MAN’S BEST FRIEND COULD HELP SAVE HIM FROM PROSTATE CANCER
Brian H. Waters,
Dogs have been called man’s best friend because of their loyalty and protection, but now, thanks to Johns Hopkins Medicine researchers and an international team of collaborators, canines may provide an even greater service for their human male companions: prostate cancer screening.
Prostate cancer is the second leading cause of cancer death in men in the developed world. Clinicians have been seeking accurate and reliable noninvasive diagnostic tools to differentiate early stage, less dangerous and more treatable stages of the disease from the aggressive, high-grade and likely-to-spread forms. Standard blood tests for early detection, such as the prostate specific antigen (PSA) test, often miss cancers in men whose PSA levels are within normal levels or overdiagnose men with clinically insignificant tumors or no cancer at all.
Recently, Alan Partin, M.D., Ph.D., urologist-in-chief at The Johns Hopkins Hospital and colleagues, along with collaborators from the United Kingdom, the Prostate Cancer Foundation and the Massachusetts Institute of Technology, have been researching a dog’s extremely sensitive sense of smell as a novel way to improve testing for prostate cancer.
In a small study published Feb. 17, 2021, in the journal PLOS ONE, the researchers had two dogs sniff samples of urine from men diagnosed with high-grade prostate cancer and from men without cancer. The animals, Florin, a 4-year-old female Labrador, and Midas, a 7-year-old female wirehaired Hungarian vizsla, had been trained to respond to cancer-related chemicals — known as volatile organic compounds (VOCs) — added to urine samples and not respond to ones without them.
“Besides PSA, other methods to detect prostate cancer make use of a molecular analyzer called a gas chromatography-mass spectrometer [GC-MS] to find specific VOCs or profiling bacterial population in a urine sample looking for species associated with cancer, but these have limitations,” says Partin. “We wondered if having the dogs detect the chemicals, combined with analysis by GC-MS, bacterial profiling and an artificial intelligence [AI] neural network trained to emulate the canine cancer detection ability, could significantly improve the diagnosis of high-grade prostate cancer.”
Adding the AI analysis, says Partin, helped the researchers filter the more than 1,000 VOCs present in a typical urine sample down to those most beneficial for cancer diagnosis.
The dogs, says Partin, performed their cancer detection roles well. Both Florin and Midas identified five of seven urine samples from men with cancer, or 71.4% accuracy. Florin was able to correctly identify 16 of the 21 non-aggressive or no cancer samples (76.2%), while Midas was able to pick out 14 (66.7%).
When the canine olfactory (smell) results were combined with GC-MS, bacterial profiling and AI analysis, the multisystem approach proved a more sensitive and more specific means of detecting lethal prostate cancer than any of the methods alone.
Partin says that this recent study, and other prostate cancer research at Johns Hopkins Medicine, is only possible because of a long history of “biobanking” valuable patient samples. He says that “larger sample pools will be the key enabler of statistically powered, multi-institutional future studies seeking to fully integrate VOC and microbiota profiling.”
Partin is available for interviews.
CHANGES IN THE EYE MAY OFFER EARLY WARNING FOR ALZHEIMER’S DISEASE
Some say the eyes are the windows to the soul, but new findings from researchers at the Johns Hopkins Wilmer Eye Institute suggest they may offer insight into the mind as well. Their new proof-of-principle study shows how an imaging technique that measures blood flow in the back of the eye may offer a noninvasive way to detect early-onset Alzheimer’s disease.
Results of the small study are published as the cover article in the March 4, 2021, issue of the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.
“We set out to investigate the idea that changes in the retinal capillaries at the back of the eye can reveal changes in the brain that are otherwise undetectable and that occur before the disease is diagnosed ,” says lead study author Amir Kashani, M.D., Ph.D., associate professor of ophthalmology at the Johns Hopkins University School of Medicine.
The study involved 13 people with a rare, genetically inherited form of early-onset Alzheimer’s disease marked by mutations identified in three genes. This form of familial Alzheimer’s disease affects approximately 1% of all patients with the condition.
