Confidence In Biden Economic Stewardship Historically Low

 By Megan Brenan of Gallup

With Americans less optimistic about the state of the U.S. economy than they have been in recent months and concern about inflation persisting, their confidence in President Joe Biden to recommend or do the right thing for the economy is among the lowest Gallup has measured for any president since 2001. But Biden is not alone in facing a skeptical public, as Federal Reserve Chair Jerome Powell, the Republican and Democratic leaders in Congress, and presumptive presidential nominee Republican Donald Trump garner confidence ratings below 50%.

Forty-six percent of U.S. adults say they have "a great deal" or "a fair amount" of confidence in Trump to do or recommend the right thing for the economy, while fewer say the same of Biden (38%), Powell (39%), and Democratic (38%) and Republican (36%) leaders in Congress.

To a large degree, this reflects partisanship; Democrats are confident in Biden, Powell and Democratic congressional leaders, while Republicans are confident in Trump and Republican congressional leaders. Partisans have little to no confidence in the opposing party’s leaders. While political independents are not overly confident in any of the leaders, they have the most confidence in Trump.

These findings are from Gallup's Economy and Personal Finance poll, conducted April 1-22. During the poll’s field period, the Bureau of Labor Statistics released the latest Consumer Price Index data showing that inflation remains stubbornly elevated, though nowhere near the 40-year highs seen in 2022. After the poll was completed, Powell announced that interest rates would remain steady due to the current inflation rate.

Confidence in Biden’s Management of Economy Low Compared With Predecessors

Gallup has tracked confidence in presidents’ ability to do the right thing for the economy annually since George W. Bush took office in 2001. Bush, Barack Obama and Biden (to a lesser extent) enjoyed majority-level economic confidence ratings at the start of their presidencies, while the public's confidence in Trump never rose above his initial 48% reading. Trump’s current rating is essentially tied with that of his last year in office.

Obama’s confidence ratings were at least 50% each year except for one (42% in 2014). Biden has fared much worse as confidence in his economic management dropped precipitously in 2022 from 57% to 40% amid sharply higher inflation, and it has been below 40% since then. Only Bush earned lower confidence from Americans than Biden has since last year -- by the end of his second term, amid the Great Recession, when just 34% of Americans expressed confidence in his economic abilities.

Confidence in Powell Remains Low Historically

Powell's latest economic confidence reading of 39% is statistically similar to last year’s 36%. Alan Greenspan, who served five terms in the position, inspired majority-level confidence for each of Gallup's five readings between 2001 and 2005. In contrast, the two chairs of the Federal Reserve who followed Greenspan -- Ben Bernanke and Janet Yellen -- failed to register confidence ratings above 50%.

One reason Fed chairs typically engender less confidence than presidents is that the public is not overly familiar with them, and thus more likely to not offer an opinion on their leadership. This year, 16% do not offer an opinion on Powell. Historically, the average percentage not expressing a view on the Fed chair’s leadership has been 17%.

Below-Average Confidence in Democratic, Republican Congressional Leaders

The current economic confidence readings for both parties’ congressional leaders are statistically similar to last year’s readings but well below the historical average for each. Democratic leadership’s latest 38% confidence rating is near the all-time low of 34% recorded in 2023 and below the average of 46% since 2001. Republican leadership’s latest 36% rating is well above the 24% low for that group, in 2014, but significantly below the historical average of 43%.

Confidence ratings were last at the majority level in 2009 for Democratic congressional leaders and in 2003 for Republican congressional leaders.

Confidence in Economic Leaders Driven by Partisanship

Americans’ confidence in these key leaders is driven by partisans' differing views. Broad majorities of Republicans express confidence in the economic competence of Trump (86%), their party’s presumptive presidential nominee, and 82% of Democrats do the same of Biden.

Democrats are more likely than Republicans to say they are confident in their own party’s congressional leaders (80% vs. 67%, respectively). Democrats (56%) are also more confident than Republicans (30%) in Powell’s handling of the economy. Few in either party are confident in the opposing party’s presidential candidate or congressional leaders.

Roughly one-third of independents say they are confident in Biden, Powell and both parties’ congressional leaders. Trump earns higher confidence from independents (45%).

