Possible target for treating and preventing osteoarthritis

 Wear and tear on joints can lead to inflammation, breakdown of cartilage and development of osteoarthritis. Scientists at UF Scripps Biomedical Research have found a possible new target to fight this painful cascade.

In a study published Thursday in the journal PLOS One, biochemist Patrick Griffin, Ph.D., and colleague Mi Ra Chang, Ph.D., describe a specific protein that manages activities within chondrocytes, a critical cell type that maintains healthy cartilage in joints.

As people age and stress their joints, their chondrocytes begin to fail. The UF Scripps team found that activating a specific protein in these cells called RORβ (beta) could restore multiple factors needed for smooth joints to healthier levels, helping to control inflammation. Activating RORβ could thus present a useful new strategy to prevent or delay development of the degenerative joint disease osteoarthritis, said Griffin, a professor of molecular medicine and scientific director of UF Scripps Biomedical Research.

"People need an osteoarthritis medication that addresses the root cause of cartilage damage and depletion as there currently are no disease-modifying drugs for what is the No. 1 cause of disability in the United States," Griffin said. "While our work is in the early stages, our study suggests that the nuclear receptor RORβ could present a novel therapeutic target to protect cartilage damage and perhaps turn on cartilage regeneration."

RORβ, short for "retinoic acid receptor-related orphan receptor beta," is a type of protein called a nuclear receptor. In our cells, genes switch between periods of activity and inactivity. When nuclear receptors bind to DNA, that activates the cell's process of transcribing genes into proteins. RORβ has been linked to development of the eye's retina during fetal growth, and it can influence circadian rhythms by controlling clock genes. But its role in maintaining cartilage health was unclear.

Griffin has studied causes of bone diseases for many years. He zeroed in on RORβ for several reasons. While few studies have been focused on this receptor, some had shown correlation between the receptor's activity and bone loss. So he and Chang set out to better understand it. Chang engineered cell lines to enable the studies.

"To our surprise, the gene program upregulated by increase in RORβ activity was supportive of the formation of chondrocytes, anti-inflammatory, and protective against cartilage degradation," Chang said.

Griffin said the team has launched additional studies because of the enormous need for osteoarthritis solutions. In the United States, an estimated 32 million people live with the painful condition.

"This study suggests RORβ could be an attractive therapeutic target. However, there's much more we need to unravel," Griffin said. "Specifically, we want to understand more about the mechanism by which RORβ impacts chondrocytes and blunts the inflammatory signals that lead to cartilage destruction."

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More information: Mi Ra Chang et al, RORβ modulates a gene program that is protective against articular cartilage damage, PLOS ONE (2022). DOI: 10.1371/journal.pone.0268663

https://medicalxpress.com/news/2022-10-scientists-osteoarthritis.html

GOP Senators Warn DOJ Not To Police Speech Against Transgender Surgeries On Children

 by Bill Pan via The Epoch Times (emphasis ours),

Senate Republicans are warning Attorney General Merrick Garland not to target Americans who speak against transgender surgeries on children the way his department did to parents protesting at school board meetings.

In a letter sent on Tuesday to Garland, a group of five senators said they remain concerned that he would repeat a pattern played out in his previous handling of unruly school board protesters.

“In your confirmation hearing before the Senate Judiciary Committee, you promised that, under your watch, the Department of Justice would not be politicized or weaponized,” wrote Sens. Ted Cruz (R-Texas), Mike Lee (R-Utah), Ron Johnson (R-Wis.), Roger Marshall (R-Kan.) and Marsha Blackburn (R-Tenn.). “You have already broken that promise more than once, and we are concerned you are poised to do so once again.”

In October 2021, Garland issued a memo bringing together a coalition of federal and local law enforcement to address alleged “threats of violence” against teachers and school board members. In response to that memo, the FBI’s counterterrorism unit created the threat tag “EDUOFFICIALS,” and opened dozens of investigations into the activities of protesting parents.

According to Garland, the memo was based in part on a letter sent to President Joe Biden by the National School Boards Association (NSBA), which characterized disruptions at school board meetings as “a form of domestic terrorism and hate crime.” Specifically, the NSBA urged the federal government to invoke counterterrorism laws to quell “angry mobs” of parents, who sought to hold school officials accountable for race and sex indoctrination, and for imposing harsh COVID-19 restrictions on their children.

The senators said they had to remind Garland of his promise, because the DOJ has once again been asked to censor debate, this time, over the issue of children being put through irreversible transgender procedures.

On Oct. 3, the American Academy of Pediatrics, American Medical Association, and Children’s Hospital Association sent a letter (pdf) to Garland, asking the DOJ to help with alleged “threats” and “harassment” they face because of the “gender-affirming healthcare” they provide.

