Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

Significance Statement

Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment.

A nudibranch from the midnight zone has fingers on its tail, collects food with a hood, and glows.

WASHINGTON — Secretary of State Rex Tillerson says diplomatic efforts aimed at resolving the North Korean crisis “will continue until the first bomb drops.”

That statement comes despite President Donald Trump’s tweets a couple of weeks ago that his chief envoy was “wasting his time” trying to negotiate with “Little Rocket Man,” a mocking nickname Trump has given the nuclear-armed nation’s leader, Kim Jong Un.

“I think he does want to be clear with Kim Jong Un and that regime in North Korea that he has military preparations ready to go and he has those military options on the table. And we have spent substantial time actually perfecting those,” Tillerson told CNN’s “State of the Union” on Sunday. “But be clear: The president has also made clear to me that he wants this solved diplomatically. He’s not seeking to go to war.”

Recent mixed messaging from the top of the U.S. government has raised concerns about the potential for miscalculation amid the increasingly bellicose exchange of words by Trump and the North Korean leader.

Trump told the U.N. General Assembly last month that if the U.S. is “forced to defend itself or its allies, we will have no choice but to totally destroy North Korea.” Trump also tweeted that Korea’s leadership “won’t be around much longer” if it continued its provocations, a declaration that led the North’s foreign minister to assert that Trump had “declared war on our country.”

Tillerson acknowledged during a recent trip to Beijing that the Trump administration was keeping open direct channels of communications with North Korea and probing the North’s willingness to talk. He provided no elaboration about those channels or the substance of any discussions.

Soon after, Trump took to Twitter, saying he had told “our wonderful Secretary of State, that he is wasting his time trying to negotiate with Little Rocket Man … Save your energy Rex, we’ll do what has to be done!” Trump offered no further explanation, but he said all military options are on the table for dealing with North Korea’s nuclear and missile programs.

Analysts have speculated about whether the president and his top diplomat were playing “good cop, bad cop” with North Korea, and how China might interpret the confusing signals from Washington. Beijing is the North’s main trading partner, and the U.S. is counting on China to enforce U.N. sanctions.

“Rest assured that the Chinese are not confused in any way what the American policy towards North Korea (is) or what our actions and efforts are directed at,” Tillerson said.

Asked if Trump’s tweets undermined Tillerson, the secretary said: “I think what the president is doing is he’s trying to motivate action on a number of people’s part, in particular the regime in North Korea. I think he does want to be clear with Kim Jong Un and that regime in North Korea that he has military preparations ready to go and he has those military options on the table and we have spent substantial time perfecting those.”

He added that Trump “has made it clear to me to continue my diplomatic efforts, which we are, and I’ve told others those diplomatic efforts will continue until the first bomb drops.”

North Korea has launched missiles that potentially can strike the U.S. mainland and recently conducted its largest ever underground nuclear explosion. It has threatened to explode another nuclear bomb above the Pacific.

The post Rex Tillerson says continue diplomacy with North Korea ‘until first bomb drops’ appeared first on PBS NewsHour.

The flats are described as the first new homes on the Scottish town's High Street 'in living memory'

The plane is hailed as 'one of the most advanced aircraft available on the market'

A rail service linking Scotland, Wales and England with one train journey is to start running for the first time. 

A baroque fiddle believed to have been played by Robert Burns will be performed live on stage in the United States for the first time.

A new digital-first Gaelic language production will be launched in Scotland after a joint agreement between BBC Alba and BBC Scotland.

It’s a tiny cast with just Chris, Anna Marie, and Kelley. PS5 blood money is being thrown around, while Kelley curses the asthma tax. Chris is simulating his real life job in a game that simulates his job. Anna Marie re-discovers she doesn’t like SMT. And everyone agrees cutscenes need both pause and skip options.

The post RPG Cast – Episode 592: “First World Donut Problems” appeared first on RPGamer.

Chris sits in a time loop watching Vegeta backhand a guy. Kelley buys solar panels for her Red XIII werewolf. Were you into RPGs before they were cool? Now slide, slide, baby, slide.

The post RPG Cast – Episode 714: “Thirsty for Tactics” appeared first on RPGamer.

Richard Branson’s Virgin Group has swapped out its envoy on Virgin Australia’s board, putting in Warwick Negus.

