New treatment to reverse inflammation and arterial blockages in rheumatoid arthritis

 Researchers from Queen Mary University of London have found that the molecule RvT4 enhances the body's natural defenses against atherosclerosis (hardening of the arteries) in patients with rheumatoid arthritis.

Studies in mice undertaken by researchers from Queen Mary University of London's William Harvey Research Institute and Center for Inflammation and Therapeutic Innovation show that increasing levels of the RvT4 molecule in the body improves the ability of the body's own defense mechanisms (macrophages) to reduce local inflammation and remove blockages in blood vessels. This breakthrough in understanding the processes involved could lead to better treatments for people who have rheumatoid arthritis (RA), and who are at higher risk of developing cardiovascular disease.

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis in the UK and affects around 1% of the population. Approximately 10,000 people receive a diagnosis of RA every year. Alongside the more widely-known symptoms of joint inflammation, people with the condition are also twice as likely as others to develop blood vessel disease. This can lead to serious complications and an increased risk of premature death.

One type of blood vessel disease seen in people with RA is atherosclerosis, which is caused by a build-up of fatty material called 'plaque' along the artery walls. This build-up causes the arteries to harden and narrow, making it more difficult to circulate blood around the body. These blockages can also break free, causing heart attacks and strokes. Understanding the reasons why RA patients are at increased risk of these cardiovascular problems is critical in developing better treatments for this group and others.

To gain a better understanding of the causes of blood vessel disease in patients with RA, researchers explored the role of a group of molecules called 13-series resolvins (RvTs). In experimental arthritis the levels of one of these molecules, RvT4, are markedly reduced, a phenomenon that associates with a higher degree of blood vessel disease. This study was designed to explore why this might be the case.

Published in Nature Communications, the study found that treating arthritic mice with RvT4 reduced blood vessel inflammation by re-programming macrophages—a group of white blood cells that accumulate in the diseased vessels—to release stored lipids.

Researchers observed that these lipids were preventing the macrophage from carrying out their usual work of clearing dead cells and reducing localized inflammation in blood vessels. Once freed of their lipid burden, the macrophages were able to move and work much more effectively to reduce the causes of atherosclerosis. The observation that RvT4 restores protective macrophage biological activities is an exciting finding.

RA patients also often present with metabolic dysfunction and this is thought to exacerbate vascular disease. The study found that administration of RvT4 to mice engineered to develop characteristics of metabolic dysfunction, advanced atherosclerosis, and arthritis led to an overall decrease in lipoprotein-associated cholesterol in plasma and an increase in the ratio of HDL-associated cholesterol to total cholesterol.

Jesmond Dalli, Professor in Molecular Pharmacology and Lipid Mediator Unit Director at the William Harvey Institute, Queen Mary University of London, said, "The study is important because it identifies for the first time the loss of RvT4 production as a potential new cause of blood vessel inflammation in the context of arthritis, offering a mechanistic explanation on the cause of this important disease in RA patients. It also showed that RvT4 restores the biological activities of lipid loaded macrophages by promoting lipid breakdown and efflux from the cells, an observation that can guide the development of new treatments to limit the incidence and/or severity of cardiovascular disease in patients with RA."

Victoria King, Director of Funding and Impact at Barts Charity said, "This exciting new discovery helps to explain why certain patients with rheumatoid arthritis are more likely to develop blood vessel disease. This could pave the way for the development of new treatments for these patients to help them live longer and healthier lives."

Dysregulation of macrophage biological responses by lipid accumulation is also involved in the onset and development of many other conditions, including obesity. Medicines derived from RvT4 or RvT4-based compounds may therefore be useful to limit inflammation and promote the release of accumulated lipids out of macrophages in patients with a number of other medical conditions.

More information: Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease, Nature Communications (2024). DOI: 10.1038/s41467-024-44868-1

https://medicalxpress.com/news/2024-02-treatment-reverse-inflammation-arterial-blockages.html

Abbott rips Mayor Adams’ plan to give migrants prepaid credit cards as ‘insanity’

 Texas Gov. Greg Abbott didn’t mince words as he slammed Mayor Eric Adams’ plan to provide migrants with prepaid credit cards, calling the Big Apple proposal “insanity,” “reprehensible” and even “offensive.”

