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  • PhRMA Foundation awards grants to fight health disparities with digital health tools

    PhRMA Foundation awards grants to fight health disparities with digital health tools

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    The PhRMA Foundation (PhF) awarded $500,000 grants to David G. Armstrong, DPM, MD, PhD, of the University of Southern California and Nino Isakadze, MD, MHS, of Johns Hopkins University to conduct research using digital health technologies (DHTs) to improve health equity and health outcomes for patients. 

    Armstrong and Isakadze were selected out of a group of seven researchers awarded $25,000 planning grants in 2023 by the Foundation to develop comprehensive research proposals to study the use of DHTs for advancing patient health, especially in underserved populations. 

    Digital health technologies have great potential to improve health care broadly, but they could be especially impactful for underserved communities if we design and test them with equity in mind. These studies will engage diverse populations to develop digital health solutions targeting treatment challenges for patients with diabetes and heart arrhythmia.” 


    Amy M. Miller, PhD, President of the PhRMA Foundation

    Armstrong, a professor of surgery and neurological surgery at Keck School of Medicine of USC, will lead a project that aims to improve treatment for diabetic foot ulcers (DFU) using special smart boots that relieve pressure from specific areas of the foot. DFUs affect 15% of patients with diabetes -; more than 1 million people annually -; and if inadequately treated, can lead to amputation. Individuals from racial and ethnic minority groups are more likely to develop DFUs, receive amputations, and experience complications, leading to a lower survival rate. 

    While pressure offloading boots are considered the gold standard of care for DFU, patients struggle with using them because of discomfort, aesthetics, and mobility restrictions. Armstrong’s team seeks to improve patient outcomes with a new smart boot design that allows for remote monitoring of patient activity and adherence to the treatment. 

    “This grant from the PhRMA Foundation empowers us to enhance our smart offloading boots, tailoring them to fit the unique cultural and behavioral aspects of minority populations who are most at risk for hospitalization and amputation,” Armstrong said. “Our project is a step forward in making state-of-the-art health care accessible and equitable for all, particularly those in underserved communities.” 

    Isakadze, a clinical cardiac electrophysiology fellow and incoming faculty at Hopkins’ School of Medicine, will lead a project to test a digital health intervention for the management of atrial fibrillation (Afib), the most common type of heart arrhythmia. Afib is associated with poor quality of life and increased risk of stroke, heart attack, and death. Evidence shows that modifying risk factors such as weight, physical activity, and tobacco and alcohol use can reduce Afib burden. 

    Isakadze’s team is working with diverse patients, clinicians, and key stakeholders to design and test an Afib care management program that integrates 1) an Apple watch to track heart health data 2) a mobile app to educate and empower patients in tracking their health and setting health goals, 3) a clinician dashboard with patient data from the mobile app and smartwatch, and 4) individualized weekly health coaching to promote adherence to the virtual program. 

    “Receiving the PhRMA Foundation grant will allow us to generate robust evidence to support the use of digital health technologies to enable risk factor modification for diverse patients with Afib and bridge the critical gap in Afib management,” Isakadze said. “I am confident that digital health tools have tremendous potential to reach people where they are and transform health care delivery.” 

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  • Innovative shoe insole technology mitigates the risk of diabetic foot ulcers

    Innovative shoe insole technology mitigates the risk of diabetic foot ulcers

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    Researchers have developed a new shoe insole technology that helps reduce the risk of diabetic foot ulcers, a dangerous open sore that can lead to hospitalization and leg, foot or toe amputations.

    The goal of this innovative insole technology is to mitigate the risk of diabetic foot ulcers by addressing one of their most significant causes: skin and soft tissue breakdown due to repetitive stress on the foot during walking.”


    Muthu B.J. Wijesundara, principal research scientist at The University of Texas at Arlington Research Institute (UTARI)

    Affecting about 39 million people in the U.S., diabetes can damage the small blood vessels that supply blood to the nerves, leading to poor circulation and foot sores, also called ulcers. About one-third of people with diabetes develop foot ulcers during their lifetime. In the U.S., more than 160,000 lower extremity amputations are performed annually due to complications from diabetic foot ulcers, costing the American health system about $30 billion a year. Those who have foot ulcers often die at younger ages than those without ulcers.

