
Click the link below the picture
.
.
Ūla Šveikauskaitė
.
.
Click the link below for the complete article:
.
__________________________________________
Assorted human interest posts.
November 10, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.
.
Ūla Šveikauskaitė
.
.
Click the link below for the complete article:
.
__________________________________________
November 10, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment
Click the link below the picture
.
There is a meatball to fit every mood. There are the classics like Italian-style spaghetti and meatballs and slow cooker grape jelly meatballs, and new recipes like coq au vin meatballs for dinner-party vibes on a weeknight schedule. The seasonings and sauces can change, but the thing that makes a great meatball dinner stays the same? Meatballs that are tender, juicy, and full of flavor. For that, every meatball begins with the same three ingredients: ground meat, egg, and a filler. Breadcrumbs were my go-to filler for years, but I’ve recently changed course to a new, more flavorful ingredient. Buttery Ritz crackers are the best thing to happen to my meatballs, and they can do wonders for yours too.
Why You Should Add Ritz Crackers (Not Breadcrumbs) to Meatballs
I have a love-hate relationship with store-bought breadcrumbs. The canisters of crumbs are more convenient than making fresh breadcrumbs, and they last practically forever in the pantry, but that’s where the benefits end. These breadcrumbs fail to add flavor to recipes. In meatballs, the fine crumbs are often mixed with milk into a panade, and act as a binder to hold the mixture together as it cooks. But sometimes breadcrumbs leave behind a gluey texture or, worse, claylike lumps within a meatball.
I’ve tried panko breadcrumbs, but they aren’t the best choice for meatballs either. Panko breadcrumbs’ raison d’être is to add a light and crispy texture to whatever they touch, so it would be a waste to mash this ingredient into a meatball mixture.
Thrifty cooks have been coming up with breadcrumb alternatives for their meatball and meatloaf recipes for years. Maybe they ran out of store-bought crumbs or didn’t have time to make them from scratch. It’s possible that they were stretching their budgets by using what they had on hand, like a bright red box of buttery crackers. Crushed Ritz crackers are the best binder for meatballs that I’ve tried. Ritz crackers are crisp, buttery, and salty. They add rich, seasoned flavor to the meat mixture, and are easy to crush into crumbs with your hands or a rolling pin.
I’ve started using crushed Ritz crackers in every meatball recipe I make, and my family noticed the difference. They loved how flavorful and juicy the meatballs were, even when they were digging into leftovers the second day! If your recipe still calls for breadcrumbs, remember to use crushed Ritz crackers instead. It’s so easy because the finely ground cracker crumbs can be substituted one-for-one with breadcrumbs. The next time you’re faced with meatballs on the menu, reach into your snack cabinet for an instant upgrade.
.
Credit: Photo: Ryan Liebe; Food Styling: Spencer Richards
.
.
Click the link below for the complete article:
.
__________________________________________
November 10, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.
In December 2023, a Chinese executive who goes by Alice Huang met with Nvidia’s chief executive, Jensen Huang, and a small group of colleagues at an Italian restaurant in Singapore.
In a photo of the previously unreported meeting, which was confirmed by The New York Times, Ms. Huang smiled as she posed next to Mr. Huang, who was in his trademark black leather jacket. He held a glass of red wine.
For Ms. Huang, there was reason to celebrate. Backed by wealthy investors in Shanghai, she had just restructured a company that would soon buy billions of dollars in Nvidia artificial intelligence chips. The U.S. government had barred Chinese companies from buying the advanced chips, but Ms. Huang had sidestepped this prohibition by creating a firm, Megaspeed, through a Singaporean shell company.
Her close relationship with Nvidia’s leader also appeared to smooth the way. Four days after the ownership change Megaspeed was named a Nvidia cloud partner, giving it access to the coveted components.
Their relationship is now at the center of a global geopolitical competition between China and the U.S. government to dominate A.I. It has also shaken and captivated the tech industry on both sides of the Pacific, surfacing often invisible details of the fierce technological race, like spy craft and the human vulnerabilities of A.I. kingmakers like Mr. Huang.
