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Category Archives: Health

DNA as a weapon of immune defense

To defend themselves, our immune cells have two mechanisms. The first, called phagocytosis, kills bacteria within the phagocytic cell itself. The cell envelops the foreign body and exterminates it specifically by using reactive oxygen species (ozone, hydrogen peroxide, bleach), generated thanks to the enzyme NOX2. However, when the invader is too large to be taken up, cells use a second defense mechanism which consists of expelling their genetic material, that is to say their DNA. This DNA transforms into sticky and poisoned nets called “neutrophil extracellular traps” (NETs). These DNA nets then capture bacteria outside of the cell and kill them.

The ancestor of our innate immune system

In collaboration with researchers from Baylor College of Medicine in Huston (USA), Professor Thierry Soldati’s team from the Department of Biochemistry of the Faculty of Science at UNIGE studies the social amoeba Dictyostelium discoideum. These microorganisms are bacteria predators. But when food is short, they come together and form a “mini animal” of more than 100,000 cells, called a slug. This will then turn into a “fruiting body” made up of a mass of spores on top of a stalk. Dormant spores will survive without food until the wind or other elements disperse them to new areas where they can germinate and find something to eat.

To make up the slug, approximately 20% of cells sacrifice themselves to create the stalk and 80% will become spores. However, there is a small remaining 1% that keeps its phagocytic functions. “This last percentage is made up of cells called “sentinel” cells. They make up the primitive innate immune system of the slug and play the same role as immune cells in animals. Indeed, they also use phagocytosis and DNA nets to exterminate bacteria that would jeopardize the survival of the slug. We have thus discovered that what we believed to be an invention of higher animals is actually a strategy that was already active in unicellular organisms one billion years ago,” explains Thierry Soldati, last author of the study.

From social amoeba to humans

This discovery plays a primordial role in understanding immune system diseases in humans. Patients with chronic granulomatous disease (CGD) are for example incapable of expressing the functional NOX2 enzyme. Therefore, they suffer recurrent infections, since their immune system lacks the reactive oxygene species that kill bacteria inside the phagosome or via DNA nets. By genetically modifying the social amoeba Dictyostelium discoideum, the microbiologists from UNIGE are able to conduct all sorts of experiments on the mechanisms of the innate immune system. This microorganism can therefore serve as a scientific model for the research on defects in these defense processes, opening the way to possible treatments.

Time to put TB on a diet

TB kills over 1.5 million people a year. Although the mortality rate has dropped by 47% since 1990 due to advances in preventive and treatment options, the tuberculosis bacillus is growing increasingly resistant to antibiotics. For this reason, biochemists at the University of Geneva (UNIGE), Switzerland, are attempting to identify the mechanisms that enable the bacterium to reproduce, spread and survive in latent form in our macrophages. The scientists have discovered that the bacterium has the ability to “reprogramm” the cell it infects so that it can feed on its lipids. The UNIGE research results, which will be published in the PLOS Pathogens journal, will pave the way for new treatment opportunities based on starving and weakening the bacterium.

Tuberculosis is a highly contagious disease that spreads through the air via droplets of saliva. Although treatments exist for tuberculosis, new antibiotic-resistant strains are preventing TB from being eradicated. The goal is to find new ways to tackle the disease, which requires a thorough understanding of how the bacterium, known as Mycobacterium tuberculosis, behaves once it takes hold of the macrophages in our lungs. The team headed by Thierry Soldati, Professor at the Biochemistry department in UNIGE’s Science faculty, has been working on a model system that acts like the macrophages in our immune system: the social amoeba Dictyostelium, a unicellular microorganism.

“We infected the amoebae with the Mycobacterium marinumbacterium, which induces tuberculosis in fish,” explains Caroline Barisch, a researcher at UNIGE and the study’s first author. “The pathogen behaves in the same manner as the TB bacillus, which means that we were able to use our simple and ethically responsible system to undertake experiments that could not be carried out directly on humans.” Scientists had previously recognised that for the bacterium to survive, replicate and spread, it needed to consume the lipids that exist in the form of droplets in macrophages. Without this source of food, the bacillus cannot survive latently and wait for a weakness in the immune system in order to develop. It is well worth remembering that 30% of the world’s population is infected by a dormant form of the TB bacillus.

