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Comment by Dr. Krishna Kumari Challa on March 2, 2024 at 8:54am

An overgrowth of nerve cells appears to cause lingering symptoms after recurrent UTIs

A perplexing problem for people with recurring urinary tract infections (UTIs) is persistent pain, even after antibiotics have successfully cleared the bacteria.

researchers have identified the likely cause—an overgrowth of nerve cells in the bladder.

The finding, appearing  in the journal Science Immunology on March 1, provides a potential new approach to managing symptoms of recurring UTIs that would more effectively target the problem and reduce unnecessary antibiotic usage.

Urinary tract infections account for almost 25% of infections in women. Many are recurrent UTIs, with patients frequently complaining of chronic pelvic pain and urinary frequency, even after a round of antibiotics. 

This new study, for the first time, describes an underlying cause and identifies a potential new treatment strategy.

Researchers collected bladder biopsies from recurrent UTI patients who were experiencing pain despite no culturable bacteria in their urine. Using biopsies from people without UTIs as a comparison, they found evidence that sensory nerves were highly activated in the UTI patients, explaining the persistent sense of pain and urinary frequency.

Further studies in mice revealed the underlying events, with unique conditions in the bladder that prompt activated nerves in the lining to bloom and grow with each infection.

Typically, during every bout of UTI, epithelial cells  laden with bacteria are sloughed off, and significant destruction of nearby nerve tissue occurs. These events trigger a rapid repair program in the damaged bladder involving massive regrowth of destroyed nerve cells.

This immune response, including repair activities, is led by mast cells—which are immune cells that fight infection and allergens. Mast cells release chemicals called nerve growth factor, which drive overgrowth and increase sensitivity of nerves. The result is pain and urgency.

The researchers were able to address these symptoms by treating study mice with molecules that suppress production of the mast-cell generated nerve growth factor.

 Byron Hayes et al, Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity, Science Immunology (2024). DOI: 10.1126/sciimmunol.adi5578. www.science.org/doi/10.1126/sciimmunol.adi5578

Comment by Dr. Krishna Kumari Challa on March 2, 2024 at 8:44am

However, when applied to patients who received just one of the immunotherapy drugs, targeting the immune checkpoint receptor PD-1 only, the machine learning model could not identify those who would respond to treatment.

This suggests that the relationship between gut microbiota and treatment response is specific for particular therapeutic combinations. The researchers therefore suggest that future development of diagnostics tests or therapeutics that rely on the gut microbiome should be tailored to the immunotherapy regimen, regardless of cancer type.

This step towards personalized medicine may help extend cancer treatments to more people and can match individuals to therapies that would benefit them the most.

 A gut microbial signature for combination immune checkpoint blockade across cancer types, Nature Medicine (2024). DOI: 10.1038/s41591-024-02823-z

Part 2

Comment by Dr. Krishna Kumari Challa on March 2, 2024 at 8:43am

New microbiome insights could help boost immunotherapy for a range of rare cancers

The microbiome can identify those who benefit from combination immunotherapy across multiple different cancers, including rare gynecological cancers, biliary tract cancers and melanoma.

Researchers have identified specific strains of bacteria that are linked with a positive response to combination immunotherapy in the largest study of its kind.

The study, published in Nature Medicine, details a signature collection of microorganisms in an individual's gut bacteria that may help identify those who would benefit from combination immunotherapy and help explain why the efficacy of this treatment is otherwise hard to predict.

In the future, understanding more about these bacteria strains can help drive the development of next-generation probiotics, known as "live biotherapeutic products," that focus on modulating the microbiome to support combination immunotherapy from the inside.

Immunotherapy is a type of treatment that harnesses the body's immune system to target the cancer. While it can be very effective, it only works in a proportion of recipients across a wide range of cancers. As with all cancer treatments, immunotherapy can have multiple side effects. Therefore, being able to predict who is most likely to respond to treatment helps ensure that patients do not endure these unnecessary side effects for no medical benefit.

This study used samples collected in a large, multi-center Australian clinical trial where combination immunotherapy was effective in 25% of people with a broad range of advanced rare cancers, including rare gynecological cancers, neuroendocrine neoplasms, and upper gastrointestinal and biliary cancers.

The clinical trial focused on a type of combination immunotherapy known as immune checkpoint inhibitors. These anti-cancer agents block the body's immune checkpoint proteins, allowing the immune cells to destroy cancer cells. In this case, the immunotherapy blocked the PD-1 and CTLA-4 checkpoints.

Researchers used stool samples from clinical trial patients and performed deep shotgun metagenomic sequencing to map all the organisms within the participants' microbiomes, down to the strain level.

