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Freegrass

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Medical science
« on: September 23, 2022, 12:43:41 PM »
Cancer-killing virus shows promise in patients

https://www.bbc.com/news/health-62833581

A new type of cancer therapy that uses a common virus to infect and destroy harmful cells is showing big promise in early human trials, say UK scientists.

One patient's cancer vanished, while others saw their tumours shrink.

The drug is a weakened form of the cold sore virus - herpes simplex - that has been modified to kill tumours.

Larger and longer studies will be needed, but experts say the injection might ultimately offer a lifeline to more people with advanced cancers.

Krzysztof Wojkowski, a 39-year-old builder from west London, is one of the patients who took part in the ongoing phase one safety trial, run by the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust.

He was diagnosed in 2017 with cancer of the salivary glands, near the mouth. Despite surgery and other treatments at the time, his cancer continued to grow.

"I was told there was no options left for me and I was receiving end-of-life care. It was devastating, so it was incredible to be given the chance to join the trial."

A short course of the virus therapy - which is a specially modified version of the herpes virus which normally causes cold sores - appears to have cleared his cancer.

"I had injections every two weeks for five weeks which completely eradicated my cancer. I've been cancer-free for two years now."

The injections, given directly into the tumour, attacks cancer in two ways - by invading the cancerous cells and making them burst, and by activating the immune system.

About 40 patients have tried the treatment as part of the trial. Some were given the virus injection, called RP2, on its own. Others also received another cancer drug - called nivolumab - as well.

The findings, presented at a medical conference in Paris, France, show:
  • Three out of nine patients given RP2 only, which included Krzysztof, saw their tumours shrink
  • Seven out of 30 who had combined treatment also appeared to benefit
  • Side effects, such as tiredness, were generally mild
Lead researcher Prof Kevin Harrington told the BBC the treatment responses seen were "truly impressive" across a range of advanced cancers, including cancer of the gullet (oesophagus) and a rare type of eye cancer.

"It is rare to see such good response rates in early stage clinical trials, as their primary aim is to test treatment safety, and they involve patients with very advanced cancers for whom current treatments have stopped working," he said.

"I am keen to see if we continue to see benefits as we treat increased numbers of patients."

It is not the first time scientists have used a virus to fight cancer. The NHS approved a cold-virus-based therapy, called T-Vec, for advanced skin cancer a few years ago.

Prof Harrington calls RP2 a souped-up version of T-Vec.

"It's had other modifications to the virus so that when it gets into cancer cells it effectively signs their death warrant."

Dr Marianne Baker, from Cancer Research UK, said the encouraging findings might change the course of cancer treatment.

"Scientists discovered that viruses could help to treat cancer 100 years ago, but it's been challenging to harness them safely and effectively.

"This new viral therapy shows promise in a small-scale early trial - now we need more studies to find out how well it works.

"Research suggests that combining multiple treatments is a powerful strategy, and virus therapies like this one could become a part of our toolkit for beating cancer."
When computers are set to evolve to be one million times faster and cheaper in ten years from now, then I think we should rule out all other predictions. Except for the one that we're all fucked...

Human Habitat Index

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There is a principle which is a bar against all information, which cannot fail to keep a man in everlasting ignorance. That principle is contempt prior to investigation. - Herbert Spencer

vox_mundi

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Re: Medical science
« Reply #2 on: February 16, 2024, 01:30:22 PM »
Study Provides First Evidence of Direct Impact of Serotonin On Development of Prefrontal Cortex
https://medicalxpress.com/news/2024-02-evidence-impact-serotonin-prefrontal-cortex.html

A new study published in Nature Communications provides direct evidence that antidepressant use during pregnancy can impact a child's brain development and contribute to the risk of mental health disorders later in life.

The study, led by researchers at the University of Colorado Anschutz Medical Campus, focused on the effect of fluoxetine, commonly used in medications such as Prozac and Sarafem for treating depression and perinatal depression, on a developing prefrontal cortex.

Since fluoxetine works by increasing the levels of serotonin in the brain, the researchers looked at the impact serotonin has on prefrontal cortex development in a fetus.

"While it is known that serotonin plays a role in brain development, the mechanisms responsible for this influence, specifically in the prefrontal cortex, have been unclear. The prefrontal cortex, the most evolved brain region, plays a central role in highest-order cognition, which is why we focused our study on finding the answer from this brain area," said lead author Won Chan Oh, Ph.D., assistant professor in the Department of Pharmacology at CU Anschutz.