Bottom Line

Americans’ assessments of the national economy are bleak, and they lack confidence in U.S. leaders’ ability to manage it properly. Democrats trust Biden and Powell on the economy, while Republicans trust Trump -- but relatively few independents trust any of the current leaders who have a hand in managing the economy. The net result is that, unlike as recently as 2021, none of the key national figures who can influence the economy earns the trust of a majority of Americans.

Biden's subpar rating could have significant electoral implications as not only does he have the lowest economic rating of any president seeking reelection since Gallup began tracking this in 2001, but independents trust his opponent more than him.

https://www.zerohedge.com/markets/confidence-biden-economic-stewardship-historically-low

DHS Shuts Down Expert Group That Denied Hunter Biden Laptop Story

 by Naveen Athrappully via The Epoch Times,

The Biden administration has agreed to shut down a national security experts’ group as part of settling a lawsuit accusing the group of being politically biased in favor of Democrats.

On Sept. 19, 2023, the Department of Homeland Security (DHS) launched the Homeland Intelligence Experts Group to provide advice on intelligence and national security efforts. In November, America First Legal (AFL) and former Acting Director of National Intelligence Richard Grenell sued the DHS, the group, and Secretary of Homeland Security Alejandro Mayorkas, arguing that the experts group violated provisions of the Federal Advisory Committee Act (FACA).

Section 5 of FACA requires that an advisory committee be “fairly balanced in terms of the points of view.” It also mandates there be provisions to ensure that “the advice and recommendations of the advisory committee will not be inappropriately influenced by the appointing authority or by any special interest.”

The lawsuit noted that “the Experts Group’s members are political allies of the Biden Administration. Most members have applauded the Administration’s decisions and fervidly condemned former President Trump’s America First approach to foreign policy.”

“They have overwhelmingly donated to President Biden or other Democrats. Defendant Mayorkas selected members that are agreeable, not balanced,” it stated.

Some of the members were also signatories of a letter that dismissed the Hunter Biden laptop story as Russian disinformation.

On May 2, plaintiffs and the defendants in the case agreed to settle the matter, with the DHS agreeing to wind up the experts group in 30 days.

The group “will not hold any future meetings, and the Department will not reconstitute the Experts Group inconsistent with the FACA or the Homeland Security Act of 2002,” the joint notice of the agreement stated.

The DHS agreed to provide AFL with the group’s meeting agendas and minutes, which have to be submitted within 15 days. “Based on these representations, Plaintiffs have agreed to dismiss their lawsuit with prejudice.”

The department did not admit any wrongdoing and maintained its position that the group did not violate FACA.

“Thanks to the courage of Ric Grenell in standing up to the Deep State, we have just achieved an unqualified legal victory over Mayorkas and Biden. As a result of our lawsuit in federal court, DHS is surrendering in total to our demands,” said Stephen Miller, president of America First Legal.

The “partisan” experts group “would have been used to promote censored, unethical spying, and gross civil rights invasions of political enemies,” he added.

Mr. Grenell said that DHS “surrendered” on the issue because they knew AFL was in the right and that “Biden’s team broke the law.”

This is the second time that the Biden administration has agreed to disband an advisory group due to violating FACA provisions. In December 2022, the Department of Education disbanded its National Parents and Families Engagement Council after legal action brought by AFL and its clients.

Partisan Committee

When the DHS experts group was first announced, the panel comprised seventeen members. In its lawsuit, AFL stated that these members “do not represent a fair balance of viewpoints.”

Two of the panel members were John Brennan, a former director of the CIA, and James Clapper, former director of national intelligence. Both of them were signatories of the “Letter of 51,” using their intelligence credentials to outrightly dismiss the Hunter Biden laptop story ahead of the 2020 election.

Despite the FBI having validated the authenticity of the laptop, the letter claimed that the story had “all the classic earmarks of a Russian information operation.”

Another panel member, Tashina Gauhar, a former associate deputy attorney general and deputy assistant attorney general, is linked to the 2016 Trump–Russia collusion probe.

She was “extensively involved in the FBI’s corrupt, partisan probe into the baseless allegations that former President Trump’s campaign colluded with Russia before the 2016 election, including drafting the FISA applications that were used to spy on the Trump campaign,” the lawsuit noted.

Out of the 17 panel members, 13 have a history of political contributions, collectively making 945 contributions to candidates for political office that are reportable to the Federal Election Commission.

