Lives could be saved from tropical disease with new rapid test

Globally, more than half of patients die after infection with the neglected tropical disease, melioidosis, often before they are diagnosed. A new rapid test could save lives by diagnosing patients in hours, rather than several days taken by current bacterial culture methods, meaning they receive the correct antibiotics faster.
The test uses CRISPR to detect a genetic target that is specific to Burkholderia pseudomallei, the bacterium that causes melioidosis, with 93 per cent sensitivity. It was developed by researchers at the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Chiang Mai University, Vidyasirimedhi Institute of Science and Technology (VISTEC) in Thailand, and the Wellcome Sanger Institute in the UK.
The results, published today (14 March) in Lancet Microbe, mean more lives could be saved from melioidosis, with a rapid, easy-to-use diagnostic test that could be rolled out globally.
Melioidosis is a neglected tropical disease that is estimated to affect 165,000 people worldwide each year, of whom 89,000 die from the disease. It is caused by the bacterium, Burkholderia pseudomallei, which lives in soil and water in tropical and subtropical regions, and enters human bodies via inoculation through skin abrasions, ingestion or inhalation.
It is difficult to diagnose melioidosis as symptoms vary from localised abscess or pneumonia to acute septicaemia, or may present as a chronic infection. As a result of this, and the locations of isolated communities in rural areas that it mostly affects, the disease remains hugely underreported.
Currently, melioidosis is diagnosed in patients after bacterial samples are cultured, which takes three to four days. In Thailand, approximately 40 per cent of patients with melioidosis die, many of whom die within the first one to two days following admission to hospital, while waiting for a diagnosis.
There is no licensed vaccine for melioidosis, but patients can be effectively treated with intravenous antibiotics — ceftazidime or carbapenem — during the first intensive phase of treatment. However, current practices often involve initially treating patients with a range of unnecessary antibiotics to target the various symptoms the disease produces, which can waste time and resources.

In a new study, the team set out to develop a new rapid test to reduce the time taken to correctly diagnose and treat patients with melioidosis.
The researchers identified a genetic target specific to B. pseudomallei byanalysing over 3,000 B. pseudomallei genomes, most of which were sequenced at the Sanger Institute. They searched for conserved regions of the genome and screened the targets against other pathogens and human host genomes, to ensure their chosen target was specific to B. pseudomallei.
Their test, called CRISPR-BP34, involves rupturing bacterial cells and using a recombinase polymerase amplification reaction to amplify the bacterial target DNA for increased sensitivity. Additionally, a CRISPR reaction is used to provide specificity, and a simple lateral flow ‘dipstick’ read-out is employed to confirm cases of melioidosis.
To assess the efficacy of the test, the team collected clinical samples from 114 patients with melioidosis and 216 patients without the disease at Sunpasitthiprasong Hospital, a hospital in northeast Thailand where melioidosis is endemic. The CRISPR-BP34 test was then applied to these samples.
The new test showed enhanced sensitivity at 93 per cent, compared to 66.7 per cent in bacterial culture methods. It also delivered results in less than four hours for urine, pus, and sputum samples, and within one day for blood samples. This is a significant improvement over the current bacterial culture diagnostic method, which typically takes three to four days.
This new rapid diagnostic test will enable health professionals to prescribe the correct antibiotics faster, meaning fewer patients will die while waiting for a diagnosis. While saving precious time, the new test will also save resources and money, with fewer unnecessary antibiotics prescribed and less time for patients in hospital.