Oh and his student, Roberto Ogelman, a neuroscience Ph.D. candidate, found serotonin directly influences nascent and immature excitatory synaptic connections in the prefrontal cortex, which if disrupted or dysregulated during early development can contribute to various mental health disorders.

"Our research uncovers the specific processes at the synaptic level that explain how serotonin contributes to the development of this important brain region during early-life fluoxetine exposure," adds Oh. "We are the first to provide experimental evidence of the direct impact of serotonin on the developing prefrontal cortex when fluoxetine is taken during pregnancy, because fluoxetine not only crosses the placenta but also passes into breast milk."

Serotonin modulates excitatory synapse maturation in the developing prefrontal cortex, Nature Communications (2024).
https://www.nature.com/articles/s41467-024-45734-w
“There are three classes of people: those who see. Those who see when they are shown. Those who do not see.” ― anonymous

Insensible before the wave so soon released by callous fate. Affected most, they understand the least, and understanding, when it comes, invariably arrives too late

Sigmetnow

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Re: Medical science
« Reply #3 on: February 22, 2024, 03:48:09 PM »
Erik Hoel ⁦‪
 
They buried the lede on this new study. It's not that exercise beats out SSRIs for depression treatment, but that *just* dancing has the largest effect of *any treatment* for depression.
 
That's kind of beautiful.
 
2/21/24, https://x.com/erikphoel/status/1760338273153568956

—-
Quote
Emmett Shear
 
I don’t know if this study will replicate…but I’ve long believed humans have a basic need for synchronization.
It’s available through team sports, dancing (especially if everyone is dancing the same dance), choir, complicated group photos where everyone jumps…
   —
There is a special feeling to being physically synchronized in motion with other people. It is not replaceable with other forms of connection or belonging. You can’t get it over the internet.
   —
It’s sort of similar to sunlight, human touch, real green nature…their lack will eventually give you a disease of deficiency.
If vitamins are “minerals” required for life, perhaps these are vitaqals — the qualia needed for life.
 
< If you go to any park in China you’ll find a group of elderly people doing tai chi together, wonder if they are onto something…
 
ES: They absolutely are. That’s like four vitaqals at once!
2/21/24, https://x.com/eshear/status/1760361698278744193
« Last Edit: February 22, 2024, 03:57:01 PM by Sigmetnow »
People who say it cannot be done should not interrupt those who are doing it.

Sigmetnow

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Re: Medical science
« Reply #4 on: March 29, 2024, 10:42:41 PM »
Quote
The Surfing CyberSurgeon©️ 🔪 🏄‍♂️🤙 ☮️
 
I have treated over 15 melanomas and pre-melanomas this month. I typically average 2 to 4 melanomas a month. What is going on? Melanoma is the leading cause of skin cancer deaths worldwide. this is a very dangerous cancer that can affect everyone from someone in their 20s all the way up to someone in their 90s. By doing routine skin checks with a dermatologist, we are able to pick up on these early and possibly prevent a melanoma from developing.
   —
My intention of this post is to save at least one person’s life
7/18/23, 3:34 PM  https://x.com/pmgraham86/status/1681387075507978253
People who say it cannot be done should not interrupt those who are doing it.

Sigmetnow

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Re: Medical science
« Reply #5 on: May 10, 2024, 04:07:37 PM »
The gene therapy – DB-OTO – is specifically for children with OTOF mutations. A harmless virus is used to carry the working gene into the patient. The trial is “just the beginning of gene therapies”, Bance said. “It marks a new era in the treatment for deafness.”

UK toddler has hearing restored in world first gene therapy trial
 
Opal Sandy, who was born completely deaf because of a rare genetic condition, can hear almost perfectly after groundbreaking surgery that took just 16 minutes
Quote
A British toddler has had her hearing restored after becoming the first person in the world to take part in a pioneering gene therapy trial, in a development that doctors say marks a new era in treating deafness.

Opal Sandy was born unable to hear anything due to auditory neuropathy, a condition that disrupts nerve impulses travelling from the inner ear to the brain and can be caused by a faulty gene.

But after receiving an infusion containing a working copy of the gene during groundbreaking surgery that took just 16 minutes, the 18-month-old can hear almost perfectly and enjoys playing with toy drums.