The meeting in Singapore was a sign of how Ms. Huang’s relationship with Mr. Huang goes back further than previously known. It also speaks to the close social and business ties that grew during years of tech collaboration between China and the United States, and how they have persisted despite the icy geopolitical divide of the past decade.
The Times was the first to report Mr. Huang’s dealings with Megaspeed and Ms. Huang last year. Last month, The Times reported that U.S. officials had concluded she was a Chinese intelligence asset who had developed a close relationship with the Nvidia leader, and that President Trump had taken no action when briefed on the situation last year. Last week, The Times reported that Ms. Huang had been recruited to spy by China’s Ministry of State Security. On Sunday, Mr. Huang, 63, acknowledged that he had an affair with her, and Nvidia said it was conducting an internal investigation.
Many details of the relationship between Mr. Huang and Ms. Huang, including when they met and when she may have been recruited by Chinese intelligence, are not known. But Ms. Huang’s work with Megaspeed put her in the middle of a sprawling effort to accumulate A.I. chips across Southeast Asia and provide access to the technology to China’s companies.
Photos from Ms. Huang’s social media, which were verified by The Times, show that she and Mr. Huang met across the globe over the past three years, including in Shanghai; at Nvidia’s Silicon Valley headquarters; at a golf resort south of San Jose, Calif., and in Taiwan.
After the 2023 meeting in Singapore, Ms. Huang, whose Chinese name is Huang Le, used her experience and connections in the world of Shanghai finance to work her way into tech circles. She turned Megaspeed into a destination for Nvidia technology, working with a longtime business partner who was often introduced as her husband.
The success attracted the attention of authorities. By 2024, the United States had dispatched a Commerce Department official to check on Ms. Huang’s company. She was monitored by Taiwan’s government during her visits to the island, including when she appeared publicly with Mr. Huang. For part of 2025, she was not allowed to leave Singapore because of an investigation.
Behind Megaspeed was a network of wealthy tech investors in China with links to domestic data centers, the government and the defense industry. Between 2024 and 2026, the firm bought billions of dollars of Nvidia’s advanced A.I. technology, bringing Ms. Huang further into Mr. Huang’s orbit.
Details about Ms. Huang, much of which have not been previously reported, are based on a Times analysis of 15 years of corporate documents, as well as interviews with more than half a dozen people and government officials familiar with her and her business.
Ms. Huang did not respond to a request for comment. Nvidia and Megaspeed declined to comment. China has denied the espionage claims.
A Life in Finance
For many years, Ms. Huang’s life was rooted in the high-flying world of Shanghai finance. She mingled easily with tech executives from China and the United States alike, according to people who have met her.
In China, Ms. Huang is closely linked to a business partner named Kang Wei. Mr. Kang, a 51-year-old fund manager, has been introduced as Ms. Huang’s husband to Chinese investors and Megaspeed employees, according to people familiar with the matter. The Times could not verify whether the two are married.
Mr. Kang rose to prominence at a young age, earning a reputation as a savvy stock market strategist in the 2000s. Chinese financial media treated him as a sort of boy wonder. By the 2010s, he had moved into private equity, including investing in online gaming firms.
China’s securities regulator has fined Mr. Kang at least twice for failing to disclose his stakes in listed companies. He has also struggled with fellow investors for corporate control, according to regulatory filings. Mr. Kang has bragged about Ms. Huang’s connections to Nvidia’s Mr. Huang and used those ties to raise money for their businesses, according to one of the people.
Mr. Kang did not respond to a request for comment.
Ms. Huang’s career mirrored Mr. Kang’s focus on finance. According to her online résumé, she spent four years as a television reporter before working at HSBC’s private bank and CITIC Securities, a Chinese state-backed investment bank.
Occasionally, she appeared with Mr. Kang. In an August 2023 photo, the two visited a state-backed, auto-tech company in the eastern city of Nanjing.
