Publisher Health

Patients with advanced ankle osteoarthritis who undergo surgery see equally good outcomes from the two main surgical treatments for osteoarthritis, a new study led by UCL researchers has shown.
The TARVA randomised clinical trial compared total ankle joint replacement with ankle fusion (when the ankle joint is pinned to prevent movement). It was led by the Comprehensive Clinical Trials Unit at UCL, and involved 17 NHS Trusts across the UK.
The new study, published in Annals of Internal Medicine, analysed the outcomes from just over 280 patients aged between 50 and 85, half of whom had total ankle replacement and half had ankle fusion surgery. Both procedures are intended to relieve pain and restore movement that was lost due to advanced osteoarthritis.
The outcomes were measured using standard assessments which covered quality of life, pain levels and ability to carry out daily activities — including, where relevant, participation in sport. Patients were assessed before their operation and twelve months after surgery.
The study found that both total ankle replacement and ankle fusion improved patients’ quality of life considerably, with overall no statistically significant differences between them. But when the ankle replacement type most used in the UK, a fixed bearing joint replacement, was looked at separately, it showed a significant improvement in clinical scores and quality of life over ankle fusion.
The study also found that total joint replacement saw better clinical outcomes than ankle fusion in patients with arthritis in surrounding joints. In ankle fusion, the shin bone is pinned to the talus, the uppermost bone in the foot. This prevents movement in the ankle joint, but movement is retained in the 30 other joints within the foot. All patients underwent an MRI scan before their operation, and 42% were found to have arthritis in surrounding joints, although many of them had no symptoms. Patients receiving joint replacement were found to have a better range of movement than those that underwent ankle fusion.
Andrew Goldberg (Honorary Associate Professor, UCL Surgery & Interventional Science), the consultant orthopaedic surgeon who led the trial, said: “The TARVA study shows how important it is to know the health of the surrounding joints before the patient undergoes surgery, which may involve an MRI, as it could help inform which procedure might be better for the patient.”
The research also highlighted some differences in complications following surgery between the two procedures. Patients undergoing total ankle replacement were more likely to see their wound take longer to heal than those having ankle fusion. Total ankle replacement was also more likely to result in some nerve damage than ankle fusion, leaving patients with numbness or tingling in the foot. Patients who underwent ankle fusion surgery were more likely to suffer blood clots in the legs — treatable through medication — as the procedure requires patients to be immobilised for longer than ankle replacement.
Mr Goldberg added: “Although the risks are not life threatening, understanding the different risks involved in each procedure is essential. Our aim in this trial was to provide the data that patients need to make informed decisions about these operations. We’ve clearly shown that both joint replacement and fusion provide significant patient benefits. We also found that the type of joint replacement seems to have an effect but this needs further research.”
Corresponding author of the study, Kashfia Chowdhury (Comprehensive Clinical Trials Unit at UCL), said: “This is the largest study of its kind to be completed in this field, providing robust findings thanks to the teams across the UK who contributed and ensured high data quality.”
The study was funded by the National Institute for Health and Care Research (NIHR).
Story Source:
Materials provided by University College London. Note: Content may be edited for style and length.

Oregon State University scientists have invented a way to make magnetic nanoparticles that get hotter than any previous nanoparticle, improving their cancer fighting ability.
Faculty from the OSU College of Pharmacy spearheaded a collaboration that developed an advanced thermal decomposition method for producing nanoparticles able to reach temperatures in cancer lesions of up to 50 degrees Celsius, or 122 degrees Fahrenheit, when exposed to an alternating magnetic field.
Findings of the preclinical study led by Oleh Taratula and Olena Taratula were published today in the journal Small Methods.
Magnetic nanoparticles have shown anti-cancer potential for years, the scientists said. Once inside a tumor, the particles — tiny pieces of matter as small as one-billionth of a meter — are exposed to an alternating magnetic field. Exposure to the field, a non-invasive process, causes the nanoparticles to heat up, weakening or destroying the cancer cells.
“Magnetic hyperthermia shows great promise for the treatment of many types of cancer,” Olena Taratula said. “Many preclinical and clinical studies have demonstrated its potential to either kill cancer cells directly or enhance their susceptibility to radiation and chemotherapy.”
