis and treatment. "For example, c-KIT is a key marker of the luminal progenitor cell and I expect we will see an increase in pathologists routinely using this as a diagnostic marker for basal-like tumours," she said. "It may even be possible to develop new drugs that target c-KIT, since drugs are already available that target different forms of this marker."

Dr Lindeman said the identification of stem cells, luminal progenitor cells and other cell types in the breast was now beginning to reveal a breast cancer roadmap - highlighting cancer-prone cell types and key genetic pathways. "Hopefully this will lead to new, tailored therapies for the next generation of women."

Dr Visvader said the research had only been possible through the generous donation of breast tissue by women undergoing breast surgery, together with the support of their surgeons and pathologists. The study was facilitated by the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer.

The research was supported by the Victorian Breast Cancer Research Consortium, the Susan G. Komen Foundation, the National Breast Cancer Foundation, the National Health and Medical Research Council, the Australian Stem Cell Centre, the US Department of Defense and the Australian Cancer Research Foundation.


Tuesday, August 4, 2009

Breakthrough Brain Surgery Neurosurgeons Can Now Remove Brain Cancer Endoscopically

For more than a century, neurosurgeons have accessed the brain through the nose, but only recently did they successfully removed tumors with such minimally invasive procedures, leading to patients' quicker recovery. Not all tumors can be treated this way, but surgeons are now able to reach 60 percent of the brain by going through the nose.

PITTSBURGH--Imagine checking into the hospital for brain surgery on a Wednesday and being home to enjoy your weekend with no scars or side effects. High-tech medicine is making that all possible, and the key to its success is as plain as the nose on your face.

Within just two days of her surgery, Lori Cimino was living a normal life with no signs of the tumor that threatened her optic nerve. The key to her quick recovery was the unusual way doctors got into her brain.

Neurosurgeons guided the telescope, called an endoscope, through the nose and directly into Lori's tumor. Then, with tiny surgical instruments attached to the scope, they removed the tumor the same way they went in.

"We go into the center of a tumor and take it out in small little pieces and take these little pieces out through the nose one at a time," otorhinolaryngologist Carl Snyderman of University of Pittsburgh Medical Center, tells DBIS.

For a hundred years, surgeons have been accessing the brain through the nose, but it was just recently that they succeeded in removing a tumor in a minimally invasive way.

Neurosurgeon Amin Kassam, also of the University of Pittsburgh Medical Center, says, "Because we don't have to disarticulate the face and the bones to get there, it allows for these patients to be much more comfortable."

Cimino got rid of her tumor but kept her appearance, something almost impossible had she relied on the old methods of brain surgery. She says, "Pretty much I would be disfigured. They'd cut into my skull. I'd have staples ... My head would be shaved." She is one of 400 successful operations performed by the doctors at the University of Pittsburgh, a success that will allow her to continue to enjoy the beauty around her everyday.

Doctors caution this surgery is not for everyone: some tumors are too hard to reach or are too large to be removed through the nose.

BACKGROUND: The brain has critical tissues at its base and at the top of the spinal cord. Surgery to those areas to remove brain tumors used be very invasive. Now a new approach, called endoscopic transnasal brain surgery (ETBS), allows surgeons to operate safely on large tumors and problematic blood vessels near those important areas. ETBS also offers hope of successful treatment and recovery to those with deep-seated brain tumors that were previously considered inoperable.

HOW IT WORKS: ETBS uses miniature instruments and cameras at the end of long tubes. Surgeons thread these narrow scopes and tools into the soft tissue of the nasal cavity, enabling them to access tumors in previously hard-to-reach areas of the brain.

BENEFITS: The more traditional surgical technique for accessing brain tumors is called a craniotomy. It involved peeling away skin from the face and cutting the skull open. There was a high risk of infection, substantial blood loss and considerable facial scarring from this method, among other complications. ETBS is much less invasive and causes far fewer lingering side effects than traditional skull base surgery. Although the procedure is not without its own risks, patients are usually discharged within several days and incur no scarring from incisions.

WHERE TO FIND IT: The University of Pittsburgh Medical Center will open a 3,000 square foot operating room at its Minimally Invasive Neurosurgical Center, specifically for the ETBS procedure, in July.

