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Every 30 seconds, a leg is amputated somewhere in the world due to diabetes. These patients often suffer from neuropathy, a loss of sensation in the lower extremities, and are therefore unable to detect damage resulting from an ill-fitting prosthesis, which leads to the amputation of a limb.
In Biomicrofluidics, by AIP Publishing, Canadian scientists reveal their development of a new type of prosthetic using microfluidics-enabled soft robotics that promises to greatly reduce skin ulcerations and pain in patients who have had an amputation between the ankle and knee.
More than 80% of lower-limb amputations in the world are the result of diabetic foot ulcers, and the lower limb is known to swell at unpredictable times, resulting in volume changes of 10% or more.
Typically, the prosthesis used after amputation includes fabric and silicone liners that can be added or removed to improve fit. The amputee needs to manually change the liners, but neuropathy leading to poor sensation makes this difficult and can lead to more damage to the remaining limb.
“Rather than creating a new type of prosthetic socket, the typical silicon/fabric limb liner is replaced with a single layer of liner with integrated soft fluidic actuators as an interfacing layer,” said author Carolyn Ren, from the University of Waterloo. “These actuators are designed to be inflated to varying pressures based on the anatomy of the residual limb to reduce pain and prevent pressure ulcerations.”
The scientists started with a recently developed device using pneumatic actuators to adjust the pressure of the prosthetic socket. This initial device was quite heavy, limiting its use in real-world situations.
To address this problem, the group developed a way to miniaturize the actuators. They designed a microfluidic chip with 10 integrated pneumatic valves to control each actuator. The full system is controlled by a miniature air pump and two solenoid valves that provide air to the microfluidic chip. The control box is small and light enough to be worn as part of the prosthesis.
Medical personnel with extensive experience in prosthetic devices were part of the team and provided a detailed map of desired pressures for the prosthetic socket. The group carried out extensive measurements of the contact pressure provided by each actuator and compared these to the desired pressure for a working prosthesis.
All 10 actuators were found to produce pressures in the desired range, suggesting the new device will work well in the field. Future research will test the approach on a more accurate biological model.
The group plans additional research to integrate pressure sensors directly into the prosthetic liner, perhaps using newly available knitted soft fabric that incorporates pressure sensing material.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Mount Sinai-led researchers have shown that tiny, robust immune particles derived from the blood of a llama could provide strong protection against every COVID-19 variant, including Omicron, and 18 similar viruses including SARS-CoV-2 and SARS-CoV-1, which was responsible for the 2003 SARS outbreak.
In a paper published in Cell Reports on June 28, the team suggests that these “super-immunity” molecules, known as nanobodies, could be precursors to a fast-acting, inhalable antiviral treatment or spray that could potentially be stockpiled and used globally against the evolving pandemic and future viruses.
Compared to the rest of the animal kingdom, llamas, camels, and alpacas have unique immune systems: they produce antibodies with a single polypeptide chain instead of two. This construct results in antibodies that are roughly one-tenth the size of normal ones, are exceptionally stable, and can firmly bind to disease targets. Because of these unique properties, researchers can readily link multiple nanobodies like a daisy chain, so if a virus attempts to escape by mutating, another nanobody is ready to keep it in check.
“Because of their small size and broad neutralizing activities, these camelid nanobodies are likely to be effective against future variants and outbreaks of SARS-like viruses,” says lead author Yi Shi, PhD, Associate Professor of Pharmacological Sciences and Director of the Center of Protein Engineering and Therapeutics at the Icahn School of Medicine at Mount Sinai. “Their superior stability, low production costs, and the ability to protect both the upper and lower respiratory tracts against infection mean they could provide a critical therapeutic to complement vaccines and monoclonal antibody drugs if and when a new COVID-19 variant or SARS-CoV-3 emerges.”