Auditory neuropathy can be caused by a fault in the OTOF gene, which makes a protein called otoferlin. This enables cells in the ear to communicate with the hearing nerve. To overcome the fault, the new therapy from biotech firm Regeneron sends a working copy of the gene to the ear.

A second child has also recently received the gene therapy treatment at Cambridge university hospitals, with positive results.

The overall Chord trial consists of three parts, with three deaf children including Opal receiving a low dose of gene therapy in one ear only.

A different set of three children will get a high dose on one side. Then, if that is shown to be safe, more children will receive a dose in both ears at the same time. In total, 18 children worldwide will be recruited to the trial.

The gene therapy – DB-OTO – is specifically for children with OTOF mutations. A harmless virus is used to carry the working gene into the patient.

The trial is “just the beginning of gene therapies”, Bance said. “It marks a new era in the treatment for deafness.” …
https://www.theguardian.com/science/article/2024/may/09/uk-toddler-has-hearing-restored-in-world-first-gene-therapy-trial
People who say it cannot be done should not interrupt those who are doing it.

Freegrass

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Re: Medical science
« Reply #6 on: May 13, 2024, 01:16:11 AM »
Not sure where to post this. Are we a step closer to figuring out consciousness?

When computers are set to evolve to be one million times faster and cheaper in ten years from now, then I think we should rule out all other predictions. Except for the one that we're all fucked...

Ranman99

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Re: Medical science
« Reply #7 on: May 13, 2024, 12:45:34 PM »
Hmmm, all things, later than or on top of or whatever semaphore on top of memory quip you would like, the substratum. Then, those things must have some relationship to the substratum. My only thing is perhaps the substratum matters, but perhaps everything else is just like a dream, so which direction is best in a dream? Maybe not, but I like to see the look on their faces!! I mean my cats. Just when I think they are getting it, they just turn and start scratching the couch, little bastages!! 🤣🤣🤣🤣 Can't discount Maya!!!
😎

morganism

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Re: Medical science
« Reply #8 on: May 15, 2024, 08:33:05 PM »
(another gene edit trick, here to get into the nerves and clean out latent virus)

Gene editing breakthrough could soon cure herpes for good


SEATTLE — A revolutionary new treatment may forever get rid of the painful and embarrassing blisters that come from a herpes flare-up. The herpes viruses that cause either cold sores around the mouth or blisters near the genitals stick around for life, lying dormant in nerve cells only to reactivate and cause sores again down the road. However, scientists in Seattle believe gene editing may be the solution. Researchers at the Fred Hutchinson Cancer Center have taken a big step towards genetically zapping those viruses out of the body entirely.

In a new study published in the journal Nature Communications, scientists are reporting positive results from an experimental gene therapy that eliminated up to 97 percent of herpes virus infections in mice. The clever therapy works by injecting gene editing molecules into the bloodstream that can hunt down and destroy the DNA code of herpes hiding out in nerve clusters.

“Herpes is very sneaky. It hides out among nerve cells and then reawakens and causes painful skin blisters,” says Dr. Keith Jerome, a professor in the Vaccine and Infectious Disease Division at Fred Hutch, in a media release. “Our aim is to cure people of this infection, so that they don’t have to live with the worry of outbreaks or of transmitting it to another person.”

Most people have been exposed to at least one of the two main herpes viruses, HSV-1 and HSV-2. Around two-thirds of people under 50 carry HSV-1, the virus that causes cold sores around the mouth, often spread through oral contact. About 13 percent have HSV-2, the culprit behind most genital herpes cases typically contracted through sexual transmission.

While herpes infections are usually more of an occasional nuisance than a serious health threat, they can have serious consequences. HSV-2 raises the risk of contracting HIV, the virus that causes AIDS. Some research has also linked HSV-1 to an increased risk of dementia later in life. Unfortunately, there’s also a social stigma surrounding patients with herpes, as well as stress that outbreaks will eventually return.

“If you talk to people living with herpes, many are worried about whether their infection will transmit to others,” Jerome explains.
Herpes simplex virus, 3D illustration
Most people have been exposed to at least one of the two main herpes viruses, HSV-1 and HSV-2. Around two-thirds of people under 50 carry HSV-1, the virus that causes cold sores around the mouth. (© Dr_Microbe – stock.adobe.com)

Existing antiviral medications can help reduce herpes outbreaks, but they don’t get rid of the viruses completely. That’s because herpes is what’s known as a latent or persistent virus. Its DNA is able to integrate into the genomes of the human nerve cells it infects, staying put for life and randomly reactivating to cause more viral shedding and sores.

