Seeing with radio waves

Scientists from the Division of Physics at the University of Tsukuba used the quantum effect called "spin-locking" to significantly enhance the resolution when performing radio-frequency imaging of nitrogen-vacancy defects in diamond. This work may lead to faster and more accurate material analysis, as well as a path towards practical quantum computers.

Nitrogen-vacancy (NV) centers have long been studied for their potential use in quantum computers. A NV center is a type of defect in the lattice of a diamond, in which two adjacent carbon atoms have been replaced with a nitrogen atom and a void. This leaves an unpaired electron, which can be detected using radio-frequency waves, because its probability of emitting a photon depends on its spin state. However, the spatial resolution of radio wave detection using conventional radio-frequency techniques has remained less than optimal.

Now, researchers at the University of Tsukuba have pushed the resolution to its limit by employing a technique called "spin-locking." Microwave pulses are used to put the electron's spin in a quantum superposition of up and down simultaneously. Then, a driving electromagnetic field causes the direction of the spin to precess around, like a wobbling top. The end result is an electron spin that is shielded from random noise but strongly coupled to the detection equipment. "Spin-locking ensures high accuracy and sensitivity of the electromagnetic field imaging," first author Professor Shintaro Nomura explains. Due to the high density of NV centers in the diamond samples used, the collective signal they produced could be easily picked up with this method. This permitted the sensing of collections of NV centers at the micrometer scale. "The spatial resolution we obtained with RF imaging was much better than with similar existing methods," Professor Nomura continues, "and it was limited only by the resolution of the optical microscope we used."

The approach demonstrated in this project may be applied in a broad variety of application areas -- for example, the characterizations of polar molecules, polymers, and proteins, as well as the characterization of materials. It might also be used in medical applications -- for example, as a new way to perform magnetocardiography.

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How medical schools can transform curriculums to undo racial biases

 Medical school curriculums may misuse race and play a role in perpetuating physician bias, a team led by Penn Medicine researchers found in an analysis of curriculum from the preclinical phase of medical education. In a perspective piece published Tuesday in the New England Journal of Medicine, the researchers identified five key categories in which curriculum misrepresented race in class discussions, presentations, and assessments. The authors recommend that rather than oversimplifying conversations about how race affects diseases' prevalence, diagnosis, and treatment, medical school faculty must widen the lens to "impart an adequate and accurate understanding of the complexity of these relationships."

"In medical school, 20 years ago, we often learned that higher rates of hypertension in certain racial and ethnic groups, was due to genetic predisposition, personal behaviors, or unfortunate circumstances. Now we know this is not true. There are no characteristics innate to racial and ethnic groups, biological or otherwise, that adequately explains these differences. They stem, instead, from differential experiences in our society -- it's structural racism, not race," said the study's senior author Jaya Aysola, MD, MPH, assistant dean of Inclusion and Diversity in the Perelman School of Medicine and executive director at the Penn Medicine Center for Health Equity Advancement. "When we speak of dismantling structural racism, we must begin with medical education, where these sorts of race-based biases are still being reinforced in the classroom."

Though the researchers focused on lectures from a single medical school, the study authors from other institutions found similar misrepresentations of race in their preclinical medical curriculums. The five categories of biases that the research team identified were: semantics, prevalence of disparities without context, race-based diagnostic bias, pathologizing race, and race-based clinical guidelines.

For example, the study authors noted the use of "African American," is a socially and politically meaningful identity for many people, but not for all people of African descent. Moreover, they write, it is a poor proxy for genetic difference, since it lumps people from many different ancestral populations together. The researchers also found that students were taught about the disproportionate burden of type 2 diabetes among the U.S. Akimel O'odham (formerly known as Pima) people, without sufficient historical and social context. Despite high degrees of genetic similarity, the Akimel O'odham living in Mexico have significantly lower rates of diabetes and obesity than those living in the U.S. The authors explain that a the construction of the Hoover Dam in 1930 that pushed the Akimel O'odham from their lands and into poverty, not a genetic predisposition, explains this pattern. The researchers also highlighted the teaching of guidelines that endorse the use of racial categories in the diagnosis and treatment of diseases. One course they analyzed, for instance, encouraged the use of race-adjusted glomerular filtration rate, or GFR, equations, which many experts now say limits care for Black patients and exacerbates health disparities.

"Race is not a biomedical term, and it is a poor proxy for ancestry. Yet, we continue to generate, impart, and assess medical knowledge with this imprecision. In doing so, we perpetuate biases and ignore the actual contributors to the race-based differences we see," Aysola said. "There are several aspects of the medical education apparatus that we have to fundamentally change in order to get to the ideal state where we're dismantling the structures that perpetuate racism."

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Mortality costs of air pollution in US

A team of University of Illinois researchers estimated the mortality costs associated with air pollution in the U.S. by developing and applying a novel machine learning-based method to estimate the life-years lost and cost associated with air pollution exposure.

Scholars from the Gies College of Business at Illinois studied the causal effects of acute fine particulate matter exposure on mortality, health care use and medical costs among older Americans through Medicare data and a unique way of measuring air pollution via changes in local wind direction.

The researchers -- Tatyana Deryugina, Nolan Miller, David Molitor and Julian Reif -- calculated that the reduction in particulate matter experienced between 1999-2013 resulted in elderly mortality reductions worth $24 billion annually by the end of that period. Garth Heutel of Georgia State University and the National Bureau of Economic Research was a co-author of the paper.

"Our goal with this paper was to quantify the costs of air pollution on mortality in a particularly vulnerable population: the elderly," said Deryugina, a professor of finance who studies the health effects and distributional impact of air pollution. "Understanding how air pollution affects mortality, health care use and medical costs is essential for crafting efficient environment policies because outside factors such as a person's preexisting health conditions can make it challenging to accurately estimate the causal effects of pollution on health."

About 25% of the elderly Medicare population was vulnerable to acute pollution shocks, according to the researchers.

"Our analysis shows that the most vulnerable Medicare beneficiaries are those who suffer from chronic conditions and have high health care spending," said Reif, a professor of finance and a faculty member of the Institute of Government and Public Affairs. "We estimate that members of the most vulnerable group -- those with a life expectancy of less than one year -- are over 30 times more likely to die from pollution than the typical Medicare beneficiary."

"Because we take a big data approach, we're able to see how air pollution affects the entire elderly population of the U.S. over those 14 years," said Miller, the Daniel and Cynthia Mah Helle Professor of Finance. "Medicare data is great because it has every interaction with the health care system in our sample for virtually every elderly person."

The typical air pollution research is more of a case study, Miller said.

"There's a pollution event in a certain city, and there's a mortality count around this event, but it's hard to get an accurate general estimate of the overall impact," he said. "Pollution is produced as a package: You burn stuff and it produces particulate matter, but it also produces other pollutants. Our methodology is able to take a lot of data, people and pollution events into account. And that allows us to more accurately identify the overall impact of pollution, because wind patterns affect these different pollutants in different ways. So we can tease apart which of these pollutants we think is most important and driving these mortality effects."

By exploiting the daily variation in acute fine particulate pollution exposure driven by changes in wind direction, the researchers found significant effects of exposure on mortality, hospitalizations and medical spending.

"A key part of the study was harnessing 40 billion observations with machine learning techniques," said Molitor, a professor of finance. "We used machine learning to predict how long people would have lived in the absence of the pollution event and to illuminate who is most vulnerable to pollution. One takeaway is that an individual's life expectancy -- how much longer they can expect to live -- is a much better measure of vulnerability to pollution than their age."

The scholars also found that increases in particulate matter lead to more emergency room visits, hospitalizations and higher patient spending.