Using an imaging technology called optical coherence tomography angiography (OCTA), the researchers took images of blood vessels in the back of the eyes of study participants with and without the mutation leading to the familial form of Alzheimer’s disease. They also cataloged the disease stage for the people with Alzheimer’s and the cognitive abilities of both groups.
Kashani and his team found that abnormal blood flow through the smallest vessels at the back of the eye correlated with the mutation status of subjects at risk for the familial form of Alzheimer’s disease. Patients with the Alzheimer’s-causing mutations who had no signs of disease had abnormally high and heterogeneous blood flow in their retinal capillaries. The researchers believe this may be a sign of the early inflammatory changes involved in the pathogenesis of Alzheimer’s disease.
The researchers say these data support the belief that changes in the eye can demonstrate the earliest signs of brain disease before symptoms are present. With further evidence from larger studies over time, they believe that the method could offer clinicians a tool for earlier diagnosis and enable intervention to slow cognitive decline in patients.
Kashani is available for interviews.
ADDICTION TREATMENT CENTERS USING ELECTRONIC HEALTH RECORDS LESS AND MAY HINDER CARE
Despite their existence for decades, electronic health records — digitized patient information and medical histories available instantly and securely to authorized users — are not commonly used by many addiction and substance use disorder treatment facilities in the United States. Now, a recent study by Johns Hopkins Medicine researchers suggests why this is happening. It also describes how not using this technology may hinder coordination between treatment programs and health care providers, leaving patients to flounder through the system on their own.
In their findings, published online on Jan. 9, 2021, in the journal Drug and Alcohol Dependence, the researchers conclude that electronic health records are less commonly used by substance use disorder programs compared with other mental health treatment facilities, and that this difference is significant. Overall, only 9.6% of substance use disorder treatment programs and 15% of mental health centers report exclusively using electronic health records. Even more troubling, they say, is that fewer than 25% of both these facility types are using electronic health records for core clinical activities, such as progress notes, laboratory monitoring and medication prescriptions.
Since their general acceptance by the medical community, electronic health records have provided a number of benefits, including increased storage capability and faster access to a patient’s health information. They also enable the secure exchange of a patient’s records between facilities and providers.
“This is key, because without electronic health records, patients may experience disjointedness in their care, and for the most part, these records have to be the link between the treatment facilities and care providers,” says Stanislav Spivak, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
Compared with other settings, the researchers say that implementing electronic health records can be more difficult in addiction treatment facilities because these centers often face unique regulatory and funding challenges. The researchers also found that mental health facilities had more diverse sources of funding from insurance than addiction treatment centers.
“Traditionally, substance use disorder programs are smaller and may lack the resources and funding that other mental health treatment facilities might have,” says Spivak.
According to Spivak, the initial hurdle to substance use disorder programs adopting electronic health records may be cost and technology.
“For example,” Spivak explains, “if you need computers powerful enough to encrypt the data or special printers to access the information, the cost of electronic health records may be prohibitive to a low-funded substance use disorder facility.”
Spivak is available for interviews.
STEWARDSHIP PROGRAM HELPS HOSPITALS REDUCE ANTIBIOTIC USE AND PREVENT BACTERIAL INFECTIONS
Michael E. Newman,
The overuse of antibiotics in hospitals can lead to the emergence of drug-resistant strains of bacteria or outbreaks of infections by bacteria such as Clostridioides difficile. Over the past decade, efforts to combat the overuse problem have included antibiotic stewardship programs (ASPs) that ensure patients only receive antibiotics when needed, and then, only in the correct amounts and for the prescribed dosage period. However, ASPs have not been established in all medical facilities, particularly smaller and rural hospitals where access to experts in the use of antibiotics may not be available.
Researchers at Johns Hopkins Medicine and NORC at the University of Chicago developed a comprehensive stewardship intervention, the Safety Program for Improving Antibiotic Use, which is applicable for all types of hospitals and enables frontline clinicians to make informed and responsible decisions about prescribing antibiotics. In a recent study, the researchers evaluated the effectiveness of the program over a year’s time at 402 hospitals across the nation — the largest project of its kind to date. As a measure of success, they looked at overall antibiotic use and C. difficile infection rates in the hospitals during the study period.