“From Boston to Akron, [Ohio], to Nashville, [Tennessee], to Seattle, children’s hospitals, academic health systems, and physicians are being targeted and threatened for providing evidence-based healthcare,” the organizations wrote in language similar to that of the NSBA letter. “These attacks have not only made it difficult and dangerous for institutions and practices to provide this care, [but] they have also disrupted many other services to families seeking care.”

“Our organizations have called on technology companies to do more to prevent this practice on digital platforms, and we now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter read.

Censoring Speech of Critics

The reason that the DOJ continues to get such requests is because Garland’s response to the NSBA letter set a very bad precedent, the senators argued.

“Your actions in regard to the NSBA letter sent an inappropriate message that federal law enforcement can and will be used to aid one side of a political debate, and to either silence or chill the speech of the other,” they told Garland. “Now, in a remarkably similar fashion, medical associations have written to you asking you to again treat any speech critical of their position on a sensitive matter of public policy as a physical threat warranting a law enforcement response.”

“We call upon you to reaffirm that you will faithfully protect the First Amendment rights of all Americans to peacefully debate this and all other policy questions, irrespective of viewpoint,” the senators continued. “The weaponization of federal law enforcement agencies like the DOJ, in order to produce preferred policy outcomes, cannot continue—our democracy depends on it.”

The senators’ warning comes amid a growing number of pediatric health care providers embracing “gender affirmation care,” a concept rooted in progressive gender ideology.

The American Academy of Pediatrics, a national organization of pediatric health professionals, in its latest guidelines encourages providers to adopt a “gender-affirmative care model” and offer services that are “oriented toward understanding and appreciating the youth’s gender experience.”

In such a model, transgender identities and “diverse gender expressions” aren’t considered to be mental disorders but “normal aspects of human diversity.” The model also recognizes gender identity as something that “evolves as an interplay of biology, development, socialization, and culture.”

Meanwhile, many health professionals who hold a different view of best standard of care for those with gender dysphoria have been pushed out of their profession, like sex researcher Dr. Kenneth Zucker.

https://www.zerohedge.com/political/republican-senators-warn-doj-not-police-speech-against-transgender-surgeries-children

Moderna CEO Confirms New mRNA 'Injection' To Repair Heart Muscles After Heart Attack

 by Jack Phillips via The Epoch Times (emphasis ours),

The CEO of Moderna announced his company has a program that involves injecting messenger RNA (mRNA) into people’s hearts following a heart attack.

“We are now in a super exciting program where we inject mRNA in people’s hearts after a heart attack to grow back new blood vessels and re-vascularize the heart,” Stephane Bancel, the CEO, told Sky News in a recent interview.

Bancel did not elaborate on the nature of the program. His company produced one of the world’s most-used mRNA vaccines for COVID-19—as did pharmaceutical giant Pfizer.

When the reporter suggested that there is an “irony” within the COVID-19 pandemic that it allowed companies like Moderna to “develop these other areas because of the revenues that came through the door,” Bancel agreed. “You’re 100 percent right,” he said.

In August, Moderna reported second-quarter 2022 revenue of $4.7 billion, up $300 million from the second quarter of 2021. For the first half of this year, its total revenue stood at $10.8 billion, or a growth from $6.3 billion in the same period last year.

The company attributed the significant spike in its revenue growth to the rise in sales of the company’s COVID-19 vaccine.

Before the U.S. Food and Drug Administration (FDA) handed down emergency use authorizations for the Moderna and Pfizer COVID-19 vaccines in 2020, no mRNA products received full FDA approval within the United States.

Research

Meanwhile, an Australian government agency last month granted $1.1 million to target three major cardiovascular diseases using mRNA technology, with officials claiming that mRNA-based therapies will reduce inflammation in connection to three major heart diseases including atherosclerosis, pulmonary hypertension, and abdominal aortic aneurysm.

“The mRNA-based targeted strategies that we are investigating can stop the progression of inflammation, providing the opportunities of preventing cardiovascular disease events like heart attack, stroke, and heart failure without the unwanted side effects,” one researcher, Baker Institute’s head of molecular imaging and theranostics Xiaowei Wang, said in a statement after the grant.

https://www.zerohedge.com/political/moderna-ceo-confirms-new-mrna-injection-repair-heart-muscles-after-heart-attack

CMS agrees to release Medicare Advantage audits to settle lawsuit

 The Centers for Medicare and Medicaid Services (CMS) has agreed to publicly release dozens of private Medicare Advantage health plan audits to settle a 2019 lawsuit filed by Kaiser Health News (KHN).