"Mortality is only one of many potential costs of air pollution," Molitor said. "The elderly who aren't dying may engage in other costly activities such as going to the hospital for preventive or emergency care. Those steps may help them avoid death, but it doesn't mean that pollution has no cost to their health or finances."

Notably, the researchers also found that the failure to adjust for the preexisting health of those who die from an acute pollution event tends to overstate the mortality-reduction benefits of decreasing air pollution.

"An issue that arises when estimating mortality effects is whether those who die from pollution exposure would have passed away soon anyway without that external pollution shock," Molitor said. "If deaths caused by pollution occur disproportionately among the least healthy, then ignoring this factor could lead to an overstatement of the life years lost due to pollution."

"But we found that the typical person who dies as a result of pollution exposure isn't someone you would expect to die in a week or a month," Miller said. "It's people who have 3.6 years on average to live, compared with about 11 years for the typical elderly Medicare enrollee. So, although they are less healthy than the average Medicare recipient, these are people who we expect to have three and a half reasonably healthy years of life, and this should definitely not be ignored."

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Many younger patients with stomach cancer have a distinct disease

Many people under 60 who develop stomach cancer have a "genetically and clinically distinct" disease, new Mayo Clinic research has discovered. Compared to stomach cancer in older adults, this new, early onset form often grows and spreads more quickly, has a worse prognosis, and is more resistant to traditional chemotherapy treatments, the study finds. The research was published recently in the journal Surgery.

While rates of stomach cancer in older patients have been declining for decades, this early onset cancer is increasing and now makes up more than 30% of stomach cancer diagnoses.

"I think this is an alarming trend, as stomach cancer is a devastating disease," says senior author Travis Grotz, M.D., a Mayo Clinic surgical oncologist. "There is little awareness in the U.S. of the signs and symptoms of stomach cancer, and many younger patients may be diagnosed late -- when treatment is less effective."

The research team studied 75,225 cases using several cancer databases to review stomach cancer statistics from 1973 to 2015. Today, the average age of someone diagnosed with stomach cancer is 68, but people in their 30s, 40s and 50s are more at risk than they used to be.

Although there's no clear cutoff age for the definition of early onset and late-onset stomach cancer, the researchers found the distinctions held true whether they used an age cutoff of 60, 50 or 40 years. The researchers found that the incidence of late-onset stomach cancer decreased by 1.8% annually during the study period, while the early onset disease decreased by 1.9% annually from 1973 to 1995 and then increased by 1.5% through 2013. The proportion of early onset gastric cancer has doubled from 18% of all cases in 1995 to now more than 30% of all gastric cancer cases.

"Typically, we see stomach cancer being diagnosed in patients in their 70s, but increasingly we are seeing 30- to 50-year-old patients being diagnosed," Dr. Grotz says.

The increased rate of the early onset disease is not from earlier detection or screening, Dr. Grotz adds. "There is no universal screening for stomach cancer, and the younger patients actually presented with later-stage disease than the older patients," he says.

In addition to being more deadly, early onset stomach cancer is also genetically and molecularly distinct, researchers found. Furthermore, traditional risk factors for developing stomach cancer among older Americans, such as smoking tobacco, did not appear to correlate with its early onset counterpart.

"Hopefully, studies like this will raise awareness and increase physician suspicion of stomach cancer, particularly in younger patients," Dr. Grotz says. Younger patients who feel full before finishing a meal, or have reflux, abdominal pain, unintentional weight loss and difficulty eating should see their health care provider, he adds.

Stomach cancer is the 16th most common cancer in the U.S., according to the American Cancer Society. It has a five-year survival rate of 31.5%, and there will be an estimated 27,510 new cases in 2019, according to the National Cancer Institute. The World Health Organization reports that cancer was the second leading cause of death globally in 2018 and that stomach cancer was the third most common cause of cancer death that year.

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Medical guidelines may be biased, overly aggressive in US

Dr. Sunita Sah practiced general medicine for several years in the United Kingdom's National Health Service. When she came to the United States, she noticed something strange.

The U.K. guidelines for tests such as mammograms and colon cancer screenings drastically differed from those in the U.S. -- even though they were based on the same medical evidence.

"Having colonoscopy at the age of 50 -- that struck me as rather odd when I moved to the U.S., because you don't really hear about people having colonoscopies as a screening procedure in the U.K.," said Sah. "It's much less invasive to test for blood in the stool. It's also less costly and doesn't have the risks of undertaking a colonoscopy."

Now an assistant professor of management and organizations at Cornell, Sah and Ismail Jatoi of the University of Texas Health, San Antonio, say the treatment guidelines recommended by medical specialist organizations are more likely to call for greater use of health care services and exacerbate overdiagnosis, overtreatment and spiraling health care costs. Their commentary, "Clinical Practice Guidelines and the Overuse of Health Care Services: Need for Reform," appeared March 18 in the Canadian Medical Association Journal.

The implications are significant, she said, because guidelines are supposed to provide standard evidence-based treatment practices for all doctors.

"The recommendations put out by specialty organizations -- like the American College of Cardiology or the American College of Radiology -- show specialty bias in recommending more aggressive and/or more frequent screening procedures," said Sah, an expert on conflict of interest. "In the U.S. in particular, where the fee-for-service compensation model dominates medicine, which is different from countries like the U.K., you see even more recommendations for greater use of health care services."

Specialty bias refers to the tendency of physicians to recommend the treatments in which they are trained to deliver. For example, localized prostate cancer can be treated with either surgery or radiation.

"If you go to a surgeon, chances are that they are more likely to recommend that you have surgery; if you go to a radiation oncologist, they are more likely to recommend that you have radiation," she said. "They each often believe that the treatment that they're trained in is the better one."

In the case of screening for colorectal cancer, the American College of Gastroenterology's panel -- all of whom were gastroenterologists -- recommended colonoscopy as the best strategy.

But the United States Preventive Task Force, with no gastroenterologists or gastrointestinal surgeons, recommended testing the stool, sigmoidoscopy (an exam of only the lower part of the colon) or colonoscopy as a last resort. Stool testing was also recommended by the European Society of Medical Oncology panel, which consisted of six medical oncologists, no gastroenterologists and one gastrointestinal surgeon. The panel said there was limited evidence that screening colonoscopy is effective.

"Colonoscopies are more invasive than stool testing and come with potentially greater risks and costs for patients -- but increased clinical volume and profits for gastroenterologists," Sah said.

Specialty guidelines are also subject to fee-for-service bias, according to the commentary. Doctors who receive a payment for each treatment may tend to recommend that treatment more often, because they have a financial interest in it.

"The bias is not necessarily malicious or intentional," Sah said. "In a fee-for-service environment, they may be biased to do more rather than less, so it becomes a habit."

But more is not necessarily better, she said. "Sometimes the risks of those procedures are just not worth the benefits."

The authors call for a reduction in conflicts of interest in the fee-for-service model, and more professional diversity in the makeup of the guideline committees. "You need a variety of different voices on those committees," Sah said.

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Electricity-conducting bacteria yield secret to tiny batteries, big medical advances

An atomic model for the microbial nanowires that conduct electricity is in the foreground, while two bacteria are seen in the electron micrograph in the background, surrounded by the nanowires.

Scientists have made a surprising discovery about how strange bacteria that live in soil and sediment can conduct electricity. The bacteria do so, the researchers determined, through a seamless biological structure never before seen in nature -- a structure scientists can co-opt to miniaturize electronics, create powerful-yet-tiny batteries, build pacemakers without wires and develop a host of other medical advances.