In next steps for the team, they are currently designing randomised clinical trials to show the effectiveness of these tests in hospital settings. Plus, members of the team will begin investigating the role of human genetics in susceptibility and immune response to melioidosis infection.
Dr ClaireChewapreecha, co-lead author at the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Thailand, and Wellcome Sanger Institute International Fellow, said: “Working in rural Thailand has many limitations. But we have shown that limitations breed innovation, and what succeeds here can succeed anywhere. I am so proud of the team behind this new, robust rapid diagnostic test for melioidosis, and hope that it can potentially be used anywhere in the world to get the right treatments to patients faster, ultimately saving lives.”
Dr Somsakul Wongpalee, co-lead author at Chiang Mai University, Thailand, said: “We carefully designed the rapid diagnostic test based on CRISPR-BP34, with a robust algorithm, and tested its performance in vitro. We are thrilled that the CRISPR-BP34 test demonstrates outstanding diagnostic efficacy when tested on clinical samples, showcasing its potential to significantly impact patient outcomes and potentially save lives in the near future.”
Professor Nick Thomson, senior author and Head of Parasites and Microbes at the Wellcome Sanger Institute, said: “This research is a testament to international collaboration and how the application of genomics at scale leads to clinical intervention. Using a genetic target mined from a bank of thousands of bacterial genomes, the team was able to produce an incredibly sensitive test that is specific to the bacterium behind melioidosis. I look forward to seeing the clinical impacts of this research.”
Professor Nick Day, senior author and Director of the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Thailand, and the Wellcome Trust Thailand Asia and Africa Programme, said: “Melioidosis has been neglected despite its high mortality rate and high incidence in many parts of Asia. Early diagnosis is essential so that the specific treatment required can be started as soon as possible. The new rapid diagnostic tool developed through this collaboration has the potential to be a game-changer.”

Read more →

Revolutionary chronic wound treatment could help millions

An effective treatment for chronic wounds that does not involve antibiotics, but an ionised 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 ionised 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,” said Dr Szili.

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 tumour.
“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 optimise the electrochemical technology for treatment in human patients.
A video explaining the treatment is available at: https://youtu.be/TdwfA9narMg

Read more →

‘Junk DNA’ no more: New method to identify cancers from repeat elements of genetic code

Repeats of DNA sequences, often referred to as “junk DNA” or “dark matter,” that are found in chromosomes and could contribute to cancer or other diseases have been challenging to identify and characterize. Now, investigators at the Johns Hopkins Kimmel Cancer Center have developed a novel approach that uses machine learning to identify these elements in cancerous tissue, as well as in cell-free DNA (cfDNA) — fragments that are shed from tumors and float in the bloodstream. This new method could provide a noninvasive means of detecting cancers or monitoring response to therapy. Machine learning is a type of artificial intelligence that uses data and computer algorithms to perform complex tasks and accelerate research.
In laboratory tests, the method, called ARTEMIS (Analysis of RepeaT EleMents in dISease) examined over 1,200 types of repeat elements comprising nearly half of the human genome, and identified that a large number of repeats not previously known to be associated with cancer were altered in tumor formation. The investigators also were able to identify changes in these elements in cfDNA, providing a way to detect cancer and determine where in the body it originated. A description of the work is to be published March 13 in Science Translational Medicine.
“When you think about existing cancer genes and the DNA sequences around them, they’re just chock full of these repeats,” says Victor E. Velculescu, M.D., Ph.D., a professor of oncology and co-director of the Cancer Genetics and Epigenetics Program at the Johns Hopkins Kimmel Cancer Center, who led the study with Akshaya Annapragada, an M.D./Ph.D. student at the Johns Hopkins University School of Medicine, and Robert Scharpf, Ph.D., an associate professor of oncology at Johns Hopkins.
“Until ARTEMIS, this dark matter of the genome was essentially ignored, but now we’re seeing that these repeats are not occurring randomly,” Velculescu says. “They end up being clustered around genes that are altered in cancer in a variety of different ways, providing the first glimpse that these sequences may be key to tumor development.”
In a series of laboratory tests, the researchers first examined the distribution of 1.2 billion kmers (short sequences of DNA) defining unique repeats, finding them enriched in genes commonly altered in human cancers. For example, of 736 genes known to drive cancers, 487 contained an average fifteenfold higher than expected number of repeat sequences. These repeat sequences also were significantly increased in genes involved in cell signaling pathways that are commonly dysregulated in cancers.Using next-generation sequencing, technology that allows researchers to rapidly examine the sequences of entire genomes, the researchers also looked to see if repeat sequences were directly altered in cancers. They used ARTEMIS to analyze over 1,200 distinct types of repeat elements in tumor and normal tissues from 525 patients with different cancers participating in the Pan-Cancer Analysis of Whole Genomes (PCAWG), and found a median of 807 altered elements in each tumor. Nearly two-thirds of these elements (820 of 1,280) had not previously been observed as being altered in human cancers. Then, they used a machine-learning model to generate an ARTEMIS score for each sample to provide a summary of genome-wide repeat element changes that were predictive of cancer. ARTEMIS scores distinguished the 525 PCAWG participants’ tumors from normal tissues with a high performance (AUC=0.96) across all cancer types analyzed, where 1 is a perfect score. Increased ARTEMIS scores were associated with shorter overall and progression-free survival regardless of tumor type.
The investigators next evaluated ARTEMIS’ potential for noninvasive detection of cancer. They applied the tool to blood samples from 287 individuals with and without lung cancer participating in the Danish Lung Cancer Screening Study (LUCAS). ARTEMIS classified patients with lung cancer with an area under the curve (AUC) of 0.82. But when used with another method called DELFI (DNA evaluation of fragments for early interception) — an assay previously developed by Velculescu, Scharpf and other members of their group that detects changes in the size and distribution of cfDNA fragments across the genome — the combination model classified patients with lung cancer with an AUC of 0.91. Similar performance was observed in a group of 208 individuals at risk for liver cancer, in which ARTEMIS detected individuals with liver cancer among others with cirrhosis or viral hepatitis with an AUC of 0.87. When combined with DELFI, the AUC increased to 0.90.
Finally, they evaluated whether the ARTEMIS blood test could identify where in the body a tumor originated in patients with cancer. When trained with information from the PCAWG participants, the tool could classify the source of tumor tissues with an average 78% accuracy among 12 tumor types. The investigators then combined ARTEMIS and DELFI to assess blood samples from a group of 226 individuals with breast, ovarian, lung, colorectal, bile duct, gastric or pancreatic tumors. Here, the model correctly classified patients among the different cancer types with an average accuracy of 68%, which improved to 83% when the model was allowed to suggest two possible tumor types instead of a single cancer type.