But at present, magnetic hypothermia can only be used for patients whose tumors are accessible by a hypodermic needle, Oleh Taratula said, and not for people with hard to reach malignancies such as metastatic ovarian cancer.
“With currently available magnetic nanoparticles, the required therapeutic temperatures — above 44 degrees Celsius — can only be achieved by direct injection into the tumor,” he said. “The nanoparticles have only moderate heating efficiency, which means you need a high concentration of them in the tumor to generate enough heat. And numerous studies have shown that only a small percentage of systemically injected nanoparticles accumulate in tumors, making it a challenge to get that high concentration.”
To tackle those problems, the scientists developed a new chemical manufacturing technique that resulted in magnetic nanoparticles with more heating efficiency. They demonstrated in a mouse model that the cobalt-doped nanoparticles will accumulate in metastatic ovarian cancer tumors following low-dose systemic administration, and that when exposed to an alternating magnetic field, the particles can rise in temperature to 50 degrees Celsius.
“To our knowledge, this is the first time it’s been shown that magnetic nanoparticles injected intravenously at a clinically recommended dose are capable of increasing the temperature of cancer tissue above 44 degrees Celsius,” Olena Taratula said. “And we also demonstrated that our novel method could be used for the synthesis of various core-shell nanoparticles. It could serve as a foundation for the development of novel nanoparticles with high heating performance, further advancing systemic magnetic hyperthermia for treating cancer.”
Core-shell nanoparticles have an inner core structure and an outer shell made from different components, she said. Researchers are especially interested in them because of the unique properties that can result from the combination of core and shell material, geometry and design.
In addition to Olena and Oleh Taratula, the collaboration also included College of Pharmacy researchers Youngrong Park, Abraham Moses, Peter Do, Ananiya Demessie, Tetiana Korzun, Fahad Sabei, Conroy Sun, Prem Singh, Fahad Sabei and Hassan Albarqi, as well as Pallavi Dhagat from the Oregon State College of Engineering and researchers from Oregon Health & Science University.
The National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the OSU Advantage Accelerator Innovation Development program funded this research.
Story Source:
Materials provided by Oregon State University. Original written by Steve Lundeberg. Note: Content may be edited for style and length.

A new study in mice from researchers at The University of Texas at Dallas suggests that a short-term exposure to a high-fat diet may be linked to pain sensations even in the absence of a prior injury or a preexisting condition like obesity or diabetes.
The study, published Sept. 1 in the journal Scientific Reports, compared the effects of eight weeks of different diets on two cohorts of mice. One group received normal chow, while the other was fed a high-fat diet in a way that did not precipitate the development of obesity or high blood sugar, both of which are conditions that can result in diabetic neuropathy and other types of pain.
The researchers found that the high-fat diet induced hyperalgesic priming — a neurological change that represents the transition from acute to chronic pain — and allodynia, which is pain resulting from stimuli that do not normally provoke pain.
“This study indicates you don’t need obesity to trigger pain; you don’t need diabetes; you don’t need a pathology or injury at all,” said Dr. Michael Burton, assistant professor of neuroscience in the School of Behavioral and Brain Sciences and corresponding author of the article. “Eating a high-fat diet for a short period of time is enough — a diet similar to what almost all of us in the U.S. eat at some point.”
The study also compared obese, diabetic mice with those that just experienced dietary changes.
“It became clear, surprisingly, that you don’t need an underlying pathology or obesity. You just needed the diet,” Burton said. “This is the first study to demonstrate the influential role of a short exposure to a high-fat diet to allodynia or chronic pain.”
Western diets are rich in fats — in particular saturated fats, which have proved to be responsible for an epidemic of obesity, diabetes and associated conditions. Individuals who consume high amounts of saturated fats — like butter, cheese and red meat — have high amounts of free fatty acids circulating in their bloodstream that in turn induce systemic inflammation.

A research team led by the University of Houston has developed a vaccine targeting the dangerous synthetic opioid fentanyl that could block its ability to enter the brain, thus eliminating the drug’s “high.” The breakthrough discovery could have major implications for the nation’s opioid epidemic by becoming a relapse prevention agent for people trying to quit using opioids. While research reveals Opioid Use Disorder (OUD) is treatable, an estimated 80% of those dependent on the drug suffer a relapse.