The UNIGE biochemists observed the infection in vitro, analysing each stage of the process whereby the bacterium feeds on the lipids of its host. As Thierry Soldati explains: “We subsequently discovered that the mycobacterium can “reprogramm” the infected cell so that it diverts and attracts all the amoeba’s fat reserves — not just the lipid droplets but also the membranes — so that it can feed on them.” The researchers suppressed the lipid droplets of the host cells, the bacterium’s preferred food source, and found that the bacterium has a back-up plan that allows it to compensate for this shortage by drawing on the lipids within the host’s membranes. This shows that this lipid diet is most likely crucial for the survival of the bacterium.

“We now know that the bacillus is extremely ‘addicted’ to this high-fat food,” continues Caroline Barisch. “Our current aim is to find a way to starve the bacillus by depriving it of access to the fat stores in our macrophages. The goal will be to target the enzymes of the bacillus and render them incapable of absorbing lipids.” It is a discovery that opens the door to the prospect of new forms of treatment for neutralising the strains that are resistant to antibiotics.

Pain often overlooked in premature infants

Premature infants receiving intensive care are exposed to a great deal of pain, and this pain causes damage to the child. Despite this half of the infants admitted to neonatal intensive units will not receive any pain relief, according to a new European study published in The Lancet Respiratory Medicine.

– That is, no one assesses if the infant is experiencing pain or how much pain relief the infant requires, says Mats Eriksson, researcher at Örebro University.

“Premature infants are sensitive to pain because their brain and nervous systems are still in development. But we cannot administer pain relief or sedation simply as a precaution, because pain relief at the wrong time will also lead to damage. Therefore, correct pain assessment is extremely important,” says Mats Eriksson, a specialist nurse in intensive care and researcher in medical science, who has worked on this survey, together with Hugo Lagercrantz at the Karolinska Institute and Ricardo Carbajal from Université Pierre et Marie Curie in Paris, and in cooperation with researchers from 17 other countries.

The international EU project has investigated 6,700 premature infants in 243 neonatal intensive care units in 18 countries, the largest study of its kind. The study shows that just over half of the children received no pain assessment, and a fifth received no pain relief or sedative medication at all.

“It is astonishing that so many children were not assessed. Proper pain assessment is the basis for a good treatment. By checking the baby’s facial expressions, heart rate and breathing, the amount of analgesic needed can be estimated,” says Mats Eriksson.

It is uncertain if the 20 per cent of infants, who never received any pain relief, needed it. However, the study does show that in those cases the infant’s pain was assessed, it was almost double so likely that the child received opioid analgesic such as morphine, or sedative drugs. On the other hand, the earlier a premature child is born, the less likely the child will receive analgesic or sedative drugs.

“20 per cent of the infants never received analgesia, and it is quite likely that many of them may have needed it at least at some point,” says Mats Eriksson.

“In Sweden, we have made considerable progress. We are quite apt at pain assessment and at adapting treatment. We are also good at using alternative methods, such as relieving pain with a sucrose solution or with skin-to-skin contact with a parent. In this way we can relieve pain for the infant without using excessive analgesia or sedatives.”

A good balance between analgesia and sedatives makes it possible to avoid future problems. Experiencing a lot of pain as a newborn may lead to behavioural changes with regards to pain later as an adult. That is, that one is quite simply being more sensitive to pain. In addition, many children develop attention and concentration problems, perhaps developing ADHD.

But there are significant differences between European countries regarding pain assessment and pain management. For example Greece stands out by providing much less analgesia than other countries.

“The goal is that all children should receive similar treatment, not simply based on chance, traditions or what an individual doctor believes or doesn’t believe. There are international guidelines, but they are old and need to be updated. The next step is to develop common European guidelines.”