The new gene therapy aims to use molecular tools to surgically remove the herpes DNA from nerve cells in a highly precise way. Here’s how it works:

The researchers injected into the bloodstream a mixture of gene editing components packaged inside a modified virus shell. This virus shell, called a vector, can penetrate into cells and deposit its cargo. The cargo contains gene editing enzymes called meganucleases, which act like molecular scissors.

Once the vectors reach the nerve cell clusters harboring the latent herpes viruses, the molecular scissors get to work. They literally “snip away” at two different spots in the herpes genetic code, cutting it up so badly that it becomes corrupted beyond repair. The body’s cellular repair systems then recognize the mangled viral DNA as a foreign object and destroy it.

“We are using a meganuclease enzyme that cuts in two different places in the herpes virus’s DNA,” says study co-author Dr. Martine Aubert. “These cuts damage the virus so much that it can’t repair itself. Then the body’s own repair systems recognize the damaged DNA as foreign and get rid of it.”

In mice infected with the HSV-1 strain, a single treatment with the gene therapy eliminated over 90 percent of the virus from nerves involved in oral herpes and 97 percent from those linked to genital herpes after about a month. Even better, it also dramatically reduced the amount of infectious virus particles being shed from nerves, which is key for stopping it from passing to another person through skin-on-skin contact.

“Our new study shows that we can reduce both the amount of virus within the body and how much virus is shed,” Jerome says.

The researchers have steadily improved and simplified the gene therapy too. Earlier versions required multiple editing enzymes, while this latest iteration uses just one vector and one meganuclease that cuts the viral DNA in two spots.

“Our streamlined gene editing approach is effective at eliminating the herpes virus and has less side effects to the liver and nerves,” Jerome continues. “This suggests that the therapy will be safer for people and easier to make, since it has fewer ingredients.”

Turning this gene editing approach into an approved treatment for humans will take more time and research, including clinical trials. The team is also working to adapt it for HSV-2 infections. However, they’re still excited that a cure could be on the horizon after decades of fruitless efforts.

“We’re collaborating with numerous partners as we approach clinical trials so we align with federal regulators to ensure safety and effectiveness of the gene therapy,” Jerome concludes. “We deeply appreciate the support of herpes advocates as they share our vision for curing this infection.”

The researchers received funding from the National Institutes of Health, the Caladan Foundation, and more than 2,000 donors. The meganucleases used in this research are derivatives of commercially-available meganucleases.

https://studyfinds.org/gene-editing-cure-herpes-for-good/

morganism

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Re: Medical science
« Reply #9 on: May 21, 2024, 08:45:41 AM »
 The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart)

Abstract

Objective: To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts.

Design: A prospective, randomized controlled trial with 2 treatment arms for warts in children.

Setting: The general pediatric and adolescent clinics at a military medical center.

Patients: A total of 61 patients (age range, 3-22 years) were enrolled in the study from October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for analysis.

Intervention: Patients were randomized using computer-generated codes to receive either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a maximum of 2 months. Patients had their warts measured at baseline and with return visits.

Main outcome measure: Complete resolution of the wart being studied.

Results: Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did so within the first month of treatment.

Conclusion: Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.

https://pubmed.ncbi.nlm.nih.gov/12361440/

morganism

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Re: Medical science
« Reply #10 on: May 23, 2024, 12:16:58 AM »

New Startup Brainbridge Wants to Perform Head Transplants  (advancing longevity for the ultra-wealthy)

BrainBridge, the world’s first concept for a head transplant system, which integrates advanced robotics and artificial intelligence to execute complete head and face transplantation procedures. This state-of-the-art system offers new hope to patients suffering from untreatable conditions such as stage-4 cancer, paralysis, and neurodegenerative diseases like Alzheimer’s and Parkinson’s.

History of Whole Brain and Head Transplant Research

BRAVE, the BRain Anastomosis Venture is part of a larger scope project – PERSEUS – that aims at moving an old brain into a young immunoconditioned body (or a nonsentient clone tout court when this becomes available) and kick off rejuvenation of the brain, as afforded by Progressive Brain Replacement (J Hebert, accompanying editorial).