“Our study shows that ARTEMIS can reveal genome-wide repeat landscapes that reflect dramatic underlying changes in human cancers,” Annapragada says. “By illuminating the so-called ‘dark genome,’ the work offers unique insights into the cancer genome and provides a proof-of-concept for the utility of genome-wide repeat landscapes as tissue and blood-based biomarkers for cancer detection, characterization and monitoring.”
Next steps are to evaluate the approach in larger clinical trials, says Velculescu: “You can imagine this could be used for early detection for a variety of cancer types, but also could have uses in other applications such as monitoring response to treatment or detecting recurrence. This is a totally new frontier.”
Additional study co-authors were Noushin Niknafs, James R. White, Daniel C. Bruhm, Christopher Cherry, Jamie E. Medina, Vilmos Adleff, Carolyn Hruban, Dimitrios Mathios, Zachariah H. Foda and Jillian Phallen.
The work was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Stand Up to Cancer (SU2C) in-Time Lung Cancer Interception Dream Team Grant, SU2C-Dutch Cancer Society International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415), the Gray Foundation, The Honorable Tina Brozman Foundation, the Commonwealth Foundation, the Mark Foundation for Cancer Research, the Cole Foundation, a research grant from Delfi Diagnostics and U.S. National Institutes of Health grants CA121113, CA006973, CA233259, CA062924, CA271896 and 1T32GM136577.
Annapragada, Scharpf and Velculescu are inventors on patent applications submitted by The Johns Hopkins University related to genome-wide repeat landscapes in cancer and cfDNA. Annapragada, Bruhm, Adleff, Mathios, Foda, Phallen and Scharpf are inventors on patent applications submitted by The Johns Hopkins University related to cell-free DNA for cancer detection that have been licensed to Delfi Diagnostics. White is the founder and owner of Resphera Biosciences LLC and serves as a consultant to Personal Genome Diagnostics Inc. and Delfi Diagnostics Inc. Cherry is the founder and owner of CMCC Consulting. Phallen, Adleff and Scharpf are founders of Delfi Diagnostics, and Adleff and Scharpf are consultants for this organization.
Velculescu is a founder of Delfi Diagnostics, serves on the board of directors and owns Delfi Diagnostics stock, which is subject to certain restrictions under university policy. Additionally, The Johns Hopkins University owns equity in Delfi Diagnostics. Velculescu divested his equity in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. He is an inventor on patent applications submitted by The Johns Hopkins University related to cancer genomic analyses and cell-free DNA for cancer detection that have been licensed to one or more entities, including Delfi Diagnostics, LabCorp, Qiagen, Sysmex, Agios, Genzyme, Esoterix, Ventana and ManaT Bio. Under the terms of these license agreements, the university and inventors are entitled to fees and royalty distributions. Velculescu is also an adviser to Viron Therapeutics and Epitope. These arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Read more →