Scientists had believed Geobacter sulfurreducens conducted electricity through common, hair-like appendages called pili. Instead, a researcher at the University of Virginia School of Medicine and his collaborators have determined that the bacteria transmit electricity through immaculately ordered fibers made of an entirely different protein. These proteins surround a core of metal-containing molecules, much like an electric cord contains metal wires. This "nanowire," however, is 100,000 times smaller than the width of a human hair.

This tiny-but-tidy structure, the researchers believe, could be tremendously useful for everything from harnessing the power of bioenergy to cleaning up pollution to creating biological sensors. It could actually serve as the bridge between electronics and living cells.

"There are all sorts of implanted medical devices that are connected to tissue, like pacemakers with wires, and this could lead to applications where you have miniature devices that are actually connected by these protein filaments," said UVA's Edward H. Egelman, PhD. "We can now imagine the miniaturization of many electronic devices generated by bacteria, which is pretty amazing."

Small but Effective

Geobacter bacteria play important roles in the soil, including facilitating mineral turnover and even cleaning up radioactive waste. They survive in environments without oxygen, and they use nanowires to rid themselves of excess electrons in what can be considered their equivalent to breathing. These nanowires have fascinated scientists, but it is only now that researchers at UVA, Yale and the University of California, Irvine, have been able to determine how G. sulfurreducens uses these organic wires to transmit electricity.

"The technology [to understand nanowires] didn't exist until about five years ago, when advances in cryo-electron microscopy allowed high resolution," said Egelman, of UVA's Department of Biochemistry and Molecular Genetics. "We have one of these instruments here at UVA, and, therefore, the ability to actually understand at the atomic level the structure of these filaments. ... So this is just one of the many mysteries that we've now been able to solve using this technology, like the virus that can survive in boiling acid, and there will be others."

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Even psychological placebos have an effect

The color green can have a positive effect on the personal condition, as long as this effect was previously attributed to it.

Placebo effects do not only occur in medical treatment -- placebos can also work when psychological effects are attributed to them. Psychologists from the University of Basel reported these findings in the journal Scientific Reports, based on three studies with over 400 participants.

Psychotherapy and placebos are both psychological interventions that not only have comparable effects, but that are also based on very similar mechanisms. Both forms of treatment are heavily influenced by the relationship between patients and those treating them, as well as by the expectations of recovery. Whereas placebo research mostly focuses on a biomedical model -- an inert pill is provided with a medical rationale, which produces a corresponding effect -- little is known about the effect of placebos provided with a psychological rationale.

"Green is calming"

Placebos can also have effects when specific psychological effects are attributed to them. This is the conclusion that researchers from the Division of Clinical Psychology and Psychotherapy at the University of Basel reached in three independent experiments with 421 healthy participants. The accompanying explanation -- the narrative -- played a key role when dispensing the placebos, as did the relationship between the researchers and the participants.

The researchers used the color green as the placebo in the video experiments, examining it both with and without a psychological narrative ("green is calming because it activates early conditioned emotional schemata"), as well as in the context of a neutral or a friendly relationship.

After viewing the videos, the participants assessed their subjective condition with questionnaires over several days. The results showed that the placebo had a positive effect on the participants' well-being when it was prescribed together with a psychological narrative and in the context of a friendly relationship. The observed effect was strongest after administering the placebo but remained evident for up to one week.

Ethical implications

"The observed effects were comparable with those of psychotherapeutic interventions in the same populations," says principal investigator Professor Jens Gaab. The fact that psychological placebos can have significant effects is not only important for understanding psychological interventions: "It challenges both research and clinical practice to address these mechanisms and effects, as well as their ethical implications."

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Novel HIV vaccine candidate is safe and induces immune response in healthy adults and monkeys

Scientists are working to develop a preventative vaccine that could finally put an end to the epidemic for which there are 1.8 million new infections each year.

New research published in The Lancet shows that an experimental HIV-1 vaccine regimen is well-tolerated and generated comparable and robust immune responses against HIV in healthy adults and rhesus monkeys. Moreover, the vaccine candidate protected against infection with an HIV-like virus in monkeys.

Based on the results from this phase 1/2a clinical trial that involved nearly 400 healthy adults, a phase 2b trial has been initiated in southern Africa to determine the safety and efficacy of the HIV-1 vaccine candidate in 2,600 women at risk for acquiring HIV. This is one of only five experimental HIV-1 vaccine concepts that have progressed to efficacy trials in humans in the 35 years of the global HIV/AIDS epidemic.

Previous HIV-1 vaccine candidates have typically been limited to specific regions of the world. The experimental regimens tested in this study are based on 'mosaic' vaccines that take pieces of different HIV viruses and combine them to elicit immune responses against a wide variety of HIV strains.

"These results represent an important milestone. This study demonstrates that the mosaic Ad26 prime, Ad26 plus gp140 boost HIV vaccine candidate induced robust immune responses in humans and monkeys with comparable magnitude, kinetics, phenotype, and durability and also provided 67% protection against viral challenge in monkeys," says Professor Dan Barouch, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School, Boston, USA who led the study.

He adds: "These results should be interpreted cautiously. The challenges in the development of an HIV vaccine are unprecedented, and the ability to induce HIV-specific immune responses does not necessarily indicate that a vaccine will protect humans from HIV infection. We eagerly await the results of the phase 2b efficacy trial called HVTN705, or 'Imbokodo', which will determine whether or not this vaccine will protect humans against acquiring HIV."

Almost 37 million people worldwide are living with HIV/AIDS, with an estimated 1.8 million new cases every year. A safe and effective preventative vaccine is urgently needed to curb the HIV pandemic.

In the 35 years of the HIV epidemic, only four HIV vaccine concepts have been tested in humans, and only one has provided evidence of protection in an efficacy trial -- a canarypox vector prime, gp120 boost vaccine regimen tested in the RV144 trial in Thailand lowered the rate of human infection by 31% but the effect was considered too low to advance the vaccine to common use.

A key hurdle to HIV vaccine development has been the lack of direct comparability between clinical trials and preclinical studies. To address these methodological issues, Barouch and colleagues evaluated the leading mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel clinical and pre-clinical studies to identify the optimal HIV vaccine regimen to advance into clinical efficacy trials.

The APPROACH trial recruited 393 healthy, HIV-uninfected adults (aged 18-50 years) from 12 clinics in east Africa, South Africa, Thailand, and the USA between February 2015 and October 2015. Volunteers were randomly assigned to receive either one of seven vaccine combinations or a placebo, and were given four vaccinations over the course of 48 weeks.

To stimulate, or 'prime', an initial immune response, each volunteer received an intramuscular injection of Ad26.Mos.HIV at the start of the study and again 12 weeks later. The vaccine containing 'mosaic' HIV Env/Gag/Pol antigens was created from many HIV strains, delivered using a nonreplicating common-cold virus (Ad26).

To 'boost' the level of the body's immune response, volunteers were given two additional vaccinations at week 24 and 48 using various combinations of Ad26.Mos.HIV or a different vaccine component called Modified Vaccinia Ankara (MVA) with or without two different doses of clade C HIV gp140 envelope protein containing an aluminium adjuvant.

Results showed that all vaccine regimens tested were capable of generating anti-HIV immune responses in healthy individuals and were well tolerated, with similar numbers of local and systemic reactions reported in all groups, most of which were mild-to-moderate in severity. Five participants reported at least one vaccine-related grade 3 adverse event such as abdominal pain and diarrhea, postural dizziness, and back pain. No grade 4 adverse events or deaths were reported.

In a parallel study, the researchers assessed the immunogenicity and protective efficacy of the same Ad26-based mosaic vaccine regimens in 72 rhesus monkeys using a series repeated challenges with simian-human immunodeficiency virus (SHIV) -- a virus similar to HIV that infects monkeys.

