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Comment by Dr. Krishna Kumari Challa on July 4, 2024 at 9:49am

Fighting COVID-19 with a cancer drug: A new approach to preventing irreversible organ damage in infectious diseases

Twelve years ago, cancer researchers identified a molecule that helps cancer cells survive by shuttling damaging inflammatory cells into tumor tissue. In new research, they show that the same molecule does the same thing in lung tissue infected with COVID-19—and that the molecule can be suppressed with a repurposed cancer drug.

The work, published in Science Translational Medicine, represents a new approach to preventing irreversible organ damage in infectious diseases like COVID-19 and methicillin-resistant Staphylococcus aureus (MRSA).

The two key players in this scenario are inflammatory cells called myeloid cells, and an enzyme called PI3K gamma (phosphatidylinositol 3,4,5-kinase gamma). Myeloid cells belong to our innate immune system—the immunity we're born with before we're exposed to pathogens in the environment—and work very quickly to kill deadly agents like SARS-CoV-2, the virus that causes COVID-19.

This work shows that drugs that can prevent the recruitment of damaging myeloid cells into tissues that are infected with severe agents like COVID-19 or MRSA have a significant benefit in preserving tissue function if given early enough in an infection.

Most other COVID-19 drugs target the virus, either preventing infection in the first place or preventing the virus from making more of itself after infection. The current approach targets the host, keeping the immune system from overreacting or fibers building up in the lungs.

Myeloid cells protect us, but they can also do a lot of damage. 

If you have a little infection, myeloid cells come in, kill bacteria, release alerts that recruit even more potent killer immune cells, and produce substances that can heal the damage. But if you get an infection that's too strong, you get overproduction of these alert signals, and the substances they release to kill these infective agents can also kill yourself. That's what happens in COVID-19.

Part 1

Comment by Dr. Krishna Kumari Challa on July 4, 2024 at 9:41am

Scientists discover PVP-037, a potent vaccine adjuvant

Many vaccines are only partially effective, have waning efficacy, or do not work well in the very young or the very old. For several years researchers have tried improving vaccines by adding compounds known as adjuvants to boost vaccine recipients' immune responses.

Now they've identified a new and promising adjuvant of their own, dubbed PVP-037. The finding is published in Science Advances.

In principle, this compound can be added to any vaccine to enhance its action.

 Adjuvants are like rocket fuel for the immune system. PVP-037 is one of the most active adjuvants scientists 've discovered, and they think it induces a greater, more durable, and broader immune response to vaccines.

The researchers began by screening more than 200,000 small molecules from a Harvard Medical School library in human immune cells—specifically, in primary peripheral blood mononuclear cells, obtained from donors and cultured in their own plasma using a method developed within the Precision Vaccines Program. This yielded about 25 confirmed hits, with PVP-037 being the most active.

PVP-037 belongs to a family of molecules called imidazopyrimidines, which the study found to be active immunomodulators. PVP-037 and its analogs target the innate immune system, stimulating the pattern-recognition receptors TLR7 and TLR8 on antigen-presenting cells such as monocytes and dendritic cells.

An optimized version of PVP-037 demonstrated broad innate immune activation in the donor immune cells, inducing NF-κB and production of TNF and other cytokines, signaling molecules that rally a wider immune response. Notably, PVP-037 did not provoke such a response in cultured cell lines. In live mice, it enhanced antibody responses against influenza and SARS-CoV-2 vaccine proteins.

In addition to inducing robust immune activity, the compound is stable, easy to work with, and lends itself to chemical optimization for medical use. It can be formulated in most standardly-used drug delivery systems, such as oil-in-water emulsions.

 Dheeraj Soni et al, From Hit to Vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation, Science Advances (2024). DOI: 10.1126/sciadv.adg3747. www.science.org/doi/10.1126/sciadv.adg3747

Comment by Dr. Krishna Kumari Challa on July 4, 2024 at 9:27am

While some factors that favor scratching—such as the cat's personality or the presence of children—cannot be changed, others can, the researchers said. Placing scratch posts in areas the cat frequently passes or near to their preferred resting spot, or the use of pheromones, for example, can lessen cats' scratching on furniture.

Providing safe hiding places, elevated observation spots, and ample play opportunities can also help alleviate stress and engage the cat in more constructive activities.

The key is to establish multiple short play sessions that mimic successful hunting scenarios. These play sessions are more likely to sustain cats' interest and reduce stress, which ultimately can reduce excessive scratching on furniture. They can also foster the bond between cats and their caretakers, the researchers say.

Understanding the underlying emotional motivations of scratching behavior, such as frustration, which seem to be linked to personality traits and environmental factors, allows caregivers to address these issues directly.