“Of those 945 contributions, 932 (98.62 percent) were made to Democrat candidates for office, while only 12 (1.27 percent) were made to Republican candidates for office,” the lawsuit stated.

“Of the 13 contributors, 9 contributed only to Democrats, whereas 1 contributed only to a Republican (with a single donation of $250). Three contributed to members of both parties, but of those, 2 were heavily lopsided in favor of Democrat candidates. The other contributor gave 8 contributions to Democrat candidates and 7 to Republican candidates.”

In total, the political contributions made by the panel members came to over $168,000 since January 2012, out of which more than $156,000 went to Democrat candidates.

On Sept. 29 after the DHS announced the experts group, GOP lawmakers had written a letter to Mr. Mayorkas, asking him to rescind appointments of people like Mr. Clapper and Mr. Brennan as they were “individuals known to spread lies and disinformation.”

A few days earlier on Sept. 26, Rep. August Pfluger (R-Tex.) introduced HR 5729 which sought to “prohibit the use of Federal funds to establish a Homeland Intelligence Experts Group and for other purposes.”

https://www.zerohedge.com/political/dhs-shuts-down-expert-group-denied-hunter-biden-laptop-story

Panama Elects New President Who Vows To Shut Migrant Trail, Restore Economy

Voters in the Republic of Panama on Sunday elected a new president who has vowed to sever a key segment of the Latina American migrant trail that leads to the United States while restoring the country's reputation as an investment destination.   

Former security minister Jose Raul Mulino won via an approximate 34% plurality of the vote. He was a late entrant to the race -- subbing in for former President Ricardo Martinelli, who was banned from running after being convicted for money laundering and sentenced to nearly 11 years in prison.

The conviction arose from the use of public money to buy a media firm, which then gave Martinelli a majority ownership position. Martinelli is currently living in the Nicaraguan embassy in Panama City, where he's been granted asylum. That didn't stop him from being an active voice in the campaign, urging voters to choose Mulino via messages from his makeshift home in an embassy storeroom. On Sunday, Mulino acknowledged the boost, visiting Martinelli at the Nicaraguan compound after he'd cast his own vote: 

Mulino, whose five-year term will begin on July 1, has vowed to stem the massive flow of illegal migration that transits Panama en route from South America to the United States. In 2023, more than 500,000 migrants traveled through Panama; most of them were Venezuelan, reports Bloomberg. 

“I will not permit thousands of illegals to pass through our territory like nothing, without control,” said 64-year-old Mulino as he campaigned for office. Making good on that promise will require major attention to Panama's notorious Darien Gap, a roadless, 60-mile stretch of of swamps, mountains and rain forest that is the only terrestrial connection between South and Central America.

Passage through the gap is filled with perils, not least of which are assault, robbery and rape at the hands of criminal gangs. Aid groups say the criminals in the zone are extraordinarily evil, and are known to steal food -- including baby formula -- and abandoning beaten, hungry victims in the jungle. 

Mulino has also promised to confront the country's many economic challenges -- which have prompted credit downgrades. Fitch lowered Panamanian debt to junk status in March. For now, S&P and Moody's score Panamanian bonds one slot above junk.

Lashing out against inflation and government corruption: In 2022, demonstrators imposed roadblocks across the country 

The shuttering of a single enterprise has hit Panama's economic and fiscal prospects hard. It's the $10 billion Cobre copper mine run by First Quantum Materials, which accounted for 5% of Panama's GDP and 1.5% of the global copper supply. In December, the Supreme Court said the company's contract -- which it took over through a hostile takeover -- was unconstitutional.

The terms of that contract were perceived by Panamanians as leaving too much on the table, and the mine has been the subject of major protests. Some of the opposition springs from ecological concerns. Mulino's challenge: Strike a new deal and get the mine working again, bringing money into the economy and taxes into government coffers.

The country has also suffering an economic hit from a drought that has lowered water levels in Gatun Lake. The lake an important component of the Panama Canal route, and the lower water level forced restrictions that slashed canal transits and total tonnage. "The run rate for fiscal year 2024 of vessels through the canal is 9,700, 23% lower than the 2023 fiscal year throughput," FreightWaves reported in February. 

Nudging the canal back toward normal operations will require identifying a new water source. One proposal calls for the construction of a $900 million water reservoir, something the US Army Corp of Engineers explored in the late 1990s. If it gets the green light, construction is expected to span five years. 