The Ad26/Ad26 plus gp140 vaccine candidate induced the greatest immune responses in humans and also provided the best protection in monkeys -- resulting in complete protection against SHIV infection in two-thirds of the vaccinated animals after six challenges.

The authors note several limitations, including the fact that that the relevance of vaccine protection in rhesus monkeys to clinical efficacy in humans remains unclear. They also note that there is no definitive immunological measurement that is known to predict protection against HIV-1 in humans.

Writing in a linked Comment, Dr George Pavlakis and Dr Barbara Felber from the National Cancer Institute at Frederik, Maryland, USA say: "Efficacy studies are necessary to determine protective ability in humans and also for the discovery of correlates of protection and for determining whether the same or different immune correlates apply for different vaccine regimens. It remains to be determined whether improved efficacy over RV144 will be achieved by either of the present efficacy trials (NCT02968849; NCT03060629). New vaccine concepts and vectors are in development and can progress to efficacy trials, which is an important process since development of an AIDS vaccine remains urgent. Despite unprecedented advances in HIV treatment and prophylaxis, the number of people living with HIV infection continues to increase worldwide. Implementation of even a moderately effective HIV vaccine together with the existing HIV prevention and treatment strategies is expected to contribute greatly to the evolving HIV/AIDS response. It is therefore essential that a commitment to pursue multiple vaccine development strategies continues at all stages."

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Combining antibiotics changes their effectiveness

Combining antibiotics changes their effectiveness.

The effectiveness of antibiotics can be altered by combining them with each other, non-antibiotic drugs or even with food additives. Depending on the bacterial species, some combinations stop antibiotics from working to their full potential whilst others begin to defeat antibiotic resistance, report EMBL researchers and collaborators in Nature on July 4.

In the first large-scale screening of its kind, scientists profiled almost 3000 drug combinations on three different disease-causing bacteria. The research was led by EMBL group leader Nassos Typas.

Overcoming antibiotic resistance

Overuse and misuse of antibiotics has led to widespread antibiotic resistance. Specific combinations of drugs can help in fighting multi-drug resistant bacterial infections, but they are largely unexplored and rarely used in clinics. That is why in the current paper, the team systematically studied the effect of antibiotics paired with each other, as well as with other drugs and food additives in different species.

Whilst many of the investigated drug combinations lessened the antibiotics' effect, there were over 500 drug combinations which improved antibiotic outcome. A selection of these positive pairings was also tested in multi-drug resistant bacteria, isolated from infected hospital patients, and were found to improve antibiotic effects.

Clinical vanillin?

When vanillin -- the compound that gives vanilla its distinctive taste -- was paired with one particular antibiotic known as spectinomycin, it helped the antibiotic to enter bacterial cells and inhibit their growth. Spectinomycin was originally developed in the early-1960s for treating gonorrhoea but is rarely used nowadays due to the bacterial resistance that was developed against it. However, in combination with vanillin it could become clinically relevant once again and used for other disease-causing microbes. "Of the combinations tested, this was one of the most effective and promising synergies we identified," says Ana Rita Brochado, first author on the paper and research scientist at EMBL. Pairings such as this could extend the arsenal of weapons in the war against antibiotic resistance.

Curiously, however, vanillin lessened the effect of many other types of antibiotics. The paper showed that vanillin works in a similar way to aspirin to decrease the activity of many antibiotics -- although its effects in human cells have not been tested, they are most likely different.

According to Nassos Typas, combinations of drugs that decrease the effect of antibiotics could also be beneficial to human health. "Antibiotics can lead to collateral damage and side effects because they target healthy bacteria as well. But the effects of these drug combinations are highly selective, and often only affect a few bacterial species. In the future, we could use drug combinations to selectively prevent the harmful effects of antibiotics on healthy bacteria. This would also decrease antibiotic resistance development, as healthy bacteria would not be put under pressure to evolve antibiotic resistance, which can later be transferred to dangerous bacteria."

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Spider's web inspires removable implant that may control type 1 diabetes

Doctoral students Alan Chiu, left, and Duo An hold a sample of TRAFFIC (Thread-Reinforced Alginate Fiber for Islets enCapsulation). In the background, left to right, are Minglin Ma, Dan Luo, Meredith Silberstein and Dr. James Flanders.

For the more than 1 million Americans who live with type 1 diabetes, daily insulin injections are literally a matter of life and death. And while there is no cure, a Cornell University-led research team has developed a device that could revolutionize management of the disease.

In Type 1 diabetes, insulin-producing pancreatic cell clusters (islets) are destroyed by the body's immune system. The research group, led by assistant professor Minglin Ma from the Department of Biological and Environmental Engineering, has devised an ingenious method for implanting hundreds of thousands of islet cells into a patient. They are protected by a thin hydrogel coating and, more importantly, the coated cells are attached to a polymer thread and can be removed or replaced easily when they have outlived their usefulness.

Transplantation of stem cell-derived, insulin-producing islet cells is an alternative to insulin therapy, but that requires long-term immunosuppressive drug administration. One well-researched approach to avoid the immune system's response is to coat and protect the cells in tiny hydrogel capsules, hundreds of microns in diameter. However, these capsules cannot be taken out of the body easily, since they're not connected to each other, and there are hundreds of thousands of them.

And the ability to remove the transplant is key because of its potential to form tumors.

"When they fail or die, they need to come out," Ma said. "You don't want to put something in the body that you can't take out. With our method, that's not a problem."

Taking inspiration from the way water beads on a spider's web, Ma and his team first attempted to connect the islet cell-containing capsules through a string but realized that it would be better to put the hydrogel layer uniformly around a string instead. That string: an ionized calcium-releasing, nanoporous polymer thread.

This thread -- which the group has dubbed TRAFFIC (Thread-Reinforced Alginate Fiber For Islets enCapsulation) -- was inspired by a spider's web but, according to Ma, is even better because the hydrogel covers the thread uniformly.

"You don't have any gaps between capsules," he said. "With a spider's silk, you still have gaps between the water beads. In our case, gaps would be bad in terms of scar tissue and the like."

This therapy would involve minimally invasive laparoscopic surgery to implant approximately six feet of hydrogel-coated thread into the patient's peritoneal cavity.

TRAFFIC has received patent protection with the help of Danish pharmaceutical giant Novo Nordisk, which developed injectable insulin more than 90 years ago and is a collaborator on the paper. Other co-authors include professor Dan Luo in the Department of Biological and Environmental Engineering, postdoctoral researcher Wei Song, doctoral students Jason Lu and Yehudah Pardo, fiber science postdoc Dahua Shou, nutritional science professor Ling Qi and postdoc Yewei Ji.

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An Opioid Vaccine Developed by the US Military Could Combat Addiction

A heroin user prepares to shoot up on the street in a South Bronx neighborhood which has the highest rate of heroin-involved overdose deaths in the city on October 7, 2017 in New York City.

For the first time in a half a century, life expectancy in the United States declined for the second year in a row — and America’s opioid epidemic is to blame. A child born in 2016 is expected to live 78.6 years, down from 78.7 years in 2015 and 78.9 in 2014, according to statistics released by the US Centers for Disease Control and Prevention.

"Two years in a row is quite shocking," Robert Anderson, chief of the mortality statistics branch at the National Center for Health Statistics, told AFP. "The key factor in all this is the increase in drug overdose deaths."

Yet amid the overdose epidemic, another opioid vaccine has shown promising — albeit early — results in the laboratory.

Scientists at the US Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR) recently developed a vaccine that blocks the opioids in heroin from reaching the brain in mice and rats, offering a potential breakthrough in treating opioid addiction.

