In a significant scientific breakthrough, researchers have successfully reversed memory and learning deficits in a mouse model of Down syndrome (DS) by targeting the body’s response to cellular stress. The findings, published in Science on November 14, 2019, offer new hope for improving cognitive function in individuals with DS — the most common genetic cause of intellectual disability.

What Is The Research About?

A team led by researchers at UC San Francisco and Baylor College of Medicine found that in the brains of DS-model mice, learning impairments were linked to disrupted protein production in the hippocampus — a key brain region responsible for learning and memory. But by using specific drugs that modulate the body’s stress response, they were able to restore protein synthesis and significantly improve cognitive performance.

Traditionally, DS research has focused on how an extra copy of chromosome 21 affects gene expression. However, this study took a different route. The scientists zeroed in on "proteostasis," the process by which cells maintain a healthy balance of protein production and regulation. They discovered that in DS mice, the integrated stress response (ISR) — a natural protective mechanism that reduces protein production during cellular stress — was unusually active in hippocampal cells. This reduction in protein synthesis, while generally protective, was impairing the brain’s ability to form long-term memories.

“The cell is always checking in on its own health,” said Dr. Peter Walter, professor of biochemistry at UCSF and co-senior author of the study. “When something’s off, like an extra chromosome, it can trigger a stress response that shuts down protein production — and that’s detrimental for cognitive function.”

Using three different methods, including a drug called ISRIB, the researchers suppressed this stress response and observed dramatic improvements in learning and memory among DS mice. The animals performed significantly better in two behavioural tests and showed enhanced synaptic activity in the brain, suggesting real physiological change.

To strengthen their findings, the team examined brain tissue from people with DS. They found that the ISR was similarly activated in those with the extra chromosome — reinforcing the link between the stress response and DS symptoms.

Interestingly, they identified a specific enzyme, PKR, as the main culprit behind this stress activation. By blocking PKR, either genetically or pharmacologically, the team was able to prevent the decline in protein production and restore cognitive function in mice.

Although these results are preliminary and require further investigation in human models, the study marks a promising first step toward developing treatments for DS. “We started with a situation that looked hopeless,” Walter said. “Nobody thought anything could be done. But we may have struck gold.”

The study was supported by the NIH and the Howard Hughes Medical Institute. While some of the researchers have industry ties related to the drug ISRIB, they report no additional conflicts of interest.

This research signals a paradigm shift — from solely genetic approaches to exploring how cellular stress management could hold the key to treating cognitive disorders like Down syndrome.

Utah has become the first state to ban fluoride in public drinking water. This has been opposed by dentists and national health organizations who had warned that this move could lead to more medical problems, dental problems and could also disproportionately affect low-income communities.

Spencer Cox, Republican Gov. signed the legislation on Thursday that barred cities and communities from deciding whether to add the mineral to their water systems.

What Does Fluoride Do?

Fluoride strengthens teeth and reduces cavities by replacing minerals lost during normal wear and tea. The US Centers for Disease Control and Prevention (CDC) notes that they are naturally occurring compounds and when used in low levels, it can help prevent dental cavities.

The CDC notes that fluoride repairs and prevents damage to teeth caused by bacteria in the mouth. Bacteria in the mouth produce acid when a person eats or drinks. The acid then dissolves minerals in a tooth’s surface and makes the tooth weaker and open to cavities.

Fluoride also replaces the minerals lost from a tooth due to acid breakdown. Some fluoride can replace minerals in the tooth surface, which makes the outer enamel layer harder to dissolve. Fluoride also could reduce the amount of acid that cavity-causing bacteria produce, as well as making it harder for these bacteria to stick to the teeth.

CDC notes that teeth requires consistent, low levels of fluoride in the mouth, in the saliva and on tooth surfaces. Fluoride can also be incorporated into developing dental enamel before a tooth erupts into the mouth, enhancing the tooth’s resistance to acid breakdown and preventing cavities later in life.

As per the US Food and Drug Administration, the fluoride levels in the water is regulated and are safe and effective when used as directed. However, despite this, Utah has banned its use.

ALSO READ: Utah To Become The First State To Ban Fluoride In Drinking Water

What Happened In Utah, Why The Ban?

Utah lawmakers pushed for fluoride ban stating that it was too expensive. As per Cox, he grew up and raised his own children in a community without fluoridated water. The ban will be effective from May 7. This move has been promoted by the US Health Secretary Robert F Kennedy Jr, who expressed skepticism about water fluoridation.

As per the American Dental Association, this is a move worth criticizing. They said that the ban showed “wanton disregard for the oral health and well-being of their constituents.” The group said that cavities are the most common chronic childhood disease.

“As a father and a dentist, it is disheartening to see that a proven, public health policy, which exists for the greater good of an entire community’s oral health, has been dismantled based on distorted pseudoscience,” said the association’s president, Denver dentist Brett Kessler, as reported by the CNN.

In elsewhere too, including Ohio, South Carolina, and Florida, similar proposals have been made to restrict local governments or water system operators from adding fluoride to water. Whereas such proposed restrictions have been rejected in New Hampshire, Tennessee and North Dakota.

Kristen Fischer, an American woman living in India who works in web development sparked a new debate. This is between the healthcare systems of two big countries, the United States and India. The woman took to her Instagram @kristenfischer3 with 143K followers and shared a video titled 'Healthcare in India and the USA'. The video garnered over 51.6K views and with many more interactions.