The earliest corporate records bearing Ms. Huang’s name trace back to a small “sports and leisure club” company registered in 2010 inside Beihu No. 9, a private golf club in Beijing that drew officials and featured themed saunas, steam rooms and a buffet of foie gras, hairy crabs and Häagen-Dazs.
Over the next few years, Ms. Huang branched out, investing in a Chinese medical equipment maker that would list its shares in Hong Kong. She acquired her stake through an offshore company, corporate records show.
By 2020, Ms. Huang and Mr. Kang were known in some of Shanghai’s investment circles. They operated an interconnected web of companies to carry out corporate takeovers and invest in companies. That spring, their network landed a major project, helping build and operate an A.I. computing center in Shanghai for the internet giant Tencent.
That set the stage for Ms. Huang’s next effort: a push abroad to acquire critical chips.
Building Megaspeed
In late 2022, the U.S. government began instituting restrictions on the sale of advanced A.I. chips to China. The United States feared that the components could potentially give Beijing an economic and military edge.
To have any hope of getting the chips, a company had to be domiciled outside China and have no obvious ownership ties leading to the country.
In 2023, Ms. Huang used a British Virgin Islands company to buy a Singaporean subsidiary of an online gaming company that was linked to her Shanghai network, called 7Road. It was renamed Megaspeed. It would become her first major venture into chips.
Later that year, Megaspeed was transferred to a Singaporean shell company, Singapore records show. After the transfer, Ms. Huang remained in control of Megaspeed’s day-to-day operations, according to people familiar with the company.
By June 2024, Ms. Huang was close enough to Mr. Huang that she bragged about her access to Mr. Huang at a tech event in Taipei. Just after midnight, she was mingling with a crowd of tech executives when she offered to ask Mr. Huang to join them, recalled Parker Schmitt, who attended.
“She said, ‘I bet you guys I can get Jensen here,’ and then Jensen immediately showed up,” said Mr. Schmitt, who is chief executive of NetThunder, a data software provider. Shortly after, Mr. Huang arrived and drank a whiskey shot with the group.
Mr. Huang was with two other Nvidia executives and had planned to attend the party, said a person close to the company.
Mr. Schmitt, who stayed in touch with Ms. Huang, said her social media was littered with photos of her and Mr. Huang, including pictures of them at a golf course and at restaurants drinking wine. She wanted to be seen as a talented sales executive, Mr. Schmitt said, and “photos with Jensen are a point of pride” in the tech industry.
Business Takes Off
That same month, Ms. Huang’s fledgling business had a series of breakthroughs. Megaspeed began receiving large shipments of Nvidia’s most advanced A.I. chips, eventually securing more than $4 billion of the precious hardware.
The company also landed a major new customer: the Chinese e-commerce giant Alibaba. Months after its sale to the Singaporean shell company, Megaspeed had created a Malaysian subsidiary, which then pledged its servers and intellectual property to a subsidiary of Alibaba called Apex. Alibaba became Megaspeed’s dominant customer, according to a person familiar with the business.
Before long, Ms. Huang’s large A.I. chip orders began to attract attention. In late 2024, the U.S. Commerce Department sent an official to inspect a Megaspeed data center and confirm that the Nvidia chips delivered were on site. Some Nvidia equipment was still packed in boxes, raising concerns that it was being shipped in or out and was not installed at the location.
That year, Taiwanese authorities began to monitor Ms. Huang’s trips to the island at the suggestion of the U.S. government, a person familiar with the matter said. She entered Taiwan on a Hong Kong passport and made trips beyond her public appearances with Mr. Huang.
.
Jensen Huang and Alice Huang have been photographed together on several occasions. In this photo, posted to Weibo, they are at a Shanghai restaurant, Pujiang Huaiyan.
.
.
Click the link below for the complete article:
.
__________________________________________
November 9, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.
Foundayo, an oral antiobesity pill, significantly improved obstructive sleep apnea, according to new clinical trial data. The results signal the potential uses of the GLP-1 (glucagonlike peptide 1) drug beyond weight loss.