    “Although many shoe insoles have been created over the years to try to alleviate the problem of foot ulcers, studies have shown that their success in preventing them is marginal,” Wijesundara said. “We took the research a step further by creating a pressure-alternating shoe insole that works by cyclically relieving pressure from different areas of the foot, thereby providing periods of rest to the soft tissues and improving blood flow. This approach aims to maintain the health of the skin and tissues, thereby reducing the risk of diabetic foot ulcers.”

    In an article in the peer-reviewed International Journal of Lower Extremity Wounds, Wijesundara and UTA colleagues Veysel Erel, Aida Nasirian and Yixin Gu, along with Larry Lavery of UT Southwestern Medical Center, described their innovative insole technology. After this successful pilot project, the next step for the research team will be refining the technology to make it more accessible for users with varying weights and shoe sizes.

    “Considering the impact of foot ulcers, it’s exciting that we may be able to make a real difference in the lives of so many people,” Wijesundara said.

    Source:

    University of Texas at Arlington

    Journal reference:

    Erel, V., et al. (2024). Development of Cyclic Pressure Offloading Insole for Diabetic Foot Ulcer Prevention. The International Journal of Lower Extremity Wounds/International Journal of Lower Extremity Wounds. doi.org/10.1177/15347346241234825.

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  • A call for targeted research and therapies

    A call for targeted research and therapies

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    In a recent review published in the journal Cell Metabolism, researchers elucidated mechanisms and evaluated therapies for impaired skeletal muscle regeneration in diabetes, identifying research gaps and future directions.

    Study: Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments. Image Credit: Crevis / ShutterstockStudy: Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments. Image Credit: Crevis / Shutterstock

    Background 

    Diabetes, a growing public health issue, continues to surge despite extensive research and healthcare efforts. It leads to various forms of diabetic myopathy, irrespective of its type, causing a decline in skeletal muscle mass and function. This decline not only worsens obesity and hyperglycemia but also affects locomotion, energy metabolism, and glucose regulation, further deteriorating muscle structure and function. Additionally, diabetes impairs muscle regeneration, potentially worsening conditions like ischemia and foot ulcers by promoting fibrosis and hindering myofiber recovery. Further research is needed to better understand and develop targeted interventions for the complex mechanisms underlying impaired muscle regeneration in diabetes.

    Skeletal muscle abnormalities in diabetes

    Diabetes, alongside its comorbidities like obesity, hypertension, and dyslipidemia, significantly affects skeletal muscle structure, function, and metabolism. The complex nature of diabetes complicates the identification of effective therapeutic targets. Other contributing factors include aging, inactivity, and poor nutrition. Key observed abnormalities in diabetic patients include reduced muscle mass and strength, abnormal lipid deposition, fiber atrophy, and altered myokine secretion, contributing to decreased functional capacity and quality of life.

    Diabetes not only leads to muscle degeneration but also impairs the muscle’s ability to regenerate, complicating injuries such as ischemia and foot ulcers. The regeneration process, involving both muscle stem cells (MuSCs) and non-MuSCs, is hampered, as indicated by excessive fibrosis and delayed myofiber maturation.

    Skeletal muscle regeneration in diabetes Diabetes and its associated complications, including obesity and hyperglycemia, impact multiple cell populations (MuSCs, neutrophils, macrophages, T cells, FAPs, and mast cells) that play a vital role in the process of muscle regeneration (i.e., degeneration and inflammation, regeneration, and maturation and functional recovery).

    Skeletal muscle regeneration in diabetes Diabetes and its associated complications, including obesity and hyperglycemia, impact multiple cell populations (MuSCs, neutrophils, macrophages, T cells, FAPs, and mast cells) that play a vital role in the process of muscle regeneration (i.e., degeneration and inflammation, regeneration, and maturation and functional recovery).

    Degeneration and inflammation

    Muscle injuries trigger necrosis and inflammation, marked by fiber breakdown and protein leakage into the serum. The process, essential for tissue repair, draws in immune cells like neutrophils and macrophages. Diabetes compounds this degeneration, amplifying damage, and hampering regeneration, highlighting the metabolic impact on muscle recovery.