The findings, published in the journal Pharmaceutics, could not be timelier or more in demand: Over 150 people die every day from overdoses of synthetic opioids including fentanyl, which is 50 times stronger than heroin and 100 times stronger than morphine. Consumption of about 2 milligrams of fentanyl (the size of two grains of rice) is likely to be fatal depending on a person’s size.
“We believe these findings could have a significant impact on a very serious problem plaguing society for years — opioid misuse. Our vaccine is able to generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys. Thus, the individual will not feel the euphoric effects and can ‘get back on the wagon’ to sobriety,” said the study’s lead author Colin Haile, a research associate professor of psychology at UH and the Texas Institute for Measurement, Evaluation and Statistics (TIMES), and a founding member of the UH Drug Discovery Institute.
In another positive finding, the vaccine did not cause any adverse side effects in the immunized rats involved in lab studies. The team plans to start manufacturing clinical-grade vaccine in the coming months with clinical trials in humans planned soon.
Fentanyl is an especially dangerous threat because it is often added to street drugs like cocaine, methamphetamine and other opioids, such as oxycodone and hydrocodone/acetaminophen pills, and even to counterfeit benzodiazepines like Xanax. These counterfeit drugs laced with fentanyl add to the amount of fentanyl overdoses in individuals who do not ordinarily consume opioids.
“The anti-fentanyl antibodies were specific to fentanyl and a fentanyl derivative and did not cross-react with other opioids, such as morphine. That means a vaccinated person would still be able to be treated for pain relief with other opioids,” said Haile.
The vaccine tested contains an adjuvant derived from E. coli named dmLT. An adjuvant molecule boosts the immune system’s response to vaccines, a critical component for the effectiveness of anti-addiction vaccines. The adjuvant was developed by collaborators at the Tulane University School of Medicine and has proven vital to the efficacy of the vaccine. Also on the team are Greg Cuny, Joseph P. & Shirley Shipman Buckley Endowed Professor of Drug Discovery at the UH College of Pharmacy along with researchers from Baylor College of Medicine and Michael E. DeBakey Veteran’s Affairs Medical Center.
Current treatments for OUD are methadone, buprenorphine and naltrexone, and their effectiveness depends upon formulation, compliance, access to medications and the specific misused opioid.
Therese Kosten, professor of psychology and director of the Developmental, Cognitive & Behavioral Neuroscience program at UH, calls the new vaccine a potential “game changer.”
“Fentanyl use and overdose is a particular treatment challenge that is not adequately addressed with current medications because of its pharmacodynamics and managing acute overdose with the short-acting naloxone is not appropriately effective as multiple doses of naloxone are often needed to reverse fentanyl’s fatal effects,” said Kosten, senior author of the study.
The study was funded by the Department of Defense through the Alcohol and Substance Abuse Disorders Program managed by RTI International’s Pharmacotherapies for Alcohol and Substance Use Disorders Alliance, which has funded Haile’s lab for several years to develop the anti-fentanyl vaccine.
Story Source:
Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

Muscles waste as a result of not being exercised enough, as happens quickly with a broken limb that has been immobilized in a cast, and more slowly in people reaching an advanced age. Muscle atrophy, how clinicians refer to the phenomenon, is also a debilitating symptom in patients suffering from neurological disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), and can be a systemic response to various other diseases, including cancer and diabetes.
Mechanotherapy, a form of therapy given by manual or mechanical means, is thought to have broad potential for tissue repair. The best-known example is massage, which applies compressive stimulation to muscles for their relaxation. However, it has been much less clear whether stretching and contracting muscles by external means can also be a treatment. So far, two major challenges have prevented such studies: limited mechanical systems capable of evenly generating stretching and contraction forces along the length of muscles, and inefficient delivery of these mechanical stimuli to the surface and into the deeper layers of muscle tissue.
Now, bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a mechanically active adhesive named MAGENTA, which functions as a soft robotic device and solves this two-fold problem. In an animal model, MAGENTA successfully prevented and supported the recovery from muscle atrophy. The team’s findings are published in Nature Materials.
