Scrambler therapy may offer lasting relief for chronic pain, review paper suggests

 A new review paper co-authored by two Johns Hopkins pain experts suggests that scrambler therapy, a non-invasive pain treatment, can yield significant relief for approximately 80%–90% of patients with chronic pain, and it may be more effective than another non-invasive therapy: transcutaneous electrical nerve stimulation (TENS). The write-up was published online July 13 in The New England Journal of Medicine

Scrambler therapy, approved by the U.S. Food and Drug Administration in 2009, administers electrical stimulation through the skin via electrodes placed in areas of the body above and below where chronic pain is felt.

The goal is to capture the nerve endings and replace signals from the area experiencing pain with signals coming from adjacent areas experiencing no pain, thereby "scrambling" the pain signals sent to the brain, explains the study's primary author, Thomas Smith, M.D., the Harry J. Duffey Family Professor of Palliative Medicine at the Johns Hopkins Kimmel Cancer Center and a professor of oncology and medicine at the Johns Hopkins University School of Medicine.

All chronic pain and almost all nerve and neuropathic pain result from two things: pain impulses coming from damaged nerves that send a constant barrage up to pain centers in the brain, and the failure of inhibitory cells to block those impulses and prevent them from becoming chronic, says Smith, who also is the director of palliative medicine for Johns Hopkins Medicine.

"If you can block the ascending pain impulses and enhance the inhibitory system, you can potentially reset the brain so it doesn't feel chronic pain nearly as badly," Smith says. "It's like pressing Control-Alt-Delete about a billion times."

Many patients "get really substantial relief that can often be permanent," he says. They receive from three to 12 half-hour sessions.

As a physician who treats chronic pain, Smith says, "Scrambler therapy is the most exciting development I have seen in years—it's effective, it's non-invasive, it reduces opioid use substantially and it can be permanent."

TENS therapy also administers low-intensity electrical signals through the skin, but it uses a pair of electrodes at the sites of pain. Pain relief often disappears when or soon after the electrical impulses are turned off, Smith says. A study cited in the review paper evaluated the impact of TENS in 381 randomized clinical trials, and the authors found a non-statistically significant difference in pain relief between TENS and a placebo procedure.

More information: Thomas J. Smith et al, Cutaneous Electroanalgesia for Relief of Chronic and Neuropathic Pain, New England Journal of Medicine (2023). DOI: 10.1056/NEJMra2110098

https://medicalxpress.com/news/2023-07-scrambler-therapy-relief-chronic-pain.html

Study raises possibility of immunotherapy treatment for ALS

 New research reveals a type of monoclonal antibody already tested in certain forms of cancer may be a promising treatment in stopping the progression of amyotrophic lateral sclerosis, or ALS, a fatal neurodegenerative disease.

The study, led by scientists at Oregon Health & Science University, published today in the Proceedings of the National Academy of Sciences.

The study, involving a mouse model and confirmed in the tissue of human brains affected by ALS and donated after death, revealed for the first time that modulating immune cells can slow the progression of the disease. Previous research suggested a role for immune cells in ALS, but researchers this time used a high-throughput screening technique to identify a particular type of protein expressed on immune cells in the brain and spinal cord in people with ALS.

Researchers implicated the protein, known as alpha-5 integrin.

"When we blocked its expression in mice, we were able to slow down the disease," said senior author Bahareh Ajami, Ph.D., assistant professor of molecular microbiology and immunology and behavioral neuroscience in the OHSU School of Medicine. "We hope that it will get to the clinic very soon."

The team used a monoclonal antibody targeting a5 integrin, which had already been developed and used in treating certain forms of cancer. This means that it's already undergone extensive safety studies to achieve approval through the Food and Drug Administration.

"Hopefully, it could be repurposed," she said.

Using postmortem tissue from 139 brains donated for research, scientists confirmed the presence of a5 integrin within areas of the brain associated with motor function. Specifically, they found a5 integrin expressed by microglial cells and macrophages in blood—cells associated with the immune system—to be highly pronounced in the spinal cord, motor cortex and peripheral nerves during ALS.