Their findings were published Feb. 26, 2021, in JAMA Network Open.
According to the U.S. Centers for Disease Control and Prevention, C. difficile is a bacterium that causes severe diarrhea and colitis (an inflammation of the colon), and is estimated to cause nearly 500,000 infections in the United States each year. Most cases occur in people taking antibiotics during or just after hospitalization. This is because antibiotics may destroy some of the intestinal bacteria that normally keep C. difficile at bay.
“The Safety Program for Improving Antibiotic Use was designed to reduce the harm associated with antibiotic overuse by making stewardship part of the decision-making process for clinicians,” says study lead author Pranita Tamma, M.D., M.H.S., director of the Pediatric Antimicrobial Stewardship Program at Johns Hopkins Children’s Center and associate professor of pediatrics at the Johns Hopkins University School of Medicine. “We wanted to see how much of a difference an ASP could make in a one-year period,” she says.
The ASP used in the study consisted of 17 webinars — each repeated three times, as well as recorded for online viewing — over a 12-month timespan (January to December 2018). Conducted by Tamma and her colleague, Sara Cosgrove, M.D., M.S., professor of medicine at the Johns Hopkins University School of Medicine, the webinars focused on how to establish and maintain an ASP at a hospital, methods for improving teamwork and communication, and best practices for diagnosing and managing infections without overusing antibiotics.
Participants in the program received additional coaching and tools to enhance their ASP activities.
The 402 hospitals that completed the one-year study program included 28 academic medical centers, 122 mid-level teaching hospitals, 167 community hospitals and 85 critical access hospitals. Compliance with the four key components of antibiotic stewardship (interventions before and after prescribing of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% overall during the 12 months. Antibiotic use (measured by days of antibiotic therapy per 1,000 patient days) decreased 30% and C. difficile infections decreased 20%.
“These results are particularly remarkable as a large proportion of the hospitals in the study were under-resourced and did not have access to infectious disease specialists,” says Cosgrove. “They show that no matter their size, all hospitals can develop, establish and conduct good stewardship practices with the proper resources — and remind us of the importance of organized strategies to assist hospitals and clinicians in implementing medical care best practices.”
Hospitals wanting more information can access the “Toolkit Implementation Guide for Acute Care Antibiotic Stewardship Programs.”
Tamma and Cosgrove are available for interviews.
Researchers discover unique ‘spider web’ mechanism that traps, kills viruses
Immunologists at McMaster University have discovered a previously unknown mechanism which acts like a spider web, trapping and killing pathogens such as influenza or SARS-CoV-2, the virus responsible for COVID-19.
The researchers have found that neutrophils, the most abundant white blood cells in the human body, explode when they bind to such pathogens coated in antibodies and release DNA outside of the cell, creating a sticky tangle which acts as a trap.
The findings, published online in the Proceedings of the National Academy of Science, are significant because little is understood about how antibodies neutralize viruses in the respiratory tract.
The discovery has implications for vaccine design and delivery, including aerosol and nasal spray technologies that could help the body head off infections before they have a chance to take hold.
“Vaccines can produce these antibodies that are present in our lungs, which are the first type of antibody to see viruses like flu or COVID-19, which infect our lungs and respiratory tracts,” says the study’s lead author Matthew Miller, an associate professor at McMaster’s Michael G. DeGroote Institute for Infectious Disease Research and Canada’s Global Nexus for Pandemics and Biological Threats. “Mechanisms that can stop the infection at the site where it enters our body can prevent the spread and serious complications.”
By comparison, injectable vaccines are designed to bolster antibodies in the blood, but those antibodies are not as prevalent at the sites where infection begins.
“We should be thinking carefully about next generation COVID-19 vaccines that could be administered in the respiratory tract to stimulate antibodies. We don’t have many candidates right now that are focused on raising the mucosal response,” says Hannah Stacey, a graduate student in the Miller Lab and lead author of the paper, who recently won a major national scholarship from the Canadian Society for Virology for her work on COVID-19.
“If you want a lot of these antibodies that are really abundant in blood, then injections make the most sense, but if you want antibodies that are abundant in the respiratory tract, then a spray or an aerosol makes sense,” she says.