KHN in September 2019 filed a lawsuit asking that CMS provide 90 government audits, including documents from the years 2011, 2012 and 2013.

These documents were reviews of the Medicare Advantage Risk Adjustment Data Validation. Risk adjustment is used by health insurance providers to determine expected medical costs of enrolled individuals.

KHN argued in its lawsuit that CMS was improperly withholding audits of Medicare Advantage plans, with these reviews allegedly having identified more than $650 million in improper charges.

By settling the lawsuit, CMS did not admit to wrongfully withholding the requested documents and also agreed to pay $63,000 in legal fees, according to KHN. The agency will make “best efforts” to provide the documents over the next six weeks.

Medicare Advantage, also known as Medicare Part C, is largely run through contracted private insurance companies. Around the time that the lawsuit was filed in 2019, it had been reported that Medicare Advantage plans had overcharged the federal government by about $30 billion over the preceding three years, prompting scrutiny from both the media and lawmakers.

As of 2022, more than 28 million Medicare beneficiaries are enrolled in Medicare Advantage, accounting for nearly half of all beneficiaries.

These documents are expected to reveal hundreds of million of dollars in overcharges, KHN reported.

Thomas Burke, an attorney who represented KHN in the suit, said, “It’s incredibly frustrating that it took a lawsuit and years of pushing to make this vital information public.”

The Hill has reached out to CMS for comment.

https://thehill.com/policy/healthcare/3688861-cms-agrees-to-release-medicare-advantage-audits-to-settle-lawsuit/

Abbott Nutrition recalls certain baby formula products over risk of spoilage

 Abbott Nutrition issued a voluntary recall for some of its baby formula products on Friday over a risk of spoilage. 

Abbott said in a post on its website that it is recalling certain lots of its 2-fluid-ounce bottles of Ready-to-Feed liquid products for infants and children because a small percentage of the bottles have bottle caps that may not have sealed completely. 

Abbott said less than 1 percent of the bottles have the bottle cap issue. The bottles were manufactured at Abbott’s facility in Columbus, Ohio. 

The post states that the recalled amount is equal to less than one day’s worth of the total number of ounces of infant formula fed to babies in the United States and should not affect the overall national formula supply. 

Abbott issued a voluntary recall earlier this year of several of its powdered baby formula products following reports that four infants became ill with a rare infection after consuming the formula from Abbott’s Sturgis, Mich., plant. 

The recall contributed to a nationwide baby formula shortage that was fueled by supply chain issues as demand rose. 

Abbott said in the post that it is continuing to produce its Similac 2-fluid-ounce Ready-to-Feed liquid formula products for hospitals and health care providers’ offices on a different line. The company will continue to produce Similac infant formula in different sizes and formats for delivery to retail locations. 

The recalled products were primarily distributed to hospitals and some doctors’ offices, distributors and retailers in the United States. Many products were sent to Barbados, Jamaica, Bermuda, Colombia, the Dominican Republic, Haiti, St. Croix and St. Thomas. 

“We take our responsibility to deliver high-quality products very seriously,” said Joe Manning, the executive vice president of nutritional products for Abbott. “We internally identified the issue, are addressing it, and will work with our customers to minimize inconvenience and get them the products they need.”

https://thehill.com/blogs/blog-briefing-room/3689033-abbott-nutrition-recalls-certain-baby-formula-products-over-risk-of-spoilage/

BQ.1 COVID-19 variant becomes increasingly prevalent in US infections: CDC

 A new subvariant of the omicron variant of the coronavirus is becoming increasingly prevalent in the United States, according to data from the Centers for Disease Control and Prevention (CDC). 

CDC data shows that the BQ.1 and BQ.1.1 variants each made up 5.7 percent of the total number of cases in the country in the past week. The BA.5 subvariant, which has dominated the cases in the U.S. for months, made up 67.9 percent, down from its peak in late August when it made up almost 90 percent of all cases in the country. 

The BQ.1 and BQ.1.1 variants have increasingly spread in recent weeks, only trailing the BA.5 and BA.4.6 subvariants in making up the most cases. 

Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and President Biden’s chief medical adviser, told CBS News in an interview that people need to “keep our eye out” for emerging variants despite cases and hospitalizations being down. 

“When you get variants like that, you look at what their rate of increase is as a relative proportion of the variants, and this has a pretty troublesome doubling time,” he said. 

Fauci said he is worried that subsequent variants may be more effective at evading medications that scientists have developed to help patients manage the virus. 

“That’s the reason why people are concerned about BQ.1.1, for the double reason of its doubling time and the fact that it seems to elude important monoclonal antibodies,” he said. 