They then tested the monoclonal antibody targeting a5 integrin in mice genetically predisposed to carry ALS and found that it protected motor function, delayed disease progression and increased mouse survival.

"We couldn't believe they were doing so much better," Ajami said.

Ajami, whose lab focuses on modulating the immune system to treat neurodegenerative diseases, said the study suggests the potential for applying immunotherapies to ALS as it's already used in cancer and more recently through the use of monoclonal antibodies targeting Alzheimer's disease.

"At this point, we cannot say it's a cure but it's a very interesting start," she said. "It may be similar to what immunotherapy did for cancer or will do for Alzheimer's by targeting immune cells."

Ajami previously studied microglia in ALS. The study's first author, Audie Chiot, Ph.D., of OHSU previously identified peripheral nerves macrophages as therapeutic targets in ALS mice. Today's study complements their previous work by identifying a targetable protein on these cells.

Ajami came to OHSU in September of 2019, after beginning this line of research as a postdoctoral researcher at Stanford University. She said the next step in the research will be to develop dose response studies in the mouse model, and she ultimately hopes to see it progress to the point that it can be used to treat people with ALS.

In addition to Ajami and Chiot, co-authors on the study include Lawrence Steinman, M.D., Ph.D., of Stanford; co-first author Shanu F. Roemer, M.D., of the Mayo Clinic; Lisa Ryner and Michael Leviten of Pasithea Therapeutics; Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A. Jimenez, Randall Woltjer, M.D., Ph.D., of OHSU; and Dennis Dickson, M.D., of the Mayo Clinic.

More information: Aude Chiot et al, Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2306731120

https://medicalxpress.com/news/2023-07-possibility-immunotherapy-treatment-als.html

Protein inhibits development of COVID-19 in live animals

A mammalian protein previously shown by UT Southwestern microbiologists to inhibit the virus that causes COVID-19 in cell culture also protected live mouse models, significantly limiting infection in the lung cells and diminishing the symptoms. The findings, published in Nature Microbiology, could lead to new strategies to treat COVID-19, which still infects thousands and kills hundreds in the U.S. every week.

"Our 2020 paper showed that LY6E could inhibit SARS-CoV-2 in cultured cells. But the proof is showing that it has the same role in living models," said study senior author John Schoggins, Ph.D., Associate Professor of Microbiology at UT Southwestern. "We have demonstrated for the first time that the naturally occurring antiviral protein LY6E reduces COVID-19 illness in a living model."

Human bodies use a variety of strategies to fight viral infections, including producing antiviral proteins, which are the focus of the Schoggins lab. In 2020, he and colleagues discovered that one of these proteins, LY6E, blocked infection in cell culture against a variety of coronaviruses, including one specific to mice called mouse hepatitis virus (MHV), as well as the viruses responsible for the severe acute respiratory syndrome (SARS) outbreak in 2003 and the Middle East respiratory syndrome (MERS) outbreak in 2012. But how LY6E protects against coronavirus infection and whether it could perform the same feat in COVID-19 animal models was unknown.

To answer these questions, Dr. Schoggins and colleagues used a genetic technique to generate seven live mouse models, each one engineered to turn LY6E off in specific immune cells, in all immune cells, or throughout the body. Mice missing this protein throughout their bodies or in all of their immune cells typically died of MHV infection. The mice models also became more vulnerable when the gene was turned off only in immune cells (B cells or monocytes), demonstrating the importance of LY6E in these cells for fighting coronavirus infections.

Mouse models without LY6E but infected with SARS-CoV-2 developed moderate symptoms including weight loss and inflammation and bleeding in their lungs, all signs of illness not seen in models with typical levels of LY6E.

A genetic analysis of the lungs showed that epithelial cells had significant changes in gene expression. A closer look showed that two subsets of these cells, called club cells and ciliated cells, appeared to take the brunt of infection in models without LY6E. The findings suggest the LY6E produced by these lung epithelial cell types is critical for limiting SARS-CoV-2 infection, said Dr. Schoggins, a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell.