Great differences in the view of withdrawing futile

The views among physicians and the general public when it comes to deciding whether to withhold or withdraw treatment of terminally ill patients differ greatly. However, in a hypothetical case study at Umeå University in Sweden of a clearly hopeless medical case, great unanimity among physicians’ and the public’s assessments could be seen with regards to cancelling treatment or offering relief at the final stages of life.

Anders Rydvall, physician at the University Hospital of Umeå and doctoral student at the Department of Surgical and Perioperative Sciences, has completed two surveys in Sweden that investigate attitudes and what arguments seem most significant. The development of techniques to prolong life support in intensive care, which is a relatively young speciality, has advanced at high speed and the opportunities are hence greater than ever. At the same time, there are limiting factors set by human physiology that can often be difficult to relate to. In turn, this leads to continuous treatment beyond what is reasonable when the patient is beyond rescue.

“This ethical dilemma is something that many, including family members, are aware of. But the difficulties in these types of situations often arise when caregivers are afraid of receiving criticism for not doing everything in their power. Also, there is a perceived discomfort in being the bearer of bad news and being on the receiving end of the reactions, as well as holding differing views on what rules and regulations actually imply,” explains Anders Rydvall.

The elderly woman with an unpromising prognosis

In a first survey, the attitudes and arguments for and against active treatment (operation) were compared between neurosurgeons (112 of which 70 per cent responded), anaesthesiologist and intensive care physicians (298 of which 70 per cent responded), and the general public (998 of which 50 per cent responded). The hypothetical patient case concerned an older woman with a severe brain haemorrhage and a poor clinical condition. The results showed that caregivers among themselves generally made the same assessments and prioritised the argument “Quality of Life” as the most important one. But anaesthesiologist and intensive care physicians also pointed particularly at the importance of the patient’s previous desires.

A comparison between physicians’ and the general public’s attitudes to this case showed great variations in opinions for or against operation and also in what arguments were considered most important. Out of the physicians, 82 per cent assessed to refrain from operation while only 40 per cent made the same choice out of the general public. But when the case developed to a more hopeless situation, both groups made more unanimous assessments, albeit prioritising different arguments.

The premature baby with severe brain injury

The second survey posed questions regarding a case with a severely brain-injured newborn baby. The survey was submitted to anaesthesiologist and intensive care physicians (299 of which 63 per cent responded), paediatricians and neonatologists (329 of which 67 per cent responded) as well as the general public (585 of which 46 per cent responded). The study compared arguments for the attitude for or against continued respiratory care. A majority of both physicians and the general public supported arguments to withdraw treatment.

The second survey also included questions on whether it could be considered acceptable to give anaesthetics and pain-relief in a dosage to minimize pain or in a higher dosage aimed at shortening the dying process. A large majority of physicians and the general public supported arguments to soothe and minimize pain, also if it in reality and as a consequence could shorten the dying process. Although, when the intention was to actively bring about the inevitable death, the general public seemed much more inclined to accept such an act than caregivers.

“To avoid misunderstandings and communication problems it is important that caregivers take into consideration and has knowledge of the views, expectations and prioritisations of the family. It’s also important that caregivers maintain a setting where information is honest and appropriate and communications open,” says Anders Rydvall.

Anders Rydvall comes from Stockholm and moved to Umeå in the 1970s. He works as a chief physician at the Centre of intensive and postoperative care at the University Hospital of Umeå.

Umeå University — located in the north of Sweden — is characterised by strong research where many of our researchers belong to the global elite in for instance global health, epidemiology, molecular biology, ecology, plant physiology, marine biology and Arctic research. Umeå University is one of Sweden’s largest teaching universities that offers a wide-spanning and attractive selection of courses and programmes, and stimulating environments for working and studying for the over 4,300 employees and 31,000 students. For instance, it was from Umeå University that the work in discovering the gene-editing tool CRISPR-Cas9 was led.

Precision medicine advances pediatric brain tumor diagnosis

Precision medicine — in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers — has advanced to the point where it can now impact the care of a majority of children with brain tumors, a new study by investigators at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggests.