Tryptophan in diet, gut bacteria protect against E. coli infection

Gut bacteria and a diet rich in the amino acid tryptophan can play a protective role against pathogenic E. coli, which can cause severe stomach upset, cramps, fever, intestinal bleeding and renal failure, according to a study published March 13 in Nature.
The research reveals how dietary tryptophan — an amino acid found mostly in animal products, nuts, seeds, whole grains and legumes — can be broken down by gut bacteria into small molecules called metabolites. It turns out a few of these metabolites can bind to a receptor on gut epithelial (surface) cells, triggering a pathway that ultimately reduces the production of proteins that E. coli use to attach to the gut lining where they cause infection. When E. coli fail to attach and colonize the gut, the pathogen benignly moves through and passes out of the body.
The research describes a previously unknown role in the gut for a receptor, DRD2. DRD2 has otherwise been known as a dopamine (neurotransmitter) receptor in the central and peripheral nervous systems.
“It’s actually two completely different areas that this receptor could play a role in, which was not appreciated prior to our findings,” said Pamela Chang, associate professor of immunology in the College of Veterinary Medicine and of chemical biology in the College of Arts and Sciences. “We essentially think that DRD2 is moonlighting in the gut as a microbial metabolite sensor, and then its downstream effect is to help protect against infection.”
Samantha Scott, a postdoctoral researcher in Chang’s lab, is first author of the study, “Dopamine Receptor D2 Confers Colonization Resistance via Microbial Metabolites.”
Now that Chang, Scott and colleagues have identified a specific pathway to help prevent E. coli infection, they may now begin studying the DRD2 receptor and components of its downstream pathway for therapeutic targets.
In the study, the researchers used mice infected with Citrobacter rodentium, a bacterium that closely resembles E. coli, since certain pathogenic E. coli don’t infect mice. Through experiments, the researchers identified that there was less pathogen and inflammation (a sign of an active immune system and infection) after mice were fed a tryptophan-supplemented diet. Then, to show that gut bacteria were having an effect, they gave the mice antibiotics to deplete microbes in the gut, and found that the mice were infected by C. rodentium in spite of eating a tryptophan diet, confirming that protection from tryptophan was dependent on the gut bacteria.

Then, using mass spectrometry, they ran a screen to find the chemical identities of tryptophan metabolites in a gut sample, and identified three such metabolites that were significantly increased when given a tryptophan diet. Again, based on pathogen levels and inflammation, when these three metabolites alone were fed to the mice, they had the same protective effect as giving the mice a full tryptophan diet.
Switching gears, the researchers used bioinformatics to find which proteins (and receptors) might bind to the tryptophan metabolites, and from a long list they identified three related receptors within the same family of dopamine receptors. Using a human intestinal cell line in the lab, they were able to isolate receptor DRD2 as the one that had the protective effect against infection in the presence of tryptophan metabolites.
Having identified the metabolites and the receptor, they analyzed the downstream pathway of DRD2 in human gut epithelial cells. Ultimately, they found that when the DRD2 pathway was activated, the host’s ability to produce an actin regulatory protein was compromised. C. rodentium (and E. coli) require actin to attach themselves to gut epithelial cells, where they colonize and inject virulence factors and toxins into the cells that cause symptoms. But without actin polymerization they can’t attach and the pathogen passes through and clears.
The experiments revealed a new role of dopamine receptor DRD2 in the gut that controls actin proteins and affects a previously unknown pathway for preventing a pathogenic bacteria’s ability to colonize the gut.
Jingjing Fu, a former postdoctoral researcher in Chang’s lab, is a co-author.
The study was supported by the Arnold and Mabel Beckman Foundation, a President’s Council of Cornell Women Affinito-Stewart Grant, the National Institutes of Health and a Cornell Institute of Host-Microbe Interactions and Disease Postdoctoral Fellowship.