As a critical part of their study, Dr. Shi’s team immunized the llama, named “Wally,” with the SARS-CoV-2 receptor binding domain (RBD), the short fragment or spike of the virus that latches onto the protein on the surface of human cells to gain entry and spread infection. They found that repeated immunization with the RBD resulted in Wally producing nanobodies that recognized not just SARS-CoV-2, the virus that causes COVID-19, but a vast array of other coronaviruses — conferring what researchers referred to as “super-immunity.” From this discovery, the team isolated and validated a large repertoire of highly potent antiviral nanobodies effective against a broad spectrum of SARS-like viruses.
“We learned that the tiny size of these nanobodies gives them a crucial advantage against a rapidly mutating virus,” explains co-author Ian Wilson, PhD, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research in La Jolla, California. “Specifically, it allows them to penetrate more of the recesses, nooks, and crannies of the virus surface, and thus bind to multiple regions to prevent the virus from escaping and mutating.”
From this structural information, the team designed an ultrapotent nanobody that can simultaneously bind to two regions on the RBD of SARS-like viruses to prevent mutational escape. The resulting molecule (PiN-31) is extremely stable and, in its aerosolized form, can be used as an inhaled treatment or spray, which the same team showed in previous work can be effective against SARS-CoV-2.
“While more research is needed, we believe that the broad protection, ultrapotent nanobodies we were able to isolate in the lab can be harnessed for use in humans,” says Dr. Shi, who conducted most of the research at the University of Pittsburgh before moving his lab to Icahn Mount Sinai. Increasing the attractiveness of this potential form of treatment, these highly versatile antiviral agents can be rapidly produced virtually anywhere from microbes such as E.coli or yeast cells, he adds. In the past, nanobody therapies have been clinically proven as safe and effective against human diseases, such as a blood clotting disorder and cancer.
“Winning the race against the current pandemic, as well as future viral outbreaks, will depend on fast development and equitable distribution of an arsenal of cost-effective and convenient technologies,” Dr. Shi emphasizes. “We strongly believe that the novel, inhalable, and extremely potent nanobodies we’ve discovered can meet that demand on a global scale, particularly in developing countries that are most vulnerable to viruses and the lack of therapies to treat them.”
In addition to Scripps Research, experts from Case Western Reserve University in Cleveland, the University of Pittsburgh, Hebrew University in Jerusalem, and Tel Aviv University in Israel contributed to this study.

Chinese researchers may have found a new approach to treat cancer by using a plasma treatment to induce apoptosis, the death of cancer cells, without any obvious side effect to normal cells.
The catch is that while a plasma-activated medium (PAM) can be treated as a drug, there is always a dose-effect relationship. And within the plasma community, many researchers are defining the plasma dose as either the plasma treatment time or the power deposited to plasma per surface.
In Physics of Plasmas, from AIP Publishing, the scientists’ definition of a plasma dose, the equivalent total oxidation potential (ETOP), can be used for PAM to reveal the plasma dose-response relationship for different cell types. ETOP is based on the oxidation potential of reactive oxygen and nitrogen species.
Plasma treatment time and the power deposited to plasma per surface “are not the right choices to define the plasma dose,” said Xinpei Lu, from Huazhong University of Science and Technology. “The essential part of the plasma treatment is the reactive species delivered to PAM. The definition of the plasma dose we present is based on this reactive species concentration.”
The goal of plasma medicine is to exploit a differentiated interaction of specific plasma components with specific elements or functionalities of living cells to control and, ideally, normalize therapeutic effects. One critical constraint on the path from the laboratory bench to bedside is the dose-response relationships of plasma on biological objects.
“Therefore, the determination of plasma dose is of critical biological importance for plasma’s clinical application,” said Lu. “For future plasma therapies, such as cancer treatment, our results suggest ETOP may be a well-defined strategy to evaluate its effects, because it provides the basis for significant lethality differences between normal and cancer cells.”
A plasma dose should be representative of the plasma’s contribution to the biological effect. In clinical pharmacology, this dose is most commonly measured by compounds in medicine for therapeutic purposes.
Although a broad spectrum of biological effects of plasma has been found and most distinctive plasma agents have been detected, two questions remain. How are these elements integrated into the plasma dose? How can we study the plasma dose-effect relationship?