It’s tempting to frame Straftat as a throwback to an older, better time for the multiplayer FPS, when the lingo was coded in frags and gibs and sucking it down, when satisfaction was drawn entirely from performance rather than some convoluted, artificial system of progression. Not only would this be inaccurate, but it would also do a disservice to what Straftat truly is, namely a wild overcorrection in response to the direction of modern multiplayer gunfests, one that careens straight through retro stations to arrive somewhere new and exciting.

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Call Of Duty: Black Ops 6 has been out for a little while already, what with me giving its multiplayer largely a thumbs up. Still, it's an ever-evolving thing and Activision have announced the game's first seasonal drop. It's a hefty one with a lot of additions, so I'll try my best to break down the good stuff. TLDR: there's some new maps for multiplayer and zombies, new modes, and a few extra bits. I'm mildly excited for more. More in this case is good.

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The first generation of stars changed the course of cosmic history. Now, thanks to the James Webb Space Telescope, we have a real chance of spotting them

Four private astronauts are riding a SpaceX Crew Dragon capsule further from Earth than any human since 1972, where they will attempt the first ever civilian spacewalk

If you were standing on Mars as it was hit by charged particles from the sun, you might be able to see an aurora just like on Earth

The Euclid space telescope's massive “cosmic atlas” promises to shed light on fundamental questions in physics and cosmology

The first “failed star” ever discovered has been a weird outlier since it was found nearly 30 years ago. New observations show that it is unusually massive because it isn’t a single star after all

Complex carbon-based molecules crucial to life on Earth originated somewhere in space, but we didn't know where. Now, huge amounts of them have been spotted in a huge, cold cloud of gas

Scientists are using machine learning to decode and eventually translate how sperm whales communicate with Morse code-like clicks and pauses.

Senate Republicans on Wednesday will elect a new party leader for the first time in nearly two decades.

Marin Cilic has experienced many great moments on court in recent years, but the 18-time tour-level titlist announced that he will enjoy a milestone moment off the court in 2020. Speaking to his 170,000 followers on Twitter, the Croat shared the news that he will become a father next year. The news comes just 18 months after Cilic married Kristina Milkovic in Dubrovnik. Cilic’s announcement was accompanied by a photo of the 31-year-old shopping for a pushchair. New ride ?? ?? Excited to share with you all that #teamCilic will be growing. New member joining us in 2020 ???????? pic.twitter.com/m0Qxn6AdQB — Marin Cilic (@cilic_marin) 7 October 2019 Cilic will compete at next week’s VTB Kremlin Cup in Moscow, where he will be aiming to achieve his 500th tour-level victory. If Cilic achieves the feat, he would become the 10th active player on the ATP Tour to reach that mark..

A comet that has not been seen for more than 80,000 years is expected to be visible from Earth, potentially during two separate time periods in the next month.

The first ever piece of the Antarctic amber was found in a sediment core from the mid-shelf section of Pine Island trough in Antarctica.

The post Amber Discovered in Antarctica for the First Time appeared first on Sci.News: Breaking Science News.

Despite his own isolationist musings, the first picks of President-elect Donald Trump's incoming administration hail from a decidedly more traditionalist wing of the Republican Party.

This is a sponsored article brought to you by BESydney.

In July 2024, Sydney woman Katherine Bennell-Pegg made history as the first astronaut to graduate under the Australian flag and the first female astronaut in Australia. Her journey, marked by determination and discipline, showcases Australia’s growing prominence in space exploration and research.

From her academic achievements at the University of Sydney (USYD) to her rigorous training at the European Space Agency (ESA), Bennell-Pegg’s success has paved a path forward for aspiring space and aerospace professionals in Australia and globally.

A journey to the stars begins in Sydney

Katherine Bennell-Pegg was born in Sydney, New South Wales, and grew up in the Northern Beaches area. Her fascination with space began at an early age.

“I always dreamed of being an astronaut,” Bennell-Pegg shared in her “Insights from an Australian Astronaut” Space Forum Speech in July 2024. “When I was young, it was for the adventure, but after more than a decade working in space, it’s now because I know the role it plays in tackling real-world problems and developing new knowledge that can benefit our society, environment and science.”

Sydney: A Hub for Space Innovation

Sydney, the vibrant heart of the state of New South Wales (NSW), stands at the forefront of aerospace innovation in Australia. With its world-class research facilities, leading academic institutions and strategic geographic positioning, Sydney is not only Australia’s gateway to the Indo-Pacific but also a burgeoning hub for international aerospace endeavours.