In the future, he added, researchers may be able to develop treatments for COVID-19 that depend on delivering extra genes that make LY6E or mimicking its action with a drug. In addition, mice missing LY6E could be used as more realistic models for SARS-CoV-2 infection to study drugs or vaccines. Rather than developing a fatal infection as most existing COVID-19 animal models with other genetic alterations do, or no symptoms as mice with normally functioning LY6E do, mice missing LY6E get a mild to moderate COVID-19-like illness that more closely imitates most cases of the disease in humans.

More information: Katrina B. Mar et al, LY6E is a pan-coronavirus restriction factor in the respiratory tract, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01431-w

https://medicalxpress.com/news/2023-07-protein-inhibits-covid-animals.html

Inflation Adjusted, Men Making Less Money Than in 1979, Women Doing Better

 BLS charts show interesting trends in real (inflation-adjusted) weekly earnings. Men are getting clobbered relative to women, but everyone is losing lately.

Median real earnings from the BLS, inflation adjusted to the 1982-1984 CPI Index, chart by Mish.

Median Weekly Real Earnings

• In the first quarter of 1979 men were making $408 weekly. Today, men are making $391.
• In the first quarter of 1979 women were making $250 weekly. Today women are making $330 weekly.
• Collectively, people were making $335 then and now they are making $365.

Men are getting clobbered, down 4.2 percent, while median women’s earnings have risen 32 percent. These numbers may look silly but you can verify them on the St. Louis Fed FRED database.

Wait, you say, people are taking home more than $365 weekly. Yes they are, in nominal terms. Normally I take numbers and adjust them for inflation. This data is already inflation adjusted, so I had to un-adjust the data.

Median Weekly Earnings and Real Earnings Since 1979

Median real earnings from the BLS, nominal earnings and chart by Mish.

In nominal terms, men were making $282 weekly in 1979 and $1,186 weekly today. Adjusted for inflation, $282 bought 4.2 percent more in 1979 than $1,186 does today.

Women have certainly fared better. In nominal terms, women were making $179 in 1979 and $1,001 today. In real terms that’s a jump from $250 to $330, a gain of 32 percent.

Nominal and Real Average Wages

Nominal hourly wages from the BLS, real wages and chart by Mish.

In contrast to the first set of data where wages are weekly, and calculated quarterly, the BLS produces hourly data monthly. The calculation for this set is the reverse. The BLS shows nominal hourly wages and I calculate real wages.

Last week, someone on Twitter asked what earnings look like adjusted by the PCE price index. Economists tend to use 2012 as the base year for PCE so that is what I used as well. It doesn’t matter, so don’t dwell on the difference in the index year.

For both charts, I went back as far as the data was available. This chart is for production and nonsupervisory workers, not all workers. The hourly data for all workers only dates to March of 2006.

The BLS does not break out average hourly wages by sex. In terms of average hourly wage, the peak was February of 1973. For comparison purposes it’s too bad that data for the first chart does not go back as far.

As a cross check of the first chart calculation, take $28.82 hourly x 40 hours per week and you get $1,153 weekly.

February 1973 vs Today

• In nominal terms, production workers were making $4.06 per hour. Today they are making $28.83.
• In real PCE terms, production workers were making $17.56 then and $22.67 now, a 29 percent total jump over 30 years, about 1 percent a year.
• In real CPI terms, production workers were making $21.05 then and $21.72 now, a 3.2 percent total jump over 30 years, essentially nothing.

We can deduce from the first chart that men are getting clobbered relative to women in both median and average terms. You can also say women are slowly catching up to men. Since we do not have a job-by-job breakdown, it’s not easy to quantify these expressions accurately.

What About Housing?

Case Shiller National and 10-City home prices indexes plus OER, CPI, and Rent indexes from the BLS.

Chart Notes

• The latest Case-Shiller home price indexes is for May. It represents repeat sales of the same house in roughly a March-April timeframe.
• OER stands for Owners’ Equivalent rent. It’s the price one would pay to rent one’s own home, unfurnished, without utilities.
• CPI is the consumer price index.
• Rent of primary resident is just what it sounds.
• CPI, OER, and Rent as as measured by the Bureau of Labor Statistics (BLS).

Home prices wildly disconnected from the CPI in 2000 and in 2013. The disconnect accelerated in 2020.