ETOP is a preliminary attempt to answer these questions. Although it was already validated by a previous study done by the same team of researchers, whether ETOP is applicable for PAM was unclear. They note the applicability of ETOP or PAM, as well as corresponding plasma dose-response relationships, should be further studied.
“To our surprise, through data analysis, a good fit between experimental data and ETOP was found,” said Lu. “This suggests ETOP as a plasma dose is also suitable for PAM. We also found ETOP can be used to maximize the lethality difference between normal/cancer cells. Further validation by the published literature again indicates ETOP may provide a well-defined strategy to evaluate the selectivity of PAM treatment on different cell types.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Research into the causes of type 1 diabetes often focuses on the autoimmune response, where the immune system destroys pancreatic islet beta cells that produce insulin. A new study by scientists at the University of Chicago instead looks at the role of the beta cells themselves in triggering autoimmunity. The research also raises the possibility that new medications could block the immune system from destroying beta cells and prevent type 1 diabetes from developing in at risk or early onset patients.
The study, published today in Cell Reports, describes how the researchers used genetic tools to knock out or delete a gene called Alox15 in mice that are genetically predisposed to developing type 1 diabetes. This gene produces an enzyme called 12/15-Lipoxygenase, which is known to be involved in processes that produce inflammation in beta cells. Deleting Alox15 in these mice preserved their amount of beta cells, reduced the number of immune T cells infiltrating the islet environment, and prevented type 1 diabetes from developing in both males and females. These mice also showed increased expression of the gene encoding a protein called PD-L1 that suppresses autoimmunity.
“The immune system doesn’t just decide one day that it’s going to attack your beta cells. Our thinking was that the beta cell itself has somehow fundamentally altered itself to invite that immunity,” said senior author Raghavendra Mirmira, MD, PhD, Professor of Medicine and Director of the Diabetes Translational Research Center at UChicago.
“When we got rid of this gene, the beta cells no longer signaled to the immune system and the immune onslaught was completely suppressed, even though we didn’t touch the immune system,” he said. “That tells us that there is a complex dialogue between beta cells and immune cells, and if you intervene in that dialogue, you can prevent diabetes.”
The study is the result of a long-term collaboration that began when Mirmira and several members of his lab were at Indiana University. Jerry Nadler, MD, Dean of the School of Medicine and Professor of Medicine and Pharmacology at New York Medical College discovered the role of the 12/15-Lipoxygenase enzyme, and Maureen Gannon, PhD, Professor of Medicine, Cell and Developmental Biology, and Molecular Physiology and Biophysics at Vanderbilt University, provided a strain of mice that was used in the study, which allowed for the knockout of the Alox15 gene when given the drug tamoxifen.
In 2012, Sarah Tersey, PhD, Research Associate Professor at UChicago and co-senior author of the new study, led a project that was among the first to suggest that the beta cell might be a central player in the development of type 1 diabetes.
“This allows us to understand the underlying mechanisms leading to the development of type 1 diabetes,” Tersey said. “This has been a huge, changing part of the field where we focus more on the role of beta cells and not just autoimmunity.”
The study also has interesting connections to cancer treatments that harness the immune system to fight tumors. Cancer cells often express the PD-L1 protein to suppress the immune system and evade the body’s defenses. New drugs called checkpoint inhibitors target this protein, inhibiting or removing the PD-L1 “checkpoint” and unleashing the immune system to attack tumors. In the new study, increased PD-L1 in the knockout mice serves its intended purpose by preventing the immune system from attacking the beta cells.
In the new study, the researchers also tested a drug that inhibits the 12/15-Lipoxygenase enzyme on human beta cells. They saw that the drug, called ML355, increases levels of PD-L1, suggesting that it could interrupt the autoimmune response and prevent diabetes from developing. Ideally, it would be given to patients who are at high risk because of family history and show early signs of developing type 1 diabetes, or shortly after diagnosis before too much damage has been done to the pancreas. Mirmira and his team are taking the first steps to start clinical trials to test a possible treatment using ML355.