The proposed Rio Indio Reservoir would be situated southwest of Lake Gatun (via Engineering News-Record)

In 2022, the country was rocked the largest civil unrest since the end of dictator Manuel Noriega's reign in 1989. The action included strikes by teachers and construction workers -- and demonstrators using fiery roadblocks -- as citizens lashed out against rising prices, as well as government corruption in the form of legislators' families and cronies being granted bloated contracts and salaries. Members of the ruling Democratic Revolutionary Party threw fuel on the fire when photos captured them drinking $340 bottles of Macallan whisky while celebrating the start of a new legislative session.  

Order was restored after President Cortizo ordered 10% government payroll cuts and imposted price controls. Of course, government market interventions are never a path to lasting prosperity and stability. That's a fact President-Elect Mulino may not fully grasp: One of his promised economic remedies is a boost in the country's minimum wage.  

https://www.zerohedge.com/geopolitical/panama-elects-new-president-who-vows-shut-migrant-trail-restore-economy

Red light therapy for repairing spinal cord injury passes milestone

Patients with spinal cord injury (SCI) could benefit from a future treatment to repair nerve connections using red and near-infrared light.

The method, invented by scientists at the University of Birmingham, U.K. and patented by University of Birmingham Enterprise, involves delivering light directly to the site of the injury.

Their latest research, published in the journal Bioengineering and Translational Medicine has determined an optimal 'dose' for this novel therapeutic approach, and shown that it can deliver significant therapeutic improvements including significant restoration of sensation and movement, and regeneration of damaged nerve cells.

Researchers led by Professor Zubair Ahmed used cell models of SCI to determine the frequency and duration of light required to achieve maximum restoration of function and stimulate nerve cell regrowth.

They found that delivery of red light at a wavelength of 660nm for one minute a day increased cell viability (a measurement of the number of live cells) by 45% over five days of treatment.

Professor Ahmed said, "Excitingly, this aspect of the study showed the effect of 660nm light was both neuroprotective, meaning it improved survival of nerve cells, and neuroregenerative, meaning it stimulated nerve cell growth."

The researchers also investigated the effect of light therapy in preclinical models of SCI. Here they used two different methods, an implantable device and transcutaneous delivery, where the light source is placed against the skin.

Their study showed comparable results for both delivery methods, with a one-minute dose of 660nm light, delivered daily for seven days, resulting in reduced tissue scarring at the site of injury, and significant functional recovery.

The researchers also found significant reductions in both cavities and scarring as well as increases in the levels of proteins associated with nerve cell regeneration and improvements in the connections between cells in the injured area of the spine.

This is the first time transcutaneous and direct delivery of light have been compared in SCI, and the results are a milestone for the researchers, who have already received further funding and are planning to develop an implantable device for use in humans with traumatic SCI, where there are currently no approaches that preserve cells or improve neurological function.

Mr. Andrew Stevens, first author of the study and Neurosurgery Registrar explains, "Surgery after spinal cord injury is common, but currently these operations are only aimed at stabilizing injuries to the bones of the spine that have been damaged by the trauma. This concept is incredibly exciting as it could offer surgeons the opportunity during the same operation to implant a device which could help protect and repair the spinal cord itself."

Professor Ahmed continued, "To make light therapy viable for treating SCI in humans an implantable device will be required, to provide a line of sight to the damaged tissue and provide the opportunity for greater accuracy and standardize dosing without impedance due to the thickness of the skin and other tissues surrounding the spinal cord.

"Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near-infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI."

The research team is now seeking commercial partners or investors to take the next steps towards developing a prototype device that can be taken into first-in-man clinical trials.

About light therapy

In the study, the researchers are using a form of light therapy called photobiomodulation (PBM), which aims to improve healing and reduce inflammation. There is established evidence for its effectiveness in a wide variety of dermatological and oral applications, where metered light dosing can be achieved with precision in direct-to-tissue delivery. For example, PBM is already NICE approved for oral mucositis, where it has been shown to reduce the debilitating ulcers and painful inflammation in the mouth caused by cancer treatments.

In the central nervous system, PBM has been widely studied in preclinical models of Parkinson's disease, where it has been shown to be safe and effective. In SCI, PBM delivers its therapeutic benefit by mitigating the inflammation that follows injury, in nerve cells, macrophages (immune cells) and astrocytes.