NSW is home to more than 40 per cent of Australia’s aerospace industry. Substantial investments from both the state and federal governments support this concentration of capabilities, underpinning Sydney’s role as a leader in aerospace. From advanced manufacturing and cybersecurity to quantum technologies and space exploration, this progressive city is truly thriving.

Sydney’s appeal as a desirable location for hosting aerospace conferences and business events is bolstered by its comprehensive infrastructure, vibrant startup community and strategic position as a transport hub.

Sydney’s track record of successfully hosting events highlights the city’s ability to organise impactful international gatherings, including:

• Australian Space Summit
• New Horizons Summit
• CubeSatPlus2024 - NEW SPACE: Unbounded Skies

Sydney will also host the 76th International Astronautical Congress from 29 September to 3 October 2025 and the 34th Congress of the International Council for the Aeronautical Sciences (ICAS) to be held 13 to 17 September 2026. Both will take place at ICC Sydney, further solidifying Sydney’s status as a central hub for aerospace events.

Would you like to know more about Sydney’s credentials in Aerospace? Download our Aerospace eBook or visit besydney.com.au

Sydney proved to be the ideal location for Bennell-Pegg’s journey to begin. She studied at the University of Sydney, where she earned a Bachelor of Engineering (Honors) in Aeronautical Engineering (Space) and a Bachelor of Science (Advanced) in Physics.

Sydney’s universities are at the forefront of aerospace education and research. Institutions such as the University of Sydney (USYD), the University of New South Wales (UNSW Sydney) and the University of Technology Sydney (UTS) attract students from around the world. UNSW Sydney, with its School of Aerospace, Mechanical, and Mechatronic Engineering, is renowned for its innovative research in space technology and satellite systems, while UTS provides cutting-edge programs in aerospace engineering and physics, emphasizing practical applications and industry partnerships. USYD excels in aeronautical engineering and space science, supported by advanced facilities and strong ties to major aerospace organisations. Together, these universities offer comprehensive programs that integrate theoretical knowledge with hands-on experience, preparing students for dynamic careers in the rapidly evolving aerospace and space sectors.

Having excelled in her studies at USYD, Bennell-Pegg was awarded the Charles Kuller Graduation Prize for her top-placed undergraduate thesis. Subsequently, her quest for knowledge took her to Europe, where she earned two Master of Science degrees: one in Astronautics and Space Engineering from Cranfield University and another in Space Technology from Luleå University of Technology.

Reflecting on her educational path, Bennell-Pegg stated, “With the encouragement of my parents, I researched what it would take to become an astronaut and worked hard at school, participating in everything from aerobatic flying lessons to amateur astronomy.”

Inside the rigorous training regimen of an astronaut

Bennell-Pegg’s professional career began with roles at Airbus UK, where she contributed to numerous space missions and concept studies, such as Martian in-situ resource utilisation and space debris removal. Her expertise led her to the Australian Space Agency, where she became the Director of Space Technology.

In 2021, Bennell-Pegg was invited by the European Space Agency (ESA) to undertake Basic Astronaut Training at the European Astronaut Centre in Germany. When the ESA application opened in 2021, it was the first opening in 15 years. Bennell-Pegg jumped at the opportunity to apply alongside over 22,000 others from 22 countries. She endured six knock-out rounds, including medical, psychometrics, psychology and technical tests and made it to the group of 25 who passed.

This historic invitation marked the first time an international astronaut candidate was offered training by the ESA.

“The training was demanding, but it was also an incredible opportunity to learn from some of the best minds in the field and to be part of a team that is pushing the boundaries of human exploration.”—Katherine Bennell-Pegg

Bennell-Pegg’s training regimen was intense, encompassing physical conditioning, complex simulations, and theoretical classes designed to prepare candidates for long-duration missions to the International Space Station (ISS) and beyond. This included:

• Studies in biology, astronomy, earth sciences, meteorology, materials, medical and fluids, both in theory and in labs.
• Radiation research – an area of expertise for Australia. This will increase as humans travel back to the Moon.
• Medical operations: Astronauts need to be able to perform medical procedures on themselves and others.
• Training for expeditions: This included honing team dynamics through behavioral training, ocean and winter survival training, rescue and firefighting.

Sharing her thoughts on this transformative experience, Bennell-Pegg said, “The training was demanding, but it was also an incredible opportunity to learn from some of the best minds in the field and to be part of a team that is pushing the boundaries of human exploration.”

