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Comment by Dr. Krishna Kumari Challa on August 19, 2024 at 9:44am

Study of fasting and ketogenic diet reveals a new vulnerability of pancreatic tumors

Scientists  have discovered a way to get rid of pancreatic cancer in mice by putting them on a high fat, or ketogenic, diet and giving them cancer therapy.

The cancer therapy blocks fat metabolism, which is the cancer's only source of fuel for as long as the mice remain on the ketogenic diet, and the tumors stop growing.

A scientific team made the discovery, which appears August 14 in Nature, while they were trying to figure out how the body manages to subsist on fat while fasting.

The research team first uncovered how a protein known as eukaryotic translation initiation factor (eIF4E) changes the body's metabolism to switch to fat consumption during fasting. The same switch also occurs, thanks to eIF4E, when an animal is on a ketogenic diet.

They found that a new cancer drug called eFT508, currently in clinical trials, blocks eIF4E and the ketogenic pathway, preventing the body from metabolizing fat. When the scientists combined the drug with a ketogenic diet in an animal model of pancreatic cancer, the cancer cells starved.

The scientists first treated pancreatic cancer with a cancer drug called eFT508 that disables eIF4E, intending to block tumor growth. Yet, the pancreatic tumors continued to grow, sustained by other sources of fuel like glucose and carbohydrates. Knowing that pancreatic cancer can thrive on fat, and that eIF4E is more active during fat burning, the scientists first placed the animals on a ketogenic diet, forcing the tumors to consume fats alone, and then put them on the cancer drug. In this context, the drug cut off the cancer cells' only sustenance—and the tumors shrank.

This method is to treat cancer after knowing its vulnerability and attaining success.

Davide Ruggero, Remodeling of the translatome controls diet and its impact on tumorigenesis, Nature (2024). DOI: 10.1038/s41586-024-07781-7. www.nature.com/articles/s41586-024-07781-7

Comment by Dr. Krishna Kumari Challa on August 18, 2024 at 12:29pm

Bacteria Put on an Invisibility Cloak to Cause Asymptomatic Infections 

Biofilms prevent Pseudomonas aeruginosa toxins from being detected by sensory neurons, tricking the body into not looking sick.

When someone catches a lung infection, be it viral or bacterial, they usually show tell-tale symptoms, such as weakness, breathing difficulties, or brain fog. These indicators signal others to keep a safe distance from the contagious individual. But Pseudomonas aeruginosa can cause a range of lung infections, from mild bronchitis to life-threatening pneumonia, that are acutely asymptomatic yet cause inflammation and destruction of tissue.

In chronic infections, these bacteria form a biofilm of extracellular polymer matrix around themselves that shields them from antimicrobials, enzymes, and neutrophils.² Now, in a paper published in Cell, a group of scientists investigated the underlying mechanism and reported that the biofilm hides Pseudomonas bacteria from sensory neurons in mice, preventing signals from reaching the brain and reducing sickness symptoms. These findings provide a deeper understanding of how biofilm-forming bacteria evade the lung-to-brain communication channel, a potentially crucial tactic in persistent infections. 

https://www.cell.com/cell/abstract/S0092-8674(24)00249-6#%20

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 11:23am

Cell death types and their relations to host immune pathways

A new review was published as the cover paper of Aging, titled "Types of cell death and their relations to host immunological pathways."

Various immune pathways in the host, such as TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ, have been identified. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways against viruses, intracellular microorganisms (like bacteria, protozoa, and fungi), and extracellular microorganisms utilize programmed cell death mechanisms to initiate immune responses and effectively eliminate pathogens.

These relationships can help us understand the host defense mechanisms against invading pathogens and provide new insights for developing better therapeutic strategies against infections or autoimmune disorders.

Types of Cell Death and Relations to Host Immunological Pathways | Aging-US

Kuo-Cheng Lu et al, Types of cell death and their relations to host immunological pathways, Aging (2024). DOI: 10.18632/aging.206035

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Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 11:06am

Risk for developing type 1 diabetes doubled with paternal link

Individuals are less likely to have type 1 diabetes if their mother has the condition than if their father is affected, according to a study scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes, being held from Sept. 9 to 13 in Madrid.

Researchers conducted a meta-analysis across five cohorts of individuals with type 1 diabetes (total, 11,475 individuals) to compare the proportion of individuals with affected fathers versus mothers.

