Two top White House officials held indirect discussions with Iranian officials in Oman this week in an effort to tamp down regional attacks, according to a report.
The talks — the first since January, when similar conversations were held in the Persian Gulf state over heightened conflicts in the Red Sea — included Brett McGurk, President Biden’s Middle East adviser, and Abram Paley, the acting US envoy for Iran, two sources told Axios.
The discussions focused on clarifying the potential fallout from Iran and its proxies’ actions in the Middle East, as well as the United States’ concerns over Tehran’s nuclear program, the sources said.
Biden Middle East advisor Brett McGurk reportedly took part in held indirect discussions with Iranian officials in an effort to tamp down regional attacks.Getty ImagesThe indirect talks, which included Abram Paley, the acting US envoy for Iran, were the first between the Washington and Tehran since January.U.S Department of State
The talks came a little over a month after Iran’s first-ever direct missile attack on Israel, when Tehran launched 350 missiles and drones at the Jewish state in retaliation for assassinating a top Islamic Revolutionary Guard general in Damascus.
In recent weeks, Tehran has threatened that it could revise its nuclear doctrine and develop nuclear weapons if its existence is threatened by Israel.
It is unclear who represented the Iranians in the Oman talks, Axios reported.
State Department deputy spokesman Vedant Patel told the outlet that the Biden administration has ways to communicate with Iran when necessary, but declined to comment on the talks in Oman.
“The Biden administration continues to assess that Iran is not currently undertaking the key activities that would be necessary to produce a testable nuclear device,” he said.
Two Alzheimer’s sufferers are publicly claiming to havebeaten back the deadly disease— merely by adopting simple but strict changes in lifestyle.
A new CNN documentary, “The Last Alzheimer’s Patient,” features Cici Zerbe, who reported feeling “much better” after switching to a plant-based diet and adopting a serious exercise and wellness routine.
Zerbe, who confessed to missing her beloved veal cutlets — she hasn’t eaten her favorite food in five years, she said — credited meditation, exercise and diet specifically for the “reverse” of her symptoms.
Cici Zerbe saw her symptoms “reverse” after a series of lifestyle changes, according to a new documentary.CNN
Zerbe is a participant in a clinical trial led by Dr. Dean Ornish, which has been exploring the impacts of significant lifestyle change on early dementia and mild cognitive impairment due to Alzheimer’s Disease. The findings are set to be published next month, the Daily Mail reported.
Gupta also interviewed another study participant, Simon Nicholls, who shared his own, similar experience.
In possession of two copies of the APOE4 gene, known to dramatically increase Alzheimer’s risk — Avengers starChris Hemsworth is famously affected— the 55-year-old saw dramatic improvements after making the lifestyle changes.
“I was very worried,” Nicholls told Dr. Sanjay Gupta on camera. “I have a three-year-old son and an eight-year-old son. It’s really important for me, as I get older, to try and be there for them in the future.”
Simon Nicholls, 55, said that being around for family was a major motivator.CNN
“There are many [changes] in lifestyle you can do to hopefully push the disease backwards and give yourself more time, which is all we need until we find a cure,” he said.
Nicholls appeared to have found considerable motivation from previous experience with dementia in his family — his mother passed away from what was assumed to be Alzheimer’s in her 70s.
Nicholls made serious changes to diet and lifestyle to achieve results that doctors found impressive.CNN
“For the last 10 years of her life, she just sat in a chair, rocking, while on about 14 medications. I’d much rather have a longer health span and then just go quickly,” he said.
“Simon was on a mission, as if the Grim Reaper was peering over his shoulder. He was going to kick ass and take names,” preventative neurologist Dr. Richard Isaacson, who oversaw Nicholls’ case, told CNN.
Isaacson said he was surprised to see Nicholls’ biomarkers for Alzheimer’s disappear in just a little over a year.
Zerbe’s journey was featured in the new CNN documentary film, “The Last Alzheimer’s Patient.”CNN
The regimen began with a prescription for tirzepatide, found in the trendy medications Mounjaro and Zepbound, approved by the FDA for Type 2 diabetes and weight loss, respectively.
Besides taking the shots and submitting to new dietary restrictions — elimination of sugar and ultra-processed foods, switching to a plant-based diet — Nicholls alsoadopted a serious exercise routine, including strength training. His mornings began with a combination of walking, jogging and cycling.
‘When I first saw Simon, he had a bit of a middle, like most guys in their 50s. When I saw him at nine weeks, I did a double take. He was totally buff, ripped even,” Dr. Isaacson said.
“I love going for a walk every morning at sunrise for an hour and a half with a podcast. I get in 10,000 steps or more every day. I’m very consistent,” Nicholls revealed. “I also do a very slow full-body workout with weights three times a week for an hour’s time.”
