and for our understanding of how infections take hold in medical devices. The findings the result of microscopic analysis of bacteria inside microfluidic devices were made by MIT postdoc Roberto Rusconi former MIT postdoc Jeffrey Guasto (now an assistant professor of mechanical engineering at Tufts
Stocker says in some cases that phenomenon could lead to new approaches to tuning flow rates to prevent fouling of surfaces by microbes potentially averting everything from bacteria getting a toehold on medical equipment to biofilms causing drag on ship hulls.
Guasto says the new understanding could help in the design of medical equipment to reduce such infections:
Since the phenomenon peaks at particular rates of shear he says Our results might suggest additional design criteria for biomedical devices which should operate outside this range of shear rates when possible either faster or slower.
#Hitchhiking vaccines boost immunity Many vaccines, including those for influenza, polio, and measles, consist of a killed or disabled version of a virus. However, for certain diseases,
this type of vaccine is ineffective, or just too risky. An alternative, safer approach is made a vaccine of small fragments of proteins produced by a disease-causing virus or bacterium.
This has worked for some diseases, but in many cases these vaccines don provoke a strong enough response.
Now a team of engineers at MIT has developed a new way to deliver such vaccines directly to the lymph nodes
where huge populations of immune cells reside: These vaccines hitch a ride to the lymph nodes by latching on to the protein albumin, found in the bloodstream.
In tests with mice, such vaccines produced very strong immune responses, the researchers report in the Feb 16 online edition of Nature. he lymph nodes are where all the action happens in a primary immune response.
T cells and B cells reside there, and that where you need to get the vaccine to get an immune response.
The more material you can get there, the better, says Darrell Irvine, a professor of biological engineering and of materials science and engineering,
and the senior author of the paper. This approach could be especially useful for delivering HIV vaccines
and for stimulating the body immune system to attack tumors, says Irvine, who is also a member of MIT Koch Institute for Integrative Cancer Research.
Free ride Vaccines made of protein or sugar fragments, also known as subunit vaccines, have been successful against a few diseases, such as hepatitis and diphtheria.
To develop subunit vaccines for other diseases, scientists have tried targeting them to lymph nodes using nanoparticles to deliver them,
or tagging them with antibodies specific to immune cells in the lymph nodes. However these strategies have had limited only success,
because it is difficult to get all of the vaccine to the lymph nodes without some escaping to the rest of the body,
which can cause unwanted side effects. Irvine team took a new approach, based on an existing procedure for targeting imaging dyes to the lymph nodes.
Surgeons use this procedure, known as entinel lymph node mapping, to determine the extent of cancer metastasis after removing a tumor.
The dye used for this imaging binds tightly to albumin, allowing it to accumulate in the lymph nodes.
Previous studies have revealed that when foreign particles such as the dye bind to albumin immune cells in the lymph nodes efficiently capture the albumin. e realized that might be an approach that you could try to copy in a vaccine design a vaccine molecule that binds to albumin
and hitchhikes to the lymph node, Irvine says. To get protein fragments, known as peptides, to bind to albumin,
the researchers took advantage of albumin function as a transporter of molecules called fatty acids. Albumin has binding pockets that can capture fatty, hydrophobic molecules,
so the researchers added a fatty tail called a lipid to their vaccine peptides. They created a few different vaccines
targeting HIV, melanoma, and cervical cancer, and tested them in mice. Each one generated a large population of memory T cells specific to the viral
or tumor peptide. e knew we were on the right track because we saw you could get immune responses that were just tremendous,
Irvine says. hen you look in the blood, one in three T cells in the blood was a vaccine-specific T cell,
which is something you usually only see with vaccines delivered by viruses. The albumin-targeted vaccines provoked immune responses five to 10 times stronger than those generated by the peptide antigens alone.
The melanoma vaccine slowed cancer growth and the cervical cancer vaccine shrank tumors. t certainly is an interesting approach,
and the results are very convincing, says Pal Johansen, a professor of dermatology at University Hospital Zurich who was not part of the research team. oth the effect on the stimulated immune responses
and the consequential suppression of tumor growth are results that would suggest further development and clinical testing.
Controlled inflammation The researchers also tested this delivery strategy with an adjuvant a molecule that enhances the immune responses of vaccines.
Targeting a commonly used adjuvant called Cpg to albumin dramatically boosted the resulting inflammatory response.