Cases and hospitalizations have dropped since July, and deaths have been decreasing since August. But health officials have warned the public to expect an increase in cases as the winter approaches. 

The Food and Drug Administration has authorized an updated booster dose of Pfizer and Moderna’s COVID-19 vaccines to address the omicron subvariants. The booster is a bivalent vaccine, meaning it contains the mRNA vaccine for the original strain of the coronavirus and the vaccine for another strain. 

This booster is targeting the BA.4 and BA.5 subvariants.

https://thehill.com/policy/healthcare/3689127-bq-1-covid-19-variant-becomes-increasingly-prevalent-in-us-infections-cdc/

Will Pandemic Learning Loss Cost $700 Billion to Fix?

 A new study released on Tuesday by Kenneth Shores and Matthew Steinberg tackles the question of whether federal pandemic relief for public schools was provided in the right way and in the right amount. The study does some informed but essentially back-of-the-envelope math to estimate how much it would take to fix learning loss, and although the authors give a range, the number circulating in the headlines is $700 billion. Not only is that estimate far more than the $190 billion in Elementary and Secondary School Emergency Relief (ESSER) federal COVID relief funding that went to schools: It’s also more than the Census’s figure for total current expenditures for all public schools in the US in FY 2020. However, this rough figure has a host of estimation problems, and a perspective problem to boot.

The totals Shores and Steinberg provide range between $325 billion and $1.4 trillion. That enormous range—roughly 150 percent of total current public school spending—should cast some doubt on the middle $700B figure the media latched on to, and some estimation problems bear out such doubts. Shores and Steinberg’s total costs estimates are the product of three measures: 1) The duration of students’ remote instruction, 2) remote students’ learning loss and 3) the cost to recover that lost learning. All three of these measures are hard to pin down (disclosure: they use my AEI Return To Learn (R2L) data for some of their estimates) and thus result in wildly different cost estimates.

For calculating the duration of students’ remote instruction, the authors base their high-end estimates on anonymized cellphone tracking data. My technical concerns about these data’s precision aren’t hard to see. If you gauge how many students are in school based on the relative number of cellphones that show up in the building, you might get decent estimates for high schools, but not for elementary grades. High schoolers were both more likely to have cell phones and stay remote longer, so the cell data probably overestimates remote instruction.

The lower end estimates of remote instruction use my R2L data, but even that data tracks districts instructional offerings, not how many students showed up in-person when they could choose to stay remote. For these reasons, all estimates of the duration of remote instruction are uncertain.

Estimates of learning loss (from America) are reasonable to a point. Estimates from studies by Goldhaber et al and Kuhfeld et al are quite similar (and the Goldhaber paper also uses R2L data, which helps with apples to apples comparisons), and both lean towards the lower end. Nevertheless, even these estimates don’t mesh with the rapid progress already seen in some states. In Tennessee, Texas, and Mississippi, spring 2022 test scores in reading almost bounced back to pre-pandemic levels, and test scores in math saw significant progress as well. Most states are making slower but still substantial progress, which suggests that the durability of learning loss may be less than measurements from fall 2021 suggest.

Primarily, the totals the study provides hinge on how much it costs to make up a given unit of lost learning. The authors do their best to find an informed estimate of that unit cost, but that estimate is, to put it bluntly, a guess and one that doesn’t wash with the progress we have already seen in states. As mentioned above, academic recovery is already progressing to some degree without anything like the spending Shores and Steinberg suggest. That’s important, because it suggests that their unit cost is excessive and that so are their estimated totals.

Overall, these estimates have problems, but they are not the only problems here. This study, and news coverage of it, willfully ignores why remote instruction, and the learning loss it drove, was so uneven. The R2LTracker shows 2020-21’s closures differed tremendously between districts. Those closures were local policy choices and these policy choices had consequences—terrible consequences for students. The authors’ suggestion that “adapting ESSER allocations to remote learning would have been a feasible adjustment the federal government could have made in real time” would have meant that more federal relief would flow to districts’ whose excessive COVID caution overextended school closures and resulted in greater learning loss. Such a policy would have both treated that excessive caution as acceptable and shortchanged districts who reopened sooner.

A thorough discussion of what else needs to be done to make up for learning loss is worth having. Recovering from the pandemic will be schools’ primary challenge for years to come, and no doubt, it will be difficult to do with the limited data on hand. However, that discussion needs a clear-eyed look at what caused pandemic learning loss if it is to honestly deal with what should be done and spent, and by whom.

Nat Malkus is Senior Fellow and Deputy Director, Education Policy Studies at the American Enterprise Institute.

https://www.aei.org/education/will-pandemic-learning-loss-cost-700-billion-to-fix/