PBM achieves these effects by working principally on mitochondria, which are photoactive and present in every cell in the body where they generate adenosine triphosphate (ATP) which is used within cells as a source of chemical energy. PBM increases the availability of ATP, and this triggers multiple pathways that mitigate apoptosis (cell death), neuronal damage and neuroinflammation and promote neuronal regeneration.

About the implantable device

The implantable device was originally envisaged by neurosurgeon Mr. David Davies, who works in the field of traumatic brain injury in the NIHR Surgical Reconstruction and Microbiology Research Center, and PBM expert Professor Will Palin from Birmingham's School of Dentistry.

University of Birmingham Enterprise has patented the apparatus and methods for treating traumatic brain injury and traumatic spinal injury, and the research team involved with its development now includes Professor of Neuroscience, Zubair Ahmed and Clinical Research Fellow and Neurosurgery Registrar, Mr. Andrew Stevens from Birmingham's Institute of Inflammation and Aging.

More information: Andrew R. Stevens et al, Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury, Bioengineering & Translational Medicine (2024). DOI: 10.1002/btm2.10674

https://medicalxpress.com/news/2024-05-red-therapy-spinal-cord-injury.html

Almost all individuals with two copies of the APOE4 gene develop signs of Alzheimer's

Researchers from the Research Area on Neurological Diseases, Neuroscience, and Mental Health at the Sant Pau Research Institute, led by Dr. Juan Fortea, Director of the Memory Unit of the Neurology Service at the same hospital, have found that over 95% of individuals over 65 years old who have two copies of the APOE4 gene—APOE4 homozygotes—show biological characteristics of Alzheimer's pathology in the brain or biomarkers of this disease in cerebrospinal fluid and PET scans.

The study, published in Nature Medicine, also concludes that those individuals homozygous for APOE4 also develop the disease earlier than those with other variants of the APOE gene. These findings suggest that having two copies of the APOE4 gene could represent a new genetic form of Alzheimer's disease.

"These data represent a reconceptualization of the disease or what it means to be homozygous for the APOE4 gene. This gene has been known for over 30 years and it was known to be associated with a higher risk of developing Alzheimer's disease. But now we know that virtually all individuals with this duplicated gene develop Alzheimer's biology. This is important because they represent between 2 and 3% of the population," explains Dr. Fortea.

New paradigm

It is known that mutations in three genes, APP, PSEN1, and PSEN2, are involved in the development of autosomal dominant early-onset Alzheimer's disease—which is clearly considered genetic and can appear from the age of 40—while variants of other genes have been associated with an increased risk of developing sporadic or late-onset forms. Additionally, it was already known that APOE was one of the genes considered the strongest genetic risk factor for late-onset Alzheimer's disease.

In this work, researchers evaluated clinical, pathological, and biomarker changes in APOE4 homozygotes to determine their risk of developing Alzheimer's disease.

They used data from 3,297 brain donors, including samples from 273 APOE4 homozygotes from the National Alzheimer's Coordinating Center (United States) and clinical and biomarker data from over 10,000 individuals, including 519 APOE4 homozygotes from five large multicenter cohorts (from Europe and the United States) of subjects with Alzheimer's disease biomarkers.

The results suggest that virtually all APOE4 homozygotes showed Alzheimer's pathology and had higher levels of disease-associated biomarkers at age 55 compared to individuals with the APOE3 gene. At age 65, over 95% of APOE4 homozygotes showed abnormal levels of amyloid in cerebrospinal fluid—a key early pathological feature in Alzheimer's disease—and 75% had positive amyloid scans.

Based on these results, the authors suggest that the genetic variant of the APOE4 gene is not only a risk factor for Alzheimer's disease, as previously thought, but could also represent a distinct genetic form of Alzheimer's disease.

"This reconceptualization of the disease is similar to what we proposed from Sant Pau with Down syndrome, which a few years ago was also not considered a genetically determined form of Alzheimer's," adds Dr. Fortea.

The authors note that these findings could be useful for the development of individualized prevention strategies, clinical trials, and targeted treatment approaches for this specific population.