This delivery method could also improve the safety of adjuvants by confining their effects to the lymph nodes.
Otherwise, the adjuvant could spread through the bloodstream and provoke inflammation in other parts of the body. his lymph-node-targeting modification causes pretty much all of the material to get caught in the draining lymph nodes,
so that means it more potent because it getting concentrated in the lymph nodes, and it also makes it more safe
because it not getting into the systemic circulation, Irvine says. The researchers are planning to test this method to deliver HIV vaccines in nonhuman primates,
and they are also working on further developing cancer vaccines, including one for lung cancer. The research was funded by the Koch Institute Support Grant from the National Cancer Institute, the National institutes of health, the U s. Department of defense,
and the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard university l
#Boosting science math technology and ethics in Tibetan communities To many Westerners science monks and technology may not be an obvious trio.
But to Tenzin Priyadarshi and others at MIT s Dalai lama Center for Ethics and Transformative Values they are a means of improving the lives of Tibetans dispersed throughout India and elsewhere.
The program called the Science Monks and Technology Leadership Program was launched a year ago to help members of the Tibetan diaspora find solutions to the challenges they face in some of India s poorest regions.
Davide Zaccagnini a vascular surgeon and program manager for the Science Monks and Technology Leadership Program says he was motivated to join because
Drug companies spend years testing safety and dosage in the clinic, only to find in Phase III clinical efficacy trials that target compounds have little to no benefit.
the company can pursue other therapeutic avenues. If, however, a drug improves performance in 240 robot-measured patients,
The researchers, including senior author Bruce Volpe of the Feinstein Institute for Medical Research in Manhasset, N y,
a professor of physical medicine and rehabilitation at the University of California at Irvine. obotic measurements will help us identify promising treatments with smaller numbers of patients
#Cochlear implants with no exterior hardware Cochlear implants medical devices that electrically stimulate the auditory nerve have granted at least limited hearing to hundreds of thousands of people worldwide who otherwise would be totally deaf.
low-power signal processing chip that could lead to a cochlear implant that requires no external hardware.
The implant would be recharged wirelessly and would run for about eight hours on each charge. The researchers describe their chip in a paper theye presenting this week at the International Solid-state Circuits Conference.
to charge the cochlear implant, so you don have to be plugged in, says Anantha Chandrakasan,
Adaptive reuse Existing cochlear implants use an external microphone to gather sound, but the new implant would
instead use the natural microphone of the middle ear, which is almost always intact in cochlear-implant patients.
The researchersdesign exploits the mechanism of a different type of medical device known as a middle-ear implant.
Delicate bones in the middle ear, known as ossicles, convey the vibrations of the eardrum to the cochlea,
the small, spiral chamber in the inner ear that converts acoustic signals to electrical. In patients with middle-ear implants, the cochlea is functional,
but one of the ossicles the stapes doesn vibrate with enough force to stimulate the auditory nerve.
but the MIT researchers tailored it for cochlear implants and found a low-power way to implement it in hardware.
Two of their collaborators at MEEI Konstantina Stankovic, an ear surgeon who co-led the study with Chandrakasan,
and Don Eddington tested it on four patients who already had cochlear implants and found that it had no effect on their ability to hear.
director of the Cochlear Implant Center at the University of California at San francisco. here a much greater stigma of having a hearing loss than there is of having a visual loss.
Lustig points out that the new cochlear implant would require a more complex surgery than existing implants do. current cochlear-implant operation takes an hour, hour and a half,
he says. y guess is that the first surgeries will take three to four hours.
It could also shed light on processes that underlie conditions such as memory disorders or dyslexia, and could benefit patients suffering from paralysis
or neurodegenerative diseases. his is the first time that MEG and fmri have been connected in this way, giving us a unique perspective,
Pantazis says. e now have the tools to precisely map brain function both in space and time,
Many Kenyans also face financial crises due to health problems. In all, about 50 percent of households in the study reported serious negative income shocks in the six months preceding the survey. hey face very high-risk environments
or over edge of a wall, going that fast could mean crashes and injuries. So for some customers that operate in dangerous terrain,
that sheds empirical light on the inner workings of health care in the U s. The study takes advantage of Oregon recent use of a lottery to assign access to Medicaid, the government-backed health-care plan for low-income
along with Katherine Baicker, a professor at the Harvard School of Public health. The study, which is being published today in the journal Science,
and medical conditions, including types of conditions that may be most readily treatable in primary-care situations. n no case were we able to find any subpopulations,
however, suggest nuances to the current debates over the expansion of Medicaid, medical costs, and the role of emergency rooms in providing care.
by lowering out-of-pocket costs, would increase the use of medical care. Or, as Finkelstein observes,
However, Medicaid also lowers the out-of-pocket costs of other types of health care, such as primary-care doctors.