When injected, the heroine vaccine releases antibodies into the blood that prohibit the drug from breaking through the blood-brain barrier. This means that even if a heroin addict shoots up, they won’t experience a high. The vaccine includes a potent adjuvant, a substance that boosts the body’s immune response to a toxin, called the Army Liposome Formulation, also developed by researchers at WRAIR.

“All vaccines to substances of abuse function through causing the body to make antibodies that bind the drug of interest and prevent it from entering the brain,” Dr. Gary Matyas, chief of adjuvants and formulations for the US Military Research Program and one of the study authors, told Seeker.

While Matyas and his team have not directly tested their vaccine against vaccines from other research facilities, they have tested it against an older vaccine developed by WRAIR and found that the new one is more effective and very stable. “[Its stability] should increase its shelf-life and keep it from degrading during vaccine manufacturing and storage,” Matyas said.

Their study, published in the Journal of Medicinal Chemistry, found that this new vaccine was not only effective in preventing heroin from reaching the brain but worked with other commonly abused opioids as well, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine. It also lowered the toxic effect of very high doses of heroin, which could be key in preventing overdoses.

The antibodies in the vaccine did not bind to several other opioids like methadone, tramadol, sufentanil, nalbuphine, buprenorphine, and fentanyl. Fentanyl is one of the most widely abused synthetic forms of heroin and 100 times more powerful, which makes it extremely deadly. Due to the high risk of overdose, some researchers have prioritized the development of a treatment method specifically for fentanyl abuse. Along with their heroin vaccine, the Scripps Institute tested a fentanyl vaccine in mice and found it to be similarly effective, but clinical trials are still needed.

The discovery that the WRAIR vaccine does not interfere with opioids like methadone and buprenorphine turned out to be a positive development, as these drugs are often used in current treatment methods for opioid addiction. Because the vaccine’s antibodies do not bind with methadone, buprenorphine, or naltrexone, it can potentially be used in combination with these therapies.

Most importantly, the vaccine did not react with naloxone, which is used in emergency overdose rescue treatments to reverse respiratory complications. And it did not react to non-opioid pain relievers like ibuprofen or aspirin.

While this research is an important advancement in treating opioid addiction, it could be several years before the vaccine is commercially available. “Vaccines typically take many years to develop, test, and manufacture, and we are still in the early stages,” Matyas said. “We are currently pursuing funding for a clinical trial [and] we have licensed the product to Opiant Pharmaceuticals to continue development and manufacture at the appropriate point.”

Administering methadone or buprenorphine is the most common treatment option for heroin addicts, but these methods are often expensive and require inconvenient daily trips to a clinic. What’s more, the chance of relapse afterwards is very high. 91 people die every day from an opioid overdose in the US, according to the CDC. By addressing the issue of relapse due to intense cravings, this new vaccine offers one additional solution for treatment.

The US military’s vaccine, funded by the National Institute of Health, the Henry M. Jackson Foundation for the Advancement of Military Medicine, and the US Army, is not the only one in development. In June, the Scripps Research Institute published their work on a similar vaccine that was found to be effective in mice, as well as rhesus monkeys, and other opioid vaccines are also being developed and tested in order to address the growing epidemic.

Read more at Seeker

Ancient feces reveal parasites described in earliest Greek medical texts

Ancient faeces from prehistoric burials on the Greek island of Kea have provided the first archaeological evidence for the parasitic worms described 2,500 years ago in the writings of Hippocrates -- the most influential works of classical medicine.

University of Cambridge researchers Evilena Anastasiou and Piers Mitchell used microscopy to study soil formed from decomposed faeces recovered from the surface of pelvic bones of skeletons buried in the Neolithic (4th millennium BC), Bronze Age (2nd millennium BC) and Roman periods (146 BC -- 330 AD).

The Cambridge team worked on this project with Anastasia Papathanasiou and Lynne Schepartz, who are experts in the archaeology and anthropology of ancient Greece, and were based in Athens.

They found that eggs from two species of parasitic worm (helminths) were present: whipworm (Trichuris trichiura), and roundworm (Ascaris lumbricoides). Whipworm was present from the Neolithic, and roundworm from the Bronze Age.

Hippocrates was a medical practitioner from the Greek island of Cos, who lived in the 5th and 4th centuries BC. He became famous for developing the concept of humoural theory to explain why people became ill.

This theory -- in which a healthy body has a balance of four 'humours': black bile, yellow bile, blood and phlegm -- remained the accepted explanation for disease followed by doctors in Europe until the 17th century, over 2,000 years later.

Hippocrates and his students described many diseases in their medical texts, and historians have been trying to work out which diseases they were. Until now, they had to rely on the original written descriptions of intestinal worms to estimate which parasites may have infected the ancient Greeks. The Hippocratic texts called these intestinal worms Helmins strongyle, Ascaris, and Helmins plateia.

The researchers say that this new archaeological evidence identifies beyond doubt some of the species of parasites that infected people in the region. The findings are published today in the Journal of Archaeological Science: Reports.

"The Helmins strongyle worm in the ancient Greek texts is likely to have referred to roundworm, as found at Kea. The Ascaris worm described in the ancient medical texts may well have referred to two parasites, pinworm and whipworm, with the latter being found at Kea," said study leader Piers Mitchell, from Cambridge's Department of Archaeology.

"Until now we only had estimates from historians as to what kinds of parasites were described in the ancient Greek medical texts. Our research confirms some aspects of what the historians thought, but also adds new information that the historians did not expect, such as that whipworm was present."

The mention of infections by these parasites in the Hippocratic Corpus includes symptoms of vomiting up worms, diarrhea, fevers and shivers, heartburn, weakness, and swelling of the abdomen.

Descriptions of treatment for intestinal worms in the Corpus were mainly through medicines, such as the crushed root of the wild herb seseli mixed with water and honey taken as a drink.

"Finding the eggs of intestinal parasites as early as the Neolithic period in Greece is a key advance in our field," said Evilena Anastasiou, one of the study's authors. "This provides the earliest evidence for parasitic worms in ancient Greece."

Read more at Science Daily

Rise of ampicillin resistance began years before human use

Low doses of penicillin routinely fed to livestock in the 1950s in North America and Europe may have encouraged antibiotic-resistant bacteria to evolve and spread.

Bacteria that can pass on genes resistant to ampicillin, one of the most commonly used antibiotics today, emerged several years before the widespread use of this antibiotic in humans, according to new research published in The Lancet Infectious Diseases.

Molecular analysis of historical samples of Salmonella by researchers at the Institut Pasteur (Paris, France) suggests that the ampicillin resistance gene (blaTEM-1) emerged in humans in the 1950s, several years before the antibiotic was released onto the pharmaceutical market. The findings also indicate that a possible cause was the common practice of adding low doses of penicillin to animal feed in the 1950s and 60s.

The study comes just weeks after WHO called for the end to routine antibiotic use to promote growth and prevent disease in healthy farm animals.

"Our findings suggest that antibiotic residues in farming environments such as soil, waste water, and manure may have a much greater impact on the spread of resistance than previously thought," says Dr Francois-Xavier Weill, Institut Pasteur, who led the study.

Antibiotic resistance kills around 25,000 people a year in Europe, and this is predicted to rise to over 10 million people worldwide by 2050. Many bacteria that cause serious infections in humans like Salmonella, have already developed resistance to common antibiotics.

Ampicillin, the first broad-spectrum penicillin for the treatment of infections due to Enterobacteria, was released on the market in the UK in 1961. Shortly after (in 1962-1964), the first outbreaks of disease in humans caused by ampicillin-resistant strains of the common zoonotic (which cause disease that can be spread between animals and humans) bacterium, Salmonella enterica var Typhimurium (S. Typhimurium), were identified in the UK.