Researchers caution that while the body’s spider-web mechanism has the potential to be hugely beneficial, it can cause harm too, including inflammation and further illness when the web formation is uncontrollable.
They point to the early waves of the pandemic, prior to vaccinations, when these NETs, or neutrophil extracellular traps, were found in some patients’ lungs, and had made their breathing more difficult.
“An immune response that is meant to protect you can end up harming you if it’s not properly controlled,” says Miller. “It’s important to understand the balance of the immune system. If you have a lot of these antibodies before you get infected, they are likely going to protect you, but if the infection itself stimulates a lot of those antibodies it might be harmful.”
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Making seawater drinkable in minutes
According to the World Health Organization, about 785 million people around the world lack a clean source of drinking water. Despite the vast amount of water on Earth, most of it is seawater and freshwater accounts for only about 2.5% of the total. One of the ways to provide clean drinking water is to desalinate seawater. The Korea Institute of Civil Engineering and Building Technology (KICT) has announced the development of a stable performance electrospun nanofiber membrane to turn seawater into drinking water by membrane distillation process.
Membrane wetting is the most challenging issue in membrane distillation. If a membrane exhibits wetting during membrane distillation operation, the membrane must be replaced. Progressive membrane wetting has been especially observed for long-term operations. If a membrane gets fully wetted, the membrane leads to inefficient membrane distillation performance, as the feed flow through the membrane leading to low-quality permeate.
A research team in KICT, led by Dr. Yunchul Woo, has developed co-axial electrospun nanofiber membranes fabricated by an alternative nano-technology, which is electrospinning. This new desalination technology shows it has the potential to help solve the world’s freshwater shortage. The developed technology can prevent wetting issues and also improve the long-term stability in membrane distillation process. A three-dimensional hierarchical structure should be formed by the nanofibers in the membranes for higher surface roughness and hence better hydrophobicity.
The co-axial electrospinning technique is one of the most favorable and simple options to fabricate membranes with three-dimensional hierarchical structures. Dr. Woo’s research team used poly(vinylidene fluoride-co-hexafluoropropylene) as the core and silica aerogel mixed with a low concentration of the polymer as the sheath to produce a co-axial composite membrane and obtain a superhydrophobic membrane surface. In fact, silica aerogel exhibited a much lower thermal conductivity compared with that of conventional polymers, which led to increased water vapor flux during the membrane distillation process due to a reduction of conductive heat losses.
Most of the studies using electrospun nanofiber membranes in membrane distillation applications operated for less than 50 hours although they exhibited a high water vapor flux performance. On the contrary, Dr. Woo’s research team applied the membrane distillation process using the fabricated co-axial electrospun nanofiber membrane for 30 days, which is 1 month.
The co-axial electrospun nanofiber membrane performed a 99.99% salt rejection for 1 month. Based on the results, the membrane operated well without wetting and fouling issues, due to its low sliding angle and thermal conductivity properties. Temperature polarization is one of the significant drawbacks in membrane distillation. It can decrease water vapor flux performance during membrane distillation operation due to conductive heat losses. The membrane is suitable for long-term membrane distillation applications as it possesses several important characteristics such as, low sliding angle, low thermal conductivity, avoiding temperature polarization, and reduced wetting and fouling problems whilst maintaining super-saturated high water vapor flux performance.
Dr. Woo’s research team noted that it is more important to have a stable process than a high water vapor flux performance in a commercially available membrane distillation process. Dr. Woo said that “the co-axial electrospun nanofiber membrane have strong potential for the treatment of seawater solutions without suffering from wetting issues and may be the appropriate membrane for pilot-scale and real-scale membrane distillation applications.”
The Korea Institute of Civil Engineering and Building Technology (KICT) is a government sponsored research institute established to contribute to the development of Korea’s construction industry and national economic growth by developing source and practical technology in the fields of construction and national land management.
This research was supported by an internal grant (20200543-001) from the KICT, Republic of Korea. The outcomes of this project were published in the international journal, Journal of Membrane Science, a renowned international journal in the polymer science field (IF: 7.183 and Rank #3 of the JCR category) in April 2021.