Some policy analysts have suggested that expanding Medicaid could reduce emergency department visits by the formerly uninsured by bringing them into more regular contact with primary-care doctors and clinics for preventive care.
In theory, that could also reduce overall system costs, since urgent care is expensive. Indeed, prior work by Finkelstein, Baicker,
they showed that Medicaid coverage increases doctor visits, prescription drug use, and hospital admissions; reduces out-of-pocket expenses or unpaid medical debt;
and increases self-reported good health. In a 2013 paper published in the New england Journal of Medicine,
they showed that Medicaid coverage reduces the incidence of depression but does not produce measured improvements in physical health.
#Creating synthetic antibodies MIT chemical engineers have developed a novel way to generate nanoparticles that can recognize specific molecules, opening up a new approach to building durable sensors for many different compounds
To create these ynthetic antibodies, the researchers used carbon nanotubes hollow, nanometer-thick cylinders made of carbon that naturally fluoresce
such as natural antibodies, that bind to a particular target. When the target is encountered, the carbon nanotube fluorescence brightens
and could be used to create sensors to monitor diseases such as cancer, inflammation, or diabetes in living systems. his new technique gives us an unprecedented ability to recognize any target molecule by screening nanotube-polymer complexes to create synthetic analogs to antibody function,
says Michael Strano, the Carbon P. Dubbs Professor of Chemical engineering at MIT and senior author of the study,
Synthetic antibodies The new polymer-based sensors offer a synthetic design approach to the production of molecular recognition sites enabling, among other applications, the detection of a potentially infinite library of targets.
Moreover, this approach can provide a more durable alternative to coating sensors such as carbon nanotubes with actual antibodies,
does not require the use of antibodies or equivalent molecules to achieve specific molecule recognitions
#Biologists ID new cancer weakness About half of all cancer patients have a mutation in a gene called p53
which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA.
A new study from MIT biologists has found that tumor cells with mutated p53 can be made much more vulnerable to chemotherapy by blocking another gene called MK2.
In a study of mice tumors lacking both p53 and MK2 shrank dramatically when treated with the drug cisplatin while tumors with functional MK2 kept growing after treatment.
The findings suggest that giving cancer patients a combination of a DNA-damaging drug and an MK2 inhibitor could be very effective says Michael Yaffe the David H. Koch Professor in Science
and senior author of a paper describing the research in the Nov 14 issue of the journal Cell Reports.
Several drugs that inhibit MK2 are now in clinical trials to treat inflammatory diseases such as arthritis
and colitis but the drugs have never been tested as possible cancer treatments. What our study really says is that these drugs could have an entirely new second life in combination with chemotherapy says Yaffe who is a member of MIT s Koch Institute for Integrative Cancer Research.
We re very much hoping it will go into clinical trials for cancer. Sandra Morandell a postdoc at the Koch Institute is the paper s lead author.
To kill a tumorp53 is a tumor suppressor-protein protein that controls cell division. Before cell division begins p53 checks the cell s DNA
or apoptosis. Tumors that lack p53 can avoid this fate. Usually p53 is the main driver of cell death
if you block the MK2 pathway tumor cells wouldn t recognize that they had DNA damage
if this would hold true in tumors in living animals as well as cells grown in a lab dish.
To do that they used a strain of mice that are programmed genetically to develop non-small-cell lung tumors.
or off allowing them to study tumors with and without MK2 in the same animal.
This new approach allows them for the first time to compare different types of tumors in the same mice where all genetic factors are identical except for MK2 expression.
Using these mice the researchers found that before treatment tumors lacking both MK2 and p53 grow faster than tumors that have MK2.
This suggests that treating tumors with an MK2 inhibitor alone would actually do more harm than good possibly increasing the tumor s growth rate by taking the brake off the cell cycle.