Her video starts with comparing the wait time of a GP. In the US, the average wait time, she mentions is 2 to 4 weeks, whereas in India, it is a walk-in or same-day appointment. She mentions in the caption that in India, healthcare is more accessible and there is an easy to access doctors, medicines, and quality care. She also talks about how easily medicines are accessible in India and over-the-counter medicines could be picked without a prescription.

What Really Are The Big Differences In Healthcare Between The Two Countries?

Wait Time

One of the biggest differences that Kristen highlights is of the wait time for medical consultation. In the US, scheduling an appointment with a GP can lead to even a month of wait time. It can further extend to three months. For elective surgeries or planned and non-emergency surgeries, the wait time could be for as long as six months.

Whereas, if one looks at India, the access is faster. There are appointments, which can be booked within a few days, furthermore, walk-in services are also available in most cases. Elective surgeries are usually performed within one to four weeks in India.

Cost Of Medical Consultation

Healthcare in the US is costly. Kristen writes in her caption: "In America, we hardly went to the doctor because it was just so expensive and you had to wait weeks to get in. But I have peace of mind in India knowing that I can go to a doctor any day even for something small because it is affordable.”

It is true, on an average, for a visit to a doctor in America could cost anyone between $150 to $600, which is around 12k to 50k INR. Whereas in India, the consultation cost is between $7 to $17, which could be around 500 to 1,500 INR. The affordability is what ensures that people do not hesitate to reach out to doctors or healthcare professionals when in need.

Hospitalization Expense

Not just appointments with doctors, but in the US, the hospitalization costs are also skyrocketing. For one-night hospital stay, the cost is around $3,000, which is somewhere around 2.5 lakhs INR. This makes hospitalisation a financial burden, even for those under insurance.

In India, one day stay at a hospital is around $80, which could be around 6,000 INR.

Medical Insurance

There are also arguments that the US healthcare system is manageable as it is covered in medical insurance. However, the reality may be different, because the medical insurance too is not quite affordable. The average cost of medical insurance in the US could range somewhere between $800 and $1,500, which could be around 64k to 1.2 lakh INR per month. There are also high premiums.

Whereas in India, the medical insurance is far for affordable, ranging between $23 and $58, around 2k to 5k INR.

Quality of healthcare services

While the US is home to the best medical facilities, world-class research and top-tier doctors, it does come at a very high price. However, the Indian healthcare system is a mix of both, private and public hospitals, where experts come from all walks of life. In fact, at this time, many private hospitals too have been technologically equipped and have internationally accredited doctors.

The biggest point to be noted, as Kristen also mentions, is the affordability the Indian healthcare system offers and the understanding of treating medical cases with urgency.

A new formula which is made with citrus oil could help cancer patients to relieve their dry mouth. Dry mouth is a common and one of the painful side effect of radiation treatment.

Dry mouth is called xerostomia, which is a common side effect of cancer treatment, especially radiation therapy to the head and neck. In fact, some chemotherapy trugs too can damage the salivary glands and reduce saliva production.

Researchers from the University of South Australia and Stanford University created this formula by mixing limonene, a citrus oil which is found in lemons, limes, and oranges. The oil has healthy fats known as lipids. The research has been published in the International Journal of Pharmaceuticals.

When mixed, the oil gets easily absorbed in the body and reduces the common side effects like dry mouth and stomach pain.

What Do The Trials Say?

In the lab tests, the new mix was 180 times more soluble than pure limonene. Even in the earlier trials, it increased absorption in the body by more than 4000%.

Dry mouth or xerostomia, affects up to 70% of patients who get radiation for head and neck. It can also make speaking and swallowing very difficult and can lower quality of life.

“Cancer patients undergoing radiotherapy and other medical treatments regularly experience dry mouth, which not only prevents them from comfortably swallowing, but can also have other negative and potentially life-threatening outcomes,” said co-researcher Leah Wright, a professor of chemical engineering at The University of Adelaide in Australia.

More About Limonene: It has been long known to help with saliva production. However, high doses were needed for it to work well. The doses though did cause side effects like indigestion and "citrus burps". Clive Prestidge, lead author, and head of Nanostructure and Drug Delivery research group at the University of South Australia says that the new formula solves that very problem.

“The therapeutic benefits of limonene are well known. It’s used as an anti-inflammatory, antioxidant and mood-enhancing agent, and can also improve digestion and gut function. But despite its widespread use, its volatility and poor solubility have limited its development as an oral therapy,” Prestidge said.

Wright also added that even though limonene can be ingested directly, it cannot be tolerated, especially for people who have dry mouth. It has poor absorption, which prevents it from effectively reaching the salivary glands.

“This inventive and highly impactful limonene-lipid formulation could provide a simple, effective oral solution for dry mouth, offering cancer patients long-lasting relief and comfort, improved oral health, and a higher quality of life during a difficult time,” Wright said.

Is Dry Mouth Common?

It affects around 1 in 5 people and the risk of it increases with age. One of the most common symptoms is feeling that your tongue is sticking to the roof of your mouth.

Other common symptoms include:

• Bad breathe
• Constant sore throat
• Difficulty eating, speaking or swallowing
• Dry feeling in your nose
• Hoarseness
• Increased thirst
• Lip, tongue and mouth sores or pain
• Taste disorders
• Trouble wearing dentures
• Tooth decay
• Dry eyes and skin
• Skin rash
• Joint pain