Read more →

Do astronauts experience ‘space headaches’?

Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. The study was published in the March 13, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Changes in gravity caused by space flight affect the function of many parts of the body, including the brain,” said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands. “The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull.”
The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.
Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year. None of them had a history of recurrent headaches or had ever been diagnosed with migraine.
Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3,596 days in space for all participants.
Astronauts completed health screenings and a questionnaire about their headache history before the flight. During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.
The astronauts reported 378 headaches in flight.

Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.
Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine.
Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight. During this time, 21 astronauts had one or more headaches for a total of 51 headaches. Of the 51 headaches, 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.
In the three months after return to Earth, none of the astronauts reported any headaches.
“Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth,” said Van Oosterhout. “Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights.”
This research does not prove that going into space causes headaches; it only shows an association.
A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.
The study was supported by the Netherlands Organization for Scientific Research.

Read more →

Water droplet spun by sound screens for colon cancer

Mechanical engineers at Duke University have devised a new type of diagnostic platform that uses sound waves to spin an individual drop of water up to 6,000 revolutions per minute. These speeds separate tiny biological particles within samples to enable new diagnostics based on exosomes.
A very light disc placed on top of the spinning drop features etched channels that are equipped with star-shaped nanoparticles tailored to enable the label-free detection of specific disease-relevant bioparticles called exosomes. The technique is much more efficient than current approaches, requiring less time and sample volume while inflicting less damage to the delicate exosomes.
Exosomes are released by cells and carry cell-specific cargos of proteins, lipids and genetic materials, and can be selectively taken up by other cells as a means of communication. Their specific makeup has shown potential for use for non-invasive diagnostics.
Compared to the bulky machines that cost upwards of $100,000 that currently isolate these biomarkers, the technique could allow new point-of-care applications ranging from precision bioassays to cancer diagnosis.
The research appears online March 8 in the journal Science Advances.
“The most common way to separate exosomes is ultrasound centrifugation, which takes at least eight hours, needs large sample sizes and often damages the exosomes,” said Ty Naquin, a PhD student working in the laboratory of Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke. “Other methods all have their problems as well, such as having low purity or low yield. Our initial demonstrations seem to provide a path to a better solution.”
The device centers on a drop of water placed within a ring of polydimethylsiloxane, a type of silicon commonly used in microfluidic technologies, which confines the water’s boundaries and keeps it in place. The researchers then placed a sound wave generator on each side of the device and slanted them so that sound waves travel through the underlying platform to enter the droplet.

The sound wave generators create surface acoustic waves that push on the sides of the droplet like Donald Duck getting blown over by a gigantic pair of speakers. At high enough powers, the droplet stabilizes and spins around thousands of times per minute.
“We went up to 6000 RPMs in the paper, but beyond that the droplet begins leaning and runs the risk of spitting water out and getting crushed by the disc sitting on top,” said Naquin.
The light disc placed on top features four channels etched into its surface. Rapid rotation causes exosomes to migrate to the ends of the channels while smaller proteins and other contaminants remain behind.
To detect the presence of specific biomarkers, the researchers turned to technology developed by Tuan Vo-Dinh, the R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering and Professor of Chemistry at Duke.
His approach tethers DNA probes dubbed “Inverse Molecular Sentinels” to the points of star-shaped gold nanoparticles. While these tethers naturally want to curl up on themselves, they are held straight by a segment of DNA that is tailored to bind with the target microRNA being tested for. When that microRNA comes by on its exosome carrier, it sticks to and removes the DNA, allowing the tether to curl and bring the label molecule in close contact with the nanostar.
When exposed to a laser, that label molecule emits a light called a Raman signal, which is generally very weak. But the shape and composition of the nanostars amplifies Raman signals several million-fold, making them easier to detect.

“Our platform detected biomarkers for colorectal cancer patients with results that strongly correlate with the gold standard for this type of diagnostic but with much less time and effort required,” said Aidan Canning, a PhD student working in the Vo-Dinh laboratory. “This is such a great marriage of two technologies.”
While still in the early stages, Naquin and Canning are now thinking of new ways to wed these platforms with other advances for new types of investigations or commercialization.
“Our technology can discriminate between cancer and control groups with 95.8% sensitivity and 100% selectivity,” said Huang. “Its potential is enormous in fundamental biological research and the early diagnosis and health monitoring of cancers, neurodegenerative and other diseases.”
This work was supported by the National Institutes of Health (R01GM135486, R01GM132603).