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McIndoe leading $6.2 million innovative research initiative
Dr. Richard A. McIndoe, bioinformatics expert and associate director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia, is leading a dynamic, new $6.2 million federally funded initiative to support highly innovative research ideas in three areas with tremendous impact on health.
This Innovative Science Accelerator, or ISAC, program establishes an expedited but still extensive review process that will enable scientists to pursue some of their most innovative research ideas in diseases of the kidneys; the urinary tract in both sexes as well as the male reproductive organs; and the blood and bone marrow.
“The idea is that ISAC will provide seed funds to investigators who have high-risk, high-reward ideas, and they will get one year of money to try to figure out if their idea is going to work. If it works, they will be able to use the data they generate to apply for a larger grant,” says McIndoe, who wants the new program to be as innovative as the ideas scientists bring to it.
The five-year initiative is a new program of the Division of Kidney, Urologic and Hematologic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
The goal is to move science forward that matters to people’s lives, and the opportunities include giving particularly new scientists experience writing grants, going through the review process and generating findings, McIndoe says.
ISAC will provide scientists an efficient path to secure a one-time $100,000 grant that should ease application for a larger, traditional NIH grant, the gold standard for biomedical research in the U.S., or conversely to acknowledge that their idea does not merit additional pursuit.
Another primary function of ISAC is to host an annual scientific meeting for scientists working in these areas where awardees can present their work, and that will help fuel discussion and collaboration, says McIndoe, Regents’ Professor and Georgia Research Alliance Distinguished Investigator.
High-risk research with high-reward potential often doesn’t get funded in the traditional, highly competitive process of seeking NIH funding, McIndoe says. For example, the 2019 payline for the NIDDK was 13%, which means only 13 of 100 submitted grants get funded.
About half of submitted grants, don’t even make it through the NIH study section manned by experts in the field who do the frontline review of grant proposals, says McIndoe, who at points in his career has sat on more than a half-dozen study sections annually.
As director of ISAC’s coordinating unit, McIndoe will also work with NIH program officers with expertise in the area of interest of an application to identify other experts across the country. He’ll then manage the review process from there, including assigning reviewers and making sure reviews are done on time.
He’ll ensure that the scores and critiques get back to the NIH program officers who also will rank the grant proposals, and that information along with what the ISAC office determines to be a fundable score range will then go to one more group of experts in the field, ISAC’s External Evaluation Committee, and if they agree with the determinations, the decision is made.
Although the review process is extensive, it’s about half of the standard process for submitting for scientists and reviewers alike, starting with a three-page research plan rather than up to a dozen pages for an RO1, the NIH’s oldest grant mechanism, and the application is easier for reviewers to digest, McIndoe says.
The ISAC Working Group recently opted to have three application review times annually to further expedite the process, and applications can be submitted at any time, McIndoe says. Scientists can begin submitting applications this fall, and the first annual meeting likely will be next Spring.
The local ISAC Working Group, which will advise McIndoe on kidney, urologic and hematology research, includes Dr. David Mattson, chair of the MCG Department of Physiology and an established hypertension researcher; Dr. Jennifer Sullivan, pharmacologist and physiologist in the Department of Physiology who is also interim dean of The Graduate School at AU and studies blood pressure regulation and kidney health, with a particular interest in gender differences; and Dr. Betty Pace, pediatric hematologist in the MCG Department of Pediatrics, an established sickle cell physician scientist who leads a federally funded national initiative to inspire the next generation of investigators.
ISAC’s target areas may change annually based on what’s happening in the scientific literature and what experts in respective fields identify as hot topics that need pursuing. The Working Group and the annual meetings will further enable those discussions and decisions.
McIndoe, an expert in managing and analyzing large amounts of data, has already managed two other innovative NIH funding approaches and consequently has a solid infrastructure in place to support this new initiative. For 20 years he has led the Coordinating and Bioinformatics Unit for the Diabetic Complications Consortium to fund shorter-term laboratory and human studies to better understand the complications of diabetes, like heart and kidney disease and vision problems. The consortium began as the Animal Models of Diabetes Complications, which specifically designed and shared good mouse models.