Foundayo is the brand name for the drug orforglipron, which is made by Eli Lilly. It was approved for treating obesity by the Food and Drug Administration in April. At the same time, the pharmaceutical company has been probing the drug’s potential to treat other obesity-related conditions, including obstructive sleep apnea. The condition is characterized by pauses in air flow to the lungs during sleep that are longer than 10 seconds; it can cause loud snoring, choking, sleep deprivation, headaches and other symptoms. Globally, as many as 936 million adults are estimated to experience the condition, although most are never formally diagnosed.
Because it causes drops in oxygen, obstructive sleep apnea can also increase the risks of heart problems. That suggests treatment with Foundayo may also have cardiovascular health benefits, says Daniel Drucker, an endocrinologist at the Lunenfeld-Tanenbaum Research Institute in Ontario. Drucker was not involved with the new trial but has previously worked as a consultant for Eli Lilly.
“Every time we tinker with the GLP-1 backbone, the question of overall safety and cardiovascular safety resurfaces,” he says.
“We know there’s a two-way relationship between sleep and cardiovascular health, and the repeated drops in oxygen that happen with obstructive sleep apnea can strain blood pressure and the heart over time,” said study co-author Vaishnavi Kundel, an associate professor of medicine at the Icahn School of Medicine at Mount Sinai, who has also consulted for Eli Lilly, in a statement. “Foundayo significantly reduced breathing interruptions and drops in oxygen during sleep, while also improving blood pressure and inflammation.”
In the new clinical trial results, published today in the Journal of the American Medical Association, after 52 weeks, the drug reduced the severity of sleep apnea by 43.8 percent in participants who were clinically classified as being overweight or having obesity and did not use a positive airway pressure (PAP) machine—such devices are commonly employed to treat sleep apnea. The GLP-1 pill reduced severity of sleep apnea symptoms by 27.5 percent in participants who were overweight or had obesity who did use a PAP machine. Both groups also lost around 28 pounds of weight on average over the course of the study.
The results add to other evidence suggesting that Eli Lilly’s injectable GLP-1 medications may improve obstructive sleep apnea, too, Drucker says. “If approved, orforglipron may represent a new option for individuals preferring once-daily administration of a GLP-1 medicine for treatment of [obstructive sleep apnea],” he adds.
Eli Lilly plans to submit the drug for FDA review for the treatment moderate to severe obstructive sleep apnea in adults who are overweight or have obesity by the end of the year, according to a company statement.
.

.
.
Click the link below for the complete article:
.
__________________________________________
November 9, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.

Country profile
The United States is a vast North American country with a diverse geography that includes mountains, plains, and bustling urban centers, known for its democratic ideals and cultural innovation.
Its history is marked by indigenous heritage, colonial settlement, a revolutionary struggle for independence, and rapid industrial growth that reshaped the nation.
Today, the United States is a global leader in technology, entertainment, and politics, continually evolving while celebrating a rich tapestry of cultural and regional identities.
Its capital city is Washington, D.C.
.
14 out of 27 (52%) performance indicators improved in the United States
.
.
Click the link below for the complete article:
.
__________________________________________
November 9, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.
Defense Secretary Pete Hegseth could face an impeachment vote in the House as early as this week, as lawmakers return to Washington after an election in which voters delivered a sweeping rebuke of the Trump administration and the president’s handling of the war with Iran.
The effort is being led by
Representative Thomas Massie, Republican of Kentucky, who on Monday called up a resolution accusing Mr. Hegseth of violating federal law and the Constitution, and abusing his authority on a number of fronts.
Democrats have signaled broad support for the effort, and several Republicans have expressed discontent with Mr. Hegseth, though the outcome remains uncertain in a narrowly divided House.
Here is what to know about the charges, the process and what could happen next.
The measure charges Mr. Hegseth with violating the Constitution.
Mr. Massie, who lost his primary in May to a challenger backed by President Trump, has introduced eight articles of impeachment against Mr. Hegseth, three of them focused on his conduct of the war with Iran.