In April 2024, Bennell-Pegg completed her training, graduating with her ESA classmates from “The Hoppers” group. Upon graduation, she became fully qualified for assignments on long-duration missions to the ISS, making her the first Australian female astronaut and the first person to train as an astronaut under the Australian flag.

“I want to use this experience to open doors for Australian scientists and engineers to utilize space for their discoveries,” Bennell-Pegg said. “I hope to inspire the pursuit of STEM careers and show all Australians that they too can reach for the stars.”

Elevating Australia’s role in space exploration

Katherine Bennell-Pegg’s achievements represent a significant milestone. Her journey from the University of Sydney to the rigorous training programs at the European Astronaut Centre showcases the potential of Australian talent in the global space community.

“Being the first astronaut trained under the Australian flag is an incredible honor,” Bennell-Pegg said. “I’m grateful for the support that has fueled me through intense training and opened doors for more Australians in space exploration. Whether I fly or not, there is much to accomplish here on Earth. I’m excited to leverage this experience to inspire future generations in STEM and elevate Australia’s presence in the global space community. Becoming an astronaut is just the beginning.”

Bennell-Pegg’s dream to become an Australian astronaut is more than just a personal triumph; it is a win for anyone who aspires to a career in space or aerospace. Sydney, with its world-class educational institutions, advanced manufacturing facilities scheduled for the Western Sydney Aerotropolis and expanding opportunities in aerospace and defence, is an ideal starting point for anyone looking to make their mark in these sectors.

Would you like to know more about Sydney’s credentials in Aerospace? Download our Aerospace eBook or visit besydney.com.au

The experts behind Beyoncé, Kerry Washington and Serena Williams' tresses reveal their all-time favorite products for natural hair.

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On Nov. 19, join Benj Edwards and Simon Willison's live YouTube chat about the "Great Bing Chat Fiasco of 2023."

1. Netflix's The Great Indian Kapil Show: Navjot Singh Sidhu is back after 5 years of exit, Archana Puran Singh says, 'He’s taken over my...'  Firstpost
2. Did you know! Navjot Singh Sidhu was ousted from The Kapil Sharma Show for this reason  The Times of India
3. Navjot Singh Sidhu makes a roaring comeback; Archana Puran Singh worried about her The Great Indian Kapil Show throne  Hindustan Times
4. The Great Kapil Sharma Show: Navjot Sidhu shares his fast-track fatherhood plan. Kapil’s response is too f  The Economic Times
5. Navjot Singh Sidhu shares BTS pics from The Great Indian Kapil's show set with Archana Puran Singh and...  Moneycontrol

Arjun Sarja is set to direct ‘Seetha Payana’ starring daughter Aishwarya Arjun and Niranjan Sudhindra. The movie will release in multiple languages

The Hindu’s First Day First Show newsletter brings you news and reviews from the world of cinema and streaming

New show is on the hunt for high-profile stars to play Hogwarts staff

Sibert and Red Cloud, black-footed ferret siblings at the Smithsonian’s National Zoo and Conservation Biology Institute, are the first members of an endangered species born to a cloned animal.

Le corps ligoté en état de décomposition retrouvé le 30 octobre dans l’un des parcs les plus achalandés de Montréal est celui de Kevin Mirshahi.

L’une des lubies des wokes est d’enfermer les gens dans leur identité raciale ou sexuelle.

Canadian political leaders are congratulating Donald Trump on winning back the U.S. presidency — a victory that raises questions about what Canada-U.S. relations will look like over the next four years.

Donald Trump is returning to the White House with big plans to remake the global trade landscape. That could be a disaster for Canada's economy. But key players of the last trade war believe they can mitigate the damage.

This year won’t just be the hottest on record—it could be the first to surpass 1.5 degrees Celsius. The Paris climate accord aims to keep warming below that level when looking over multiple years

The FDA doesn’t care about the First Amendment rights of the companies it regulates. It cares even less about the “free speech” rights of those companies’ sales and marketing representatives. And why should the agency care? One of FDA’s primary missions is to protect the public health and safety of the American people from illegal, adulterated and misbranded products. Doing so involves restraining food, drug, device and cosmetics companies from committing fraudulent and deceptive acts that are not protected by companies’ commercial free speech rights. Nonetheless, FDA Matters envisions opportunities for FDA and industry to broaden permissible product communications. The key is understanding history, not constitutional law.

