jueves, 27 de abril de 2017

Pelvic prolapse surgery using mesh no more effective than standard repair?

Pelvic prolapse surgery using mesh no more effective than standard repair?

News-Medical

Pelvic prolapse surgery using mesh no more effective than standard repair?

An interview with Professor Cathryn Glazener conducted by April Cashin-Garbutt, MA (Cantab)

What does pelvic prolapse surgery using mesh or graft involve and how does it differ from the existing standard repair technique?

Women who have surgery for their prolapse have a 3 in 10 chance of needing at least one more operation, so the success rate is not great.
Gynecologists hoped that using non-absorbable synthetic mesh or biological graft material as a patch to reinforce their standard repairs, the success rate would get better.
This approach has worked very successfully for patients having hernia repairs while initial summaries of evidence seemed to show that it might work for women having prolapse surgery too.

Why is the use of mesh and graft in prolapse surgery a controversial topic?

However, some women have reported long-term health problems after prolapse surgery with mesh, and this has led to considerable medico-legal interest as well as several investigations by regulatory bodies.
The evidence for the benefits of using mesh or grafts was of poor quality or inconclusive until the publication of PROSPECT.

Can you please outline your recent research project comparing the outcome of pelvic organ prolapse repairs?

PROSPECT was a pragmatic, multicenter randomized controlled trial conducted in 35 centers across the UK.  Women undergoing their first operation for prolapse were randomized to having a standard repair of the front or back wall of the vagina, or a repair reinforced by synthetic non-absorbable mesh, or a biological graft.
We measured the outcomes of surgery at 6 months and 1 and 2 years afterwards, mostly by asking women to fill in questionnaires about their symptoms and health. We also examined them at 1 year.

What were your main findings?

We found that, in contrast to previous research, women were just as likely to be cured after standard surgery as after the reinforced repairs. They were just as likely to have other symptoms such as bladder or sexual problems, and other adverse effects such as infection, bleeding or pain.
However, about 1 in 10 of the women who had mesh did have mesh exposure (when a, usually small, portion of the mesh becomes visible through the vaginal wall). Although not all women had symptoms, about half of those women needed a small operation to remove or bury the exposed mesh.
So there were no clear benefits from the use of mesh or graft over a standard repair in women having their first operation. However, synthetic mesh did result in some complications which posed extra risk.
Two other papers published on line in the Lancet on 21 December 2016 have drawn attention to other aspects of care for women with pelvic floor dysfunction.
Researchers from the Information Services Division have shown that long term results from mesh prolapse surgery are no better than from standard repair, echoing the PROSPECT findings (Morling et al; http://www.thelancet.com/journals/lancet/onlineFirst).
Indeed their longer time span showed that women had increased risks of later complications as well as being more likely to need further prolapse or continence surgery.
The PrevProl study showed that pelvic floor exercises should be tried as a first line as they have been shown to reduce prolapse symptoms or prevent their progression, at least in the short term (Hagen et al; http://www.thelancet.com/journals/lancet/onlineFirst). Women can also reduce risk factors for prolapse such as by treating obesity, heavy lifting and chronic cough.
Prevention and conservative treatment such as using pessaries can avert or delay surgery. However, if these fail, women should be reassured that if they do need surgery, they ought to go ahead with standard operations, while being aware of the risks and chance of failure.
Pelvic floor illustration

Were you surprised by the results?

Yes, because the most rigorous summary of all previous RCTs on the use of mesh (most recently updated in February 2016, Maher et al) suggested that the use of non-absorbable mesh in prolapse surgery was better in terms of both anatomical cure and prolapse symptoms than surgery without mesh.
Our trial clearly showed that there was no difference in any of the outcomes measured. We did, however, provide reliable evidence to confirm the finding of no extra benefit from the use of biological grafts.
Maher CFeiner BBaessler KChristmann-Schmid CHaya NMarjoribanks JTransvaginal mesh or grafts compared with native tissue repair for vaginal prolapseCochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD012079. DOI: 10.1002/14651858.CD012079

How do your findings compare to previous studies?

Our trial has reliably shown for the first time that women having their first prolapse operation do not benefit from the use of non-absorbable mesh, in contrast to the amalgamated results of all previous RCTs (Maher et al). We also provided reliable evidence that biological grafts do not help either.