“Within those nine weeks, he had lost 21 pounds, about 80 percent of that fat, and put on muscle, which was excellent,” Isaacson recalled. “I almost didn’t recognize him.”
Isaacson said he refrains from using the term “reverse” but emphasized the excitement surrounding the promising results observed in Nicholls and other patients.
“I don’t use the term ‘reverse.’ I don’t know what reverse means when it comes to the field of Alzheimer’s,” Isaacson said.
“But the results we’ve seen with Simon and some other patients in our research are extremely exciting.”
It has long been known that a hallmark of Alzheimer's disease, and most other neurodegenerative diseases, is the clumping together of insoluble protein aggregates in the brain. During normal disease-free aging, there is also an accumulation of insoluble proteins.
To date, approaches to treatments for Alzheimer's disease have not addressed the contribution of protein insolubility as a general phenomenon, instead focusing on one or two insoluble proteins. Buck researchers have recently completed a systematic study in worms that paints an intricate picture of the connections between insoluble proteins in neurodegenerative diseases and aging. Furthermore, the work demonstrated an intervention that could reverse the toxic effects of the aggregates by boosting mitochondrial health.
"Based on our discoveries, targeting insoluble proteins could provide a strategy for the prevention and treatment of a variety of age-related diseases," said Edward Anderton, PhD, a postdoctoral fellow in Gordon Lithgow's lab and co-first author of a study that appears in the May 16 issue of the journal GeroScience.
"Our study shows how maintaining healthy mitochondria can combat protein clumping linked to both aging and Alzheimer's," said Manish Chamoli, PhD, a research scientist in Gordon Lithgow's and Julie Andersen's lab, and co-first author of the study. "By boosting mitochondrial health, we can potentially slow down or reverse these harmful effects, offering new ways to treat both aging and age-related diseases."
Results support the geroscience hypothesis
The strong link between insoluble proteins promoting normal aging and diseases also builds a case for the bigger picture of how aging and age-related diseases occur. "We would argue that this work really supports the geroscience hypothesis that there is a common pathway to Alzheimer's disease and aging itself," said Buck Professor Gordon Lithgow. PhD, Vice President of Academic Affairs and the senior author of the study. "Aging is driving the disease, but the factors that put you on the track toward the disease actually occur very early."
The fact that the team found a core insoluble proteome enriched with numerous proteins that had not been considered before creates new targets for exploration, said Lithgow. "In some ways it raises the flag about whether we should be thinking about what Alzheimer's looks like in very young people," he said.
Beyond amyloid and tau
The focus of most research on Alzheimer's disease to date has been targeting accumulations of two proteins: amyloid beta and tau. But there are actually thousands of other proteins in these insoluble aggregations, said Anderton, and their role in Alzheimer's disease was unknown. Additionally, he added, their lab and others' have observed that during the normal disease-free aging process there is also an accumulation of insoluble proteins. These insoluble proteins from aged animals, when mixed with amyloid beta in the test tube, accelerate the aggregation of the amyloid.
What was the connection between the accumulation aggregates Alzheimer's and disease-free aging, the team wondered. Focusing on the amyloid beta protein, they used a strain of the microscopic worm Caenorhabditis elegans, long been used in aging studies, that has been engineered to produce human amyloid protein.
Anderton said the team suspected they might see that amyloid beta is driving some level of insolubility in other proteins. "What we found is that amyloid beta causes a massive amount of insolubility, even in a very young animal," said Anderton. They found that there is a subset of proteins that seem to be very vulnerable to becoming insoluble, either by adding amyloid beta or during the normal aging process. They called that vulnerable subset the "core insoluble proteome."
The team went on to demonstrate that the core insoluble proteome is full of proteins that have already been linked to different neurodegenerative diseases in addition to Alzheimer's disease, including Parkinson's disease, Huntington's disease and prion disease.
"Our paper shows that amyloid could be acting as a driver of this normal aging aggregation," said Anderton. "Now we've got clear evidence, I think for the first time, that both amyloid and aging are affecting the same proteins in a similar way. It's quite possibly a vicious cycle where aging is driving insolubility and amyloid beta is also driving insolubility, and they're just making each other worse."
The amyloid protein is very toxic to the worms and the team wanted to find a way to reverse that toxicity. "Since hundreds of mitochondrial proteins become insoluble both during aging and after expressing amyloid beta, we thought if we can boost the mitochondrial protein quality using a compound, then maybe we can reverse some of the negative effects of amyloid beta," said Anderton. That's exactly what they found, using Urolithin A, a natural gut metabolite produced when we eat raspberries, walnuts, and pomegranates which is known to improve mitochondrial function: it significantly delayed the toxic effects of amyloid beta.
