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Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 11:24am

Fecal matter transplant helps half of patients with GI cancers overcome immunotherapy resistance

Findings from a small, proof-of-concept clinical trial have suggested that fecal microbiota transplants (FMTs) can boost the effectiveness of immunotherapy in a range of gastrointestinal cancers.

In the study, published July 25 in the journal Cell Host & Microbe, six of 13 patients who had previously shown resistance to immune checkpoint inhibitors benefited from receiving FMTs from donors who had previously responded to treatment. The investigators also identified specific strains of bacteria associated with better or worse responses to FMT and immune checkpoint drugs.

This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes.

Immune checkpoint inhibitors have revolutionized cancer treatment, but many patients never respond or develop resistance after an initial response. The researchers decided to study FMT in patients receiving immune checkpoint inhibitors because emerging evidence suggests that the gut microbiota plays a crucial role in modulating the immune system and can significantly impact the efficacy of these therapies.

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Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 11:20am

How epigenetics influence memory formation

When we form a new memory, the brain undergoes physical and functional changes known collectively as a "memory trace." A memory trace represents the specific patterns of activity and structural modifications of neurons that occur when a memory is formed and later recalled.

But how does the brain "decide" which neurons will be involved in a memory trace? Studies have suggested that the inherent excitability of neurons plays a role, but the currently accepted view of learning has neglected to look inside the command center of the neuron itself, its nucleus. In the nucleus, there seems to be another dimension altogether that has gone unexplored: epigenetics.

Inside every cell of a given living organism, the genetic material encoded by the DNA is the same, yet the various cell types that make up the body, like skin cells, kidney cells, or nerve cells each express a different set of genes. Epigenetics is the mechanism of how cells control such gene activity without changing the DNA sequence.

Now, scientists  have explored whether epigenetics might affect the likelihood of neurons to be selected for memory formation. Their research on mice, published in Science, shows that the epigenetic state of a neuron is key to its role in memory encoding.

The researchers  wondered if epigenetic factors could influence the "mnemonic" function of a neuron. A neuron can be epigenetically open when the DNA inside its nucleus is unraveled or relaxed; and closed when the DNA is compact and tight.

They found that it is the open ones that are more likely to be recruited into the "memory trace," the sparse set of neurons in the brain that shows electrical activity when learning something new. Indeed, the neurons that were in a more open chromatin state were also the ones demonstrating higher electrical activity.

The 

scientists then used a virus to deliver epigenetic enzymes to artificially induce openness of the neurons. They found that the corresponding mice learned much better. When the scientists used the opposite approach to close the neurons' DNA, the mice's ability to learn was canceled.

The findings open up new ways to understand learning that encompass the neuron's nucleus, and may even lead one day to medication for improving learning.

Giulia Santoni et al, Chromatin plasticity predetermines neuronal eligibility for memory trace formation, Science (2024). DOI: 10.1126/science.adg9982. www.science.org/doi/10.1126/science.adg9982

Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 11:10am

These recent patients fell ill with the same strain identified in the study as circulating in dairy cows, leading the researchers to suspect that the virus likely originated from dairy farms in the same county.

While the virus does have the ability to infect and replicate in people, the efficiency of those infections is low.

The concern is that potential mutations could arise that could lead adaptation to mammals, spillover into humans and potential efficient transmission in humans in the future. 

It is therefore critical to continue to monitor the virus in affected animals and also in any potential infected humans.

 Diego Diel, Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle, Nature (2024). DOI: 10.1038/s41586-024-07849-4. www.nature.com/articles/s41586-024-07849-4

Part 2

Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 11:08am

New study confirms mammal-to-mammal avian flu spread

A new study provides evidence that a spillover of avian influenza from birds to dairy cattle across several U.S. states has now led to mammal-to-mammal transmission—between cows and from cows to cats and a raccoon.

This is one of the first times that we are seeing evidence of efficient and sustained mammalian-to-mammalian transmission of highly pathogenic avian influenza H5N1.

Whole genome sequencing of the virus did not reveal any mutations in the virus that would lead to enhanced transmissibility of H5N1 in humans, although the data clearly shows mammal-to-mammal transmission, which is concerning as the virus may adapt in mammals.

So far, 11 human cases have been reported in the U.S., with the first dating back to April 2022, each with mild symptoms: four were linked to cattle farms and seven have been linked to poultry farms, including an outbreak of four cases reported in the last few weeks.

Part1

Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 10:20am

The notion that moderate drinking leads to a longer, healthier life goes back decades. As an example, the scientists pointed to the "French paradox"—the idea, popularized in the 1990s, that red wine helps explain why the French enjoy relatively low rates of heart disease, despite a rich, fatty diet. That view of alcohol as an elixir still seems to be "ingrained" in the public imagination, Stockwell noted.

In reality, they said, moderate drinking likely does not extend people's lives—and, in fact, carries some potential health hazards, including increased risks of certain cancers. That's why no major health organization has ever established a risk-free level of alcohol consumption.

"There is simply no completely 'safe' level of drinking," the researchers confirm.

Stockwell, T., et al. Why do only some cohort studies find health benefits from low volume alcohol use? A systematic review and meta-analysis of study characteristics that may bias mortality risk estimates. Journal of Studies on Alcohol and Drugs (2024). DOI: 10.15288/jsad.23-00283. www.jsad.com/doi/10.15288/jsad.23-00283

Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 10:18am

For the analysis,  researchers identified 107 published studies that followed people over time and looked at the relationship between drinking habits and longevity. When the researchers combined all the data, it looked like light to moderate drinkers (that is, those who drank between one drink per week and two per day) had a 14% lower risk of dying during the study period compared with abstainers.