“It sounds like insanity is behind it because it really is offensive, it may be the most reprehensible thing that I’ve seen take place over the past 48 hours,” the Texas Republican told Fox News on Sunday.

He pointed out that news of the program, first revealed by The Post, comes just days after migrants were caught on video beating two police officers near Times Square — and were released back on the streets without bail.

“What’s going on in New York is outrageous and Americans across the country are angry, not just about what’s going on in New York, but the underlying cause for it, which is Joe Biden’s open border policies,” Abbott told Maria Bartiromo on “Sunday Morning Futures.”

The Texas governor has sent busloads of migrants who crossed over the southern border into his state to New York City dozens of times over the past year.

Getty Images

Migrants who arrive in the Big Apple are sent to shelters in the Roosevelt Hotel, at Floyd Bennett Field, and a sprawling tent city on Randall’s Island.

Those at the Roosevelt Hotel will start to receive prepaid credit cards from the city to help them buy food, under a program run by the New Jersey company Mobility Capital Finance.

It will start with a group of 500 migrant families in short-term hotel stays and will replace the current food service offered there, according to City Hall.

Texas Gov. Greg Abbott called New York City Mayor Eric Adams’ plan to provide migrants with credit cards “insanity” and “offensive” on Fox Business on Sunday.Fox News

The cards can only be used at bodegas, grocery stores, supermarkets and convenience stores — and migrants must sign an affidavit swearing they will only spend the funds on food and baby supplies or they will be kicked out of the program.

The amount on each card will vary depending on the size of the family and whether they have any income coming in, according to the details of the contract obtained by The Post.  

A family of four, for instance, could be provided nearly $1,000 each month, which comes out to $35 per day for food. 

Cards will get refilled every 28 days.

If the program is a success, the city will expand it to all migrant families staying in hotels, which now number about 15,000, officials said Friday.

https://nypost.com/2024/02/05/news/texas-gov-abbott-calls-adams-plan-to-give-migrants-credit-cards-insanity/

Vagal Nerve Stimulation in Stroke: Benefit Out to 1 Year

 Use of vagal nerve stimulation in combination with intense physical rehabilitation in patients with chronic stroke led to improved hand and arm function, with benefits maintained out to 1 year, latest results from a randomized controlled trial showed.

Study author, Teresa J. Kimberley, PhD, professor of rehabilitation science and physical therapy at MGH Institute of Health Professions in Boston, Massachusetts, described this vagal nerve stimulation intervention as "an extraordinary ray of hope for people with chronic stroke."

She explained that most of the innovation in the stroke world is being seen in the acute management of the condition. "There has been almost no innovation in the treatment of chronic stroke, but this study included patients between 9 months and 10 years post stroke, and the benefits were similar across this time range."

The observation that improvements in hand and arm function were maintained out to 1 year was particularly promising, she noted.

"While we did not show much continued improvement after the initial intense treatment period, the fact that the benefits were maintained for a year is a good result," Kimberley said. "Other long-term chronic stroke studies do not generally show maintenance of benefit over long-term follow-up, and it is usually the case that short-term benefits of rehabilitation interventions are gradually lost over time, with chronic stroke patients generally following a slow downward trajectory function, so these are pretty dramatic and meaningful findings."

The study is to be presented at the upcoming International Stroke Conference 2024 (ISC 2024) to be held on February 7-9, 2024, in Phoenix, Arizona.

VNS-REHAB

The VNS-REHAB pivotal trial enrolled 108 patients with stroke who had moderate to severe impairment of function of their arm or hand. They were randomized to task-specific rehabilitation plus either active vagal nerve stimulation or sham vagal nerve stimulation.

The initial intervention period consisted of a 6-week intense in-clinic treatment phase followed by a 3-month home exercise program. The groups were then crossed over, so the initial sham group received the same active vagal nerve stimulation treatment combined with physical rehabilitation.