They discovered multiple strains of bacteria in those who responded well to treatment, many of which had not been cultivated before. This allowed them to identify a microbiome signature that was found in patients who responded well to treatment.

In addition to this, the team used this signature to train a machine learning model that could predict who would benefit from combination immunotherapy. They conducted a meta-analysis of previous studies and found that their signature could be applied to different cancers, such as melanoma; and across countries, to predict individuals whose cancer would likely respond to combination immunotherapy.

Part 1

Comment by Dr. Krishna Kumari Challa on March 2, 2024 at 7:38am

The researchers observed the body switching energy sources—from glucose to fat stored in the body—within the first two or three days of fasting. The volunteers lost an average of 5.7 kg of both fat mass and lean mass. After three days of eating after fasting, the weight stayed off—the loss of lean was almost completely reversed, but the fat mass stayed off.

For the first time, the researchers observed the body undergoing distinct changes in protein levels after about three days of fasting—indicating a whole-body response to complete calorie restriction. Overall, one in three of the proteins measured changed significantly during fasting across all major organs. These changes were consistent across the volunteers, but there were signatures distinctive to fasting that went beyond weight loss, such as changes in proteins that make up the supportive structure for neurons in the brain.

For the first time, scientists were able to see what's happening on a molecular level across the body when people fast. Fasting, when done safely, is an effective weight loss intervention. Popular diets that incorporate fasting—such as intermittent fasting—claim to have health benefits beyond weight loss.

The new results provide evidence for the health benefits of fasting beyond weight loss, but these were only visible after three days of total caloric restriction—later than scientists previously thought.

While fasting may be beneficial for treating some conditions, oftentimes, fasting won't be an option to patients suffering from ill health. Scientists hope that these findings can provide information about why fasting is beneficial in certain cases, which can then be used to develop treatments that patients are able to do.

Systemic proteome adaptions to 7-day complete caloric restriction in humans, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01008-9

Part 2

Comment by Dr. Krishna Kumari Challa on March 2, 2024 at 7:33am

Study identifies multi-organ response to seven days without food

New findings reveal that the body undergoes significant, systematic changes across multiple organs during prolonged periods of fasting. The results demonstrate evidence of health benefits beyond weight loss, but also show that any potentially health-altering changes appear to occur only after three days without food.

The study, published in Nature Metabolism, advances our understanding of what's happening across the body after prolonged periods without food.

By identifying the potential health benefits from fasting and their underlying molecular basis, researchers provide a road map for future research that could lead to therapeutic interventions—including for people that may benefit from fasting but cannot undergo prolonged fasting or fasting-mimicking diets, such as ketogenic diets.

Over millennia, humans have developed the ability to survive without food for prolonged periods of time. Fasting is practiced by millions of people throughout the world for different medical and cultural purposes, including health benefits and weight loss. Since ancient times, it has been used to treat diseases such as epilepsy and rheumatoid arthritis.

During fasting, the body changes its source and type of energy, switching from consumed calories to using its own fat stores. However, beyond this change in fuel sources, little is known about how the body responds to prolonged periods without food and any health impacts—beneficial or adverse—this may have. New techniques allowing researchers to measure thousands of proteins circulating in our blood provide the opportunity to systematically study molecular adaptions to fasting in humans in great detail.

Researchers followed 12 healthy volunteers taking part in a seven-day water-only fast. The volunteers were monitored closely on a daily basis to record changes in the levels of around 3,000 proteins in their blood before, during, and after the fast. By identifying which proteins are involved in the body's response, the researchers could then predict potential health outcomes of prolonged fasting by integrating genetic information from large-scale studies. Part 1

Comment by Dr. Krishna Kumari Challa on March 1, 2024 at 10:18am

Want fewer microplastics in your tap water? Try boiling it first

Nano- and microplastics are seemingly everywhere—water, soil and the air. While many creative strategies have been attempted to get rid of these plastic bits, one unexpectedly effective solution for specifically cleaning up drinking water might be as simple as brewing a cup of tea or coffee.

As reported in Environmental Science & Technology Letters, boiling and filtering calcium-containing tap water could help remove nearly 90% of the nano- and microplastics present.

Contamination of water supplies with nano- and microplastics (NMPs), which can be as small as one-thousandth of a millimeter in diameter or as large as 5 millimeters, has become increasingly common. The effects of these particles on human health are still under investigation, though current studies suggest that ingesting them could affect the gut microbiome. Some advanced drinking water filtration systems capture NMPs, but simple, inexpensive methods are needed to substantially help reduce human plastic consumption.