Challenges of Brain Transfer:
1. Impossibility to extract the brain proper from the dura mater, given the intimate relationship between the brain’s venous and cerebrospinal fluid (CSF) outflow and the dural cranial sinuses
2. Impossibility to resuture the internal carotid and vertebral arteries (ICAs/VAs) and the internal jugular veins (IJV) once the brain is laid on the donor’s skull base
3. Lack of an efficient technology to functionally reconnect the 12 pairs of cranial nerves
4. Lack of a technology to reconnect the severed spinal cord
5. Undetermined neuroprotective measures to deploy between the moment of physical separation of the brain from R’s skull and re-establishment of circulation after positioning on D’s skull base
6. Possible immune rejection if BT is carried out on a heterologous body rather than R’s clone.

The last three points are covered elsewhere.
* the spinal cord – once sharply severed – can be functionally reconnected in primates (GEMINI protocol: Fully reviewed in Canavero and Ren)
* Brain protection through profound hypothermia has been demonstrated by Dr. White 50 years ago in primates and more recently confirmed in China. Other techniques can boost hypothermia’s effects. The brain is a partially immunoprivileged organ.
* Brain Transfer on a clone would not require immunosuppressants. Tolerogenic protocols are being developed that may be tapped for heterologous brain transfers.

The Brain is Transplanted Along With the Dural Sac
Sparing the dural venous sinuses along with all the veins and arachnoidal granulations is currently unachievable. Besides, the subdural circulation of CSF would be totally disrupted. The solution is transplanting the brain inside the dural sac.

Briefly, both individuals are trachetomized and ventilated and installed in the upright position. Heads are secured on both sides with a fixation apparatus adapted from the maxillofacial equivalent and centered on the mastoids. A standard fixation is of course to no avail given the wide dural exposition necessary for a BT and the associated ultraextensive craniectomy.

Predicated on the complete expendability of R’s body, the approach in R starts with a nasion-C7 spinous process linear incision followed by full thickness scalping of the head down to the orbital ridges. The skull cap is removed in standard fashion, with multiple burr holes on the two sides of the superior longitudinal sinus and other holes, including along the basal circumference. A standard wide craniectomy frees the cerebellum.

https://www.nextbigfuture.com/2024/05/new-startup-brainbridge-wants-to-perform-head-transplants.html#more-195597

morganism

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Re: Medical science
« Reply #11 on: May 23, 2024, 12:23:37 AM »
Non-invasive zaps to the spinal cord can treat paralysis—but no one knows why
The benefits may seem small, but they can make a world of difference, patients say.

With a zap of electricity from well-placed electrodes on the back of the neck, patients with tetraplegia can regain some modest yet potentially "life-changing" functioning of their hands and arms, according to data from a small clinical trial published Monday in Nature Medicine.

The relatively simple stimulation method—which requires no surgery—offers an accessible and more affordable non-invasive means for those living with paralysis to regain some meaningful function, the researchers behind the trial say. However, the therapy's further potential remains limited given that scientists have yet to fully understand exactly why it works.

For the trial, 60 patients with tetraplegia underwent the stimulation therapy over at least 24 sessions during a two-month period. At the end, 72 percent (43 patients) saw clinically meaningful improvements in both strength and functional performance. Further, 90 percent (54 patients) saw improvement from at least one strength or functional outcome. There were no serious adverse events reported.

"The most exciting thing for us is that we're seeing effects that improve quality of life," Chet Moritz, a co-author of the study and co-director for the Center for Neurotechnology at the University of Washington, said in a press briefing. "And also, we believe that the stimulation may be causing neuroplasticity or, in a sense, healing part of the damage to the spinal cord injury, such that the benefits persist beyond stimulation."

Still, the researchers behind the study are confident that the gains they saw were not simply placebo effects. For one thing, all the trial participants spent two months in standard rehabilitation therapy before they underwent the stimulation therapy. And their progress in that first phase of the trial was compared to their progress in the second half, in which they received the therapy. The differences were "very dramatic for many of the measures," Edelle Field-Fote, a co-author and director of Spinal Cord Injury Research at Shepherd Center in Georgia, said in the briefing.
Real improvements

Melanie Reid, a trial participant and journalist with The Times of London who spoke at the press briefing, was quick to report that she also believed the benefits seen were not from a placebo effect. Reid broke her neck 14 years ago in a fall from a horse. She was initially left with little function below her armpits but eventually regained some function of her right hand, while her left remained "useless." She said that with the stimulation therapy, she had regained function in her left hand, allowing her to release a seat belt buckle, scroll on touchscreen devices, and put her hair in a ponytail.