Before and after the stimulation and rehabilitation therapies, motor function was assessed with the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) measurement, which assesses motor impairment, and the Wolf Motor Function Test (WMFT), which is a time-based method to evaluate upper extremity motor ability while providing a better understanding of joint-specific and total limb movements.

Results from this randomized part of the study, which were reported in 2021, showed significant improvements in both these measures with the active vagal nerve stimulation compared with those from the sham treatment.

Both groups continued with an active vagal nerve stimulation home exercise program through 1 year, after which changes from pretherapy baseline in both assessment measures were reported. Data available from 74 participants at 1 year were obtained, with others not available mainly due to the COVID-19 pandemic.

Results at 1 year showed that both FMA-UE and WMFT scores significantly improved from the pretherapy baseline. The FMA-UE score improved by 5.3 points, and WMFT score improved by 0.51 points.

The FMA-UE change at 1 year was not significantly different to the score after the initial randomized period of the trial, but the WMFT score showed an additional 0.09 points improvement.

Kimberley noted that for the home treatment, patients were encouraged to activate the vagal nerve stimulation at the same time as they were using or exercising their hand or arm (up to four times a day). She explained that the nerve stimulation is thought to boost the effects of physiotherapy or exercise, so the patient is asked to activate the nerve stimulation process before a half hour exercise session or when they may be using their arm in everyday activities.

She pointed out that the two measures used in the study evaluated different domains of function; the FMA-UE score assesses the severity of the impairment, while the WMFT score is a measurement of activity. Patients were also assessed for quality of life.

"The remarkable thing about this study is that the findings are consistent across all these three domains. People got better in the impairment measure, the activity measurement, and the quality-of-life measures, which suggests that these findings really are robust," she commented.

"We know from the literature how much of a change in each of these scores is considered clinically meaningful, and roughly 50% of all people experienced clinically meaningful improvements in both the FMA and WMFT scores," she added.

Kimberley said the positive results were all the more remarkable given that the study was conducted over the COVID pandemic. "I would imagine that the isolation, anxiety, and changes in activity levels that occurred in the COVID period may have had an adverse effect, but we were still able to show that the initial improvement was maintained."

She pointed out a previous pilot trial, which involved just 15 patients, now has follow-up out to 3 years and that has shown people continued to improve over the long term.

The technology consists of an electrode implanted in the neck and a pulse generator implanted in the chest wall. Kimberley said patients should be able to use the nerve stimulation treatment for the rest of their lives, but the battery may need to be changed after a few years.

The device used in this study, the Vivistim (MicroTransponder), was approved by the US Food and Drug Administration (FDA) for use in patients with stroke in 2021. It is so far the only vagal nerve stimulation device indicated for stroke, although there are similar devices used for the treatment of epilepsy and for depression.

Patients in this trial had moderate to severe impairment of hand/arm function, but they had to have some hand or arm movement. Patients with no function at all in their hand or arm were not included. Similarly, people with only mild impairments were excluded, as it was thought they probably wouldn't want to undergo this surgery.

Kimberly reported that there are 7 million people in the United States living with chronic stroke, 75% of whom are believed to have some hand or arm impairment. "I would estimate that at least half of these patients may qualify for this treatment. That's a lot of people," she commented.

But she added that most patients with stroke do not know about this new treatment, and even stroke neurologists are often unaware of this new therapy.

Long-Awaited Data

Commenting on the study, Joel Stein, MD, chair of the Department of Rehabilitation and Regenerative Medicine at Columbia University's Vagelos College of Physicians and Surgeons, New York City, said the stroke rehabilitation world has been waiting for quite some time for a therapy to be proven effective in this fashion.

"We have had a lot of candidates, a lot of forms of potentially stimulating the brain to encourage it or help it recover, but this is the first treatment that really has met the bar to become an FDA-approved treatment to facilitate recovery after stroke. And that's terribly important," he stated.