After a two-month decline in most markets, prices are again on the rise.

Housing Not Directly in the CPI or PCE

Please recall that housing prices are not directly in the either the CPI or PCE inflation indexes. For those wishing to buy a home, both measures of inflation are dramatically understated.

That means real hourly earnings are even dimmer than I presented above.

For discussion of home prices see The Housing Bubble, as Measured by Case-Shiller, Is Expanding Again.

And please consider this question, Is It Time to Bet on an Inflation Overshoot?

https://mishtalk.com/economics/inflation-adjusted-men-are-making-less-money-than-in-1979-women-are-doing-better/

Startup Trying To End Hangovers With Synthetic Alcohol

 For at least a year we have been writing about the secular shift in the beverage world to non-alcoholic drinks - and the corresponding ways with which alcohol giants are changing their product roadmaps to adapt.

Now, the next "big thing" in the alcohol world could wind up being synthetic alcohol, according to the Wall Street Journal. The idea of a synthetic alcohol substitute could seek to address hangovers or other ill-effects of cocktails, according to the report. 

GABA Labs is one company that is looking to try and make synthetic alcohol that can deliver the positive effects of the drink, without the negatives. Namely, the company is seeking to avoid hangovers, health problems or slurred speech. The company is using gamma-aminobutyric acid to try and hit relaxation receptors in the brain while avoiding the negatives that alcohol delivers to the body. 

David Orren, managing director of GABA Labs, told WSJ: “Alcohol is like playing the piano with boxing gloves on. You hit too many keys.”

Dr. David Nutt, the chief scientific officer of GABA Labs, is a former psychiatrist and neuropsychopharmacologist. He has spent two years as chief of section of clinical science in the National Institute of Alcohol Abuse and Alcoholism at the National Institutes of Health, the Journal notes, and has long argued about the negative effect of alcohol on society. 

“It feels like what a glass of wine feels like. It feels relaxing. It makes you a bit more chatty, a bit more socially engaged with people,” he said about the company's product, called Alcarelle. 

GABA is looking to raise $10.3 million and finish food safety testing in the U.S. by the middle of 2026, the report says. Orren and Nutt have been testing the product themselves, with Orren commenting: “It feels like a warm glow. You’re being you. And you’re being with somebody that’s being them. You’re being real.” 

The next step will be testing the product, including testing it when mixed with actual alcohol. 

Dr. Mack Mitchell, senior medical advisor for Amygdala, a company working to inhibit alcohol cravings with an oral drug that targets similar receptors, commented: “People who can’t control drinking don’t always want to stop drinking completely. They just want to be able to drink normally.” 

Another company, Indivior, is working on a nasal spray to inhibit alcohol cravings as well. Its CEO Mark Crossley added: "I arrive in the parking lot. I don’t want six or seven drinks. I’ll top up with a nasal spray.”

https://www.zerohedge.com/markets/meet-one-startup-trying-end-hangovers-synthetic-alcohol

"Too Big To Hide" - Ed Dowd Slams COVID Vax Injuries "Cover-Up... It's A Crime"

 Via Greg Hunter’s USAWatchdog.com,

Former Wall Street money manager Ed Dowd is still a skillful number cruncher.  Dowd made billions of dollars in profits by being right on the data. He’s right on the data again in his recent wildly popular book “Cause Unknown” The Epidemic of Sudden Deaths in 2021 and 2022. 

Dowd’s book documents the extreme deaths and horrible injuries that are now skyrocketing in number.  The huge problems being caused by the CV19 bioweapon/vax are increasing, unstoppable and no longer need to be proven.  Dowd says,

“I was not in the room, but at this point, it is a crime because it’s a coverup. 

I said this in my book in December of 2022.  They see the same data that I see, and the data has only gotten worse since then.  So, it’s a crime, and it’s a coverup.  That’s all you need to know...

Forget about the who and the why.  It was a bioweapon.  It was a mistake.  I don’t care at this point.  This is a joke.  They are killing people. 

They continue to mandate these jabs at some universities.  Some employers still mandate them.  The UK is requiring all school children who enter school in the fall to take these shots. 