“This study certainly suggests that inhibiting the enzyme in humans can increase levels of PD-L1, which is very promising,” Mirmira said. “With beta cell targeted therapeutics, we believe that as long as the disease hasn’t progressed to the point that there’s massive destruction of beta cells, you can catch an individual before that process starts and prevent the disease progression altogether.”
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Materials provided by University of Chicago. Original written by Matt Wood. Note: Content may be edited for style and length.

Researchers from Mass Eye and Ear have developed a word-score model capable of estimating the amount of hidden hearing loss in human ears.
In a new study published June 23 in Scientific Reports, a team of researchers at Mass Eye and Ear’s Eaton-Peabody Laboratories determined average speech scores as a function of age from the records of nearly 96,000 ears examined at Mass Eye and Ear. They then compared the data to a previous study at Mass Eye and Ear that had tracked the average loss of cochlear nerve fibers as a function of age. By combining both sets of data, researchers constructed an estimate of the relation between speech scores and nerve survival in people.
According to lead study author Stéphane F. Maison, PhD, CCC-A, principal investigator of the Eaton-Peabody Laboratories and associate professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School, the new model leads to better evaluations of the cochlear nerve damage in patients and the associated speech-intelligibility deficits that come with the neural loss. The model also offers ways to estimate the effectiveness of hearing loss interventions, including the use of personal sound amplification products and hearing aids.
“Prior to this study, we could either estimate neural loss in a living patient using a lengthy test battery or measure cochlear nerve damage by removing their temporal bones when they’ve died,” said Dr. Maison. “Using ordinary speech scores from hearing tests — the same ones collected in clinics all over the world — we can now estimate the number of neural fibers that are missing in a person’s ear.”
Uncovering hidden hearing loss
Two main factors determine how well a person can hear: audibility and intelligibility. Hair cells, the sensory cells inside the inner ear, contribute to the audibility of sounds — or how loud a sound must be to be detectable. Upon receiving a sound, hair cells pass electrical signals to the cochlear nerve, which then passes those signals to the brain. How well the cochlear nerve relays these signals contributes to the clarity, or intelligibility, of sound processed within the central nervous system.

The virus that causes COVID-19 undertakes a massive takeover of the body’s fat-processing system, creating cellular storehouses of fat that empower the virus to hijack the body’s molecular machinery and cause disease.
After scientists discovered the important role of fat for SARS-CoV-2, they used weight-loss drugs and other fat-targeting compounds to try to stop the virus in cell culture. Cut off from its fatty fuel, the virus stopped replicating within 48 hours.
The authors of the recent paper in Nature Communications caution that the results are in cell culture, not in people; much more research remains to see if such compounds hold promise for people diagnosed with COVID. But the scientists, from Oregon Health & Science University and the Department of Energy’s Pacific Northwest National Laboratory, call the work a significant step toward understanding the virus.
“This is exciting work, but it’s the start of a very long journey,” said Fikadu Tafesse, the corresponding author of the study and assistant professor of molecular microbiology and immunology at OHSU. “We have an interesting observation, but we have a lot more to learn about the mechanisms of this disease.”
Fat as fuel
The team embarked on the study based on observations that people with a high body-mass index and conditions like cardiovascular disease and diabetes are more sensitive to the disease.

Children conceived through medically assisted reproduction (MAR) fare better at school but are slightly more likely to have mental health problems by their late teens, finds a new study led by researchers at UCL and the University of Helsinki.
The researchers say the correlation for mental health is only observed when the social demographics of children’s families are taken into account, and that there is no evidence to suggest the MAR treatment itself is the source of association for mental health.
Published in the European Journal of Population, the observational study explores the link between MAR — including techniques such as IVF treatment, artificial insemination and ovulation induction — and young people’s educational outcomes and mental health.
The researchers used administrative records on 280,682 Finnish children born between 1995 and 2000, and compared a range of educational and mental health outcomes among adolescents aged between 16 and 18 who were conceived naturally (266,925) and through MAR (13,757).