What impact do you think your findings will have?

Women contemplating having their first prolapse operation can now be reliably counseled to avoid mesh inlays as these will not improve their chances of benefit from the operation. They may lead to unwanted side effects, some of which may require further surgery. Neither will they benefit from the use of biological grafts. Using either type of inlay is more expensive than standard surgery alone.

What further research is required?

We still need to find a way of making prolapse surgery work better, so that more women will be cured without needing further surgery for prolapse or side effects. The jury is still out on whether women having repeat surgery, or women at high risk of failure, may still benefit from mesh.
We also need to find acceptable alternatives to surgery which cure women’s symptoms without exposing them to excess risk.

What do you think the future holds for pelvic prolapse surgery?

With an ageing population, more women than ever before will require prolapse surgery. Traditional surgery, however carried out, has a 30% chance of failure. We need to identify which women will benefit most, and which type of surgery works best.
It may be that some women have specific risk factors which make failure more likely. The risk of failure rises with each successive operation. Perhaps the best strategy is to try to avoid surgery (for example by the use of pelvic floor muscle training or pessaries) so that surgery is reserved for women for whom other treatments are unsuitable or when all else has failed.
Whichever route is chosen to treat women with prolapse, it is essential that they are counseled in a realistic and evidence-based way so that they can truly understand the risks and benefits of different approaches.

Where can readers find more information?

About Professor Cathryn Glazener

Cathryn GlazenerCathryn Glazener graduated in Medicine at Dundee University in 1979 After training in obstetrics and gynecology, she undertook research in infertility in Bristol, being awarded an MD for her thesis on management of unexplained infertility in 1984. She completed her postgraduate training in obstetrics and gynecology in Aberdeen, gaining MRCOG in 1986 and admitted as FRCOG in 2003.
She joined the Health Services Research Unit, University of Aberdeen, in 1988 as a Wellcome Health Services Research Training Fellow. In HSRU, she evaluated postnatal care for her PhD in 1999. This work led to a number of related randomized trials in incontinence, neonatology and postnatal support.
She became Reader in Health Services Research in 2006, and was awarded a Personal Chair in 2009. She was the Chief Investigator on several large multi-center randomized controlled trials in pelvic floor dysfunction including urinary and fecal incontinence, and prolapse; and a reviewer on a number of Cochrane reviews. She was also the Co-coordinating Editor of the Cochrane Incontinence Review Group until she retired in March 2016.

Chinese scientists develop simple fluorescence-based assay to detect carbapenem-resistant pathogens

Chinese scientists develop simple fluorescence-based assay to detect carbapenem-resistant pathogens

News-Medical



Chinese scientists develop simple fluorescence-based assay to detect carbapenem-resistant pathogens

A fluorogenic probe can detect the activity of multidrug-resistant pathogens in an assay system
Carbapenems are among the "antibiotics of last resort" and can fight infections for which other drugs have long lost their effectiveness. However, even carbapenem-resistant pathogenic strains have emerged over the last decades. To find out whether a pathogen contains carbapenem-cleaving enzymes, the carbapenemases, Chinese scientists have developed a simple and fast assay based on a fluorescent probe and optical detection. They introduce their approach in the journal Angewandte Chemie.
Carbapenems are a class of β-lactam antibiotics similar to cephalosporins and penicillins. Although some bacterial strains have found powerful strategies to resist β-lactam antibiotics by producing a class of cleaving enzymes, the β-lactamases, most β-lactamases cannot affect the carbapenems. Therefore, these substances, which are called "antibiotics of last resort", are the drug of choice for several diseases such as urinary-tract and abdominal infections as well as hospital-acquired pneumonia, if they are caused by multidrug-resistant bacteria. But there is growing evidence of even carbapenem resistance, and some pathogens were found to produce carbapenem-cleaving enzymes, the carbapenemases. Now, Hexin Xie at East China University of Science and Technology and his team have set up a strategy to identify those pathogens that carry the carbapenemases.
The researchers developed a molecule that has the same structure as the carbapenems but has a fluorogenic dye attached. If this carbapenem-mimicking compound, CVB-1, is recognized by a carbapenemase, for example, in an bacteria extract, CVB-1 is cleaved and undergoes spontaneous degradation. As this destroys the electronic interaction of the attached dye with the carbapenem compound, the dye turns into a green fluorescent molecule, which means, if it is irradiated with light of a certain wavelength, it emits intense green light. Thus, the assay in principle works as follows: If there is an active carbapenemase present, for example, in a bacteria extract, a couple of minutes later the sample glows green upon excitation. Xie and his colleagues said:
CVB-1 [...] is essentially non-fluorescent [...], and the addition of [the carbapenemase] triggers the turn-on of the fluorescent signal upon excitation [...] with over 200-fold enhancement ratio.
This technique allows the detection of antibiotic resistance activity by fluorescence. Thus, using this fluorescence-based assay system, it would be possible to find out in very short time whether carbapenem-resistant bacteria (such as certain Enterobacteriaceae and Klebsiella pneumoniae strains) are indeed present during an infection. More specific treatment strategies could be designed and an overuse of noneffective drugs could be avoided. The scientists have performed several tests to prove that their CVB-1 assay is specific, that the detection limit is low, and that it can indeed be used in live systems. This fast and simple fluorescence-based assay is certainly a remarkable approach in the ongoing and urgent fight against the fast spread of antibiotic resistance.