    Regeneration process

    Diabetes negatively impacts the muscle regeneration process, notably affecting the activation, proliferation, and differentiation of MuSCs and the roles of fibro-adipogenic progenitors (FAPs). Treatments like metformin offer some hope by potentially modifying FAP activity. However, delayed regeneration in diabetic models underlines the urgent need for deeper insights into how diabetes disrupts muscle repair mechanisms.

    Challenges in muscle recovery

    Efficient muscle regeneration requires not only the formation of new myofibers but also the reconstitution of the extracellular matrix, vascular network, and innervation. Diabetes and obesity complicate this process, showing delayed functional recovery, increased collagen accumulation, and impaired neuromuscular junction adaptations.

    Diabetic impacts on muscle fiber and insulin signaling

    Diabetes shifts muscle fiber composition towards type II fibers, which are more prone to damage and impair regeneration. Insulin resistance disrupts muscle cell growth pathways, while hyperinsulinemia and lipotoxicity inhibit crucial recovery processes like autophagy and protein metabolism. These changes suggest that targeting fiber-type transitions and improving insulin signaling could enhance muscle regeneration in diabetes.

    Diabetic challenges in muscle regeneration signaling

    Diabetes triggers elevated pro-inflammatory cytokines and oxidative stress, disrupting muscle repair by inhibiting growth pathways and promoting protein breakdown. Concurrently, increased myostatin levels and NOTCH and WNT signaling alterations impair muscle cell proliferation and differentiation. Moreover, the compromised Adenosine Monophosphate-Activated Protein Kinase (AMPK) signaling pathway further hinders MuSC function and regeneration, highlighting complex challenges in diabetic muscle repair.

    Disentangling diabetes and comorbidity effects on muscle regeneration

    Diabetes significantly impairs muscle regeneration, but pinpointing whether diabetes itself or related comorbidities such as obesity and sarcopenia are responsible remains challenging. Muscle health is influenced by a number of factors, including genetics, diet, and physical activity, complicating the isolation of diabetes’ direct effects. Studies often struggle to establish control groups that adequately account for these variables, leading to ambiguity about the specific impacts of diabetes versus other conditions. For instance, research using obese diabetic mice versus lean controls has difficulty distinguishing whether observed effects are due to obesity or diabetes itself. 

    Challenges in research models and therapeutic approaches

    There is no definitive animal model for studying diabetes’ impact on muscle regeneration, complicating the translation of findings to humans. Treatments for muscle regeneration in diabetes are varied, spanning from exercise and dietary supplements to advanced cell therapies, yet their effectiveness often falls short in addressing muscle fibrosis. Despite the promise shown by certain therapies in improving muscle health in diabetes, rigorous clinical trials are needed to assess their true efficacy in muscle regeneration, specifically within diabetic populations.

    Future directions in muscle regeneration research

    Addressing these gaps requires a multifaceted approach. Research must refine its models and control groups to isolate the effects of diabetes from those of comorbidities and lifestyle factors. Advanced genetic and omics technologies offer new avenues to uncover the intricate mechanisms at play in diabetic muscle regeneration. Furthermore, integrating therapies such as exercise, dietary interventions, and possibly cell therapies may hold the key to enhancing muscle repair in diabetic patients. However, more research is essential to navigate the complexities of muscle regeneration in diabetes and develop effective treatments.

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  • Innovative plasma-activated hydrogel dressings revolutionize chronic wound care

    Innovative plasma-activated hydrogel dressings revolutionize chronic wound care

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    An effective treatment for chronic wounds that does not involve antibiotics, but an ionized gas to activate a wound dressing, has been developed by a team of international scientists.

    The treatment involves the plasma activation of hydrogel dressings (that are commonly used in wound dressings) with a unique mix of different chemical oxidants that are effective in decontaminating and aid healing in chronic wounds.

    Researchers from the University of Sheffield and University of South Australia, who led the study, believe the new method is a significant advance in tackling antibiotic resistance pathogens and has the potential to change the treatment of diabetic foot ulcers and internal wounds. 