Evaluating Undesired Scratching in Domestic Cats: A Multifactorial Approach to Understand Risk Factors, Frontiers in Veterinary Science (2024). DOI: 10.3389/fvets.2024.1403068

Part 2

Comment by Dr. Krishna Kumari Challa on July 4, 2024 at 9:25am

Strategies that could stop cats from scratching your furniture, according to science

Many cat owners are familiar with torn cushions, carpets, and couches. The feline instinct to scratch is innate, but is often perceived as a behavioral problem by cat owners, and sometimes leads to interventions that are not cat-friendly.

Now, an international team of researchers has investigated which factors influence undesired scratching behavior in domestic cats. The team has published its findings in Frontiers in Veterinary Science.

Scientists found that  certain factors—such as the presence of children at home, personality traits of cats, and their activity levels—significantly impact the extent of scratching behaviour.

The researchers' results showed that there are several factors that influence cats' scratching behaviour. They saw a clear link between certain environmental and behavioural factors and increased scratching behaviour in cats.

Specifically, the presence of children in the home as well as high levels of play and nocturnal activity significantly contribute to increased scratching. Cats described as aggressive or disruptive also exhibited higher levels of scratching.

Stress, the researchers said, was found to be a leading reason for unwanted scratching. For example, the presence of children, particularly while they are small, might amplify stress and be one of several causes that can make felines stress-scratch. The link between increased scratching and children in the home, however, is not fully understood and further study is needed. Another factor that could also be connected to stress is playfulness. When cats play for a long time, their stress levels can rise because of the uninterrupted stimulation.

Part 1

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 1:11pm

In the past, some other observational studies have also linked artificial light at night to insulin resistance, but these experiments did not measure indoor, artificial light sources nearly as closely or for as long.

Emerging evidence in animals and humans suggests exposure to artificial light can disrupt circadian rhythms, leading to reduced glucose tolerance, altered insulin secretion, and weight gain – all of which are tied to an increased risk of metabolic disorders like type 2 diabetes.

One major limitation of the study is that researchers were not able to take into account meal times, which can have an impact on both circadian rhythms and glucose tolerance. Furthermore, some socioeconomic factors, like a person's housing situation, were accounted for at a regional, not an individual level, and only older adults were considered.

There's also the fact that individual bodies respond very differently to light, with some studies suggesting the intensity of light needed to suppress the production of melatonin, which helps regulate our circadian rhythm, can range from 6 to 350 lux.
Nevertheless, previous experiments suggest that when melatonin is disrupted and the circadian rhythm is thrown out of whack, it can lead to the pancreas secreting less insulin. This could be a contributing factor to the development of diabetes.

Far more rigorous studies are needed before scientists can truly understand how light at night impacts the circadian rhythm and what that may do, in turn, to the health of the body's metabolism.

Some studies suggest that even a weekend of camping without artificial light can help reset a person's circadian rhythm. Perhaps that's just what the doctor should order.

https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00110-8/fulltext

Part 2

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Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 1:10pm

Bright Light at Night May Raise Type 2 Diabetes Risk, Study Suggests

The glow of a lightbulb or smartphone at night can mess with the body's circadian rhythm. Now, a new study suggests that exposure to artificial light after midnight may raise the risk of developing type 2 diabetes. The research was conducted among nearly 85,000 people, between the ages of 40 and 69, who wore devices on their wrists, day and night for one week, to track their exposure to different levels of light.

As part of the UK Biobank experiment, the health of the cohort was tracked for as long as nine years. Those volunteers who later went on to develop type 2 diabetes were more likely to have been exposed to light between 12:30 am and 6:00 am, during the week-long study period.

The results do not prove cause and effect, but they do reveal a dose-dependent relationship between brighter light in the middle of the night and the risk of a metabolic disorder, which bolsters the association.

Those participants in the top 10 percent for light exposure at night had as much as a 67 percent higher risk of developing type 2 diabetes than those in the bottom 50th percentile.

Research suggests that exposure to artificial light at night, whether it be yellow light from your reading lamp or blue light from your smartphone or TV, can make it harder to fall asleep. But even when researchers accounted for sleep patterns and duration in the current study, the results held, which suggests another mechanism is at play.
Other possible contributing factors, like a person's sex, their genetic risk for diabetes, their diet, physical activity, daylight exposure, smoking, or alcohol use, also had no impact on the results.

Advising people to avoid night light is a simple and cost-effective recommendation that may ease the global health burden of type 2 diabetes," conclude the authors of the study.
Part 1

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 1:06pm

Longest Cyclone on Record Crossed The Entire Southern Indian Ocean in 2023

Cyclone Freddy, which crossed the entire southern Indian Ocean before wreaking devastation on southeastern Africa last year, was the longest-lasting tropical cyclone ever recorded at 36 days, the UN confirmed Tuesday.

A panel of experts has been poring over the data surrounding the storm since its remarkable journey in February and March last year.

The United Nations' weather and climate agency concluded it had indeed broken the previous record.

The extreme weather evaluation committee "recognised Tropical Cyclone Freddy's duration of 36.0 days at tropical storm status or higher as the new world record for the longest tropical cyclone duration", the World Meteorological Organization (WMO) said in a statement.