“With MAGENTA, we developed a new integrated multi-component system for the mechanostimulation of muscle that can be directly placed on muscle tissue to trigger key molecular pathways for growth,” said senior author and Wyss Founding Core Faculty member David Mooney, Ph.D. “While the study provides first proof-of-concept that externally provided stretching and contraction movements can prevent atrophy in an animal model, we think that the device’s core design can be broadly adapted to various disease settings where atrophy is a major issue.” Mooney leads the Wyss Institute’s Immuno-Materials Platform, and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.
An adhesive that can make muscles move
One of MAGENTA’s major components is an engineered spring made from nitinol, a type of metal known as “shape memory alloy” (SMA) that enables MAGENTA’s rapid actuation when heated to a certain temperature. The researchers actuated the spring by electrically wiring it to a microprocessor unit that allows the frequency and duration of the stretching and contraction cycles to be programmed. The other components of MAGENTA are an elastomer matrix that forms the body of the device and insulates the heated SMA, and a “tough adhesive” that enables the device to be firmly adhered to muscle tissue. In this way, the device is aligned with the natural axis of muscle movement, transmitting the mechanical force generated by SMA deep into the muscle. Mooney’s group is advancing MAGENTA, which stands for “mechanically active gel-elastomer-nitinol tissue adhesive,” as one of several Tough Gel Adhesives with functionalities tailored to various regenerative applications across multiple tissues.

It is still a glimpse into the future: Astronauts could be put into artificial hibernation and in this state be better protected from cosmic radiation. At present, there are already promising approaches to follow up such considerations. An international research team led by the Biophysics Department of the GSI Helmholtzzentrum in Darmstadt now has found decisive indications of the possible benefits of artificial hibernation for radiation resistance. The research partners from Germany, Japan, Italy, the UK and the USA have recently published their results in Scientific Reports, a journal of the Nature Publishing Group.
Scientists call the state, which hibernating animals enter, torpor. In this state, life-supporting functions of an organism are reduced: Body temperature is lowered, metabolism is reduced and body functions such as heart rate and respiration rate or oxygen uptake are significantly slowed down. At the molecular level, gene activity and protein biosynthesis are also reduced to a slower pace. In the study now published on synthetic torpor (i.e. a kind of artificially produced hibernation) and protection from ionizing radiation, the scientists demonstrated biological effects suggesting that synthetic torpor increases resistance to radiation. A proof that can be very useful in the long term for astronauts.
Space radiation is acknowledged as one of the main health risks for human space exploration. Harmful effects of space radiation are a major challenge, especially for future long-term missions. The majority of radiation dose absorbed by crews in manned interplanetary missions is produced by galactic cosmic radiation (GCR), high-energy charged particles, including densely ionizing heavy ions, produced in distant galaxies. The energy of these particles is so high that shielding of the spacecraft cannot stop them and lead to exposure rates over 200 times higher than the radiation background on Earth over a very long period. For these reasons, radiation countermeasures for future missions are being investigated.
“The connections between torpor and radioresistance represent a highly innovative research approach. Our results indicate that synthetic torpor is a promising tool to enhance radioprotection in living organism during long-term space missions. It could thus be an effective strategy to protect humans as they explore the solar system,” summarizes Professor Marco Durante, Head of the GSI Biophysics Division.
It is already known that naturally hibernating animals acquire radioresistance in this state. However, the recent study is so significant because it is the first time that a hibernation-like biological state was induced in a non-hibernating animal (rat) and radioresistance to high-energy heavy ions could be proved. In experiments at Japan’s Gunma University Heavy-ion Medical Center, accelerated carbon ions were used to simulate radiation in space. The other in vitro cell experiments were performed at the GSI/FAIR campus in Darmstadt and were part of the FAIR Phase 0 experimental period.
The main results of the research team after irradiation and induction of a synthetic torpor proved the hypotheses: Synthetic hibernation may have protective effects on a lethal dose of C?ions. In addition, synthetic hibernation reduces the tissues damage from total body irradiation.