In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials. The findings, reported online by the journal Neuro-Oncology, demonstrate that testing pediatric brain tumor tissue for genetic abnormalities is clinically feasible and that in many cases the results can guide patients’ treatment.

The need for new approaches to treating brain cancer in children is urgent, the study authors say. “Although there has been a great deal of progress over the past 30 years in improving survival rates for children with cancer, advances in pediatric brain cancer haven’t been as dramatic,” says co-lead author Pratiti Bandopadhayay, MBBS, PhD, of Dana-Farber/Boston Children’s. “In a recent study, brain tumors accounted for 25 percent of all pediatric deaths attributed to cancer. In addition, many of the current therapies can result in long-term difficulties in cognitive or physical functioning.”

Since emerging from research labs more than a decade ago, targeted therapies for cancer have significantly improved the treatment of certain types of leukemia, digestive system tumors, and breast cancer, among other malignancies. The new study is unique in that it reports on the largest collection of pediatric brain tumors to be genetically profiled as patients came to clinic. Pathologists and cytogeneticists performed the testing in a federally approved clinical laboratory — certified under Clinical Laboratory Improvement Amendments (CLIA) as the only type of labs in the United States whose findings can guide patient treatment. Dana-Farber/Boston Children’s, the researchers noted, is one of the few centers in the country to regularly analyze the genetics of patients’ pediatric brain tumors.

The researchers plumbed the genomes of 203 pediatric brain tumor samples, representing all major subtypes of the disease. They analyzed 117 of the samples with OncoPanel testing, a technology that sequences the exomes — the sections of DNA that hold the blueprints for making specific cell proteins — for irregularities in 300 cancer-related genes. They also studied 146 samples tested with OncoCopy, which examines how many copies of genes are missing or overabundant within the tumor cells. Sixty samples underwent both forms of testing ,which allowed researchers to explore whether combining the two tests was more powerful than each alone.

Of the samples tested by OncoPanel, 56 percent harbored genetic abnormalities that were clinically relevant — that could impact a patient’s diagnosis or be targeted by drugs already in clinical use or under study in clinical trials. (Many of these drugs cross the blood-brain barrier, the dense web of cells that can prevent medicines from exiting the bloodstream to reach the brain.) Among the findings:

  • Alterations were found in the gene BRAF, one of the most commonly mutated genes in pediatric brain tumors, and one for which several targeted drugs are being tested.
  • The two-pronged testing approach revealed clinically relevant abnormalities in 89 percent of medulloblastomas, which account for nearly a fifth of all brain tumors in children. Combining the two tests was found to be particularly useful for these patients.

“The importance of genomic profiling in the diagnosis and treatment of pediatric brain cancers is reflected in the World Health Organization’s recent decision to classify such tumors by the genetic alterations within them, rather than by broad tumor type” says study co-senior author Susan Chi, MD, of Dana-Farber/Boston Children’s. “Targeted therapies are likely to be most effective when they’re matched to specific abnormalities within tumor cells. Our findings show that precision medicine for pediatric brain tumors can now be a reality.”

Brain stimulation used like a scalpel

Northwestern Medicine scientists showed for the first time that non-invasive brain stimulation can be used like a scalpel, rather than like a hammer, to cause a specific improvement in precise memory.

Precise memory, rather than general memory, is critical for knowing details such as the specific color, shape and location of a building you are looking for, rather than simply knowing the part of town it’s in. This type of memory is crucial for normal functioning, and it is often lost in people with serious memory disorders.

“We show that it is possible to target the portion of the brain responsible for this type of memory and to improve it,” said lead author Joel Voss, assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine. “People with brain injuries have problems with precise memory as do individuals with dementia, and so our findings could be useful in developing new treatments for these conditions.”

By stimulating the brain network responsible for spatial memory with powerful electromagnets, scientists improved the precision of people’s memory for identifying locations. This benefit lasted a full 24 hours after receiving stimulation and corresponded to changes in brain activity.

“We improved people’s memory in a very specific and important way a full day after we stimulated their brains,” Voss said.