This short timeline prompted the researchers to investigate the emergence of ampicillin resistance. In this study, they tested 288 historical samples of S. Typhimurium collected from humans, animals, and food and feed in Europe, Asia, Africa, and America between 1911 and 1969. Samples were tested for antibiotic susceptibility and were analysed by whole genome sequencing, in order to identify the mechanisms of resistance to ampicillin.

The researchers found various ampicillin-resistance genes in 11 isolates (3..8%) from human samples. Importantly, the blaTEM-1 gene was found on plasmids (mobile DNA that can be easily copied and transferred between different bacteria) in three isolates taken from humans in France and Tunisia in 1959 and 1960.

The authors note that despite the close proximity between the countries, the vectors of ampicillin resistance (mostly from France) differed from those in the strains responsible for the first outbreaks in the UK in the 1960s. Dr Weill says: "This indicates that the early emergence of ampicillin resistance was due to multiple independent acquisitions of these resistant genes by different bacterial populations and their varying spread across several countries."

"The genetic diversity of these ampicillin-resistant isolates, their resistance mechanisms, and their geographic distribution, indicate that ampicillin resistance had already spread in this prominent zoonotic bacterium in the late 1950s, several years before ampicillin became commercially available."

A report from the UK Central Public Health Laboratory in 1965 raised the idea that low doses of the narrow-spectrum antibiotic penicillin G (also known as benzylpenicillin), routinely added to animal feed, may have contributed to the emergence of ampicillin resistance in humans in the UK (a practice that was banned in the UK in 1969).

In further analyses, the authors confirm that ampicillin resistance genes can be successfully transferred between wild type S. Typhimurium strains after exposure to relatively low levels of penicillin G, similar to those found in the litter of chickens fed with antibiotics in the USA in the 1970s.

The authors note some limitations of this study, particularly the highly selective nature of the available historical isolates that were predominately from France and former French colonies in Africa and Asia.

According to Dr Weill, "Although our study cannot identify a causal link between the use of penicillin G and the emergence of transmissible ampicillin-resistance in livestock, our results suggest that the non-clinical use of penicillins like benzylpenicillin may have encouraged the evolution of resistance genes in the late 1950s. There is an urgent need to re-evaluate the use of antibiotics in animals and for a 'one health' approach to tackling resistance, recognising that bacteria know no borders. This must include close international monitoring and surveillance of resistance in both human and animal health."

Writing in a linked Comment, Dr Sandra Van Puyvelde and colleagues from the Institute of Tropical Medicine Antwerp, Belgium say, "Antibiotic growth promoters have been gradually banned in Europe since 1996 (with a complete ban in 2006), without adverse effects on animal production, but resulting in a decrease in antibiotic resistance in pigs and poultry. Extensive use of antibiotics, however, continues in low-income and middle-income countries and in booming economies, particularly in intense farming such as that of fish and shellfish."

Read more at Science Daily

Understanding the Berlin patient's unexpected cure of HIV

Research associate Jason Reed performs cell culture maintenance in the Sacha lab.

A decade ago, the medical world was shocked when a patient in Berlin, Germany, had been declared free of HIV after receiving a stem cell transplant to treat cancer. Doctors have repeatedly tried to replicate the result, but this HIV cure has evaded other patients so far.

Dr. Jonah Sacha and colleagues at OHSU's Vaccine & Gene Therapy Institute are among the many scientists who are seeking to understand why the much-studied "Berlin patient" was so fortunate. Now, they've developed a new way to understand his cure. Sacha's team has shown a species of monkey called Mauritian cynomolgus macaques can successfully receive stem cell transplants.

Researchers have long used a different monkey species to research stem cell transplants, but that species' biological characteristics means it can't be reliably used to find good donor matches to mimic human stem transplants.

In a paper published Nov. 10 in the journal Nature Communications, Sacha and colleagues report they successfully performed stem transplants on two monkeys more than a year ago that continue to lead healthy lives today. The recipients did not suffer from the many common adverse effects of stem transplants, including the grueling graft-versus-host disease, which can cause severe liver damage, rashes, diarrhea and even death.

The finding provides Sacha a critical tool needed to explore how the Berlin patient was cured. As a result of the finding, researchers can also use Mauritian cynomolgus macaques to improve stem cell transplant outcomes for human patients with other blood-related conditions such as leukemia and sickle-cell disease.

From Science Daily

Boy Who Lost 80 Percent of His Epidermis Healed with Genetically Altered Skin

Gene therapy to treat a skin disease

When the 7-year-old boy arrived at the burn center in Germany, he had already lost 60 percent of his epidermis and was being treated around the clock with morphine. The child wasn’t the victim of a terrible fire, but was the carrier of a rare genetic disease called junctional epidermolysis bullosa (JEB) that had produced blisters and open wounds all over his body since birth. A staph infection had driven him to the verge of death.

The surgical team in Germany quickly exhausted conventional skin graft techniques — skin from the boy’s father was rejected — and were ready to give up when they came upon an experimental gene therapy in Italy. The method, which had only been used twice on much smaller grafts, used genetic editing to correct a mutation that prevented the epidermis from properly binding to the underlying dermis.

As the surgeons and researchers reported in an article published in the journal Nature, the boy underwent three skin graft surgeries in late 2015 and early 2016 using sheets of his own genetically corrected skin grown in the Italian lab. At the time of the first surgery, he had lost 80 percent of his total epidermal skin layer and the prognosis was dire. Just eight months later, he walked out of the intensive care unit with a completely healthy, self-renewing, and stretchable epidermis.

“To make it clear, we didn’t have any options to treat this child,” Tobias Hirsch, a surgeon with the burn center at the Ruhr University Hospital in Bochum, Germany, told journalists during a press briefing. “We initially decided to do palliative care, because there was no chance to save his life. And now the kid is back to school, he’s playing soccer, and spending holidays with his siblings. There’s a tremendous increase in quality of life.”

The experimental gene therapy treatment was developed by Michele De Luca at the Center for Regenerative Medicine at the University of Modena and Reggio Emilia in Modena, Italy. Patients suffering from JEB have a mutation in one or more of three genes (LAMA3, LAMB3, or LAMC2) that disrupts the production of laminin 5, a protein that’s critical to forming the bottom-most layer of the epidermis.

An estimated 500,000 people worldwide suffer from various forms of epidermolysis bullosa. Without a cure, 40 percent of individuals with JEB don’t survive past early childhood, primarily due to skin cancers that are also strongly associated with the disease.

Even though the 7-year-old boy was stricken with a particularly severe form of JEB, surgeons were able to salvage a small biopsy of healthy skin tissue and send it to De Luca’s lab in Italy, where he used a retroviral vector to replace the boy’s faulty LAMB3 gene with a fully expressed version.

The new skin cells were then grown out on fibrin protein scaffolds that were shipped in sheets to the hospital in Germany. In total, the new epidermal sheets needed to cover more than nine square feet (0.85 square meters) of the boy’s body, far more than had ever been attempted with a JEB patient.

Just a few weeks after the first operation, in which all four of the boys limbs were grafted with the genetically altered skin, the new epidermis had stabilized and stratified, said De Luca in the press briefing. The second operation, which grafted the remaining skin on the back and torso, was equally successful. However, the boy needed to immobilized and fed through a tube throughout the months-long ordeal.

Nearly two years later, the boy’s new skin has gone through 20 monthly renewal cycles, and heals and stretches just like a healthy epidermis. While doctors want to avoid excessive biopsies, genetic testing shows that the regenerating skin cells all carry the fixed gene. What’s amazing, said the boy’s surgeons, is that his skin doesn’t even need to be treated with any special creams or ointments, which are a daily requirement for most burn grafts. The boy, who had once been on a constant morphine drip, doesn’t even take any medications.