    Professor Rob Short, Professor of Chemistry at the University of Sheffield who co-authored the study, said: “More than 540 million people are living with diabetes worldwide, of which 30 per cent will develop a foot ulcer during their lifetime. This is a neglected global pandemic which is set to increase further in the coming years due to a rise in obesity and lack of exercise.

    “In England alone between 60,000 and 75,000 people are being treated for diabetic foot ulcers per week. Infection is one of the major risks. Increasingly, many infections do not respond to normal antibiotic treatment due to resistant bacteria which results in 7,000 amputations per year.

    “There is an urgent need for innovation in wound management and treatment and it is a real privilege to be part of the international team who have been working on this alternative treatment for over 10 years.” 

    The cost of managing chronic wounds such as diabetic foot ulcers already exceeds $17 billion US dollars annually.

    The benefits of cold plasma ionized gas have already been proven in clinical trials, showing it controls not only infection but also stimulates healing. This is due to the potent chemical cocktail of oxidants, namely reactive oxygen and nitrogen species (RONS) it produces when it mixes and activates the oxygen and nitrogen molecules in the ambient air.

    Dr Endre Szili, from the University of South Australia who led the study, published this week in the journal Advanced Functional Materials, said: “Antibiotics and silver dressings are commonly used to treat chronic wounds, but both have drawbacks.

    “Growing resistance to antibiotics is a global challenge and there are also major concerns over silver-induced toxicity. In Europe, silver dressings are being phased out for this reason.”

    The international team of scientists have shown that plasma-activating hydrogel dressings with RONS makes the gel far more powerful, killing common bacteria.

    Although diabetic foot ulcers were the focus of this study, the technology could be applied to all chronic wounds and internal infections.

    Despite recent encouraging results in the use of plasma-activated hydrogel therapy (PAHT), we faced the challenge of loading hydrogels with sufficient concentrations of RONS required for clinical use. We have overcome this hurdle by employing a new electrochemical method that enhances the hydrogel activation.” 

    Dr. Endre Szili, University of South Australia

    As well as killing common bacteria (E. coli and P. aeruginosa) that cause wounds to become infected, the researchers say that the plasma-activated hydrogels might also help trigger the body’s immune system, which can help fight infections.

    “Chronic wound infections are a silent pandemic threatening to become a global healthcare crisis,” added Dr Szili.

    “It is imperative that we find alternative treatments to antibiotics and silver dressings because when these treatments don’t work, amputations often occur.”

    “A major advantage of our PAHT technology is that it can be used for treating all wounds. It is an environmentally safe treatment that uses the natural components in air and water to make its active ingredients, which degrade to non-toxic and biocompatible components.”

    “The active ingredients could be delivered over a lengthy period, improving treatment, with a better chance of penetrating a tumor.

    “Plasma has massive potential in the medical world, and this is just the tip of the iceberg,” Dr Szili says.

    The next step will involve clinical trials to optimize the electrochemical technology for treatment in human patients.

    Source:

    Journal references:

    Sumyea Sabrin, et al. (2024). Electrochemically Enhanced Antimicrobial Action of Plasma‐Activated Poly(Vinyl Alcohol) Hydrogel Dressings. Advanced Functional Materials. doi.org/10.1002/adfm.202314345.

     

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  • Neuroscientists link visual perception shifts to walking rhythm

    Neuroscientists link visual perception shifts to walking rhythm

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    For the first time, neuroscientists have established a link between shifts in our visual perception and the cadence of our steps while walking.

    The research, published in Nature Communications, shows that the brain processes vision in a rhythmic manner, rising and falling in sensitivity in a cycle that corresponds to the rhythm of our steps. When swinging from one step to the next, human perception is good and reactions fast.

    During footfall, however, our vision is not as sharp and reactions are slowed.

    This work reveals a previously unknown relationship between perception and movement. It bridges a gap between experimental psychology and our natural, everyday behavior.”


    Dr Matthew Davidson, Lead Author from the School of Psychology at the University of Sydney

    The study also confirms our understanding of the visual brain sensing the environment in a strobe-like way; our perception takes regular samples of the world before stitching them together to create our seamless experience.

    However, the new finding that reveals shifts in our visual perception has important implications for understanding human behaviour, how we interact with our environment and make decisions.