WHAT CAUSES BRAIN TUMORS: Brain tumors, like most other cancerous growths, are the result of uncontrolled cell divisions caused by mutations in key genes within those cells -- in this case, the neurons in the brain. Normal neurons don't divide because their genetic coding tells them not to do so. Cancerous neurons are mutated so that the growth switch is turned back on. They begin to divide and multiple uncontrollably, forming a tumor.


Nanoparticles Cross Blood-brain Barrier To Enable 'Brain Tumor Painting'

Brain cancer is among the deadliest of cancers. It's also one of the hardest to treat. Imaging results are often imprecise because brain cancers are extremely invasive. Surgeons must saw through the skull and safely remove as much of the tumor as they can. Then doctors use radiation or chemotherapy to destroy cancerous cells in the surrounding tissue.

Researchers at the University of Washington have been able to illuminate brain tumors by injecting fluorescent nanoparticles into the bloodstream that safely cross the blood-brain barrier -- an almost impenetrable barrier that protects the brain from infection. The nanoparticles remained in mouse tumors for up to five days and did not show any evidence of damaging the blood-brain barrier, according to results published this week in the journal Cancer Research.

Results showed the nanoparticles improved the contrast in both MRI and optical imaging, which is used during surgery. "Brain cancers are very invasive, different from the other cancers. They will invade the surrounding tissue and there is no clear boundary between the tumor tissue and the normal brain tissue," said lead author Miqin Zhang, a UW professor of materials science and engineering.

Being unable to distinguish a boundary complicates the surgery. Severe cognitive problems are a common side effect. "If we can inject these nanoparticles with infrared dye, they will increase the contrast between the tumor tissue and the normal tissue," Zhang said. "So during the surgery, the surgeons can see the boundary more precisely.

"We call it 'brain tumor illumination or brain tumor painting,'" she said. "The tumor will light up."

Nano-imaging could also help with early cancer detection, Zhang said. Current imaging techniques have a maximum resolution of 1 millimeter (1/25 of an inch). Nanoparticles could improve the resolution by a factor of 10 or more, allowing detection of smaller tumors and earlier treatment. Until now, no nanoparticle used for imaging has been able to cross the blood-brain barrier and specifically bind to brain-tumor cells. With current techniques doctors inject dyes into the body and use drugs to temporarily open the blood-brain barrier, risking infection of the brain. The UW team surmounted this challenge by building a nanoparticle that remains small in wet conditions. The particle was about 33 nanometers in diameter when wet, about a third the size of similar particles used in other parts of the body.

Crossing the blood-brain barrier depends on the size of the particle, its lipid, or fat, content, and the electric charge on the particle. Zhang and colleagues built a particle that can pass through the barrier and reach tumors. To specifically target tumor cells they used chlorotoxin, a small peptide isolated from scorpion venom that many groups, including Zhang's, are exploring for its tumor-targeting abilities. On the nanoparticle's surface Zhang placed a small fluorescent molecule for optical imaging, and binding sites that could be used for attaching other molecules.

Future research will evaluate this nanoparticle's potential for treating tumors, Zhang said. She and colleagues already showed that chlorotoxin combined with nanoparticles dramatically slows tumors' spread. They will see whether that ability could extend to brain cancer, the most common solid tumor to affect children. Merely improving imaging, however, would improve patient outcomes. "Precise imaging of brain tumors is phenomenally important. We know that patient survival for brain tumors is directly related to the amount of tumor that you can resect," said co-author Richard Ellenbogen, professor and chair of neurological surgery at the UW School of Medicine. "This is the next generation of cancer imaging," he said. "The last generation was CT, this generation was MRI, and this is the next generation of advances."

Other co-authors are Omid Veiseh, Conroy Sun, Chen Fang, Narayan Bhattarai, Jonathan Gunn of the UW's department of materials science and engineering; Forrest Kievit and Kim Du of UW bioengineering; Donghoon Lee of UW radiology; Barbara Pullar of the Fred Hutchinson Cancer Research Center; and Jim Olson of the Fred Hutchinson Cancer Research Center and Seattle Children's Hospital.

The research was funded by the National Institutes of Health, the Jordyn Dukelow Memorial Fund and the Seattle Children's Hospital Brain Tumor Research Endowment.