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‘Spatial-omics’ technology allows early-stage disease investigation

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How can you trace a single diseased cell in an intact brain or a human heart? The teams of Ali Ertürk at Helmholtz Munich and Ludwig Maximilians Universitat (LMU) Munich and Matthias Mann at the Max Planck Institute of Biochemistry in Martinsried, Germany, have now developed a new technology named DISCO-MS that solves the problem. DISCO-MS uses robotics technology to obtain proteomics data from ‘sick’ cells precisely identified early in the disease, writes the LMU in a press release.

Why we write about this topic:

Discovering a disease earlier often leads to better treatment. Robotics and artificial intelligence can help in anticipating detection.

Most diseases are asymptomatic initially. The affected persons usually still feel fine – symptoms are not yet present, or still too mild to realize. However, a change has already happened within the body. A virus may have started replicating, or a rogue cell might have divided more often than it should have.

The task became easier with the development of DISCO-MS. DISCO-MS combines methods to turn mouse and human tissues transparent. It does so using the latest robotics and proteomics technologies, determining their molecular makeup.

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Transparency to detect early molecular changes

DISCO-MS starts with the so-called DISCO tissue clearing, which renders the mouse body or human organs transparent. Thereby, fluorescently labeled cells can be readily identified in intact tissues of specific sites using high-resolution three-dimensional microscopy.

Once the regions of interest have been identified, they are isolated using a new robotics technology called DISCO-bot. It was developed by mechanical engineer Furkan Öztürk, a Ph.D. student in Ertürk’s lab. The robot-assisted extracted tissues are then processed for their proteome analysis using advanced mass spectrometry (MS) methods developed by Andreas-David Brunner, a former Ph.D. student in Mann’s lab. This high-tech approach allows complete molecular characterization of any desired tissue region identified in 3D in whole mouse bodies or human organs.

Early detection catches the diseases

To showcase the method’s power, first author Harsharan Singh Bhatia and colleagues applied DISCO-MS to Alzheimer’s disease (AD) mouse model and to atherosclerotic plaques (pathological hardening and narrowing of blood vessels) in the human heart. The team also applied artificial intelligence (AI) to identify the typical AD plaques at the early stages of the disease. Subsequent proteomics analyses of the plaques provided an unbiased and large-scale study of proteins affected by AD. This analysis also revealed new molecular players that could be biomarkers for Alzheimer’s disease.

In the human heart, the researchers were interested in the composition of the tissues around atherosclerotic plaques. AI detection and robotics extraction of the tissues again allowed the identification of dysregulated molecular pathways in human heart cells related to aortic plaques. These results are key findings, as they form the basis for potential therapeutic targets.

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Deadly fungal infections a concern in patients post-COVID-19, flu | CTV News – CTV News Calgary

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While fungi are not about to start turning the human race into zombies, like in the HBO blockbuster series The Last of Us, the World Health Organization (WHO) says invasive fungal infections are an increasing threat to human health.

Aspergillosis is one fungal infection common in our environment but, in some circumstances, it can turn deadly. In an average day, most of us will inhale hundreds to thousands of Aspergillus spores with no adverse effects, but for people with weakened immune systems it can cause deadly infections. That includes people undergoing cancer treatments, or bone marrow transplants, but it is now recognized that some viral infections, like influenza (flu) and SARS-CoV-2 (COVID-19) increase the risk of deadly fungal infection even in otherwise healthy people.

“When these kinds of things happen in the ICU, it can be devastating because even advanced medicines still can’t treat these infections,” said Dr. Bryan Yipp, an intensive care physician and researcher at the University of Calgary.

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“Once many of these infections really get ingrained and take over, clearing them with medications alone, antifungal or anti microbials, can be very difficult.”

Dr.Yipp began studying Aspergillus — a type of fungus that is a common mould — and its connection to viral infections in 2019, following three deaths in intensive care units of patients initially admitted for influenza, but who subsequently died of the fungal infection.