In response to a question about placebo effects, Reid recalled an instance during therapy in which she was holding a wide, weighted jar in her hand. With the stimulator on, "I was able to hold it quite comfortably," she said. But then, the stimulator was turned off, and the loss of the stimulation caused her to immediately drop the jar. "It was, to me, a real illustration of the increased power [from the therapy]," she said.

And that increased power can make a world of difference, she emphasized. "Everyone thinks that spinal injury, you know, all you want to do is be able to walk again, but if you're a tetraplegic or a quadriplegic, what matters most is working hands," she said. "There's no miracles in spinal injuries, but tiny gains can be life-changing."

Another trial participant, Sherown Campbell, echoed Reid's points at the briefing. Campbell broke his neck about 10 years ago during a wrestling match and was subsequently diagnosed with quadriplegia. During the stimulation therapy, he could see real improvements in grasping and pinching tests. But, he also saw improvements at home afterward, with no stimulation. He improved his ability to open jars, grip a steering wheel, and tie balloons. Campbell also reported that, after the therapy, he regained the ability to sweat below the level of his injury, which allows him to control his body temperature in hot weather and during exercise—a significant improvement in quality of life.
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Unknowns

While the therapy is making improvements in patients' lives, the potential for it to move past these modest (though meaningful) gains is held back by a lack of understanding of how the therapy works. In the study, the researchers describe the stimulation therapy as being from two electrodes placed along the spine, with one below and one above the point of injury. The electrodes then produce a stimulation at "30 Hz with a 10-kHz carrier frequency overlay, which consisted of 10 pulses with a 10-kHz frequency and 100-μs pulse width." But it's unclear how this stimulation is improving muscle control and, potentially, spurring neuroplasticity.

The device is similar to external spinal cord stimulators that are already used to treat chronic pain. But, even with those, researchers are still debating why it helps. The initial idea for the stimulation stems from the "gate control theory" dating back to the 1960s. In this hypothesis, pain impulses from around the body travel to the spinal cord to send a message up to the brain. But, at the spinal cord, there's a gated entry for the signal to continue on. The pain impulses, which travel along smaller fibers, can open the gate. But, if signals from larger, sensory fibers are activated (such as by a stimulator), they can close the gate, blocking the pain signal from reaching the brain. This is why, the theory initially went, sensations of hot, cold, or skin rubbing can also disrupt the feeling of pain. But in the decades since the theory's origin, researchers have come to understand that pain perception is far more complex, potentially involving various types of cells in the central nervous system, immune cell activation, ion channel alterations, epigenetics, and chemical mediators.

The researchers behind the trial call for more studies into the mechanisms responsible for the improvements seen in their patients. In the meantime, a startup called Onward Medical is preparing the non-invasive stimulator for the commercial market, calling it the ARC-EX system. In April, Onward reported that it had submitted the device to the Food and Drug Administration for review. Researchers involved in the trial also said they were working on implantable devices that they hoped could achieve greater benefits.

https://arstechnica.com/science/2024/05/non-invasive-zaps-to-the-spinal-cord-can-treat-paralysis-but-no-one-knows-why/#p3

morganism

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Re: Medical science
« Reply #12 on: May 25, 2024, 11:29:30 PM »
Kombucha Tea-associated microbes remodel host metabolic pathways to suppress lipid accumulation

The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintain C. elegans on a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture. KT microbes robustly colonize the gut of KTM-fed animals and confer normal development and fecundity. Intriguingly, animals consuming KTMs display a marked reduction in total lipid stores and lipid droplet size. We find that the reduced fat accumulation phenotype is not due to impaired nutrient absorption, but rather it is sustained by a programed metabolic response in the intestine of the host. KTM consumption triggers widespread transcriptional changes within core lipid metabolism pathways, including upregulation of a suite of lysosomal lipase genes that are induced during lipophagy. The elevated lysosomal lipase activity, coupled with a decrease in lipid droplet biogenesis, is partially required for the reduction in host lipid content. We propose that KTM consumption stimulates a fasting-like response in the C. elegans intestine by rewiring transcriptional programs to promote lipid utilization. Our results provide mechanistic insight into how the probiotics in Kombucha Tea reshape host metabolism and how this popular beverage may impact human metabolism.