"Something that was glaringly obvious from our dataset is that the importance of mitochondria keeps coming up," said Anderton. A takeaway, the authors say, is the reminder that the health of mitochondria is critical to overall health. "Mitochondria have a strong link with aging. They've got a strong link with amyloid beta," he said. "I think ours is one of the few studies that shows that insolubility and aggregation of those proteins might be the link between the two."
"Because the mitochondria are so central to all of this, one way to break the vicious cycle of decline is to replace damaged mitochondria with new mitochondria," said Lithgow. "And how do you do that? You exercise and follow a healthy diet."
Journal Reference:
Edward Anderton, Manish Chamoli, Dipa Bhaumik, Christina D. King, Xueshu Xie, Anna Foulger, Julie K. Andersen, Birgit Schilling, Gordon J. Lithgow. Amyloid β accelerates age-related proteome-wide protein insolubility. GeroScience, 2024; DOI: 10.1007/s11357-024-01169-1
Stroke is the leading cause of disability worldwide and the second leading cause of death, but the right early intervention can prevent severe consequences. A new study led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, and collaborators developed a new test by combining blood-based biomarkers with a clinical score to identify patients experiencing large vessel occlusion (LVO) stroke with high accuracy. Their results are published in the journalStroke: Vascular and Interventional Neurology.
"We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care," said senior author Joshua Bernstock, MD, PhD, MPH, a clinical fellow in the Department of Neurosurgery at Brigham and Women's Hospital.
Most strokes are ischemic, in which blood flow to the brain is obstructed. LVO strokes are an aggressive type of ischemic stroke that occurs when an obstruction occurs in a major artery in the brain. When blood supply to the brain is compromised, the lack of oxygen and nutrients causes brain cells to die within minutes. LVO strokes are major medical emergencies and require the swift treatment with mechanical thrombectomy, a surgical procedure that retrieves the blockage.
"Mechanical thrombectomy has allowed people that otherwise would have died or become significantly disabled be completely restored, as if their stroke never happened," said Bernstock. "The earlier this intervention is enacted, the better the patient's outcome is going to be. This exciting new technology has the potential to allow more people globally to get this treatment faster."
The research team previously targeted two specific proteins found in capillary blood, one called glial fibrillary acidic protein (GFAP), which is also associated with brain bleeds and traumatic brain injury, and one called D-dimer. In this study, they demonstrated that the levels of these blood-based biomarkers combined with field assessment stroke triage for emergency destination (FAST-ED) scores could identify LVO ischemic strokes while ruling out other conditions such as bleeding in the brain. Brain bleeds cause similar symptoms to LVO stroke, making them hard to distinguish from one another in the field, yet treatment for each is vastly different.
In this prospective, observational diagnostic accuracy study, the researchers looked at data from a cohort of 323 patients coded for stroke in Florida between May 2021 and August 2022. They found that combining the levels of the biomarkers GFAP and D-dimer with FAST-ED data less than six hours from the onset of symptoms allowed the test to detect LVO strokes with 93 percent specificity and 81 percent sensitivity. Other findings included that the test ruled out all patients with brain bleeds, signaling that the technology may ultimately also be employed to detect intracerebral hemorrhage in the field.
Bernstock's team also sees promising potential future use of this accessible diagnostic tool in low- and middle-income countries, where advanced imaging is not always available. It might also be useful in assessing patients with traumatic brain injuries. Next, they are carrying out another prospective trial to measure the test's performance when used in an ambulance. They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.
"In stroke care, time is brain," Bernstock said. "The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative."
Disclosures: Edoardo Guade declares grant funding from the UK Research and Innovation small business research initiative. Edoardo Guade and Joshua Bernstock have positions and equity in Pockit Diagnostics Ltd. Joshua Bernstock also has an equity position in Treovir Inc. and is on the boards of Centile Bio and NeuroX1.
Funding: This study was supported by Innovate UK grant 104640 and by private funding.
Journal Reference:
Durrani Y, et al. Prospective validation of GFAP, D-dimer and clinical scales for acute large vessel occlusion ischemic stroke detection. Stroke: Vascular and Interventional Neurology, 2024 DOI: 10.1161/SVIN.123.001304
South Park creators Trey Parker and Matt Stone have been master craftsmen at flawlessly capturing and satirizing society's absurdities since the first episode of the animated comedy series debuted on Comedy Central in August 1997.
As of May, and 330 episodes later, Parker and Stone are preparing to debut the next exclusive streaming event, "The End of Obesity."