Read more at Seeker

New Discoveries Bring Hope to the Fight Against Antibiotic Resistance

Colonies of pathogenic MRSA bacteria on a blood agar plate.

Antibiotic resistance is a worldwide threat to human health and survival. Bacteria are changing in response to the extensive overuse of antibiotics in medicine and the livestock industry, rendering these medicines ineffective while endangering the people who need them most.

Antibiotics known as β-lactams — which include penicillins, cephalosporins, and carbapenems — are the most widely prescribed around the world, and are increasingly resisted by bacteria.

The World Health Organization recently placed bacteria that are resistant to cephalosporins and carbapenems on its global priority list of antibiotic-resistant pathogens, emphasizing the critical need for a way to combat this problem. After completing two recent studies, a team of UK scientists may be close to a solution.

The papers, published in the Journal of Antimicrobial Chemotherapy and in the journal Molecular Microbiology, detail the team’s discovery of two mechanisms associated with β-lactam antibiotic resistance. This allowed the researchers — a team of chemists from the University of Bristol, the University of Oxford, and the University of Leeds — to develop a promising method for reversing resistance in the most commonly prescribed antibiotics.

“Antibiotic resistance is a growing problem, directly causing the deaths of around 750,000 people globally each year,” Dr. Matthew Avison, reader in molecular bacteriology at the University of Bristol and senior author of both studies, told Seeker. “β-lactam antibiotics are the most commonly used class, about 60 percent of all prescriptions, and they are particularly important for serious infections of patients in hospitals.”

The use of β-lactam enzymes is one important mechanism that bacteria use to resist antibiotics, by using them to destroy the medication once it enters a cell. Avison’s team was searching for a β-lactam enzyme inhibitor that would protect antibiotics in the body, allowing them to effectively fight infection.

They examined two inhibitors, one known as avibactam that is already being used in clinical trials, and another that is a bicyclic boronate inhibitor. On their own, both inhibitors failed to protect the antibiotic, known as ceftazidime. When paired with another antibiotic called aztreonam, however, they both worked extremely well, killing some of the most resistant bacteria the lab has ever observed.

“This discovery adds significantly to what we already know about β-lactam inhibitors,” Avison said. “We’ve shown that different combinations of β-lactamase inhibitors and β-lactam antibiotics work better than others, and most importantly, we have identified the biological explanation of this difference. We hope it will give clinicians the confidence to use these combinations in the treatment of serious infections where all other antimicrobials have failed.”

Earlier this year, the combination of avibactam and aztreonam helped save the lives of two patients in the US. Each case involved antibiotic-resistant illnesses, and the novel combination of the β-lactamase inhibitor with the β-lactam antibiotic cleared the infections.

“This would only be used on very seriously ill patients in hospitals,” Avidon noted, “and so would only be given intravenously, usually via an infusion pump.”

Studies on β-lactamase enzymes continue to aid in the discovery of many more β-lactamase inhibitors, like the bicyclic boronate inhibitor that this study found to be effective. According to Avison, this is the first time in 10 years that scientists are hopeful about reversing β-lactam antibiotic resistance.

Read more at Seeker

Breakthrough device heals organs with a single touch

Researchers demonstrate a process known as tissue nanotransfection at The Ohio State University Wexner Medical Center. In laboratory tests, this process was able to heal the badly injured legs of mice in just three weeks with a single touch of this chip. The technology works by converting normal skin cells into vascular cells, which helped heal the wounds.

Researchers at The Ohio State University Wexner Medical Center and Ohio State's College of Engineering have developed a new technology, Tissue Nanotransfection (TNT), that can generate any cell type of interest for treatment within the patient's own body. This technology may be used to repair injured tissue or restore function of aging tissue, including organs, blood vessels and nerve cells.

Results of the regenerative medicine study published in the journal Nature Nanotechnology.

"By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining," said Dr. Chandan Sen, director of Ohio State's Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State's College of Engineering in collaboration with Ohio State's Nanoscale Science and Engineering Center.

Researchers studied mice and pigs in these experiments. In the study, researchers were able to reprogram skin cells to become vascular cells in badly injured legs that lacked blood flow. Within one week, active blood vessels appeared in the injured leg, and by the second week, the leg was saved. In lab tests, this technology was also shown to reprogram skin cells in the live body into nerve cells that were injected into brain-injured mice to help them recover from stroke.

"This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you're off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary," said Sen, who also is executive director of Ohio State's Comprehensive Wound Center.

TNT technology has two major components: First is a nanotechnology-based chip designed to deliver cargo to adult cells in the live body. Second is the design of specific biological cargo for cell conversion. This cargo, when delivered using the chip, converts an adult cell from one type to another, said first author Daniel Gallego-Perez, an assistant professor of biomedical engineering and general surgery who also was a postdoctoral researcher in both Sen's and Lee's laboratories.

TNT doesn't require any laboratory-based procedures and may be implemented at the point of care. The procedure is also non-invasive. The cargo is delivered by zapping the device with a small electrical charge that's barely felt by the patient.

"The concept is very simple," Lee said. "As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So, this is the beginning, more to come."

Researchers plan to start clinical trials next year to test this technology in humans, Sen said.

Read more at Science Daily

New surgical strategy offers hope for repairing spinal injuries

Both ventral and dorsal roots have been detached, which is the common scenario clinically, the ventral root is implanted directly into the cord as is dorsal root, but after the ganglion has been cut out. In the final drawing the possible re-established connections and reflex arch are colored.

Scientists in the UK and Sweden previously developed a new surgical technique to reconnect sensory neurons to the spinal cord after traumatic spinal injuries. Now, they have gained new insight into how the technique works at a cellular level by recreating it in rats with implications for designing new therapies for injuries where the spinal cord itself is severed.

The brain and the neurons (nerve cells) in the rest of our body are connected in the spine. Here, motor neurons, which control muscle movement, and sensory neurons, which relay sensory information such as pain, temperature and touch, connect with the spinal cord.

Where the neurons connect with the cord, motor neurons bundle together to form a structure called the motor root, while sensory neurons form a sensory root. In patients with traumatic injuries, these roots can be torn, causing areas of the body to lose neural control.

Surgeons can implant motor roots at the area from which they are torn, and they will usually successfully reconnect, as motor neurons can regrow out of the spinal cord and into the motor root. However, this does not apply to the more troublesome sensory root, which surgeons couldn't reconnect properly until recently. "Doctors previously considered this type of spinal cord injury impossible to repair," says Nicholas James, a researcher at King's College London. "These torn root injuries can cause serious disability and excruciating pain."

Happily, Thomas Carlstedt, also at King's College London, recently helped to develop a new surgical technique to reconnect the sensory root. It involves cutting the original sensory nerve cells out of the root and implanting the remaining root directly into a deeper structure in the spinal cord. This area is called the dorsal horn, and it contains secondary sensory neurons that don't normally directly connect to sensory roots. When the team tried the technique in patients, certain spinal reflexes returned, indicating that the implanted neuron had integrated with the spine to form a functional neural circuit.

In a new study recently published in Frontiers in Neurology, James, Carlstedt and other collaborators set out to understand how the implanted sensory root was connecting with the spinal cord in the dorsal horn. By understanding the mechanism, they hope to develop new treatments for patients with other types of spinal injuries.

The scientists used a rat model of spinal injury to study the process at a cellular level. During surgery, they produced a similar spinal injury in the rats and then reattached the sensory root using the new technique. At 12-16 weeks after surgery, the researchers assessed the spinal repair by passing electricity along the neurons to see if they formed a complete neural circuit. They then sacrificed the rats and analyzed the neural tissue under a microscope.