The researchers found that almost twice as many individuals had an affected father versus mother (overall odds ratio [OR], 1.79). The proportion of individuals with an affected father was higher both among individuals diagnosed with type 1 diabetes older than 18 years (OR, 1.64) and those 18 years or younger (OR, 1.80). There was an excess of individuals with affected fathers only if parental diagnosis was before offspring birth compared with diagnosis after birth. Age at diagnosis and type 1 diabetes-free survival curves were similar among offspring of affected fathers and mothers.

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:58am

A South Asian person with a BMI of around 22 kg/m²—well within the "normal" weight range—has an equivalent risk of type 2 diabetes as a white European person with a BMI of 30 kg/m² (the conventional threshold for obesity).

The adverse metabolic consequences of weight gain in the South Asian men appeared to be related to the size of fat cells at baseline, and the change in the amount of fat in small fat cells.

The South Asians had larger fat cells before weight gain and appeared to be unable to recruit small fat cells to grow into larger fat cells with weight gain. This suggests that, unlike white Europeans, the fat was more likely to go into other areas such as the liver, which can have adverse metabolic consequences.

 found that when young, lean white European men gained a little weight—about 5 kg—they did not experience any substantial adverse metabolic consequences; but when young, lean South Asian men gained the same amount of weight, they started to exhibit metabolic dysfunction.

"Insulin sensitivity decreased by 38% in South Asians, but only by 7% in white Europeans, indicating that South Asians were not able to buffer against the adverse effects of weight gain in the way that their white European counterparts were able to.

This appears to be related, at least in part, to differences in the size of fat cells between South Asian and white European men, and how they respond to the effects of weight gain.

The South Asian men had more large fat cells, and the very small fat cells that they had were less able to grow in size as they put on weight. Both these factors were related to the adverse metabolic changes with weight gain.

Another interesting observation was that when the European men put on weight, they put on some lean tissue as well as fat tissue, but the South Asian men essentially just put on fat tissue.

This may be important, as increasing lean tissue may help protect against some of the adverse effects of weight gain, as sugar is cleared from the blood in lean tissue, or muscle.

The study's findings reinforce the need for the prevention of weight gain in South Asian men, in order to prevent further risk of type 2 diabetes.

James McLaren et al, Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01101-z

Part 2

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:55am

Weight gain appears to have greater metabolic consequences in South Asian men

Gaining even a small amount of weight may lead to adverse metabolic responses in young South Asian men according to new research.

The study— published in Nature Metabolism—may shed light on why South Asians are at greater risk of developing type 2 diabetes compared with other ethnic groups, and why their risk of diabetes increases more steeply with increasing BMI.

The research—which is part of the GlasVegas (Glasgow visceral and ectopic fat with weight gain in South Asians) study—investigated 14 young normal weight men of South Asian ethnic origin and 21 men of white European ethnicity before and after an overfeeding protocol to gain approximately 5 kg in weight ( please note the small sample size).

The main finding was that this modest weight gain resulted in substantial adverse metabolic responses in the South Asian men. In contrast, the white European men appeared to exhibit a degree of "metabolic buffering capacity," such that the same weight gain led to much smaller metabolic changes. Insulin sensitivity—or how well body tissues respond to insulin—decreased by 38% in the South Asian men, but only by 7% in the white Europeans.

South Asians comprise about a quarter of the world's population and have 3–5 times the prevalence of type 2 diabetes compared to white Europeans. South Asians also develop type 2 diabetes at much lower BMIs (Body Mass Indexes) than white Europeans.

Part 1

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:45am

Uterus transplants are leading to healthy pregnancies

till now, that is.

Uterine transplants are relatively rare and recent—the first was performed in 2011, and to date a little more than 100 transplants have been conducted worldwide.

However, a new study finds that these procedures are often successful, leading to pregnancies and live births in 14 out of the 20 patients assessed.

"A successfully transplanted uterus is capable of functioning at least on par with a native, in situ uterus," concluded a research team who assessed the outcomes.

As the researchers explained, uterus transplants are typically needed by women with what's known as "absolute uterine infertility," a condition affecting about 1 in every 500 women where the organ is either dysfunctional or absent.

In the past, these women would have had to resort to adoption or surrogacy, but 13 years ago doctors first transplanted a donated uterus into a woman with uterine infertility.

Since then, the procedure has gained acceptance.

Just how successful are these transplants?