Mice study yields important clues about protective role of Clostridia strains

Mice study yields important clues about protective role of Clostridia strains

News-Medical

Mice study yields important clues about protective role of Clostridia strains

Hundreds of thousands of babies worldwide die every year from infections that ravage their digestive systems – including those caused by Salmonella and E. coli bacteria. Millions more get sick.
Could the difference in survival come not from their immature immune systems, but rather from the mix of bacteria that grow in their tiny guts?
New research in mice offers evidence that some of those bacteria – called Clostridia --provide key protection against infection, in addition to helping digest food. But it also shows that the youngest newborn mice don't have Clostridia yet, making them the most vulnerable to invading bacteria similar to the pathogens that sicken so many human babies.
The findings, made at the University of Michigan Medical School and published in Science, could point the way to new approaches to protect human babies.
"Any parent knows that newborns are very susceptible to infections in the first year of life, including enteric, or gut, infections," says Gabriel Nunez, M.D., the study's senior author and a U-M pathology professor. "This work suggests that the lack of protective bacteria in the gut microbiota is a mechanism for that susceptibility, perhaps more than the age of the immune system."
Nunez and his colleagues, including co-first authors and research fellows Yun-Gi Kim, Ph.D. and Kei Sakamoto M. D., Ph. D., started with a blank slate: mice bred in a germ-free environment at U-M.
With no natural gut bacteria of their own, the mice offered a unique chance to see the effects of transplanted microbes from normal mice of different ages, and to test vulnerability to infection. The researchers also used advanced DNA analysis techniques that allowed them to detect the types and amounts of bacteria in mouse guts.
The bottom line of their experiments: Somewhere in the period around weaning mice from mother's milk to solid food, Clostridia bacteria begin to grow in the gut, and work to prevent the growth of two forms of illness-causing bacteria.
A series of experiments
Nunez, Kim, Sakamoto and their colleagues carried out a careful series of experiments using both newborn and adult germ-free mice, and samples of gut microbes taken from the feces of 4-day-old, 12-day-old and 16-day-old normal mice.
They found that the samples from the older normal mice had the most diversity of their gut microbes, including Clostridia and Bacteroides bacteria not seen in the younger mice that were still getting their nutrition entirely from mother's milk.
First, they gave the germ-free mice a transplant of bacteria from 4-day-old or 16-day-old normal mice, and then exposed them to a strain of Salmonella that can infect the gut but not spread body-wide. Half the mice that got the 4-day microbes died, but none of those with 16-day microbes did.
They tried it again with Citrobacter rodentium – a strain of bacteria similar to the E. colistrains that make humans sick. Germ-free mice with transplanted 4-day microbes got sick and many died. But when the researchers added bacteria from 16-day-old normal mice, the amount of C. rodentium in the guts of surviving mice went down.
Next, the researchers looked at what happened to germ-free mice that had been given a newborn mouse's microbes, but with extra doses of either Clostridia or Bacteroides bacteria added in. They exposed groups of these mice to C. rodentium – and found that only the mice given Clostridia were able to resist the infections. Ninety percent of the mice that got extra Clostridia, then Salmonella, were still alive after a week, compared with 50 percent of those that hadn't received it.
Since E. coli and Salmonella also affect adults, the researchers tested what happened when normal adult mice were given vancomycin, an antibiotic that selectively kills bacteria like Clostridia and Bacteroides. Both C. rodentium and Salmonella flourished in these environments.
To see what role the body's own immune system played in fighting infection, compared with gut microbes, the team also studied two strains of mice that have impaired immune systems. Raised in a germ-free environment, and then given a transplant of gut microbes from a four-day-old normal mouse, these mouse were still able to resist Salmonellainfection without any help from their immune system – but only when they had received a dose of added Clostridium first.
Finally, the researchers looked at the impact of adding succinate – a salt that oxygen-loving bacteria in the gut produce as a byproduct – into the drinking water of germ-free mice with 4-day microbes that had received extra Clostridia.
These mice fought off Salmonella infection even better – suggesting that the anaerobic Clostridia feed off the waste products of the aerobic bacteria that flourish in the guts of newborns.
Nunez and his colleagues are already working on further research on the role of Clostridiain defending against gut infections. They want to determine which strains of Clostridia – and there are many – have the largest effect.
They're also looking at the role of mother's milk in establishing a newborn's gut microbiome and conveying protection from infection, as well as the transition to solid foods that can carry microbes into a newborn's gut from the outside world. And, they want to test whether other components of the microbiome protect against other pathogens.
"Normally, we acquire Clostridia strains in our guts when we begin to eat solids, but this work suggests a window of vulnerability to enteric pathogens in the early stages of life," says Nunez, who holds the Paul deKruif professorship in pathology and is a member of the executive committee for the U-M Medical School's Host Microbiome Initiative. He notes that the research would have been impossible without the Medical School's Germ-Free Mouse Facility.
He says that if the protective role of added Clostridia for newborns bears out in further animal studies, it might be possible to propose a clinical trial in humans to test a combination of strains.