In this regard, Dr. Alberto Lleó, a researcher in the Dementia Neurobiology Group at the Sant Pau Research Institute and Director of the Neurology Service at the same hospital, points out that "the data clearly show that having two copies of the APOE4 gene not only increases the risk, but also anticipates the onset of Alzheimer's, reinforcing the need for specific preventive strategies."

Researcher Dr. Víctor Montal, who actively participated in this study during his time at Sant Pau and now studies the molecular structure of the APOE gene at the Barcelona Supercomputing Center, adds that "the findings emphasize the importance of monitoring APOE4 homozygotes from an early age for preventive interventions."

More information: Juan Fortea, APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease, Nature Medicine (2024). DOI: 10.1038/s41591-024-02931-w. www.nature.com/articles/s41591-024-02931-w

https://medicalxpress.com/news/2024-05-reveals-individuals-apoe4-gene-alzheimer.html

Parathyroid hormone treatment helps slow development of osteoporosis

 Applying a pretreatment of a parathyroid hormone, commonly used to increase bone mass to combat osteoporosis, can help improve cartilage health and slow the development of osteoarthritis, Cornell researchers have found.

The team, led by Marjolein van der Meulen, the James M. and Marsha McCormick Director of the Meinig School of Biomedical Engineering in Cornell Engineering, also identified gene expression signatures that could potentially be used to detect the early onset of the degenerative joint disease.

The findings were published in Science Advances. The co-lead authors are Adrien Antoinette, Ph.D. '23 and Sophia Ziemian, Ph.D. '20.

Van der Meulen specializes in exploring the role of mechanics in the skeleton and how the musculoskeletal system—bones, cartilage, joints—responds to loading, using a technique to apply weight and compress the lower leg and knee joint.

Loading is something of a mixed blessing. Because it increases bone mass, it can be used as a therapy for osteoporosis. At the same time, loading also damages the cartilage in joints, similar to the degeneration seen in osteoarthritis. Van der Meulen and her lab members have been increasingly focused on the role that bone plays in the development of this type of joint damage.

For the new study, her team conducted a two-step process. First, they pretreated mice daily with parathyroid hormone—a treatment prescribed for osteoporosis—to increase the animal's bone mass over a period of eight weeks. In the second phase, the team applied daily loading on the mouse's tibia and used another osteoporosis treatment, alendronate, that, in effect, turned off the bone's ability to renew itself—a process called remodeling—for six weeks.

"Bone is a tissue that constantly turns over. Cells continually remove bone and replace it with new bone. As you get older, this process is less efficient, and less bone gets put back," Van der Meulen said. "The way some FDA-approved osteoporosis drugs work is by shutting down this natural turnover process, so you're not losing bone mass. So we asked, if we block the ability of bone to respond, will that affect the development of the damage in the knee joint?"

The researchers found the parathyroid hormone directly improved cartilage health and slowed the development of damage, while the alendronate reduced the subchondral bone changes that are associated with osteoarthritis.

"Even after six weeks of damage, that eight-week pretreatment effect was still a very large effect. Parathyroid hormone did more than increase bone mass because, it turns out, this agent also acts on cartilage," said Van der Meulen. "The mouse knees had thicker cartilage after eight weeks, which wasn't something we expected. And so likely thicker cartilage protects you against joint damage downstream."

The team repeated the experiment and used transcriptomics to reveal the gene expression that occurred in RNA isolated from the mouse's cartilage, bone, and lymph nodes. The joint damage was reflected in early transcriptomic changes, and both treatments combined resulted in early modulation in immune signaling.

"What was really interesting is the gene expression data suggested that the two drugs paired together had the biggest effect in attenuating cartilage damage genes, and particularly altering expression of immune genes," Ziemian said.

This result suggests subtle changes occur due to the loading and treatments that can't be detected at the tissue level.

"The gene expression analysis is super useful for us in terms of seeing all these immune genes expressed in cartilage, which was not necessarily something we were expecting to see," Ziemian said. "Cartilage is a tissue that doesn't have a lot if any, immune cells present in it normally."

The next step is to determine if the parathyroid hormone treatment can slow or even reverse the progression of osteoarthritis once it's already present and to see if the gene signatures can be used in developing an early diagnosis for the disease.

"The findings imply that these treatments may be beneficial for humans as well. And the nice thing is, these treatments are FDA-approved already, they're just not approved for this application," Van der Meulen said.