The researchers found that adolescents conceived by MAR performed better in school, were less likely to drop out and were at a lower risk of not being in education or employment or leaving home early compared to naturally conceived adolescents. These differences mostly disappeared when family circumstances were accounted for, suggesting that socioeconomic background is an important factor in explaining this advantage.
The researchers also found that adolescents conceived via MAR were not more likely to experience mental health problems. However, after accounting for family circumstances, the study revealed that they were at an increased risk of developing a mental disorder — particularly anxiety or depression — with around 10 per cent of MAR conceived adolescents compared to nine per cent of naturally conceived adolescents receiving a mental health diagnosis between ages 16-18.

Visits to the emergency department and hospitalizations are 22 per cent higher among individuals who use cannabis compared with those who do not, according to a new study.
The study, published in BMJ Open Respiratory Research and led by researchers at Unity Health Toronto and ICES, found serious physical injury and respiratory-reasons were the two leading causes of ED visits and hospitalizations among cannabis users.
The findings suggest an association between cannabis use and negative health events, which the researchers say should underline the need to educate and remind the public of the harmful impacts of cannabis on health. Recreational cannabis use has increased in Canada since decriminalization in October 2018.
“Our research demonstrates that cannabis use in the general population is associated with heightened risk of clinically serious negative outcomes, specifically, needing to present to the ED or be admitted to hospital,” said Dr. Nicholas Vozoris, lead author, a respirologist at St. Michael’s and an associate scientist at the hospital’s Li Ka Shing Knowledge Institute.
“Unlike tobacco, there is some uncertainty or controversy regarding the adverse health impacts of cannabis. Some individuals may perceive that cannabis has some health benefits and is otherwise benign. Our research highlights to those using — or considering to use — cannabis, that this behaviour is associated with important negative health events.”
To compare health outcomes among cannabis users and individuals who don’t use cannabis, researchers used data collected in a survey of individuals who self-reported cannabis use and linked it with health administrative data from ICES for Ontario residents ages 12 to 65 years old.
Using propensity score matching — a statistical matching technique — researchers compared the health outcomes of nearly 4,800 individuals who reported any cannabis use in the preceding 12 months with the health outcomes of over 10,000 individuals who reported never having used cannabis, or having used cannabis only once and more than 12 months ago. Researchers incorporated 31 different variables while matching study participants to minimize an unfair comparison, including demographics, multiple physical and mental health diseases, and tobacco, alcohol and illicit drug use.
The primary goal of the study was to explore whether there was a link between cannabis use and respiratory-related hospitalization or ED visits. The researchers found no significant associations between cannabis use and respiratory-related ED visits, hospitalizations, or death from any cause. However, they did find that overall visits to the ED or hospitalizations for any reason was significantly higher among cannabis users.
In addition to having greater odds of going to the ED or being hospitalized, the findings show that one of every 25 people who use cannabis will go to the emergency department (ED) or be admitted to hospital within a year of using cannabis.
Among the reasons cannabis users went to the ED or were hospitalized, acute trauma — defined as bodily injury — was the most common, with 15 per cent of cannabis users who got medical attention receiving it for this reason, and 14 per cent receiving care for respiratory reasons.
“The results of our research support that health care professionals and government should discourage recreational cannabis consumption in the general population. Given the context of cannabis decriminalization in Canada, which has very likely facilitated the broader use of this product in the population, more efforts need to made from our health and political leaders to educate and remind citizens about the harmful impacts of cannabis on health,” said Dr. Vozoris, who is also a scientist at ICES
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Materials provided by St. Michael’s Hospital. Note: Content may be edited for style and length.

Urinary tract infections are both very common and potentially very dangerous. More than half of all Australian women will suffer from a UTI in their lifetime, and nearly one in three women will have an infection requiring treatment with antibiotics before the age of 24.
Around 80 per cent of UTIs are caused by uropathogenic E. coli (UPEC), which is increasingly resistant to antibiotics. E. coli-related death due to antimicrobial resistance is the leading cause of bacterial fatalities worldwide.