However when these tumors are treated with cisplatin the tumors lacking MK2 shrink dramatically while those with MK2 continue growing.
A nonobvious combination The potential combination of cisplatin and MK2 inhibitors is unlike other chemotherapy combinations that have been approved by the Food
While this study focused on non-small-cell lung tumors the researchers have gotten similar results in cancer cells grown in the lab from bone cervical and ovarian tumors.
They are now studying mouse models of colon and ovarian cancer. The research was funded by the Austrian Science Fund the National institutes of health Janssen Pharmaceuticals Inc. the Koch Institute MIT s Center for Environmental Health Sciences the Volkswagenstiftung the Deutsche Forschungsgemeinschaft the German
which hold potential as portable diagnostic devices for cancer and other diseases. These devices consist of microfluidic channels engraved on tiny chips,
During this process, the researchers can also load a fluorescent probe such as an antibody at one end of the dumbbell.
This type of particle can be useful for diagnosing cancer and other diseases, following customization to detect proteins
or DNA sequences in blood samples that can be signs of disease. Using a cytometer,
#Resistance is futile Cisplatin is given a chemotherapy drug to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA but if tumors become resistant to cisplatin they often grow back.
A new study from MIT and the University of Toronto offers a possible way to overcome that resistance.
Senior authors of the new paper are Stephen Lippard the Arthur Amos Noyes Professor of Chemistry at MIT and a member of MIT's Koch Institute for Integrative Cancer Research and Shana
and we were intrigued very to observe that the DNA damage caused by this drug outside of the nucleus were highly toxic Kelley says.
which contains the metal platinum was approved to treat ovarian and testicular tumors in 1978 and is used now for many other cancers including lung and bladder.
The drug forms crosslinks in DNA creating blockages that interfere with a cell s ability to read
There are other ways for a cell to die besides apoptosis. You want a therapeutic agent to induce programmed cell death
People are interested really in using metals as therapeutics but they re difficult to control and elucidating the cellular targets of metal-based drugs is challenging
By targeting specific cellular organelles with the same therapeutic molecules we can learn a lot about how the cells respond to a given compound
The research was funded by the National Cancer Institute the Canadian Institute of Health and a David H. Koch Graduate Fellowship s
and therapists better understand the physical limitations caused by strokes and other motor disorders. The researchers report their findings in the journal IEEE Transactions on Neural Systems and Rehabilitation Engineering.
moving the patient ankle back and forth and side to side, loosening up the muscles, ind of like a massage,
Many other robotic therapies are designed to do most of the work for the patient in an attempt to train the muscles to walk.
Hogan says. hat wee trying to do with machines in therapy is equivalent to helping the patients,
the ankle was least stiff a finding that suggests this direction of movement is most vulnerable to injury.
Eric Perreault, a professor of biomedical engineering and physical medicine and rehabilitation at Northwestern University, says the group findings present the first insight into how muscle activation alters the ankle mechanical properties over its normal range of motion,
hich are highly relevant to many ankle injuries including the common ankle sprain. n intriguing extension of this work is that it may be possible to train individuals to activate their ankle musculature in a way that helps reduce the chance of injury,
who did not participate in the research. more immediate benefit of the study is that it presents a method for quantifying the impact of existing rehabilitation therapies on the mechanical properties of the ankle.
Understanding the mechanics of the ankle in healthy subjects may help therapists identify abnormalities in patients with motor disorders.
#Schizophrenia linked to abnormal brain waves Schizophrenia patients usually suffer from a breakdown of organized thought often accompanied by delusions or hallucinations.
Mutations in the gene for calcineurin have previously been found in some schizophrenia patients. Ten years ago MIT researchers led by Susumu Tonegawa the Picower Professor of Biology
these mice displayed several behavioral symptoms of schizophrenia including impaired short-term memory attention deficits and abnormal social behavior.
This pattern helps to explain some of the symptoms seen in schizophrenia the researchers say.
However this network is hyperactive in schizophrenic patients before and during tasks that require the brain to focus
Further studies of these mice could help reveal more about the role of the default mode network in schizophrenia Tonegawa says.
while recovering from surgery or takes certain medications. There is no fast and easy way to diagnose these clots which often remain undetected until they break free
and cause a stroke or heart attack. However new technology from MIT may soon change that:
but existing blood tests are not consistently able to detect the formation of new clots says Bhatia who is also a senior associate member of the Broad Institute and a member of MIT s Koch Institute for Integrative Cancer Research
and Institute for Medical Engineering and Science (IMES). Lead authors of the paper are Kevin Lin a graduate student in chemical engineering and Gabriel Kwong a postdoc in IMES.