    The work was conducted by Dr Matthew Davidson with colleagues Professor David Alais and Professor Frans Verstraten in the School of Psychology, University of Sydney.

    Dr Davidson said: “We are consciously aware of a seamless stream of vision but this is deceptive. I use the analogy of a duck swimming on a pond. Beneath the smooth motion on the surface there is a lot cycling activity beneath.”

    This study extends earlier work from the same lab showing that perception of vision and sound is cyclic, with our brain taking around eight samples per second.

    Professor Alais said: “The critical new finding in this study is that these oscillations in the brain’s sampling of the world slow down when walking to match the step cycle.

    “Humans take about two steps per second when walking and generally keep to a consistent rhythm. The reported oscillations in visual sensitivity also occur at about two cycles per second and are locked to the step cycle. In some participants these rhythmic oscillations occur at four cycles per second but these were also locked to the step cycle.”

    This work is the first time that visual perception has been finely and continuously sampled during walking. Without virtual reality headsets and motion tracking it would not be possible.

    Dr Davidson said: “Thanks to VR technology we have discovered that our vision moves through a good and a bad phase on every step.”

    It is unclear why our brain’s perceptual processes are so closely linked to walking.

    Professor Alais said: “One possible explanation is that vision becomes secondary to motor control while your foot is grounded and the next step is planned. Once you are in the swing phase between footfalls, the brain switches back to prioritising perceptual sampling of the world, creating an ongoing perceptual rhythm that harmonises with your step rate.”

    The findings open questions that the research team will pursue in further studies. For example, does perception of sound and touch also modulate as we walk? And what about neural activity?

    The research team plans to follow up these questions to further understand the implications.

    Dr Davidson said: “An obvious question is whether these oscillations in perception are more pronounced in the elderly given difficulties with balance and coordination as we age.

    “It also raises the exciting possibility that we could develop cheap and easy diagnostic tests using VR headsets, or use this information to develop tests for early onset of neuro-muscular disorders or some psychiatric illnesses, which can manifest in abnormal gaits.”

    He said it could also be applied to further research in sports science to see if the findings could be applied to optimise decision-making and reaction times in athletes.

    Underlying all this research remains a persistent mystery. If the world is sampled by our brains rhythmic pulses, why is our conscious perception so seamlessly smooth?

    Professor Verstraten said: “This was once a question for philosophers, but with access to technology neuroscientists have been able to shed light on how the gaps get filled in. The current view is that the brain is a predictive machine that actively constructs perception and predicts what ought to be there and fills in the blanks. But clearly, we need more research to deepen our understanding.”

    Methods

    Researchers tracked the walking of 45 subjects walking back and forth along a 10-metre path in a virtual environment. During each walk (lasting about 9 seconds), subjects were required to respond to between zero and eight random visual stimuli. The same stimuli were also presented in stationary trials. Eye and head movement was tracked along with gait and walking information.

    Of the 45 subjects, insufficient data was collected for seven subjects. In the datasets for 38 subjects, reduced perception at footfall was recorded 83 percent of the time.

    The behavioural data generated in this study have been deposited in a public database under accession code https://osf.io/8djtq/ 

    Source:

    Journal reference:

    Davidson, M. J., et al. (2024). Walking modulates visual detection performance according to stride cycle phase. Nature Communications. doi.org/10.1038/s41467-024-45780-4.

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  • Horse sedative use among humans spreads in deadly mixture of ‘tranq’ and fentanyl

    Horse sedative use among humans spreads in deadly mixture of ‘tranq’ and fentanyl

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    Andrew McClave Jr. loved to lift weights. The 6-foot-4-inch bartender resembled a bodybuilder and once posed for a photo flexing his muscles with former pro wrestler Hulk Hogan.

    “He was extremely dedicated to it,” said his father, Andrew McClave Sr., “to the point where it was almost like he missed his medication if he didn’t go.”

    But the hobby took its toll. According to a police report, a friend told the Treasure Island Police Department that McClave, 36, suffered from back problems and took unprescribed pills to reduce the pain.

    In late 2022, the friend discovered McClave in bed. He had no pulse. A medical examiner determined he had a fatal amount of fentanyl, cocaine, and xylazine, a veterinary tranquilizer used to sedate horses, in his system, an autopsy report said. Heart disease was listed as a contributing factor.