Read more →

Poor sleep linked to migraine attacks

A new study by researchers at the University of Arizona Health Sciences identified a link between poor sleep and migraine attacks that suggests improving sleep health may diminish migraine attacks in people with migraine.
Many people with migraine report having sleeping disorders, including insomnia, trouble falling or staying asleep, poor sleep quality, excessive daytime sleepiness, waking up from sleep and being forced to sleep because of a migraine headache. Until now, it was unknown whether migraine causes poor sleep or vice versa.
“It has been recognized for quite a long time that there is a relationship between sleep and migraine,” said principal investigator Frank Porreca, PhD, research director for the Comprehensive Center for Pain & Addiction and professor of pharmacology at the UArizona College of Medicine — Tucson. “The way it has been investigated in the past has been through patient-reported information, which is subjective. We quantitatively measured sleep in preclinical models and found that migraine-like pain does not influence sleep, but if you have disrupted sleep, your chances of having a migraine attack if you’re a migraine patient are much higher.”
Porreca led a research team that used preclinical mouse models to evaluate sleep disruption, as the sleep architecture of mice closely matches that of people, including cycles of deep sleep, REM sleep and light sleep. Sleep was assessed using electroencephalogram recordings and visual observations.
Researchers found that when mice were sleep deprived, they were more likely to experience migraine-like pain, but migraine-like pain did not disrupt normal sleep.
Porreca noted that sleep deprivation can happen for many reasons, including stress. For this study, the research team ensured they were studying the effect of sleep, and not stress, on migraine by giving mice novel objects to explore to keep them awake.
“Mice are compelled to explore novel objects. They just have to go and look,” Porreca said. “It reminds me of how teenagers are often sleep deprived because they’re on their phones. Anybody who studies sleep will tell you that from a sleep hygiene point of view, you don’t want any devices in your bedroom where you’re trying to sleep.”
For people with migraine, limiting the use of electronic devices before bedtime and following other sleep health tips could be an easy way to limit the likelihood of migraine attacks.
“Early morning is one of the most common times people experience migraine attacks,” Porreca said. “Migraine is highly female prevalent — it’s 3 to 1, women to men — and almost all the women are of childbearing age. Many people with migraine probably have children. They wake up with a migraine attack and are immediately stressed. They don’t have time to take care of themselves, they have to get the kids ready for school and they have to get ready for work. That migraine attack is happening in the worst time of the day for function. Improved sleep is critically important and probably would diminish the frequency of migraine attacks.”
The American Migraine Foundation estimates more than 39 million people in the U.S. live with migraine, though that number is probably higher due to the number of people who do not get a diagnosis or treatment.

Read more →

Paul Alexander, Lawyer and TikTok Star Who Spent Decades in Iron Lung, Dies at 78

Paul Alexander, who died at 78, was paralyzed with polio at age 6 and relied on the machine to breathe. Still, he was able to earn a law degree, write a book and, late in life, build a following on TikTok.After he was paralyzed by polio at age 6, Paul Alexander was confined for much of his life to a yellow iron lung that kept him alive. He was not expected to survive after that diagnosis, and even when he beat those odds, his life was mostly constrained by a machine in which he could not move.But the toll of living in an iron lung with polio did not stop Mr. Alexander from going to college, getting a law degree and practicing law for more than 30 years. As a boy, he taught himself to breathe for minutes and later hours at a time, but he had to use the machine every day of his life.He died on Monday at 78, according to a statement by his brother, Philip Alexander, on social media.He was one of the last few people in the United States living inside an iron lung, which works by rhythmically changing air pressure in the chamber to force air in and out of the lungs. And in the final weeks of his life, he drew a following on TikTok by sharing what it had been like to live so long with the help of an antiquated machine.It was unclear what caused Mr. Alexander’s death. He had been briefly hospitalized with the coronavirus in February, according to his TikTok account. After he returned home, Mr. Alexander struggled with eating and hydrating as he recovered from the virus, which attacks the lungs and can be especially dangerous to people who are older and have breathing problems.Mr. Alexander contracted polio in 1952, according to his book, “Three Minutes for a Dog: My Life in an Iron Lung.” He was quickly paralyzed, and doctors at Parkland Hospital in Dallas put him in an iron lung so that he could breathe.“One day I opened my eyes from a deep sleep and looked around for something, anything, familiar,” Mr. Alexander said in his book, which he wrote by putting a pen or pencil in his mouth. “Everywhere I looked was all very strange. Little did I know that each new day my life was unavoidably set on a path that would become unimaginably strange and more challenging.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Read more →