The paper was published Jan. 19 in Current Biology.

The research enhances scientific understanding of how memory can be improved using noninvasive stimulation. Most previous studies of noninvasive brain stimulation have found only very general and short-lived effects on thinking abilities, rather than highly specific and long-lasting effects on an ability such as precise memory.

The scientists used MRI to identify memory-related brain networks then stimulated them with noninvasive electromagnetic stimulation. Detailed memory tests were used to show that this improved spatial precision memory, and EEG was used to show that these memory improvements corresponded to indicators of improved brain network function.

How rescue proteins dispose of harmful messages?

During protein synthesis, the genetic information stored in a gene’s DNA is translated into proteins. This process takes place inside veritable macromolecular machines known as ribosomes, and starts by transcribing genetic information from a cell’s DNA into transportable units known as messenger RNAs (mRNAs). These units, which contain detailed instructions for the synthesis of specific proteins, are then read and translated by ribosomes into proteins. Defective mRNAs will result in aberrant, potentially harmful proteins; an efficient process for recognizing and disposing of such mRNAs is therefore essential.

As part of their study, researchers led by Dr. Tarek Hilal from Charité’s Institute of Medical Physics and Biophysics studied mRNAs that lack ‘stop codons’ — genetic stop signs that signal the end of protein synthesis. Attempts to decode and translate such ‘nonstop-mRNAs’ leads to a complete stalling of the ribosomal machinery, resulting in effectively blocking continued protein synthesis. Using cryo-electron microscopy to study the structure of such ribosome-mRNA complexes, the researchers were able to show the manner in which special rescue proteins (Dom34 and Hbs1) recognize such stalled ribosomes, thereby initiating the splitting of the arrested complex and the degradation of the faulty mRNA. The rescue proteins recognize arrested ribosomes by detecting, and binding to, conserved locations normally occupied by mRNA. This direct competition-based approach ensures that only ribosomes with aberrant mRNAs are targeted.

“Research into the effects of aberrant mRNAs and the consequences of inadequate degradation is becoming increasingly significant,” says Dr. Hilal. He adds: “Aberrant mRNAs have been found to be particularly common in patients with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Gaining an understanding of the relevant cellular control mechanisms on a molecular level may help us to develop new treatment approaches.”

Help AmeriCares Save Lives in Japan

More than a week after the terrifying earthquake and tsunami struck Japan, accounts of both devastation and hope keep rolling in. As the official death toll has climbed to more than 18,000, inspiring survival stories — such as that of teenager Jin Abe and his grandmother Sumi, who were trapped in a collapsed wooden home in Ishinomaki for nine days before rescue workers heard Jin’s cries for help — have surfaced too.

Such survivors need our help now more than ever, and it’s not too late to contribute. Everyday Health members have so far donated almost $30,000 in aid to AmeriCares, a non-profit aid organization with an emergency response team on the ground in Tokyo and Sendai setting up deliveries of crucial supplies to people who lost their homes and everything they own. AmeriCares’ emergency response manager Michelle Jackson’s first-person account reaffirms why we need to keep giving.

“At one shelter, a doctor pleaded for more medicines and supplies, saying that people are getting very anxious,” says Jackson, who arrived the day after the earthquake and is overseeing a small team to identify the needs of the nearly 300,000 Japanese people living in shelters (often without heat and power) to ensure they get health care.

Jackson says that families packed into small shelters are worried about the possible spread of infectious diseases, and how they’ll get resupplied with the crucial medications they need to take regularly. For example, one woman requires seven medications to treat her hypertension, diabetes, high cholesterol, and other health problems. Since the evacuation, she’s only been able to take three. At another shelter, the AmeriCares team encountered people who haven’t had access to any of their medications for a week.

At one hospital in Fukushima (within a 12.5-mile radius of the nuclear plant), just 12 staff members of the 200 regularly employed there remain to care for the elderly patients who could not be evacuated.

It’s these people — who have lost their homes and family members and who are going without medications, blankets, and daily essentials — who gravely need our help.