“It was very much a surprise when people first started identifying the fungus in the lung.  There was a lot of discussion around the table of ICU doctors, infectious disease doctors, asking ‘Was Aspergillosis really the cause of death, or was this just a secondary finding?'” said Yipp. “The pathologists who looked at the samples and the autopsies, were convinced that it was Aspergillosis that was the main problem.”

UCalgary researchers have determined exposure to Aspergillus, a common fungal mould, can lead to a potentially dangerous Aspergillosis infection in people with weakened immune systems.

Working in Yipp’s lab, lead researcher Nicole Sarden, a PhD candidate, isolated the mechanism by which the immune system starts failing to prevent fungal infections.

“In healthy humans. specific immune cells, called B cells, produce molecules (antibodies) that basically tag invaders so that other cells in the immune system, called neutrophils, can recognize them, eat them, and clear the infection,” said Sarden

“But when you have infections with viruses, such as influenza, or if you get COVID, these molecules are no longer present, which means that the immune systems that are trying to eat, and clear the fungi cannot do it because they cannot see it.”

Working with both mice and human blood and tissue samples, the researchers discovered that following a viral infection, neutrophils could identify a fungal infection and surround it but did nothing to destroy it.  

“The virus kills the B cells, no messenger molecules exist, so the neutrophils that would normally attack, the fungus, are blinded. They sit there and don’t know what to do,” said Sarden.

The research team also discovered that reintroducing Aspergillosis reactive antibodies can protect infected mice, leading to hopes a similar treatment will be available in the near future for humans with Aspergillosis infections.

While Yipp and Sarden focused on Aspergillus, it is not the only fungus that can cause serious, or fatal infections. It is estimated fungal infections kill an estimated 1.5 million people worldwide every year. Most of those are due to four different fungi; Cryptococcus, Candida, Aspergillus, and Pneumocystis.  Since the advent of COVID, a previously rare infection of the fungus Mucormycosis has been increasing rapidly in India. It affects the sinuses, brains and lungs of its victims. The rise in Mucormycosis has also been seen in patients who are recovering or have recently recovered from COVID.

Yipp is hopeful the research being conducted at Calgary’s Cumming School of Medicine could lead to treatments for these infections as well.

“We have some hunches that that could be a similar mechanism to what we see here with what we have found.” said Yipp. “So we think that this could be applied to multiple different types of fungi around the world.”

The research team, led by Sarden, published their findings in the journal Science Translational Medicine.

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Barrie hospital declares COVID outbreak in transitional care unit – BarrieToday

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Royal Victoria Regional Health Centre (RVH), in collaboration with the Simcoe Muskoka District Health Unit, declared a COVID-19 outbreak in the Barrie hospital’s transitional care unit on Friday, Jan. 27.

According to RVH, eight patients have tested positive for COVID-19 and have been isolated.

“Enhanced cleaning measures are underway, as well as swabbing of patients and staff,” RVH said in a news release Monday afternoon. 

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Admissions to the unit are on hold at this time, and visitors are not permitted. However, RVH says some exceptions may apply.

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Guidance for diagnosing and managing migraine – News-Medical.Net

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Migraine is a major cause of disability, affecting about 12% of people. A 2-part series published in CMAJ (Canadian Medical Association Journal) on diagnosing and managing the condition with both acute and preventive therapy provides guidance for clinicians. https://www.cmaj.ca/lookup/doi/10.1503/cmaj.211969.

“The goal of treatment of migraine attacks is to provide rapid relief from pain and other migraine-related symptoms, to restore patient function and to prevent recurrence,” writes Dr. Tommy Chan, Department of Clinical Neurological Sciences, Western University, London, Ontario, with coauthors.

“A stratified approach to treatment that empowers patients to choose from different options, depending on attack symptoms and severity, and encourages them to combine medications from different classes (e.g., nonsteroidal anti-inflammatory drugs and triptans) for severe or prolonged attacks, is preferred.”

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Part 2 of the review, which will be published February 6, focuses on preventive treatment to reduce the frequency and severity of migraine attacks.

Journal reference:

Tzankova, V., et al. (2023) Diagnosis and acute management of migraine. Canadian Medical Association Journal. doi.org/10.1503/cmaj.211969.

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