Bacteriophages may help combat antibiotic-resistant 'superbugs'

Bacteriophages may help combat antibiotic-resistant 'superbugs'

News-Medical

Bacteriophages may help combat antibiotic-resistant 'superbugs'

Viruses that specifically kill bacteria, called bacteriophages, might one day help solve the growing problem of bacterial infections that are resistant to antibiotic treatment. Researchers at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center have determined that phages can effectively reduce bacterial levels and improve the health of mice that are infected with deadly, antibiotic-resistant bacterial 'superbugs.' The study appears in Scientific Reports.
"Our research team set out to determine whether phages can be effective at killing a large group of bacteria that have become resistant to antibiotics and cause deadly diseases in people," said corresponding author Dr. Anthony Maresso, associate professor of molecular virology and microbiology at Baylor. "We are running out of available options to treat patients who have these deadly bacterial infections; we need new ideas."
When bacteria grow out of control, they can enter the blood stream and infect vital organs in the body. The body's immune system, an army of cells and molecules that fights back infections and other diseases, responds to the bacterial attack, defending the body from the infection. However, the immune response sometimes is excessive and can lead to tissue damage, organ failure and death, a process called sepsis. To end sepsis, bacterial growth has to stop. Antibiotic treatment usually can control bacterial growth and prevent the deadly consequences of sepsis, but increasing number of bacteria is becoming resistant to antibiotics.
According to the National Institute of General Medical Sciences, sepsis affects more than 1 million people in the United States every year. About 50 percent of patients with sepsis die; this outnumbers the U.S. deaths caused by prostate cancer, breast cancer and AIDS combined. The number of sepsis cases per year is increasing, which underscores the need for new strategies to fight bacterial infections.
In this study, the researchers investigated the possibility of recruiting phages in the fight against antibiotic-resistant bacteria, reviving the original idea of Felix d'Herelle, proposed in 1926.
"The driving force behind this project was to find phages that would kill 12 strains of antibiotic-resistant bacteria that were isolated from patients," said co-author Dr. Robert Ramig, professor of molecular virology and microbiology at Baylor. "As the virologist on the team, my first contribution was to go phage hunting."
Phage hunting
"I have a number of phages in my lab, but none of them killed the antibiotic-resistant E. coli we were working on - the sequence type 131 currently pandemic across the globe," Ramig said.
Birds and dogs often carry the bacteria the researchers were interested in, and may be one environmental reservoir of these pathogens. They also carry phages specific for those bacteria. Ramig, Maresso and Sabrina Green, a graduate student in the Molecular Virology Program at Baylor, went phage hunting in local parks and bird refuges to collect avian and canine feces.
"We isolated a number of phages from animal feces," said Ramig. "No single phage would kill all the 12 bacterial strains, but collectively two or three of those phages would be able to kill all of those bacteria in cultures in the lab."
This good news allowed the researchers to move on to the next step - determining whether the phages also would be able to kill the antibiotic-resistant bacteria in an animal model of sepsis.
A mouse model of human sepsis
One of the animal models the researchers worked with mimics how cancer patients develop potentially life-threatening infections during their cancer treatment.
"A number of cancer patients who undergo chemotherapy sometimes develop infections that come from bacteria that normally live in their own gut, usually without causing any symptoms," Green said. "Chemotherapy is intended to kill cancer cells, but one of the side effects is that it suppresses the immune system. A suppressed immune system is a major risk factor for infections with these bacteria, which sometimes also are multi-drug resistant."