So researchers wanted to see whether boiling could be an effective method to help remove NMPs from both hard and soft tap water.

The researchers collected samples of hard tap water. 

Samples were boiled for five minutes and allowed to cool. Then, the team measured the free-floating plastic content. Boiling hard water, which is rich in minerals, will naturally form a chalky substance known as limescale, or calcium carbonate (CaCO3). Results from these experiments indicated that as the water temperature increased, CaCO3 formed incrustants, or crystalline structures, which encapsulated the plastic particles.

Researchers say that over time, these incrustants would build up like typical limescale, at which point they could be scrubbed away to remove the NMPs. They suggest any remaining incrustants floating in the water could be removed by pouring it through a simple filter such as a coffee filter.

In the tests, the encapsulation effect was more pronounced in harder water—in a sample containing 300 milligrams of CaCO₃ per liter of water, up to 90% of free-floating MNPs were removed after boiling. However, even in soft water samples (less than 60 milligrams CaCO₃ per liter), boiling still removed around 25% of NMPs. The researchers say that this work could provide a simple, yet effective, method to reduce NMP consumption.

Drinking Boiled Tap Water Reduces Human Intake of Nanoplastics and Microplastics, Environmental Science & Technology Letters (2024). DOI: 10.1021/acs.estlett.4c00081

Comment by Dr. Krishna Kumari Challa on March 1, 2024 at 9:54am

‘Epigenetic’ editing cuts cholesterol in mice

Changes to chemical tags on DNA in mice dial down the activity of a gene without cuts to the genome.

An alternative to genome editing can reduce the activity of a gene that affects cholesterol levels without changing the DNA sequence — and does so for an extended period, according to a study1 in mice.

Scientists achieved this effect by changing each animal’s ‘epigenome’, one feature of which is a collection of chemical tags that are bound to DNA and affect gene activity. After the treatment, activity of the targeted gene dropped and remained low for the 11 months over which the mice were studied.

https://www.nature.com/articles/d41586-024-00563-1?utm_source=Live+...

Comment by Dr. Krishna Kumari Challa on March 1, 2024 at 9:53am

How humans lost their tails
Researchers have shown that humans and other apes carry a DNA insertion in a gene called TBXT that other primates with tails, such as monkeys, don’t have. And mice carrying similar alterations to their genomes have short or absent tails. “They clearly show that this change contributes to tail loss. But it’s not the only one,” says human geneticist Malte Spielmann. Apes aren’t the only primates without tails, suggesting that the trait evolved multiple times. “Probably, there are multiple ways of losing a tail during development. Our ancestors chose this way,” says co-author Bo Xia.

https://www.nature.com/articles/d41586-024-00610-x?utm_source=Live+...

Comment by Dr. Krishna Kumari Challa on March 1, 2024 at 9:39am

Taking the motion sickness out of space travel

In lab experiments, aerospace engineers spin and rock human subjects--all in an effort to help prevent motion sickness when astronauts return to Earth and land in the choppy ocean.

Comment by Dr. Krishna Kumari Challa on March 1, 2024 at 9:29am

AI reveals prostate cancer is not just one disease

Artificial Intelligence has helped scientists reveal a new form of aggressive prostate cancer that could revolutionize how the disease is diagnosed and treated in the future.

The study published in Cell Genomics reveals that prostrate cancer, which affects one in eight men in their lifetime, includes two different subtypes termed evotypes.

The discovery was made by an international team led by the University of Oxford, and the University of Manchester, who applied AI on data from DNA to identify two different subtypes affecting the prostate.

The team hopes their findings could save thousands of lives in future and revolutionize how prostate cancer is diagnosed and treated. Ultimately, it could provide tailored treatments to each individual patient according to a genetic test which will also be delivered using AI.

This understanding is pivotal as it allows us to classify tumors based on how the cancer evolves rather than solely on individual gene mutations or expression patterns.

The researchers used AI to study changes in the DNA of prostate cancer samples (using whole genome sequencing) from 159 patients.

They identified two distinct cancer groups among these patients using an AI technique called neural networks. These two groups were confirmed by using two other mathematical approaches applied to different aspects of the data. This finding was validated in other independent datasets from Canada and Australia.

They went on to integrate all the information to generate an evolutionary tree showing how the two subtypes of prostate cancer develop, ultimately converging into two distinct disease types termed "evotypes."

Genomic evolution shapes prostate cancer disease type, Cell Genomics (2024). DOI: 10.1016/j.xgen.2024.100511. www.cell.com/cell-genomics/ful … 2666-979X(24)00038-7

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