Furthermore, GSI scientists were able to characterize the underlying mechanism in their studies on rat tissue cells. They showed that lower oxygen concentration in the tissues (hypoxia) and reduced metabolism at low temperature (hypothermia) could be two important factors in the prevention of cell damage. The immunohistological analyses indicated that the synthetic torpor spares the tissue from energetic ion radiation. In addition, changes in metabolism at low temperatures could also affect DNA repair.
A lot of research is still needed to investigate and better understand the radioprotective effect of synthetic torpor in organs. Currently it is not possible technically to hibernate a human in a safe and controlled way. However, research is progressing. Only recently, the neuronal pathways that control torpor are been unraveled. Now the current publication adds another important component.
The Scientific Managing Director of GSI and FAIR, Professor Paolo Giubellino, emphasizes that the international accelerator center FAIR, currently under construction at GSI, will offer unique opportunities for research in the field of cosmic radiation. “Already today, the GSI facility is able to produce beams of heavy nuclei as they occur in cosmic radiation. At FAIR, experiments with a much wider range of particle energies and intensities will be possible. This will allow researchers to study the effects of cosmic radiation on humans and on technical instrumentation, which are fundamentally necessary to make human Mars missions possible. I am very delighted that the European Space Agency ESA has a cooperation with FAIR since many years to foster this field of research.”

Researchers in the Princeton University Department of Chemistry have discovered a new multi-step pathway through which bacteria found in the mammalian gut produce antimicrobial peptides.
The newly identified biosynthetic pathway transforms a biologically inert peptide into structurally complex antibiotics, which they call enteropeptins. Enteropeptins are a class of ribosomally synthesized peptide natural products, referred to as RiPPs.
The core structure of these products is synthesized by the ribosome, which is limited to the 20 canonical amino acids. The Mo Lab discovered and characterized new metalloenzymes capable of converting arginine, a canonical amino acid, into N-methylornithine, a noncanonical amino acid, within enteropeptin.
This is the first report of a RiPP natural product containing this unusual amino acid. The discovery was made by the lab of Professor Mohammad Seyedsayamdost.
The lab’s paper, “Biosynthesis-guided discovery reveals enteropeptins as alternative sactipeptides containing N-methylornithine,” was published last month in Nature Chemistry.
Kenzie Clark, first author on the paper and a former graduate student in the Mo Lab, explained the core discoveries.

Vulnerable populations in 45 high-burden countries worldwide must be prioritised in efforts to reduce the impact of the COVID-19 pandemic on tuberculosis (TB) care, according to new research published in BMC Medicine.
Overall, as many as 195,449 children (below the age of 15 years), 1,126,133 adults (aged 15 to 64 years old) and 235,402 older individuals (aged 65 years or older) are estimated to have had a missed or delayed diagnosis of tuberculosis in 2020 as a result of COVID-19 disruptions. These figures include 511,546 women and 863,916 men.
The call to action follows the results of a new study investigating potential inequalities by age and sex of the impact of disruptions caused by the COVID-19 pandemic on access to diagnoses of this deadly disease.
The team — including researchers from the London School of Hygiene & Tropical Medicine (LSHTM) — modelled trends in TB case reporting to the World Health Organisation (WHO) for 45 high-burden countries between 2013 and 2019. Predictions for 2020 using these models were then compared to actual observations in the same year.
Although the study found no evidence for systemic disparity in risk by age or sex on a global scale, when broken down by country, setting-specific inequalities were revealed.
For example, in over half of countries (57.1%) analysed, children were at a greater risk of having their TB diagnosis delayed or missed due to COVID-19 than adults, with children in WHO regions in the Eastern Mediterranean (namely Pakistan and Somalia) and Europe (for example Tajikistan and Ukraine) found to be disproportionately affected. Similarly higher risk figures for older individuals compared to adults were also revealed, namely in over two thirds of countries (70.1%), including WHO regions in the Western Pacific (such as China and Mongolia) and Europe (for example, Kazakhstan and Belarus). In almost half of countries (45%), sex was predicted to be an influential risk factor. Men, for example, were found to be particularly susceptible to missed or delayed diagnoses in the WHO region of the Americas (namely Peru and Brazil).