    McClave is among more than 260 people across Florida who died in one year from accidental overdoses involving xylazine, according to a Tampa Bay Times analysis of medical examiner data from 2022, the first year state officials began tracking the substance. Numbers for 2023 haven’t been published.

    The death toll reflects xylazine’s spread into the nation’s illicit drug supply. Federal regulators approved the tranquilizer for animals in the early 1970s and it’s used to sedate horses for procedures like oral exams and colic treatment, said Todd Holbrook, an equine medicine specialist at the University of Florida. Reports of people using xylazine emerged in Philadelphia, then the drug spread south and west.

    What’s not clear is exactly what role the sedative plays in overdose deaths, because the Florida data shows no one fatally overdosed on xylazine alone. The painkiller fentanyl was partly to blame in all but two cases in which the veterinary drug was included as a cause of death, according to the Times analysis. Cocaine or alcohol played roles in the cases in which fentanyl was not involved.

    Fentanyl is generally the “800-pound gorilla,” according to Lewis Nelson, chair of the emergency medicine department at Rutgers New Jersey Medical School, and xylazine may increase the risk of overdose, though not substantially.

    But xylazine appears to complicate the response to opioid overdoses when they do happen and makes it harder to save people. Xylazine can slow breathing to dangerous levels, according to federal health officials, and it doesn’t respond to the overdose reversal drug naloxone, often known by the brand name Narcan. Part of the problem is that many people may not know they are taking the horse tranquilizer when they use other drugs, so they aren’t aware of the additional risks.

    Lawmakers in Tallahassee made xylazine a Schedule 1 drug like heroin or ecstasy in 2016, and several other states including Pennsylvania, Ohio, and West Virginia have taken action to classify it as a scheduled substance, too. But it’s not prohibited at the federal level. Legislation pending in Congress would criminalize illicit xylazine use nationwide.

    The White House in April designated the combination of fentanyl and xylazine, often called “tranq dope,” as an emerging drug threat. A study of 20 states and Washington, D.C., found that overdose deaths attributed to both illicit fentanyl and xylazine exploded from January 2019 to June 2022, jumping from 12 a month to 188.

    “We really need to continue to be proactive,” said Amanda Bonham-Lovett, program director of a syringe exchange in St. Petersburg, “and not wait until this is a bigger issue.”

    ‘A good business model’

    There are few definitive answers about why xylazine use has spread — and its impact on people who consume it.

    The U.S. Drug Enforcement Administration in September said the tranquilizer is entering the country in several ways, including from China and in fentanyl brought across the southwestern border. The Florida attorney general’s office is prosecuting an Orange County drug trafficking case that involves xylazine from a New Jersey supplier.

    Bonham-Lovett, who runs IDEA Exchange Pinellas, the county’s anonymous needle exchange, said some local residents who use drugs are not seeking out xylazine — and don’t know they’re consuming it.

    One theory is that dealers are mixing xylazine into fentanyl because it’s cheap and also affects the brain, Nelson said.

    “It’s conceivable that if you add a psychoactive agent to the fentanyl, you can put less fentanyl in and still get the same kick,” he said. “It’s a good business model.”

    In Florida, men accounted for three-quarters of fatal overdoses involving xylazine, according to the Times analysis. Almost 80% of those who died were white. The median age was 42.

    Counties on Florida’s eastern coast saw the highest death tolls. Duval County topped the list with 46 overdoses. Tampa Bay recorded 19 fatalities.

    Cocaine was also a cause in more than 80 cases, including McClave’s, the Times found. The DEA in 2018 warned of cocaine laced with fentanyl in Florida.

    In McClave’s case, Treasure Island police found what appeared to be marijuana and a small plastic bag with white residue in his room, according to a police report. His family still questions how he took the powerful drugs and is grappling with his death.

    He was an avid fisherman, catching snook and grouper in the Gulf of Mexico, said his sister, Ashley McClave. He dreamed of being a charter boat captain.

    “I feel like I’ve lost everything,” his sister said. “My son won’t be able to learn how to fish from his uncle.”