Working in Maresso's lab, Green developed a mouse model in which healthy mice received antibiotic-resistant bacteria that colonize their intestinal tract. "These mice showed no sign of disease," Maresso said.
"But when the mice received chemotherapy," Green said, "the bacteria moved from their intestine to major organs - this led to a fatal sepsis-like infection."
In this animal model in which the immune system cannot keep in check antibiotic-resistant bacteria, Green tested whether the phages were able to do so.
"When the phages are delivered into the animals, their efficacy in reducing the levels of bacteria and improving health is dramatic," Maresso said. "But that is not what is truly remarkable," he continued. "What is remarkable is that these 'drugs' were discovered, isolated, identified and tested in a matter of weeks, and for less money than most of us probably spend in a month on groceries."
Phages: an adaptable, specific drug
Phages are very specific for certain species or strains of bacteria, but can be made broadly acting via cocktails, if desired. Thus, unlike antibiotics, using phages may not be associated with some of the side effects observed, such as clearing beneficial intestinal microbiota. They also don't infect human cells.
Another advantage over antibiotics is that phages can evolve. Should resistance develop against one set of phages, new phages can be identified in the environment or evolved in the laboratory in a matter days.
"On the other hand, an antibiotic is a chemical; it cannot change in real time," Maresso said. "It may take years to develop a new antibiotic and at costs that can run in the billions. But a phage can evolve to efficiently kill a resistant strain and then be propagated. It gives me great personal satisfaction when I think of the irony of this - the next anti-bacterial treatment may use the very same mechanisms bacteria have been using against us for 60-plus years now."
Co-author Dr. Barbara Trautner, associate professor and director of clinical research in the Department of Surgery, associate professor of medicine at Baylor and also a researcher with Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, and Ramig previously published a paper in which they showed that it is possible to take advantage of the phages' ability to change to fight bacterial infections. "In summary, we took four phages that specifically attacked bacteria of the group Pseudomonas, and they would kill four of 26 of these bacterial strains. Then, we evolved the phages in the lab, and in a month the new ones could kill 22 of the 26," Ramig said.
"Envision the following possible future clinical scenario: a patient presents with antibiotic-resistant bacterial infection that is untreatable or only treatable with the most toxic of antibiotics. During the 48 hours it takes to identify the bacterial species and strain, physicians and scientists can go to a library of phages at hand, select those that are effective against this antibiotic-resistant bacterial strain and make a personalized cocktail of phages to treat the patient. Should resistance develop again, we will evolve another phage - right back at them!" Maresso said. "There are many ways to kill bacteria, but I know of no other way that has the potential to evolve in real time like phages do. And it's the best 'green' medicine - it's natural, safe thus far, relatively cheap and can be harnessed with the technical skills of a college biology major."
Whereas the upside may be high, there is still some caution. "Phages are not infallible medicines," reflects Maresso. "The host's immune system sometimes can neutralize their activity and some phages just don't work well in animals. But we understand very little about any of these dynamics compared to those of other classes of drugs. At the very least, I think the evidence supports the notion that we should be giving phages some experimental attention."