In a bid to aid discovery of new treatment options, researchers at the University of Technology Sydney (UTS) are using state-of-the-art microscopy to pinpoint how these bacteria spread and multiply.
Dr Bill Söderström and Associate Professor Iain Duggin, of the Australian Institute for Microbiology and Infection at UTS, said their latest research examined the shapeshifting behaviour of UPEC. During a UTI infection cycle, the bacteria form spaghetti-like filaments hundreds of times their normal lengths before reverting to their original form.
The study, which is published in Nature Communications, used a human bladder cell infection model to generate the filaments, and look at their reversal back to rod shape.
“While we don’t fully understand why they do this extreme lifestyle make-over, we know they must revert to their original size before they can reinfect new bladder cells,” Dr Söderström said.

Climate change is a reality and extremely high temperatures have been reported by India and Pakistan in the spring. In a new scientific journal article, researchers from the University of Gothenburg, amongst others, paint a gloomy picture for the rest of the century. Heat waves are expected to increase, affecting up to half a billion people every year. In turn, they can lead to food shortages, deaths and refugee flows when the heat reaches levels that exceed what humans can tolerate. But this does not have to happen if measures are put in place to reach the Paris Agreement targets, the researchers say.
In India and Pakistan, heat waves with temperatures above 40 degrees in the shade are a directly life-threatening form of extreme weather. In a new article in the journal Earth’s Future, researchers have outlined different scenarios for the consequences of heat waves in South Asia to the year 2100.
“We established a link between extreme heat and population. In the best scenario, we succeeded in meeting the targets in the Paris Agreement, which added roughly two heat waves per year, exposing about 200 million people to the heat waves. But if countries continue to contribute to the greenhouse effect as they are still doing now, clearing and building on land that is actually helping to lower global temperatures, we believe that there could be as many as five more heat waves per year, with more than half a billion people being exposed to them, by the end of the century,” says Deliang Chen, Professor of Physical Meteorology at the University of Gothenburg and one of the authors of the article.
Population growth drives emissions
The study identifies the Indo-Gigantic Plains beside the Indus and Ganges rivers as particularly vulnerable. This is a region of high temperatures, and it is densely populated. Deliang Chen points out that the link between heat waves and population works in both directions. The size of the population affects the number of future heat waves. A larger population drives emissions up as consumption and transport increase. Urban planning is also important. If new towns and villages are built in places that are less subject to heat waves, the number of people affected can be reduced.
“We hope that the leaders in the region such as India and Pakistan read our report and think about it. In our calculation model, the range for the number of people who will be exposed to heat waves is large. The actual numbers will depend on the path that these countries choose to take in their urban planning. It is future greenhouse gas and particulate emissions that will determine how many people are actually exposed. We can more than halve the population exposed to intense heat waves if we reduce emissions so that we reach the targets in the Paris Agreement. Both mitigation and adaptation measures can make a huge difference,” says Deliang Chen.
Risk of a refugee wave
Heat waves are already causing major problems in India and Pakistan. Farmers have been hit hard when drought and heat has caused their wheat crops to fail, and their crops have moved to higher altitudes to escape the extreme heat. But this move has resulted in large acreages of trees being cleared; trees that have contributed to lowering temperatures.
“With a larger population, land use increases, which in itself can drive up temperatures further. Each heat wave will result in increased mortality and decreased productivity, since few people can work in 45-degree heat. I fear that if nothing is done, it can ultimately lead to a huge wave of migrations.”
Facts: Heat wave
In the study, a heat wave is defined relatively, where the temperature is at least as high as during the 10 per cent of hottest summer days between 1975 and 2014 in the region. In this study, the authors have also used daytime temperatures above 35 degrees Celsius and nighttime temperatures above 25 degrees Celsius for at least three consecutive days as threshold values to map heat waves. A heat wave lasts around 10 days and unlike in Sweden, for example, there is no significant cooling at night. The temperature is high around the clock. The population is also acclimatised to varying degree to a certain temperature and humidity.
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Materials provided by University of Gothenburg. Note: Content may be edited for style and length.