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011003


morganism

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Re: Medical science
« Reply #13 on: May 26, 2024, 03:10:09 AM »
Male birth control breakthrough safely switches off fit sperm for a while

(we know what actually works for this. There was a problem with cottonseed oil in China long ago. It made men infertile. It reversed in all but 10% of men with time. Thats a lot less than ladies on birth control)

A non-hormonal, reversible and non-toxic male birth control could be a step closer, with scientists successfully targeting a protein that's crucial in making fertile sperm. Knocking this protein out for a period of time would give men control over their protection window, much like oral contraceptives for women – but without other side effects and no long-lasting fertility issues.

Scientists already knew that a serine/threonine kinase 33 (STK33) gene mutation results in the male being sterile. When Baylor College of Medicine researchers found a small-molecule compound that could knock out STK33 temporarily, it produced the same result. While not the first non-hormonal sperm-targeted therapy, this research finds a new target as the science world continues its long quest to find 'the pill' for men.

“Although researchers have been investigating several strategies to develop male contraceptives, we still do not have a birth control pill for men,” said corresponding author Dr Martin Matzuk, director of the Center for Drug Discovery at Baylor. “In this study we focused on a novel approach – identifying a small molecule that would inhibit serine/threonine kinase 33 (STK33), a protein that is specifically required for fertility in both men and mice.

“STK33 is therefore considered a viable target with minimal safety concerns for contraception in men,” he added.

The team screened its "multi-billion compound collection" to locate potential STK33 inhibitors, which they then modified to make more stable, targeted and powerful for trials on mice.

“Among these modified versions, compound CDD-2807 turned out to be the most effective,” said first author Dr Angela Ku, from the Matzuk lab at Baylor.

“Next, we tested the efficacy of CDD-2807 in our mouse model,” said co-author Courtney M. Sutton, also of the Matzuk lab. “We evaluated several doses and treatment schedules and then determined sperm motility and number in the mice as well as their ability to fertilize females.”

CDD-2807 was able to cross the blood-testis barrier, heading straight for STK33 and affecting sperm numbers and motility, effectively thwarting fertility even at a low drug dose.

“We were pleased to see that the mice did not show signs of toxicity from CDD-2807 treatment, that the compound did not accumulate in the brain, and that the treatment did not alter testis size," said Sutton. “Importantly, the contraceptive effect was reversible. After a period without compound CDD-2807, the mice recovered sperm motility and numbers and were fertile again.”

While we're still not likely to be able to grab a packet of these at the drugstore anytime soon, the team will move onto further testing of CDD-2807 and other potential candidate compounds.

“Our goal is to further evaluate this STK33 inhibitor and compounds similar to CDD-2807 in primates to determine their effectiveness as reversible male contraceptives,” Matzuk said.

Of course, it remains to be seen if this target molecule could have the same impact on human sperm.

Still, we're yet to crack this elusive code that would produce the very first temporary contraceptive product for men. Other research has included gel injections that block the release of sperm, ultrasound pulses that kill them and even similar binders and inhibitors to offer a non-hormonal to produce unviable sperm.

This latest study was published in the journal Science.

Source: Baylor College of Medicine

https://newatlas.com/medical/male-birth-control-stk333/


Reversible male contraception by targeted inhibition of serine/threonine kinase 33

There are numerous forms of female contraception in clinical use, but male contraception continues to be very limited and lacks a medication-based approach. A poorly understood kinase called STK33 is enriched in the testis, and both men and mice that lack this kinase are infertile. Building on these findings, Ku et al. performed large-scale drug screening to identify chemical inhibitors of STK33, obtained crystal structures of STK33 with some of the compounds, and used this information to inform structure-activity relationship studies (see the Perspective by Holdaway and Georg). The most promising compound successfully reduced fertility in vivo in male mice without any detectable safety concerns. Importantly, the effects of this treatment were reversible, and the mice recovered their fertility soon after the treatment was discontinued. —Yevgeniya Nusinovich
Abstract
Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

https://www.science.org/doi/10.1126/science.adl2688

An emerging target for male contraception
An inhibitor of a nonhormonal target is identified using a DNA-encoded chemical library

https://www.science.org/doi/10.1126/science.adp6432