    Mysterious wounds

    Another vexing challenge for health officials is the link between chronic xylazine use and open wounds.

    The wounds are showing up across Tampa Bay, needle exchange leaders said. The telltale sign is blackened, crusty tissue, Bonham-Lovett said. Though the injuries may start small — the size of a dime — they can grow and “take over someone’s whole limb,” she said.

    Even those who snort fentanyl, instead of injecting it, can develop them. The phenomenon is unexplained, Nelson said, and is not seen in animals.

    IDEA Exchange Pinellas has recorded at least 10 cases since opening last February, Bonham-Lovett said, and has a successful treatment plan. Staffers wash the wounds with soap and water, then dress them.

    One person required hospitalization partly due to xylazine’s effects, Bonham-Lovett said. A 31-year-old St. Petersburg woman, who asked not to be named due to concerns over her safety and the stigma of drug use, said she was admitted to St. Anthony’s Hospital in 2023. The woman, who said she uses fentanyl daily, had a years-long staph infection resistant to some antibiotics, and a wound recently spread across half her thigh.

    The woman hadn’t heard of xylazine until IDEA Exchange Pinellas told her about the drug. She’s thankful she found out in time to get care.

    “I probably would have lost my leg,” she said.




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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  • Research demonstrates a bat species’ resistance to cancer, pinpoints key genes

    Research demonstrates a bat species’ resistance to cancer, pinpoints key genes

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    In a recent study published in the journal Nature Communications, researchers investigated seven species of bats to verify hypotheses about their potent cancer resistance empirically. A combination of in vitro and in vivo techniques revealed that one species, Myotis pilosus, displayed particular cancer resistance despite researchers intentionally activating the ontogenetic genes in their primary cells. Analysis of this phenomenon using transcriptomic and functional tests suggested that the unexpectedly potent downregulation of HIF1A, RPS3, and COPS5 genes and the loss of a COPS5-promoting enhancer along the HIF1A sequence may be the key behind M. pilosus’ extreme cancer resistance.

    Study: Experimental evidence for cancer resistance in a bat species. Image Credit: Rudmer Zwerver / ShutterstockStudy: Experimental evidence for cancer resistance in a bat species. Image Credit: Rudmer Zwerver / Shutterstock

    Bats are proof that not all animals are built equal

    Bats are considered one of the best-adapted mammalian groups in terrestrial and particularly arboreal environments. Bats come in all spaces and sizes, from the penny-sized Kitti’s hog-nosed bat to the six-foot-wide-wingspan flying fox and all 1,400 species in between. When accounting for the fact that bats comprise approximately 20% of all known mammalian species, their success becomes evident.

    Scientists have studied bats to pinpoint the secrets of their success. Thus far, they believe the evolutionary dominance of bats to be attributable to a few crucial adaptations, most notably their evolution of actual flight, echolocation, high viral resistance, and commendable longevity. Their longevity, in particular, is extraordinary and comparable to genuine relative size-age outliers like the naked mole rat and blind mole rat. Indeed, 18 out of 19 size-corrected mammalian species with natural lifespans longer than our medically-assisted ones are bats, with some species like Myotis myotis living eight times longer (41 years) than expected by size alone.

    Given the observed evolutionary interplay between cancer and longevity, bats are hypothesized to mirror naked mole rats and elephants in having evolved adaptations that prevent cancer onset and proliferation. Unfortunately, this hypothesis remains untested within an empirical scientific framework. Verifying this hypothesis and elucidating the mechanisms responsible would provide crucial insights into natural cancer resistance and the potential for developing novel anticancer therapeutics.

    About the study

    In the present study, researchers used somatic tissues (e.g., skin grafts) and genetic material from seven bat species to investigate their cancer resistance in vitro and in vivo. The included species were Chinese and comprised the big-footed bat (Myotis pilosus; MPI), the least horseshoe bat (Rhinolophus pusillus; RPU), the Szechwan myotis (Myotis altarium; MAL), the greater horseshoe bat (Rhinolophus ferrumequinum; RFE), the great leaf-nosed bat (Hipposideros armiger; HAR), the Chinese rufous horseshoe bat (Rhinolophus sinicus; RSI), and the Leschenault’s Rousette (Rousettus leschenaultii; RLE).