The articles accuse the defense secretary of waging war without congressional authorization and continuing the military campaign after Congress voted to direct the president to terminate the conflict or seek authorization to continue it. The resolution also accuses Mr. Hegseth of violating deadlines under the War Powers Resolution, which requires the withdrawal of American forces from unauthorized hostilities after 60 days, with a possible 30-day extension.
The remaining charges accuse Mr. Hegseth of carrying out unlawful military strikes against suspected drug traffickers; unlawfully capturing Venezuela’s president, Nicolás Maduro; conducting unauthorized military operations in Yemen; disregarding laws intended to minimize civilian casualties; and abusing his power by retaliating against Senator Mark Kelly for protected speech.
It is up to Speaker Mike Johnson to decide whether the chamber will vote on each of the eight articles or if they will be considered as a package.
Mr. Hegseth has rejected the allegations, calling the impeachment effort a political sham. He is scheduled to hold a news conference on Tuesday morning to respond to the charges.
“Secretary Hegseth will not back down or be deterred by politicians seeking to score partisan points or launch phony investigations where no wrongdoing exists,” Sean Parnell, the Pentagon spokesman, said in a statement on Monday in which he said Mr. Hegseth intended to serve until the end of President Trump’s term.
Mr. Trump has backed his defense secretary and said he intends to keep Mr. Hegseth in his job.
A majority is required to impeach Mr. Hegseth.
The Constitution lays out the process for Congress to impeach and remove presidents, judges and other federal civil officers, including cabinet secretaries.
The first step is in the House, which considers articles of impeachment alleging treason, bribery or other high crimes and misdemeanors. A simple majority is required to approve any article. Impeachment amounts to a formal accusation by Congress, which is then sent to the Senate for a trial to determine whether the official should be convicted and removed from office.
House rules allow any member to propose impeachment articles and require that the body consider them within two legislative days. Congressional leaders — in this case Republicans — have no power to block a vote, but they can try to head off the impeachment by either moving to send the charges to a committee, delaying final action, or to table them, which would effectively kill the effort.
If the House were to impeach Mr. Hegseth, it would take a two-thirds vote of senators present to convict and remove him.
The outcome of the impeachment vote is uncertain.
Democrats are widely expected to support impeaching Mr. Hegseth, and Representative Hakeem Jeffries, the minority leader, declared on Sunday that he was a “hard yes.” With Republicans holding a razor-thin majority, as few as three Republican defections or a few absences could be enough to put the resolution over the top.
Apart from Mr. Massie, several Republicans have expressed frustration with the secretary without committing to impeachment. Representative French Hill, Republican of Arkansas, said Sunday that he wanted to hear the arguments but cautioned that poor performance alone did not necessarily constitute an impeachable offense.
“I don’t know if we have enough votes,” Mr. Massie told reporters on Monday. “I’m doing this because it’s the right thing to do.”
Beyond the political calculations, many lawmakers are considering whether policy decisions ordered by the president warrant impeachment. When House Republicans impeached Alejandro Mayorkas, who served as the homeland security secretary under President Joseph R. Biden Jr., over his handling of immigration enforcement, Democrats opposed the charges, arguing that policy choices did not constitute impeachable offenses. The Republican-led House impeached Mr. Mayorkas, but the Senate dismissed the charges.
There is no fixed timeline for impeachment.
If the House were to impeach Mr. Hegseth, he would remain defense secretary while the articles were pending, and it would be up to House leaders to decide when to send the matter to the Senate for a trial.
Unlike legislation, however, impeachment resolutions do not die at the end of a Congress, so Democrats, who will control the House and Senate starting Jan. 3, would be able to take up the matter when they assume power.
More on the Middle East
Israeli Claims of Iranian Chemical Weapons: Israel has shared intelligence with the United States asserting that Iran is considering the use of chemical weapons against its adversaries, information met with alarm by some American officials and deep skepticism by others, according to U.S. and regional officials.
U.S. Strike on Qeshm Island: American officials described the attack as a small-scale defensive measure against Iranians accused of planning missile strikes.