Researchers reveal molecular details of how pathogens survive human immune responses

Researchers reveal molecular details of how pathogens survive human immune responses

News-Medical

Researchers reveal molecular details of how pathogens survive human immune responses

Researchers have uncovered molecular details of how pathogenic bacteria fight back against the human immune response to infection.
Scientists at the University of East Anglia (UEA) and Institut de Biologie Structurale (CEA-CNRS-UGA, France) have identified the structure of NsrR, a bacterial protein that binds to DNA and plays a key role in the bacterium's resistance to nitric oxide (NO), which is produced in the initial immune response to infection.
In order to counter the effects of NO, which can be toxic to living organisms, many bacteria have evolved ways to detect it and mount a cellular response.
The most common, dedicated NO sensor in bacteria is the regulatory protein NsrR. Regulatory proteins bind to DNA, and in doing so control whether particular genes are switched on or off.
NsrR contains a specialized type of co-factor - an additional component of a protein needed for its activity - called an iron-sulfur cluster. These are very fragile and reactive, which makes them hard to work with, but recent work in the Schools of Chemistry and Biology at UEA have provided important new information on how NsrR functions as a sensor of NO.
The team has now identified structures of the protein in its two principal forms -- cluster-free and cluster-bound - revealing key differences that demonstrate how NsrR responds to NO.
These structural changes show how NsrR switches between DNA-binding and non-binding forms, enabling it to regulate the switching on or off of the production of enzymes which combat NO.
Prof Nick Le Brun, who led the work at UEA, said: "NsrR belongs to an important but poorly understood family of regulators, members of which are involved in a wide range of essential cellular functions in bacteria.
"Many of these regulators have been shown or are predicted to contain an iron-sulfur cluster, but our work provides the first example of a structure with the fragile cluster bound. It reveals the general mechanism by which these regulators respond to different signals.
"Furthermore, the structure reveals that the cluster is coordinated to the protein in a way that has not been observed before in biology.
"The process of how pathogens survive human immune responses is complex, and every step we take towards understanding it, the greater the possibility of developing intervention strategies that disable the response."

Adolescents involved in bullying have greater desire for cosmetic surgery than others

Adolescents involved in bullying have greater desire for cosmetic surgery than others

News-Medical

Adolescents involved in bullying have greater desire for cosmetic surgery than others

School bullies and their victims are more likely to want cosmetic surgery, according to new research by the University of Warwick.
Professor Dieter Wolke - and colleagues in the Department of Psychology and Warwick Medical School - have discovered that teenagers who are affected by bullying in any way have a greater desire than others to change their bodies by going under the knife.
Almost 2800 adolescents - aged 11 to 16 - in UK secondary schools were screened for their involvement in bullying, through self and peer assessment.
A sample group of around 800 adolescents - including bullies, victims, those who both bully and are bullied, and those who are unaffected by bullying - was analyzed for emotional problems, levels of self-esteem and body-esteem, and the extent of their desire to have plastic surgery.
They were asked to complete established questionnaires - such as the Strengths and Difficulties Questionnaire and the Acceptance of Cosmetic Surgery Scale.
The results showed that adolescents involved in bullying in any role were more interested in cosmetic surgery, compared to those uninvolved in bullying. Desire for cosmetic surgery was highest in victims of bullying, but was also increased in bullying perpetrators.
11.5% of bullying victims have an extreme desire to have cosmetic surgery, as well as 3.4% of bullies, and 8.8% of teenagers who both bully and are bullied - this is compared with less than 1% of those who are unaffected by bullying.
Girls want to go under the knife more than boys. Of the sample group, 7.3% of girls had an extreme wish to have plastic surgery, compared with 2% of boys.
The researchers state that perpetrators of bullying want to have plastic surgery to improve their appearance and increase their social status. .
Victims of bullying, on the other hand, want to go under the knife because their psychological functioning is affected by being picked on - giving them lower self-esteem, more emotional problems and a desire to change their appearance.
Between 2014 and 2015, 15.9 million surgical and minimally invasive procedures were performed in the United States. Almost 230,000 of those procedures were performed on 13-19 year olds.
Rates of cosmetic surgery are similarly increasing in the United Kingdom and across the world.
Young people could have less of a desire for plastic surgery if mental health issues arising from bullying are addressed, according to the authors.
The researchers suggest that cosmetic surgeons screen potential patients for a history of bullying, and any related psychological issues.
Professor Wolke and his co-authors comment:
"Being victimized by peers resulted in poor psychological functioning, which increased desire for cosmetic surgery. For bullies, cosmetic surgery may simply be another tactic to increase social status [...] to look good and achieve dominance.
"The desire for cosmetic surgery in bullied adolescents is immediate and long-lasting.
"Our results suggest that cosmetic surgeons should screen candidates for psychological vulnerability and history of bullying."