    Researchers additionally used tissues from Mus musculus, the typical rat lab, as controls for all experiments. To gain insights into the resistance of sampled tissue to malignant transformation, systematic investigations of the tumor resistance of primary fibroblasts were carried out by priming fibroblasts to express oncogenic HRAS(G12V) and SV40 large antigen (SV40 LT) genes, followed by protein level quantification using immunoprecipitation assays. These Vitro assays were supplemented from luciferase immunofluorescence assays carried out in genetically modified murine (MSFHRAS\SV40LT) and MPI (MPI-SFHRAS\SV40LT) fibroblasts.

    Once the atypical cancer resistance of MPI fibroblasts was established, researchers investigated the mechanism underlying observed resistance using transcriptome sequencing of fibroblasts, thereby identifying differential expression patterns of fibroblast-associated genes. Analyses included the signed weighted gene co-expression network analysis (WGCNA), the in-tandem computing of the module eigengene (ME), and the de-novo development of a protein-protein interaction network derived from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.

    To test if observed cancer resistance could be a function of specific gene downregulation, CRISPR-Cas9 gene-editing technologies were used to inhibit the expression of genes known to affect cancer resistance, including HIF1A, COPS5, RPS3, EP300, and EIF5B in MSFHRAS\SV40LT. Finally, to elucidate the molecular basis underpinning natural gene downregulations, conserved non-coding elements (CNEs) were analyzed via the creation of a de-novo MPI genome followed by the Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq assay).

    Study findings – not all bats are built equally, either

    Both in vitro and in vivo fibroblast assays revealed that MPI fibroblasts were significantly more resistant to cancer and cancer-associated proliferation than controls and the other six investigated bat species. MPI fibroblast colonies were consistently found to be substantially smaller than those of the other tested cohorts, validating its profound anticancer properties. Repeating these experiments using other tissue types (intestine and tail tissues) provided comparable results, validating these findings and the hypothesis of bats displaying natural cancer resistance.

    Transcriptomic protein expression quantification assays present that the relative expression levels of MPI HIF1A, EP300, EIF5B, COPS5, and RPS3 genes were significantly lower (downregulated) compared to the other cohorts, suggesting oncogene downregulation as the mechanism of action underpinning observed fibroblast results.

    “Our results showed that the suppression of HIF1A, COPS5, and RPS3 expression significantly inhibited cell proliferation (P < 0.05; two-tailed Student’s t tests. However, the downregulation of EP300 and EIF5B had no remarkable effect on cell proliferation. Notably, these two genes were up-regulated during aging in the long-lived bat (Myotis myotis), suggesting their potentially pleiotropic roles in the bat lifespan.”

    CNE analysis revealed a total of 437,414 CNEs across all evaluated species, 20,231 of which displayed accelerated evolution in MPI. ATAC-seq assays refined these results and highlighted that mutations in CNE143336, a potential regulatory element, could result in substantial transformation resistance via HEK 293T and NIH 3T3 gene modulation. Finally, cell-derived xenograft models revealed the essential role of COPS5 genes in malignant transformation resistance.

    Conclusion

    The present study empirically verifies preexisting hypotheses regarding bats’ natural anticancer resistance. It elucidates the mechanisms underpinning MPI’s remarkable anti-malignant-transformation potential using a combination of immunological, transcriptomic, and gene-editing techniques. Study findings highlight the role of gene downregulation and epigenetics as the basis for the natural cancer resistance of some bat species.

    It is essential to mention that while MPI was found to outcompete other investigated bats in the current study substantially, this does not invalidate their anticancer potential via other untested mechanistic routes. Identifying additional mechanisms by which these surprisingly long-lived animals combat cancer may allow us to devise new ways for humanity to follow suit.

    Journal reference:

    • Hua, R., Ma, Y., Yang, L., Hao, J., Hua, Q., Shi, L., Yao, X., Zhi, H., & Liu, Z. (2024). Experimental evidence for cancer resistance in a bat species. Nature Communications, 15(1), 1-15, DOI – 10.1038/s41467-024-45767-1, https://www.nature.com/articles/s41467-024-45767-1

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