Fifteen years ago he began providing similar services for the Mouse Metabolic Phenotyping Centers, which make the specialized, expensive mouse-testing capabilities of a select number of universities available and affordable to researchers nationwide. Expertise includes things like characterizing mouse metabolism and analyzing blood composition.
Together those NIDDK initiatives, which also hold scientific meetings and support websites to support interested scientific communities, have resulted in thousands of publications that demonstrate new findings and helped scientists secure larger NIH grants. As an example, more than 60% of those receiving a $100,000 grant through the Diabetic Complications Consortium applied for an RO1 and about 25% were successful. “That’s higher than the normal percentage and a goal of these kinds of programs,” McIndoe says. Both those programs are scheduled to phase out next year.
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Oregon State graduate student sheds light on better way to study reputedly secretive toad
CORVALLIS, Ore. – Research by a graduate student in Oregon State University’s College of Science has upended the conventional wisdom that for a century has incorrectly guided the study of a toad listed as endangered in part of its range.
Anne Devan-Song used spotlighting – shining a light in a dark spot and looking for eye reflections – to find large numbers of the eastern spadefoot toad. The study illustrates how confirmation bias – a tendency to interpret new information as ratification of existing theories – can hamper discovery and the development of better ones.
Her findings, which show that the toad spends much more time above ground than commonly believed, were published in the Journal of Herpetology.
Known for bright yellow eyes with elliptical pupils and, as the name suggests, a spade on each hind foot, the eastern spadefoot toad ranges from the southeast corner of the United States up the Atlantic Coast to New England. Known scientifically as Scaphiopus holbrooki, it is a species of conservation concern in the northern reaches of its territory.
Devan-Song, a Ph.D. student in integrative biology, grew up in Singapore, where she learned she could search for reptiles and amphibians by spotlighting. In Rhode Island, where she earned a master’s degree and then worked as a university research associate, the eastern spadefoot toad is endangered.
One rainless night while surveying for amphibians during a project in Virginia, Devan-Song’s spotlight detected one eastern spadefoot after another. That surprised her because the toads were thought to be detectable only on a few rainy nights every year, when they emerge from underground burrows to mate in wetlands.
She continued looking for eastern spadefoots and kept finding them on dry nights, including in upland forest locales not close to any damp areas. Spadefoots remain still when spotlighted so it was easy for Devan-Song to approach the eye-shines and positively identify the toads.
“They need to get above ground to hunt for insects and build up energy stores for mating,” she said. “That’s why we were finding them when and where conventional wisdom said we weren’t supposed to be finding them.”
Back in Rhode Island, she tried spotlighting for spadefoots; it took her just 15 minutes to find one. The success led to a 10-night survey in a pair of locations last summer that produced 42 sightings – nearly double the number of eastern spadefoot toad sightings in Rhode Island over the previous seven decades.
Devan-Song also learned that she wasn’t the first to question the notion that the eastern spadefoot was so “secretive” as to almost always avoid detection. As far back as 1944, Devan-Song said, it was suggested in scientific literature that the toad could be found outside of rain-induced migration and breeding aggregations. And in 1955, researchers used spotlighting to detect huge numbers of eastern spadefoots in Florida; the technique subsequently, inexplicably fell into disuse.
“Confirmation bias perpetuated the fallacy of when the eastern spadefoot could be found,” Devan-Song said. “No breeding events or migration occurred during our surveys and we detected thousands of toads in Virginia and dozens in Rhode Island. The majority of those were subadults, a demographic category mainly overlooked in the literature. Progress in learning about the toad, its ecology and its conservation has been greatly hindered by a misconception that persisted even when evidence to the contrary was presented.”
The ease with which many toads could be found during breeding, combined with a lack of data on toads in upland habitats, helped fuel confirmation bias in this case, she said.
“Everyone assumed they were underground most of the time so no one was really looking for them most of the time,” Devan-Song said. “Our research demonstrates that you can detect them year round, though they do remain rare in Rhode Island. But likely not as rare as the scientific community thought.”
The National Park Service, through a cooperative agreement with the University of Rhode Island, supported this research.
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