"It's important both as a practical matter for stroke survivors who are looking for something that will help them recover more. And it also is really establishing a new field in some sense in medicine where we now have a way to help restore function after stroke through novel means that we never had before. So, this is really the first, hopefully, of a number of treatments like this," he added.

Stein said this vagal nerve stimulation intervention is now available in many centers in the United States, and he expects increasing numbers of people to pursue it as a treatment.

He reported that in his own practice, a number of patients have asked whether they could be a candidate, and several of them have been. "And so, we're excited to now be able to offer something that is really new and impactful in their lives."

The VNS-REHAB study was sponsored by MicroTransponder. Kimberley reported no disclosures.

https://www.medscape.com/viewarticle/vagal-nerve-stimulation-stroke-benefit-out-1-year-2024a10002jk

"Take Our Border Back" Convoy Ends With Rallies In 3 States

 By Noi Mahoney of FreightWaves

Several hundred people gathered in three border states Saturday to call for stricter immigration security, ending the cross-country “Take Our Border Back” convoy that traveled from Virginia to Texas last week.

Convoy organizers and supporters initially said as many as 700,000 vehicles would take part in three separate rallies in Arizona, California and Texas, including truckers who took part in recent protest convoys in Washington, D.C., and Canada, according to U.S. Rep. Keith Self, R-Texas.

While hundreds of thousands of vehicles never materialized as the convoy moved across the country, about 100 passenger vehicles, recreational vehicles and trucks towing campers arrived in Texas, according to NBC News.

The Texas rally occurred at the Cornerstone Children’s Ranch in the town of Quemado, about 20 miles outside of Eagle Pass. The daylong event included musical performances, vendors and speakers who voiced their concerns about illegal immigration.

“The mission here is the border, that’s what we’re here for,” said Trenis Evans, one of the speakers at the Quemado rally. 

At another “Take Our Border Back” rally Saturday in San Ysidro, California, convoy organizer Scotty Saks said the border is “a national security crisis.”

“We have a human trafficking problem on the border in proportions that we’ve never imagined,” Saks told a crowd of about 200 people, according to the New York Post. 

The “Take Our Border Back” convoy also gathered for a rally in Yuma, Arizona.

The rallies were held amid a feud between Texas Gov. Greg Abbott and the Biden administration over border enforcement measures and jurisdictional authority. 

The Texas National Guard seized control of Shelby Park in Eagle Pass several weeks ago, and erected a razor wire barrier around it, limiting U.S. Border Patrol’s access to the area.

On Sunday, Abbott held a news briefing in Shelby Park accompanied by 13 Republican governors to discuss border and immigration issues.

“A state can defend itself and its citizens to protect their safety from the imminent danger that we are facing, and from an invasion of millions of people coming from across the globe into our country who are unaccounted for whatsoever,” Abbott said.

Abbott also said he is expanding Operation Lone Star, the controversial border security initiative he launched in 2021. The operation has included deploying Texas National Guard members along the Mexico border, installing a floating barrier in the Rio Grande River and initiating safety inspections on commercial trucks arriving at ports of entry from Mexico.

“As we speak right now, the Texas National Guard is undertaking operations to expand this effort,” Abbott said. “We’re not going to contain ourselves just to this park, we are expanding to further areas to make sure that we will expand our level of deterrence and denial of illegal entry into the United States.”

https://www.zerohedge.com/geopolitical/take-our-border-back-convoy-ends-rallies-3-states

China Biotech Stocks Lag Benchmark Most in Four Years on US Bill

 

China’s biotech stocks faced renewed selling pressure as geopolitical concerns add to a list of headwinds weighing on the sector.

A gauge of Chinese biotech firms has underperformed the MSCI China Index by the most since early 2020 amid a recently proposed US legislation to ban some Chinese firms from government contracts. This comes after China’s health-care sector was beaten down over the past two years by factors such as the inclusion of some companies in US’ unverified list and a government crackdown on corruption.

https://www.bloomberg.com/news/articles/2024-02-05/china-biotech-stocks-lag-benchmark-most-in-four-years-on-us-bill

Airline says Boeing is in 'last chance saloon,' cites ‘progressive decline’ in manufacturing

 The president of UAE-based airline Emirates is warning that Boeing’s manufacturing processes have declined and that the company needs a course correction following a 737 Max 9’s loss of a door plug panel and the aircraft’s subsequent grounding for inspections.