This is a joke.  This is a crime.  This is a coverup, and it’s murder at this point.”

In 2022 alone, Dowd figured 30% of the workforce had been killed, disabled and cannot work or is working chronically ill.  Dowd says the death and disability trend for 2023 is way up.  Thousands everyday are reporting they are getting sick, and Dowd says the CV19 bioweapon injections are to blame.  Supply chains and society are going to grind to a crawl, and Dowd predicts,

“Everything is slowly breaking down. 

You won’t see this on the news, but you will see this when you need something done, and you will experience this. 

You are going to be gaslit and told everything is fine. 

There is not problem here.  Don’t look over here. 

We are going to see glacial Mad Max.  

Things are going to get harder to do.  Businesses and services you take for granted are going to become scarce. 

I think we are going to see a deflation in financial assets that will start soon enough.  We will have inflation in things you need like food, medical care and much other stuff.”

Dowd also points out,

“The Justice Department is protecting the looting operation that’s been going on for 40 plus years. 

Everybody in Washington D.C. is literally stealing your taxpayer dollars...

The Deep State protects the looting operation, and they are all in on it.”

Ivermectin is being used by doctors like Pierre Kory as a base drug for treating CV19 vaxed injured patients and unvaxed patients harmed by so-called “shedding.”  Yet, it is still being withheld from a public that desperately needs it.  Why is Ivermectin being restricted?  Dowd says,

“For them to start pushing Ivermectin would expose them.  They are the ones who said what do you mean and called it horse paste.  Criminals and people in coverup mode continue as if everything is fine until they are caught. 

That’s what happened at Enron.  Enron was fraud, and the stock was down 50% from the highs... I was skeptical, and I protected my firm from it and got out of it...

This is the same thing.  Criminals are going to act as if everything is fine, and they are not going to ever admit that Ivermectin is worth anything to anybody because to do so would unravel their whole thread of lies.  I take Ivermectin and I have never been vaccinated, and I take a little dose of Ivermectin a couple times a week.”

In closing, Dowd says,

“This is going to become too big to hide.  Congress needs to act.  These people in the GOP are forming committees on J6 and other things.  That’s great and good on you.  How about the Covid vaccine committee?  Call me up, I’ll share my numbers.”

Dowd also talks about the importance of holding cash, the dollar’s near term and longer term future, gold as a core investment and the wild card of world war.

There is much more in the 49-minute interview.

Join Greg Hunter of USAWatchdog.com as he goes One-on-One with money manager and investment expert Ed Dowd, author of the book called “Cause Unknown” The Epidemic of Sudden Deaths in 2021 and 2022

https://www.zerohedge.com/medical/too-big-hide-ed-dowd-slams-covid-vax-injuries-cover-its-crime

AnaptysBio Shares Rise 11% After Jemperli Plus Chemotherapy Approved in U.S.

 AnaptysBio shares were 11% higher after GSK received U.S. Food and Drug Administration approval for a treatment indication using a drug it licenses from AnaptysBio.

The FDA on Monday approved Jemperli plus carboplatin and paclitaxel, or chemotherapy, for the treatment of adult patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer.

AnaptysBio shares hit their 52-week low of $16.66 on Thursday, and are down 9% in the past 12 months.

The supplemental Biologics License Application supporting this new indication received Priority Review and was approved ahead of the Sept. 23 Prescription Drug User Fee Act action date.

The dual-primary endpoints in Part 1 of the trial are investigator-assessed progression-free survival and overall survival.

Jemperli was discovered by AnaptysBio and licensed to Tesaro, now a part of the GSK group of companies, under a collaboration and exclusive license agreement signed in March 2014. GSK is responsible for the ongoing development and commercialization of Jemperli. AnaptysBio is entitled to receive milestones and tiered royalties of 8% for net sales of Jemperli below $1 billion and 12% up to 25% of sales above $1 billion.

https://www.marketscreener.com/quote/stock/ANAPTYSBIO-INC-33634949/news/AnaptysBio-Shares-Rise-11-After-Jemperli-Plus-Chemotherapy-Approved-in-U-S-44471372/