The electrical tests showed that the neural circuit was complete, and that the root had successfully integrated with the spinal cord. When they examined the tissue, they found that small neural offshoots had grown from structures called dendrites (branched projections at the end of neurons) in the dorsal horn. These thin offshoots had extended all the way into the implanted sensory root to create a functional neural circuit.

Read more at Science Daily

Fungal Genomic Breakthrough Unlocks a ‘Gold Rush’ of New Drug Discoveries

Several common medications, from the antibiotic penicillin to the LDL cholesterol-lowering drug lovastatin, originated in molds. Through the 1960s, molds and other fungi were at the center of largescale drug discovery, but then researchers hit roadblocks and the effort somewhat fizzled. Problems included challenges associated with culturing microbes in labs and isolating potentially useful molecules.

Now a technological breakthrough, outlined in a paper published by the journal Nature Chemical Biology, has just been developed that could unlock the floodgates for new drugs originating from fungi. The process involves using genomics and data analytics to capture fungal DNA and then identify promising new chemical molecules that could become the basis of a range of new drugs.

“New chemical matter from the fungal world can now be extracted,” senior author Neil Kelleher, a chemical biologist at Northwestern University, told Seeker. “So it’s like mining for gold, but instead of small labs panning for nuggets, the process can now be industrialized.”

The technology developed by Kelleher, lead author Kenneth Clevenger, and their colleagues consists of a three-step system. First, genomics and molecular biology are used to identify and capture broad portions of fungal DNA known as gene clusters. Next, the gene clusters are placed into a model fungus: Aspergillus nidulans.

Clevenger explained that this fungus “is one of the most studied fungi out there, so we know a lot about it biology and chemistry.” As a result, he continued, scientists can then distinguish with greater ease new molecules from those in the fungus that are already well documented.

The final step is to utilize mass spectrometry and data analytics to analyze the resulting fungal compounds.

The researchers applied the three-step technology to investigate three diverse fungal species, and discovered 17 new compounds from the 56 gene clusters that they screened. Kelleher noted that this is “a great hit rate in the business of natural products discovery.”

The team named one of the new metabolites valactamide A, and it is now the focus of additional study. Co-author Nancy Keller of the University of Wisconsin-Madison said that fungi often produce such metabolites as protectants and weapons from other microbes or environmental stresses.

“Due to these properties,” she said, “many fungal metabolites become very valuable in treating human disease by targeting pathogenic microbes or malfunctioning human enzymes.”

An oyster mushroom (Pleurotus ostreatus), which is a natural source of lovastatin.

Keller explained that fungi have complex cells like humans do and share many of the same proteins. As a result, they can interact with our bodies and change substances, such as enzymes.

For example, the fungi-sourced lovastatin targets an enzyme — HGM-CoA reductase — found in both humans and fungi. This enzyme is needed to produce cholesterol in humans as well as the fungi version of cholesterol, called ergosterol. When lovastatin interacts with the enzyme in a person, it can lower that individual’s LDL cholesterol (popularly known as the “bad” cholesterol). The drug also has antifungal properties.

“It’s likely that many fungi-sourced compounds with medical potential will be antimicrobial, but based on past history, we can also expect drugs to target the human immune response and high cholesterol, among others,” Clevenger said.

Other tech advances in recent years have led to the realization that good health often has more to do with a well-balanced microbiome than the presence — or absence — of any particular supposed beneficial or detrimental agent.

Read more at Discovery News

Final biomedical trial on captive chimpanzees is first oral Ebola vaccine for saving wild apes

One of the captive chimpanzees in the research trial receiving the oral Ebola vaccination.

The results from the final biomedical research trial on captive chimpanzees for the foreseeable future have been published in the journal Scientific Reports.

The trial was of a vaccination for Ebola: the first orally administered vaccine for any disease developed specifically for the purpose of conserving wild apes.

In addition to poaching and forest loss, diseases such as Ebola and anthrax have devastated wild ape populations. Ebola alone is estimated to have killed one third of the world's wild gorillas over the last three decades.

Now, new findings have shown an effective oral vaccine for Ebola in chimpanzees, and that the captive animals involved in the trial exhibited very few signs of stress as a result. Researchers say the work demonstrates a model that could be harnessed for other diseases and ape species in the wild.

However, after decades using chimpanzees to test vaccines destined for humans, changes in the law have seen enforced retirement of captive populations and the closing of chimpanzee research facilities in the US -- the last developed country where biomedical testing on chimpanzees was legal.

In what researchers describe as a "horrible irony," they say these reforms -- a victory for long-standing campaigns by animal welfare groups -- will ultimately prove detrimental to chimpanzees and gorillas in the wild, as any vaccination for wild animals must be tested in captivity first to ensure its safety.

Consequently, the promising new vaccine model may never progress to the point where it can be used to inoculate endangered wild apes, say the research team from the universities of Cambridge, UK, and Thomas Jefferson and Louisiana, US.

"In 2014 the world was gripped by fears of an Ebola virus pandemic. Yet few people realise that Ebola has already inflicted pandemic scale mortality on our closest relatives," says lead researcher Dr Peter Walsh from the University of Cambridge.

"African apes are also threatened by naturally occurring pathogens like anthrax, and the increasing overspill of human pathogens such as measles. A glimmer of hope lies in the fact that many of the disease threats are now vaccine preventable.

"We have developed a very promising tool for inoculating ape species against the myriad deadly diseases they face in the wild, but continued progress relies on access to a small number of captive animals.

"This may be the final vaccine trial on captive chimpanzees: a serious setback for efforts to protect our closest relatives from the pathogens that push them ever closer to extinction in the wild."

Previous attempts to vaccinate wild apes have resorted to administering individual animals with hypodermic darts -- a laborious task feasible for only a small number of apes habituated to human approach. By contrast, oral vaccines encased in appealingly edible baits could be distributed across wild ape territories to inoculate large numbers over longer periods.

Such an approach has already proved successful in other species: almost eliminating fox rabies (and the consequent need to cull foxes) across continental Europe.

The latest study was carried out with ten chimpanzees in one of the last remaining chimpanzee research facilities in the US in New Iberia, Louisiana. Six received the oral vaccine, while four were injected as a control group.

All the animals displayed a robust immunity without side effects after 28 days -- when the trial was terminated due to new Endangered Species Act regulations banning biomedical research on chimpanzees.

Throughout the trial, scientists closely monitored animal behaviour and physiology for signs of severe stress. Other than very minor weight loss (2% of body mass), they say that signs of trauma were "entirely absent."

"Some pressure groups argue that all research on captive chimpanzees is tantamount to torture, not just because of procedures but also due to confinement," says Walsh.

"Enclosures and animal care are now of a very high standard, with chimpanzees housed in large social spaces. The modest traces of stress we detected during our trial were akin to the values observed in college students anticipating exams."

Captive chimpanzee trials are technically still legal in the US in instances that benefit the species. However, Walsh says that the limited funds available for conservation research makes it unviable for biomedical facilities to retain populations, while zoos and sanctuaries are either "ideologically opposed" or unwilling to risk any public backlash from testing.

Further work to enhance the vaccine, such as ensuring effectiveness after exposure to high tropical forest temperatures, may now never get done due to the closure of captive chimpanzee facilities.

"In an ideal world, there would be no need for captive chimpanzees," says Walsh. "But this is not an ideal world. It is a world where diseases such as Ebola, along with rampant commercial poaching and habitat loss, are major contributors to rapidly declining wild ape populations.

Read more at Science Daily