• Freddy crossed the Indian Ocean basin in February-March 2023.
• Madagascar and southeastern Africa bore brunt of human and economic losses.
• Freddy was 36 days at tropical storm status or higher, beating record of John (1994)
• Freddy was 2nd longest in terms of distance travelled
• Monitoring of extremes increases understanding of weather and climate impacts.

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Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 11:13am

In tibia injuries, the flow of the hemolymph was less impeded, meaning bacteria could enter the body faster. While in femur injuries the speed of the blood circulation in the leg was slowed down.

You may expect, then, if tibia damage results in faster infections, amputating the full leg would be most appropriate, but the opposite is observed. It turns out the speed at which the ants can amputate a leg makes a difference.

An ant-assisted amputation takes at least 40 minutes to complete. Experimental testing demonstrated that with tibia injuries, if the leg was not immediately removed post-infection, the ant would not survive.

"Thus, because they are unable to cut the leg sufficiently quickly to prevent the spread of harmful bacteria, ants try to limit the probability of lethal infection by spending more time cleaning the tibia wound.

The fact that the ants are able to diagnose a wound, see if it's infected or sterile, and treat it accordingly over long periods of time by other individuals—the only medical system that can rival that would be the human one.

And they can do it without studying medicine and learning surgery! It's really all innate behaviour!

Ant behaviors change based on the age of an individual, but there is very little evidence of any learning.

"When you look at the videos where you have the ant presenting the injured leg and letting the other one bite off completely voluntarily, and then present the newly made wound so another one can finish cleaning process—this level of innate cooperation  is quite striking", say the researchers.

Erik Frank et al, Wound-dependent leg amputations to combat infections in an ant society, Current Biology (2024). DOI: 10.1016/j.cub.2024.06.021. www.cell.com/current-biology/f … 0960-9822(24)00805-4

Part 2

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 11:08am

Doctor ants: Ants too perform amputations to save injured nestmates!

Saving lives through surgery is no longer exclusive to humans. In a study published July 2 in the journal Current Biology, scientists detail how Florida carpenter ants, a common, brown species native to its namesake, selectively treat the wounded limbs of fellow nestmates—either by wound cleaning or amputation.

When experimentally testing the effectiveness of these "treatments," not only did they aid in recovery, but the research team found the ants' choice of care catered to the type of injury presented to them.

The researchers found that this mechanical care involves one of two routes. The ants would either perform wound cleaning with just their mouthparts or perform a cleaning followed by the full amputation of the leg. To select which route they take, the ants appear to assess the type of injury to make informed adjustments on how best to treat.

In this study, two types of leg injuries were analyzed, lacerations on the femur and those on the ankle-like tibia. All femur injuries were accompanied by initial cleaning of the cut by a nestmate, followed by a nestmate chewing off the leg entirely. In contrast, tibia injuries only received the mouth cleaning. In both cases, intervention resulted in ants with experimentally infected wounds having a much greater survival rate.

Femur injuries, where they always amputated the leg, had a success rate around 90% or 95%. And for the tibia, where they did not amputate, it still achieved about the survival rate of 75%.

Part1

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 11:02am

Treatment with a mixture of antimicrobial peptides found to impede antibiotic resistance

A common infection-causing bacteria was much less likely to evolve antibiotic resistance when treated with a mixture of antimicrobial peptides rather than a single peptide, making these mixtures a viable strategy for developing new antibiotic treatments. Researchers report these findings in a study published July 2 in PLOS Biology.

Antibiotic-resistant bacteria have become a major threat to public health. The World Health Organization estimates that 1.27 million people died directly from drug-resistant strains in 2019 and these strains contributed to 4.95 million deaths.
While bacteria naturally evolve resistance to antibiotics, misuse and overuse of these drugs has accelerated the problem, rendering many antibiotics ineffective. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides, which are chains of amino acids that function as broad-spectrum antimicrobial compounds and are key components of the innate immune system in animals, fungi and plants.

In the new study, researchers investigated whether antimicrobial peptide mixtures synthesized in the lab could reduce the risk of the pathogen Pseudomonas aeruginosa from evolving antimicrobial resistance, compared to exposure to a single antimicrobial peptide.

They found that using antimicrobial peptide mixtures carried a much lower risk of the bacteria developing resistance. The mixtures also helped prevent the bacteria from developing cross-resistance to other antimicrobial drugs, while maintaining—or even improving—drug sensitivity.

Overall, the findings suggest that the use of antimicrobial peptide mixtures is a strategy worth pursuing in the search for new, longer-lasting treatments for bacteria.

The researchers suspect that using a cocktail of multiple antimicrobial peptides creates a larger set of challenges for bacteria to overcome, which can potentially delay the evolution of resistance, compared to traditional antibiotics. Furthermore, these cocktails can be synthesized affordably, and previous studies have shown them to be non-toxic in mice.

Bernardo Antunes et al, The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures, PLoS Biology (2024). DOI: 10.1371/journal.pbio.3002692

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