Two former board chairs of the Coalition for Healthcare Communication (CHC) were named as the Medical Advertising Hall of Fame (MAHF) 2025 inductees – Sharon Callahan, former Chief Client Officer at Omnicom Health Group (OHG), and Nick Colucci, former Chairman and CEO of Publicis Health/COO of Publicis Groupe North America. The inductees will be honored […]

<p> <b>23rd Regulatory Affairs Conference 202</b><b>5</b><br /> <b>27</b><b>‒</b><b>28 February 2025</b><br /> Hilton Amsterdam Airport Schiphol<br />Amsterdam, The Netherlands</p>

The government implied wholesalers had more personal protective equipment in stock than was the case during the first wave of the COVID-19 pandemic, the Healthcare Distribution Association has said.

On this date 349 years ago, Samuel Pepys relates in his famous diary a remarkable story about an upcoming medical experiment. As far as I can tell, this is the first written description of a paid research subject.

According to his account, the man (who he describes as “a little frantic”) was to be paid to undergo a blood transfusion from a sheep. It was hypothesized that the blood of this calm and docile animal would help to calm the man.

Some interesting things to note about this experiment:

• Equipoise. There is explicit disagreement about what effect the experimental treatment will have: according to Pepys, "some think it may have a good effect upon him as a frantic man by cooling his blood, others that it will not have any effect at all".
• Results published. An account of the experiment was published just two weeks later in the journal Philosophical Transactions. 
• Medical Privacy. In this subsequent write-up, the research subject is identified as Arthur Coga, a former Cambridge divinity student. According to at least one account, being publicly identified had a bad effect on Coga, as people who had heard of him allegedly succeeded in getting him to spend his stipend on drink (though no sources are provided to confirm this story).
• Patient Reported Outcome. Coga was apparently chosen because, although mentally ill, he was still considered educated enough to give an accurate description of the treatment effect. 

Depending on your perspective, this may also be a very early account of the placebo effect, or a classic case of ignoring the patient’s experience. Because even though his report was positive, the clinicians remained skeptical. From the journal article:

The Man after this operation, as well as in it, found himself very well, and hath given in his own Narrative under his own hand, enlarging more upon the benefit, he thinks, he hath received by it, than we think fit to own as yet.

…and in fact, a subsequent diary entry from Pepys mentions meeting Coga, with similarly mixed impressions: “he finds himself much better since, and as a new man, but he is cracked a little in his head”.

The amount Coga was paid for his participation? Twenty shillings – at the time, that was exactly one Guinea.

[Image credit: Wellcome Images]

A person has tested positive in British Columbia, Canadian health officials said, though the results must be sent to another lab for confirmation.

The National Institutes of Health, the crown jewel of biomedical research in the U.S., could face big changes under the new Trump administration, some fueled by pandemic-era criticisms of the agency.

HONG KONG — China's National Health Commission (NHC) published its first set of guidelines to standardise the diagnosis and treatment of obesity, with more than half of China's adults already overweight and obese, and the rate expected to keep rising.  The guidelines, made public on October 17, come as China experiences an upward morbidity trend of its overweight and obese population. The rate of overweight or obese people could reach 65.3 per cent by 2030, the NHC said.   "Obesity has become a major public health issue in China, ranking as the sixth leading risk factor for death and disability in the country," the guidelines said. China is facing a twin challenge that feeds its weight problem: In a modernising economy underpinned by technological innovation, more jobs have become static or desk-bound, while a prolonged slowdown in growth is forcing people to adopt cheaper, unhealthy diets.

OTTAWA - Canada has detected its first presumptive case of H5 bird flu in a person, a teenager in the western province of British Columbia, health officials said on Saturday (Nov 9). The teenager likely caught the virus from a bird or animal and was receiving care at a children's hospital, the province said in a statement. The province said it was investigating the source of exposure and identifying the teenager's contacts. The risk to the public remains low, Canada's Health Minister Mark Holland said in posting on X. "This is a rare event," British Columbia Health Officer Bonnie Henry said in a statement. "We are conducting a thorough investigation to fully understand the source of exposure here in B.C." H5 bird flu is widespread in wild birds worldwide and is causing outbreaks in poultry and US dairy cows, with several recent human cases in US dairy and poultry workers. There has been no evidence of person-to-person spread so far. But if that were to happen, a pandemic could unfold, scientists have said.