Researchers discover new mechanism of epigenetic inheritance in fruit flies

Researchers discover new mechanism of epigenetic inheritance in fruit flies

News-Medical

Researchers discover new mechanism of epigenetic inheritance in fruit flies

Giacomo Cavalli's team at the Institute of Human Genetics (University of Montpellier / CNRS), in collaboration with the French National Institute for Agricultural Research, has demonstrated the existence of transgenerational epigenetic inheritance among Drosophila fruit flies. By temporarily modifying the function of Polycomb Group (PcG) proteins—which play an essential role in development—the researchers obtained fruit fly lines having the same DNA sequence but different eye colors. An example of epigenetic inheritance, this color diversity reflects varying degrees of heritable, but reversible, gene repression by PcG proteins. It is observed in both transgenic and wild-type lines and can be modified by environmental conditions such as ambient temperature. The scientists' work is published in Nature Genetics (Monday, April 24, 2017).
Same DNA, different color. Researchers have obtained drosophila epilines—that is, genetically identical lineages with distinct epigenetic characteristics—with white, yellow, and red eyes respectively. They achieved this by transiently disturbing interactions between target genes and PcG proteins, which are complexes involved in the repression of several genes governing development.  Cavalli and his team at the Institute of Human Genetics (University of Montpellier / CNRS) are the first to show that regulation of gene position can lead to transgenerational inheritance.
DNA is not the only medium for communicating information necessary for cell function. Cell processes are also determined by the chemical labeling (or marks) and specific spatial organization of our genomes, which are epigenetic characteristics—that is, nongenetic but nonetheless inheritable traits.  Epigenetic marks include modifications of histones, the proteins around which DNA is wound. PcG proteins, on the other hand, play a regulatory role by affecting 3D chromosomal configuration, which establishes certain interactions between genes in the cell nucleus. The position of a gene at any given moment determines whether it is active or repressed.
Through temporary disruption of these interactions, the scientists were able to produce Drosophila epilines characterized by different levels of PcG-dependent gene repression or activation. They verified that these epilines were indeed isogenic, or genetically identical, by sequencing the genome of each. Despite their identical DNA, the integrity of epilines—and the unique phenotypic characteristics they program—can be maintained across generations. But this phenomenon is reversible. Crosses between drosophilas with over- or underexpressed genes and others having no such modifications to gene activity "reset" eye color without altering the DNA sequence, thus demonstrating the epigenetic nature of this inheritance.
The researchers then showed that new environmental conditions, such as a different ambient temperature, can affect the expression of epigenetic information over several generations, but they do not erase this information. Such transient effects of environmental factors to which earlier generations were exposed on the expression of characteristics in their progeny illustrate the unique, pliable nature of this epigenetic mechanism. By conducting "microcosm" experiments that recreated natural environmental conditions, the researchers—working with INRA—confirmed that epigenetic inheritance in Drosophila can be maintained in the wild.
Giacomo Cavalli's crew has therefore proven the existence of Polycomb-mediated stable transgenerational epigenetic inheritance dependent on 3D chromosomal structure. Their findings offer new horizons for biomedical science. They suggest that epigenetics could partly solve the mystery of "missing heritability"—that is, the absence of any apparent link between genetic makeup and certain normal hereditary traits and diseases.