Aid to Israel: Trump said that the bulk of American aid to Israel would be “cut off at the end of the year,” under an agreement reached with Prime Minister Benjamin Netanyahu months ago. Instead, Trump said the United States would continue selling weaponry to Israel, but Israel would pay for it.
.
Representative Thomas Massie called up a resolution accusing Defense Secretary Pete Hegseth of being “a threat to the Constitution if allowed to remain in office.” Credit…Kenny Holston/The New York Times
.
.
Click the link below for the complete article:
.
__________________________________________
November 8, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation 25 Comments
![]()
.
.
“It is not
Necessary for a presidential candidate to be able to read or even write even a congenital idiot can run for the presidency of the United States of America and serve if you were elected “
Edgar Rice Burroughs
Proverbs 27:22
New Living Translation
22 You cannot separate fools from their foolishness,
even though you grind them like grain with mortar and pestle..
EVIL PEOPLE
They had been long accustomed to do evil. They were taught to do evil; they had been educated and brought up in sin; they had served an apprenticeship to it, and had all their days made a trade of it. It was so much their constant practice that it had become a second nature to them. – Matthew Henry
“When a clown moves into a palace, he doesn’t become a king, the palace instead becomes a circus. — Turkish proverb,”
Hmmmmm…History is repeating itself yet again!
Isaiah 59:14
New Living Translation
14 Our courts oppose the righteous,
and justice is nowhere to be found.
Truth stumbles in the streets,
and honesty has been outlawed.
Jeremiah 5:21
New Living Translation21 Listen, you foolish and senseless people,
with eyes that do not see
and ears that do not hear.
.
__________________________________________
November 8, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation 11 Comments

.
This sounds just like today’s World although it was written about Israel in Babylonian captivity.
History repeats itself
Isaiah 59:9-15
New Living Translation
9
So there is no justice among us,
and we know nothing about right living.
We look for light but find only darkness.
We look for bright skies but walk in gloom.
10 We grope like the blind along a wall,
feeling our way like people without eyes.
Even at brightest noontime,
we stumble as though it were dark.
Among the living,
we are like the dead.
11 We growl like hungry bears;
we moan like mournful doves.
We look for justice, but it never comes.
We look for rescue, but it is far away from us.
12 For our sins are piled up before God
and testify against us.
Yes, we know what sinners we are.
13 We know we have rebelled and have denied the Lord.
We have turned our backs on our God.
We know how unfair and oppressive we have been,
carefully planning our deceitful lies.
14 Our courts oppose the righteous,
and justice is nowhere to be found.
Truth stumbles in the streets,
and honesty has been outlawed.
15 Yes, truth is gone,
and anyone who renounces evil is attacked.The Lord looked and was displeased
to find there was no justice.
__________________________________________
November 8, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation 8 Comments

Click the link below the picture
.
.
.
.
Click the link below for the videos:
.
__________________________________________
November 8, 2026
Business, Food For Thought, Human Interest, Political, Science, Technical amazon, business, Business News, current-events, Future, Hotels, human-rights, medicine, mental-health, research, Science, Science News, technology, Technology News, travel, vacation Leave a comment

Click the link below the picture
.
Inflammation of lymphatic vessels, which drain brain waste, may be involved in the onset of Parkinson’s disease. The condition is associated with the build-up of a misfolded protein called alpha-synuclein, which may not be efficiently removed from the brain if the lymphatic vessels are impaired. But the accumulation of alpha-synuclein seems to further damage these vessels, creating a self-reinforcing chain of events where each problem worsens the other.
“It is a vicious cycle,” says Justin Rustenhoven at the University of Auckland in New Zealand. This may also help explain why Parkinson’s disease is a progressive condition that worsens over time, he says.
Parkinson’s disease, which affects more than 10 million people worldwide, is characterised by a loss of neurons in brain regions that control movement. This causes symptoms such as tremor and muscle stiffness. The condition is thought to be caused by alpha-synuclein, which occurs naturally in the brain, misfolding and forming clumps that damage neurons.