Tim Clark, who has served as the president of Emirates since 2003, told the Financial Times that Boeing’s manufacturing quality has been in "progressive decline" and that has landed the aviation giant in "the last chance saloon." 

He added that Emirates is sending engineers to observe production processes for the 777 at Boeing and Spirit AeroSystems, a key supplier in Boeing’s manufacturing network. In November, Emirates announced that it would order 90 Boeing 777 airliners while also adding five more 787 Dreamliners to an existing order.

"The fact that we’re having to do that is testament to what has happened. This would not have been sanctioned in the old days. You know, we trusted these people implicitly to get it done," Clark told the Times.

Emirates will join Alaska Airlines in sending engineers to audit Boeing’s production lines to address potential issues. 

Ticker	Security	Last	Change	Change %
BA	THE BOEING CO.	206.63	-2.75	-1.31%

Alaska will be monitoring the 737 Max 9 production line after one of its aircraft had its door plug panel fly off a Max 9 at 16,000 feet as it flew from Portland, Oregon, to Ontario, California, on Jan. 5 — causing a cabin decompression that forced the airliner to return to Portland for an emergency landing, with no serious injuries reported. 

The door plug covers an emergency exit that is available for airlines to use on floor plan layouts that have larger passenger capacities.

United Airlines also announced that it will at least consider a new acquisition plan that excludes Boeing’s delayed 737 Max 10, which is still awaiting certification from the Federal Aviation Administration (FAA).

Ticker	Security	Last	Change	Change %
UAL	UNITED AIRLINES HOLDINGS INC.	40.01	-1.36	-3.29%
ALK	ALASKA AIR GROUP INC.	35.28	-0.85	-2.35%

Boeing CEO Dave Calhoun has said the company is working to restore the trust and confidence of its customers. (Tom Williams/CQ-Roll Call, Inc via Getty Images / Getty Images)

Boeing's president and CEO Dave Calhoun said during an analyst call for its recent earnings release on Jan. 31 that the company understands the frustrations of its customers and that it has to focus on restoring their confidence through action.

"We understand why they are angry and we will work to earn their confidence. There’s no message, no slogan that will accomplish that. It’s all about real, demonstrated action and absolute transparency every step of the way," Calhoun said. He added that the "increased scrutiny that comes from us or a regulator or from third parties will make us better. It’s that simple."

Calhoun also pointed out that Boeing has "taken close care not to push the system too fast, and we have never hesitated to slow down, to halt production, or to stop deliveries to take the time we need to get things right… but this accident makes it absolutely clear we have more work to do."

On Monday, the FAA announced that Alaska and United, the two U.S. airlines that operate the 737 Max 9, have completed inspections on nearly 94% of the Max 9’s in their fleets and those planes have been returned to service. 

The agency had lifted its grounding of the Max 9 fleet on Jan. 24 pending the completion of inspections that the FAA and Boeing outlined for the airlines. The inspections required a close review of specific bolts, guide tracks, and fittings along with detailed inspections of door plugs and dozens of associated components. 

The National Transportation Safety Board is investigating whether bolts were missing on the plane that suffered the cabin door plug panel blowout. The FAA is also stepping up its on-site oversight of manufacturing lines at Boeing and its suppliers.

The FAA said that 78 of 79 United Airlines Max 9 planes have been inspected and returned to service, while 57 of 65 Alaska Airlines Max 9 planes have returned to service. Alaska indicated that inspections on all of its Max 9 planes except for the one involved in the emergency will be completed by Tuesday.

https://www.foxbusiness.com/markets/airline-says-boeing-last-chance-saloon-cites-progressive-decline-manufacturing