Colon Cancer Blood Test Shows Promise for Early Detection

Many patients are reluctant to undergo colonoscopies or conduct at-home fecal tests. Doctors see potential in another screening method.Early detection of colon cancer can prevent a majority of deaths from this disease, possibly as much as 73 percent of them. But just 50 to 75 percent of middle-aged and older adults who should be screened regularly are being tested.One reason, doctors say, is that the screening methods put many people off.There are two options for people of average risk: a colonoscopy every 10 years or a fecal test every one to three years, depending on the type of test.Or, as Dr. Folasade P. May, a gastroenterologist at UCLA Health puts it, “either you take this horrible laxative and then a doctor puts an instrument up your behind, or you have to manipulate your own poop.”But something much simpler is on the horizon: a blood test. Gastroenterologists say such tests could become part of the routine blood work that doctors order when, for example, a person comes in for an annual physical exam.“I think this is going to start taking off,” said Dr. John M. Carethers, a gastroenterologist and the vice chancellor for health sciences at the University of California, San Diego.About 53,000 Americans are expected to die from colorectal cancer this year. It is the second-most common cause of cancer-related deaths in the United States, and while the death rate in older adults has fallen, it has increased in people under age 55.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Read more →

Olivia Munn Had Double Mastectomy After Breast Cancer Diagnosis

Munn said she was given the diagnosis last April, two months after negative results on a test that checked for 90 cancer genes.The actress Olivia Munn said on Wednesday that she had been given a diagnosis of an aggressive form of breast cancer last year and soon after had a double mastectomy as part of her treatment.Munn, 43, who has starred in dozens of movies and television shows, including the HBO series “The Newsroom,” wrote in a lengthy social media post that she had tried to be proactive about her health.In February 2023, not long after having a normal mammogram, Munn took a robust genetic test that checked for 90 cancer genes. She said she tested negative for all of them, including BRCA, the most well-known breast cancer gene. Her sister also tested negative around the same time.“We called each other and high-fived over the phone,” Munn wrote.Two months later, Munn learned she had luminal B, a type of breast cancer. A month after that, she had the double mastectomy.“In the past ten months, I have had four surgeries, so many days spent in bed I can’t even count and have learned more about cancer, cancer, treatment and hormones than I ever could have imagined,” she wrote. “Surprisingly, I’ve only cried twice. I guess I haven’t felt like there was time to cry.”Munn’s post was in large part a plea to women to ask their doctors to calculate their breast cancer risk assessment score. That her obstetrician-gynecologist had done so helped identify Munn’s cancer early.“The fact that she did saved my life,” Munn wrote.The risk assessment includes factors like familial breast cancer history and age; Munn mentioned in her post that having her first child over the age of 30 was a factor. Munn has been in a relationship with the comic John Mulaney since 2021 and they have a 2-year-old son, Malcolm, together.The results of Munn’s risk assessment prompted her doctor to send her for an M.R.I., which led to an ultrasound. That led to a biopsy revealing the cancer.In her post, Munn thanked her doctors as well as her friends and family. She thanked Mulaney for researching all of her operations and medications for information about side effects and recovery.For the past year, Munn’s social media has shown many happy moments, as well as many glamorous ones, including family photos at the beach and others of Munn in designer looks. This weekend she shared images that showed her wearing a metallic Fendi gown for the Oscars ceremony, where Mulaney presented an award.“I’ve tended to let people see me when I have energy, when I can get dressed and get out of the house, when I can take my baby boy to the park,” she wrote.“I’ve kept the diagnosis and the worry and the recovery and the pain medicine and the paper gowns private. I needed to catch my breath and get through some of the hardest parts before sharing.”

Read more →