Things changed, however, when the investigators did a deeper dive. There were a handful of "higher quality" studies that included people who were relatively young at the outset (younger than 55, on average) and that made sure former and occasional drinkers were not considered "abstainers." In those studies, moderate drinking was not linked to a longer life.

Instead, it was the "lower quality" studies (older participants, no distinction between former drinkers and lifelong abstainers) that did link moderate drinking to greater longevity.

"If you look at the weakest studies," the researchers said, "that's where you see health benefits."

Part 2

Comment by Dr. Krishna Kumari Challa on July 26, 2024 at 9:52am

Study debunks link between moderate drinking and longer life

Probably everyone has heard the conventional wisdom that a glass of wine a day is good for you—or you've heard some variation of it. The problem is that it's based on flawed scientific research, according to a new report in the Journal of Studies on Alcohol and Drugs.

Over the years, many studies have suggested that moderate drinkers enjoy longer lives with lower risks of heart disease and other chronic ills than abstainers do. That spurred the widespread belief that alcohol, in moderation, can be a health tonic. However, not all studies have painted such a rosy picture—and the new analysis sheds light on why.

In a nutshell, studies linking moderate drinking to health benefits suffer from fundamental design flaws, said lead researcher Tim Stockwell, Ph.D., a scientist with the Canadian Institute for Substance Use Research at the University of Victoria.

The major issue: Those studies have generally focused on older adults and failed to account for people's lifetime drinking habits. So moderate drinkers were compared with "abstainer" and "occasional drinker" groups that included some older adults who had quit or cut down on drinking because they'd developed any number of health conditions.

That makes people who continue to drink look much healthier by comparison, And in this case, the researchers noted, looks are deceiving.

Part 1

Comment by Dr. Krishna Kumari Challa on July 24, 2024 at 11:44am

Bear in mind, however, that an observational study like this can't definitively conclude that microplastics are causing the downstream heart effects; only that there is an association. The study did not consider other risk factors for cardiovascular disease, such as smoking, physical inactivity, and air pollution.
"Although we do not know what other exposures may have contributed to the adverse outcomes among patients in this study, the finding of microplastics and nanoplastics in plaque tissue is itself a breakthrough discovery that raises a series of urgent questions," such as how to reduce exposure, explained pediatrician, public health physician and epidemiologist Philip J. Landrigan, of Boston College, in an accompanying editorial.

Plastic production has exploded in the past two decades, only a fraction of which has been recycled, and yet rates of cardiovascular disease have been falling in some parts of the world, so more research is needed to understand the link between the two.

https://www.nejm.org/doi/10.1056/NEJMoa2309822

Part 3

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Comment by Dr. Krishna Kumari Challa on July 24, 2024 at 11:43am

With microplastics previously found coursing through people's bloodstream, the researchers were reasonably concerned about heart health. Lab-based studies suggest microplastics can trigger inflammation and oxidative stress in heart cells, and impair heart function, alter heart rate, and cause scarring of the heart in animals such as mice.

"Observational data from occupational-exposure studies [also] suggest an increased risk of cardiovascular disease among persons who are exposed to plastics-related pollution, including polyvinyl chloride, than that seen in the general population," Marfella and colleagues write.
In the study, patients with microplastics in their excised plaques were 4.5 times as likely to have experienced a stroke, non-fatal heart attack or died from any cause after 34 months than people who had no detectable microplastics in the plaques that surgeons had removed.

The amount of microplastics, and even smaller particles called nanoplastics, was measured using a technique called pyrolysis–gas chromatography–mass spectrometry, and their presence confirmed using another method, stable isotopes analysis, which can distinguish between the carbon of human tissues and that of plastics made from petrochemicals.

Microplastics were also visible under powerful microscopes: The researchers observed plastic fragments with jagged edges inside immune cells called macrophages, and within the fatty plaques. Examining the tissue samples, the team also found higher levels of inflammatory markers in patients with microplastics in their plaques.
Part 2

Comment by Dr. Krishna Kumari Challa on July 24, 2024 at 11:42am

Plastic Was Found Inside More Than 50% of Plaques From Clogged Arteries

Plastics are now everywhere, with tiny fragments found in several major organs of the human body, including the placenta.
Given how easily the microscopic particles infiltrate our tissues, it's vital that we learn exactly what kinds of risks they could pose to our health.
Researchers have been busy studying the effects of microplastics in mini-replicas of organs, and in mice, to get a sense of how they might impact the human body. However, the concentrations of microplastics used in those studies might not reflect people's real-world exposure, and few studies have been done in humans.

In March, a small study in Italy found shards of microplastics in fatty deposits surgically removed from patients who had an operation to open up their clogged arteries – and reported their health outcomes nearly 3 years later.

Removing fatty plaques from narrowed arteries in a procedure called a carotid endarterectomy reduces the risk of future strokes.

The team behind this recent study, led by Raffaele Marfella, a medical researcher at the University of Campania in Naples, wondered how the risk of stroke – as well as heart attacks and death – compared between patients who had microplastics in their plaques and those who did not.
Following 257 patients for 34 months, the researchers found nearly 60 percent of them had measurable amounts of polyethylene in plaques pulled from their fat-thickened arteries, and 12 percent also had polyvinyl chloride (PVC) in extracted fat deposits.

PVC comes in both rigid and flexible forms, and is used to make water pipes, plastic bottles, flooring, and packaging. Polyethylene is the most commonly produced plastic, used for plastic bags, films, and bottles, too.
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