To contribute money to help meet these critical needs, go to Americares.org or text “Live” to 25383 to make a $10 donation.

Why Does a Trip Home Always Feel Shorter ?

You’ve been looking forward to this vacation for months. You started packing weeks ago, spent days mapping out family activities, and arrived at the airport hours before departure. So now that you’re finally en route, why does it feel like you’ll never get there?

According to researchers (as well as frequent business travelers and wanderlusters), your reason for traveling doesn’t matter: The outward journey always seems to take longer than the trek back home.

What’s going on? A recent study from Tilburg University in the Netherlands found this “return trip effect” all boils down to our expectations. Before you head out on that initial voyage (Paris, here we come!), you tend to underestimate the time it will take, says researcher Niels van de Ven, PhD, an assistant professor of social psychology. Chalk it up to pre-trip excitement, but when you lowball your travel time, the journey ends up feeling a whole lot longer.

And it has an effect on the trip home, too. “Based on that feeling, the traveller expects the return journey to be long as well, and this then turns out to be shorter than expected,” van de Ven said in a press release. About 17 to 22 percent shorter, to be precise.

To determine this, the researchers tested a few different “return trip effect” theories. About 350 participants were questioned during a bus trip to a theme park, a bike trip, or while watching a video of someone riding a bike to and from a destination. In all scenarios, it was clear that the phenomenon existed — participants said that the initial trip felt longer than the return trip (even though the trips were of the same time and length). When the researchers dug deeper to understand why, signs pointed to this “violation of expectations.”

This research sheds new light on the phenomenon, which was previously thought to be related to route familiarity — a trip home would feel shorter because the course was better known and more predictable. But in this study, researchers found that the “return trip effect” persisted even when respondents took a different (but equal-length) path home.

So the next time your kids are screaming “Are we there yet?” from the back seat, cut them a break: This travelling phenomenon is simply messing with their heads. Then, take comfort in the notion that they probably won’t ask the same question on the trip back home.

Why Do We Talk in Our Sleep?

The When and How of Sleep Talking

Sleep talking tends to occur during two different stages of sleep: During stage two, when it’s just a stream of thoughts not accompanied by a dream, and during rapid eye movement (REM) sleep, when it’s accompanied by active dreams. During REM sleep it’s easy to arouse a person out of sleep talking, but during stage two, it’s very hard to wake someone up, and they likely won’t remember what they were talking about. And even during REM sleep, what a sleep-talker is saying may not be related to what’s happening in their dream.

“With sleep talking, we may have active dreams — we may be speaking about what we’re dreaming. On the other hand, we could be dreaming one thing and speaking something completely different,” says Dr. Kohler.

Sleep talking can vary in frequency and intensity, and can be caused by a variety of factors, which may be as simple as drinking alcohol before going to sleep. “Having a high fever, being under emotional stress, taking certain medications, and having underlying sleep problems like sleep apnea can all cause a person to talk in their sleep,” says Kohler. Sleep talking may also run in families, he says. There aren’t any specific medications that have been singled out to cause sleep talking.

What Does All That Chitchat Mean?

Although you may be tempted to read a lot into what your partner utters in their sleep, experts don’t recommend taking too much stock in those sweet nothings. “It’s not a reflection of what’s going on in your life,” Rosenberg says. Kohler agrees: “There’s a myth that secrets can be revealed with sleep talking, but that’s not really accurate. The things people are talking about can potentially have nothing to do with reality.”

And as many parents know, sleep talking is common in kids. “This is more of a brain development issue in children,” says Rosenberg. “Most kids will grow out of it.”

If your partner or child is chattering away in their sleep, “let it play itself out — just observe and make sure they are safe,” recommends Rosenberg.

So when would sleep talking actually be a cause for concern? Only if you feel overly tired during the day, if your nocturnal chatter is disturbing your partner, or if your sleep talking is accompanied by any other “acting out,” such as sleepwalking. If you’re feeling sleepy all the time, a sleep specialist can help determine the best course of action to ensure you get better sleep.