The Dallas team tracked outcomes for 20 women averaging 30 years of age who opted for uterus transplant at their facility between 2016 and 2019.

Organs came from 18 living donors and 2 deceased donors.

In 14 of the women who underwent uterus transplant, the operation was successful, the study found, and "all 14 recipients gave birth to at least 1 live-born infant."

Complications were common and occurred in 50% of these pregnancies, with gestational high blood pressure and preterm labor being two of the most common. However, "congenital abnormalities and developmental delays have not occurred to date in [any of] the live-born children," the researchers noted. Overall, uterus transplant was "technically feasible and was associated with a high live birth rate," the team concluded.

Giuliano Testa et al, Uterus Transplant in Women With Absolute Uterine-Factor Infertility, JAMA (2024). DOI: 10.1001/jama.2024.11679

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Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:04am

Heatstroke happens when a person is exposed to high temperatures... and their body is not able to regulate that temperature. If you go out in the sun at 42C or exercise at those temperatures, your body is unable -- no matter how much it sweats, which is the main mechanism for regulating heat -- to lower and maintain its temperature at 37C.

When your body is no longer at 37C... your organs stop working properly, including your brain. Then hyperthermia sets in and the person can die.

How heat waves affects culture: (heat culture)

In 2003, Europe suffered a brutal heat wave and 70,000 people died in 15 days. People were not prepared, and there were no prevention plans, which meant it had a brutal impact on mortality. Now nobody doubts that heat kills.
But people adapt. Between 1983 to 2003, for every degree above the temperature classed as a heat wave, the mortality in Spain increased by 14 percent. But after 2003, it barely increased by three percent.

In a city like Madrid, you never used to see older people wearing shorts but nowadays they all wear them -- you see them going out for a walk wearing a hat and with a bottle of water.

In places where they are used to having heat waves, there are now much more air conditioning units and secondly, homes are much more adapted to cope with this heat.

People don't go out from 3:00 pm, that's why the siesta exists in Spain. And in the southern Andalusia region, the villages are painted white and the streets are wide so the wind can freely circulate.

Source: AFP and other news agencies

Part 2

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Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:01am

During a heat wave temperatures are not the only threat!

Isn't heat what kills during a heat wave?

Experts say, more things can kill you during a heat wave!

The impact of heat on health is far more than just temperature... its effect can be felt across income levels, age groups, socio-economic conditions, health care, and different cultural approaches to heat.

If you divide a country into several regions, 40 degrees Celsius (104 Fahrenheit) is not even classed as a heat wave in some areas, whereas in others, the temperature which defines a heat wave can be just 26 degrees.

When there is a heat wave, only 3.0 percent of mortality is due to heat stroke. Heat kills by aggravating other illnesses.

In the first heat wave (of the year) much more people are likely to be susceptible (to death) than the second because it claims the frailest, leaving fewer susceptible people in the second and fewer still in the third... That's why the first heat wave always has a greater impact on mortality. This is what epidemiology experts call the 'harvest effect'.

It's clear that the impact of heat is much greater in poorer neighborhoods.

It is not the same thing to experience a heat wave in a room with three people and one window and no air conditioning or fan, than going through the same thing in a villa with a swimming pool.

It's not even a question of having air conditioning or not, but about being able to turn it on. During a heat wave, the price of electricity in some countries can  skyrocket making it unaffordable for many!

Part 1

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 9:33am

Sounds of soil heartbeat: How underground acoustics can amplify soil health

Barely audible to human ears, healthy soils produce a cacophony of sounds in many forms—a bit like an underground rave concert of bubble pops and clicks.

Special recordings made by Flinders University ecologists in Australia show that this chaotic mixture of soundscapes can be a measure of the diversity of tiny living animals in the soil, which create sounds as they move and interact with their environment.

 Acoustic complexity and diversity of  samples are associated with soil invertebrate abundance—from earthworms, beetles to ants and spiders—and it seems to be a clear reflection of soil health.

All living organisms produce sounds, and these preliminary results suggest different soil organisms make different sound profiles depending on their activity, shape, appendages and size. Understanding it makes a better prediction of soil health.

This technology holds promise in addressing the global need for more effective soil biodiversity monitoring methods to protect our planet's most diverse ecosystems.

Sounds of the underground reflect soil biodiversity dynamics across a grassy woodland restoration chronosequence, Journal of Applied Ecology (2024). DOI: 10.1111/1365-2664.14738

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