Sensing thrombinblood clotting is produced by a complex cascade of protein interactions culminating in the formation of fibrin a fibrous protein that seals wounds.
Bhatia and her colleagues developed their new test based on a technology they first reported last year for early detection of colorectal cancer.
Once the urine is collected the protein fragments can be identified by treating the sample with antibodies specific to peptide tags included in the fragments.
However testing samples with antibodies is much simpler and cheaper the researchers say. Rapid screeningbhatia says she envisions two possible applications for this kind of test.
One is to screen patients who come to the emergency room complaining of symptoms that might indicate a blood clot allowing doctors to rapidly triage such patients
Another application is monitoring patients who are at high risk for a clot for example people who have to spend a lot of time in bed recovering from surgery.
Bhatia is working on a urine dipstick test similar to a pregnancy test that doctors could give patients
when they go home after surgery. If a patient is at risk for thrombosis you could send them home with a 10-pack of these sticks
and say Pee on this every other day and call me if it turns blue she says.
High levels of activation markers have been related to recurrent thrombosis but they don t have good sensitivity or specificity.
and diagnosing cancer. It could also be adapted to track liver pulmonary and kidney fibrosis Bhatia says.
The research was funded by the Koch Institute Frontier Research Fund the Kathy and Curt Marble Cancer Research Fund the Mazumdar-Shaw International Oncology Fellows Program the Burroughs Wellcome
Fund and the Deshpande Center r
#Creating a permanent bacteria barrier Any medical device implanted in the body attracts bacteria, proteins, and other microbes to its surface, causing infections and thrombosis (blood clotting) that lead to hundreds of thousands of deaths annually.
Devices can be coated with antibiotics, blood thinners, and other agents but these eventually dissolve, limiting their longevity and effectiveness.
Now, Semprus Biosciences, a startup co-founded by two MIT alumni Christopher Loose Phd 7
and CEO David Lucchino MBA 6 is developing a novel biomaterial for implanted medical devices that permanently barricades these troublesome microbes from the device surface.
when applied to a medical device, sprouts a thicket of polymers that attract water, creating an impenetrable barrier for microbes.
This has potential to reduce blood clots and infection and improve overall patient health, the cofounders say.
The technology was described in a paper published last year in the journal Science Translation Medicine,
In 2012, Semprus sold to a medical device-manufacturing giant for an amount that could reach $80 million.
and recently earned clearance from the Food and Drug Administration as a medical device deemed safe and effective for commercial distribution in the United states. It also recently received designation as a product meeting European union standards of health, safety,
a chemical engineering Phd student, was charged with developing medical devices that could permanently be inserted in the body without triggering an immune response in other words,
creating medical devices that ooked more human, Loose says. Loose developed a means of applying naturally occurring antibiotics,
and human sweat on medical devices. These peptides would puncture bacteria that came near, and microbes would have trouble developing resistance to them.
So they ent to schoolon the medical device market, canvassing hospitals to meet patients and to talk with nurses and doctors about unmet clinical needs. e learned quickly that the most successful entrepreneurs are good listeners,
Lucchino says. e conducted our own istening tourto understand the problem, so we could develop the most strategic business and technology solution.
They found many patients suffering from chronic diseases such as diabetes, cancer, and heart disease and a lack of permanent oatingsfor medical implants that might help these patients.
Thus Loose says, they were ahead of the curve in addressing the nmet needof the medical devices market. e realized an unmet need that was going to grow over the next few years
and we were one of the first to have a solution to it, he says. verything starts with the unmet need.
In the Science Translation Medicine paper, the cofounders exposed polysb-modified catheters to blood for 60 days.
e found that there is a mechanism that can, in principle, close cracks under any applied stress,
shows a small crack (dark horizontal bar just right of bottom center) that mends itself as the metal is put under stress.
These defects have intense stress fields, which an be so strong, they actually reverse what an applied load would do,
it can heal. he stress from the disclinations is leading to this unexpected behavior, he says.
in conjunction with stress-driven grain boundary migration, could actually heal cracks. This is indeed provocative
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