More information: Adrien Y. Antoinette et al, PTH treatment before cyclic joint loading improves cartilage health and attenuates load-induced osteoarthritis development in mice, Science Advances (2024). DOI: 10.1126/sciadv.adk8402

https://medicalxpress.com/news/2024-05-parathyroid-hormone-treatment-osteoporosis.html

Vagus nerve activation of the spleen shows promise to treat infections

 One of the main roles of the spleen is to help the body's immune system fight infections. The spleen does this through producing and regulating antibodies—antibody production is negatively affected in various conditions, including sepsis and autoimmune diseases such as lupus.

New research published in Science Advances by the Feinstein Institutes for Medical Research scientists shows that activation of the vagus nerve triggers the spleen, thereby regulating the production of antibodies.

This research highlights how the nervous system regulates immunity and suggests the potential for non-pharmacological vagus nerve modulation to treat a variety of diseases, such as lupus and sepsis.

This research was led by Betty Diamond, MD, director of the Institute of Molecular Medicine, in collaboration with Stavros Zanos, MD, Ph.D., associate professor in the Institute of Bioelectronic Medicine and Barbara Sherry, Ph.D., professor at the Feinstein Institutes.

They found that chronic stimulation of the vagus nerve led to a decrease in the production of specific antibodies by splenic B cells that attack and destroy foreign invaders and are able to prevent disease in the future by remembering what those substances look like. This decrease was associated with changes in the way B cells matured and survived in the body, as well as alterations in the functional organization of other immune cells.

Credit: Stavros Zanos, MD, Ph.D. and Betty Diamond, MD

Stimulating immunity through the vagus nerve

"Although we have a good understanding of the role of the vagus nerve in the regulation of the inflammatory response and the innate immune system, this study provides new insights in how the vagus nerve regulates adaptive immunity and the functions of B cells," said Dr. Diamond.

"Better understanding these mechanisms will elucidate how altered function of the vagus nerve in conditions like sepsis and autoimmune disease may impact immune function and could lead to new therapeutic approaches for these conditions."

In the study, the Feinstein Institutes' team discovered that acetylcholine released in response to vagus nerve stimulation (VNS) directly affects B cells by interacting with specific receptors on their surface, thereby altering their ability to produce signaling molecules and mature.

"Consistent stimulation of the vagus nerve in mice allows us to explore the therapeutic possibilities of bioelectronic medicine in new diseases," said Dr. Zanos. "These exciting findings warrant further investigation and eventually studies in humans to explore the extent to which vagus nerve stimulation, and other bioelectronic medicine approaches, could become treatment options for diseases involving adaptive immunity."

Research into antibodies and the vagus nerve

For more than four decades, Dr. Diamond has dedicated her career to the study of DNA-reactive B cells, autoantibodies and their origin and effect on the body. In May 2022, in recognition of her breakthrough achievements in molecular medicine and original research, The National Academy of Sciences elected Dr. Diamond as one of its newest members.

Dr. Zanos's research focus is on understanding the anatomy and physiology of the vagus nerve and the effects vagus nerve stimulation has in inflammation and cardiovascular diseases. This study builds on a 2021 paper by Dr. Zanos' group in which they described the development and characterization of the first chronic VNS implant in mice.

Dr. Zanos is leading a cross-institutional research team to develop a detailed map of the anatomy of the human vagus nerve and all its more than 100,000 fibers.

"While we understand the spleen is an essential part of the immune system, finding that stimulation of the vagus nerve affects the regulation of adaptive immunity by this critical organ is novel and important," said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research.

"The research by Drs. Diamond and Zanos highlights the need to continue producing knowledge about bioelectronic medicine's potential to treat or prevent autoimmune disease."

Chronic diseases such as arthritis, diabetes and cancer

Building on years of research in molecular disease mechanisms and the link between the nervous and immune systems, Feinstein Institutes' researchers discover neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body's immune response and inflammation.

If inflammation is successfully controlled, diseases—such as arthritis, pulmonary hypertension, Crohn's disease, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases—can be treated more effectively.

Beyond inflammation, using novel brain–computer interfaces, Feinstein Institutes' researchers have developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals.

More information: Izumi Kurata-Sato et al, Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response, Science Advances (2024). DOI: 10.1126/sciadv.adn3760

https://medicalxpress.com/news/2024-05-vagus-nerve-spleen-infections.html