In 2021, researchers showed that accumulation of alpha-synuclein in Parkinson’s disease may partly result from impaired drainage of brain waste via meningeal lymphatic vessels. These are found in the outermost layer of three membranes, called meninges, surrounding the brain. The vessels receive waste from a network of channels surrounding the brain’s blood vessels, called the glymphatic system, before transporting it to other parts of the body for disposal.
But what causes the lymphatic impairment in Parkinson’s disease was unknown. Rustenhoven and his colleagues wondered whether it may result from alpha-synuclein clogging up the meninges. “No one had really looked at that before,” says Rustenhoven, with most research focusing on changes to the regions that control movement, which are located deep within the brain.
The team analysed post-mortem samples of the meninges from seven people who’d had severe Parkinson’s disease and seven people who hadn’t had the condition. Only the Parkinson’s samples had alpha-synuclein clumps. “For the first time, we showed that these aggregates accumulate at the brain’s borders in people with Parkinson’s,” says Rustenhoven.
To determine whether such protein accumulation impairs clearance of brain waste, the researchers injected mice with a virus that infected cells called fibroblasts in the meninges. This caused them to continually produce alpha-synuclein at elevated levels, similar to those seen in people with Parkinson’s disease. At such high levels, alpha-synuclein misfolded and formed toxic clumps that spread across cells in lymphatic vessels in the meninges, but not inside the brain.
Two months later, brain imaging revealed that these mice’s meningeal lymphatic vessels drained waste fluid half as rapidly as those of control mice, which were injected with a virus encoding for an inert protein. What’s more, in the former group of mice, immune cells called macrophages had engulfed the alpha-synuclein clumps at the brain’s borders. This caused the macrophages to double in number and produce about triple the amount of TNF-alpha, an inflammatory molecule.
Next, the team exposed sheets of human cells, found in meningeal lymphatic vessels, to either alpha-synuclein or TNF-alpha. Both molecules caused gaps to form between the lymphatic cells, making them leaky, says Rusterhoven.
“The accumulation of alpha-synuclein in the brain borders basically drives an immune response that pokes holes in those lymphatic vessels, making them ineffective at draining,” he says. “We already know from other studies that those lymphatics are important for draining alpha-synuclein, so impaired lymphatic drainage [due to alpha-synuclein] means even more of the protein is going to build up.”
This feedback loop keeps reinforcing itself, which may cause the worsening of brain damage and symptoms associated with Parkinson’s, says Rusterhoven.
The same mechanism probably applies to other neurodegenerative conditions where proteins accumulate, such as Alzheimer’s disease, says Camille Carroll at Newcastle University in the UK. But this understanding also creates new treatment opportunities. It suggests that “therapies that dampen or modulate that immune response could prevent lymphatic dysfunction to treat Parkinson’s”, says Rusterhoven.
The team now plans to carry out similar experiments where mice are studied after they develop Parkinson’s symptoms, not just its associated brain changes. These mice will also be tracked for longer, he says.
“Their mouse model was appropriate for the question they were asking, which was looking specifically at the effects of alpha-synuclein at the brain border on lymphatics,” says Carroll. “But linking their findings to symptoms will be important.”
In ongoing work, the researchers are collecting more brain-border samples from people who died with Parkinson’s disease of varying severity. This will enable them to determine how often alpha-synuclein clogs up the brain’s borders during the condition and at what stage it may start causing lymphatic impairment.
They are also trialling, in mice and human cells, whether drugs that block TNF-alpha can reverse lymphatic damage during Parkinson’s. A prior study looked at people with inflammatory bowel disease, which is linked to a higher risk of Parkinson’s, and found that those who took drugs that block TNF-alpha were 78 per cent less likely to develop Parkinson’s.
An ongoing trial is also giving people with REM (rapid eye movement) sleep behaviour disorder, which often precedes Parkinson’s disease, a drug that blocks TNF-alpha, to determine whether this affects Parkinson’s progression. “This will be very interesting evidence to support our findings,” says Rustenhoven.
.

.
.
Click the link below for the complete article:
.
__________________________________________