ZNAK SAGITE — više od fantastike — edicija, časopis, knjižara...

"You're all going to die": A scientifically proven pep-talk for winning

Prvo marihuana, a sad, vrlo moguće i ekstazi će moći da se izdaje na recept u doglednoj budućnosti. Kao deo terapije za posttraumatski stresni poremećaj. Slutim skok u samodijagnostikovanom PTSD za jedno pola decenije    :



FDA's OK on trial opens possibility of prescription ecstasy in five years

ima preporuka da se ekstazi koristi i kod delusional disorders, a moj seal of approval bi dobili odmah! sreća pa se ne pitam.

Još jedna iz niza psihoaktivnih supstanci za koje se preispituje mogućnost korišćenja u terapijske svrhe: psilocibin.


https://www.theguardian.com/society/2016/dec/01/magic-mushroom-ingredient-psilocybin-can-lift-depression-studies-show


A single dose of psilocybin, the active ingredient of magic mushrooms, can lift the anxiety and depression experienced by people with advanced cancer for six months or even longer, two new studies show.

Researchers involved in the two trials in the United States say the results are remarkable. The volunteers had "profoundly meaningful and spiritual experiences" which made most of them rethink life and death, ended their despair and brought about lasting improvement in the quality of their lives.

The results of the research are published in the Journal of Psychopharmacologytogether with no less than ten commentaries from leading scientists in the fields of psychiatry and palliative care, who all back further research. While the effects of magic mushrooms have been of interest to psychiatry since the 1950s, the classification of all psychedelics in the US as schedule 1 drugs in the 1970s, in the wake of the Vietnam war and the rise of recreational drug use in the hippy counter-culture, has erected daunting legal and financial obstacles to running trials.

"I think it is a big deal both in terms of the findings and in terms of the history and what it represents. It was part of psychiatry and vanished and now it's been brought back," said Dr Stephen Ross, director of addiction psychiatry at NYU Langone Medical Center and lead investigator of the study that was based there.

Tiny minority of people with depression get treatment, study finds


Read moreAround 40-50% of newly diagnosed cancer patients suffer some sort of depression or anxiety. Antidepressants have little effect, particularly on the "existential" depression that can lead some to feel their lives are meaningless and contemplate suicide.
The main findings of the NYU study, which involved 29 patients, and the larger one from Johns Hopkins University with 51 patients, that a single dose of the medication can lead to immediate reduction in the depression and anxiety caused by cancer and that the effect can last up to eight months, "is unprecedented," said Ross. "We don't have anything like it."

The results of the studies were very similar, with around 80% of the patients attributing moderately or greatly improved wellbeing or life satisfaction to a single high dose of the drug, given with psychotherapy support.

Professor Roland Griffiths, of the departments of psychiatry and neuroscience who led the study at Johns Hopkins University school of medicine, said he did not expect the findings, which he described as remarkable. "I am bred as a sceptic. I was sceptical at the outset that this drug could produce long-lasting changes," he said. These were people "facing the deepest existential questions that humans can encounter - what is the nature of life and death, the meaning of life."

But the results were similar to those they had found in earlier studies in healthy volunteers. "In spite of their unique vulnerability and the mood disruption that the illness and contemplation of their death has prompted, these participants have the same kind of experiences, that are deeply meaningful, spiritually significant and producing enduring positive changes in life and mood and behaviour," he said.
Patients describe the experiences as "re-organisational", said Griffiths. Some in the field had used the term "mystical", which he thought was unfortunate. "It sounds unscientific. It sounds like we're postulating mechanisms other than neuroscience and I'm certainly not making that claim."

Ross said psilocybin activates a sub-type of serotonin receptor in the brain. "Our brains are hard-wired to have these kinds of experiences - these alterations of consciousness. We have endogenous chemicals in our brain. We have a little system that, when you tickle it, it produces these altered states that have been described as spiritual states, mystical states in different religious branches.
"They are defined by a sense of oneness – people feel that their separation between the personal ego and the outside world is sort of dissolved and they feel that they are part of some continuous energy or consciousness in the universe. Patients can feel sort of transported to a different dimension of reality, sort of like a waking dream."

Some patients describe seeing images from their childhood and very commonly, scenes or images from a confrontation with cancer, he said. The doctors warn patients that it may happen and not to be scared, but to embrace it and pass through it, he said.
The commentators writing in the journal include two past presidents of the American Psychiatric Association, the past president of the European College of Neuropsychopharmacology, a previous deputy director of the Office of USA National Drug Control Policy and a previous head of the UK Medicines and Healthcare Regulatory Authority.

The journal editor, Professor David Nutt, was himself involved in a small trial of psilocybin in a dozen people with severe depression in the UK in May. The ten commentators in the journal, he writes in an editorial, "all essentially say the same thing: it's time to take psychedelic treatments in psychiatry and oncology seriously, as we did in the 1950s and 1960s."
Much more research needs to be done, he writes. "But the key point is that all agree we are now in an exciting new phase of psychedelic psychopharmacology that needs to be encouraged not impeded."

The studies were funded by the Heffter Research Institute in the USA. "These findings, the most profound to date in the medical use of psilocybin, indicate it could be more effective at treating serious psychiatric diseases than traditional pharmaceutical approaches, and without having to take a medication every day," said its medical director George Greer.

1 Patient, 7 Tumors and 100 Billion Cells Equal 1 Striking Recovery

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The remarkable recovery of a woman with advanced colon cancer, after treatment with cells from her own immune system, may lead to new options for thousands of other patients with colon or pancreatic cancer, researchers are reporting.

Quote from: Meho Krljic on 13-12-2016, 08:49:32
1 Patient, 7 Tumors and 100 Billion Cells Equal 1 Striking Recovery

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The remarkable recovery of a woman with advanced colon cancer, after treatment with cells from her own immune system, may lead to new options for thousands of other patients with colon or pancreatic cancer, researchers are reporting.

e pa mehane, ovo je to zbog čega se imunologija voli.

ljudi su uspeli da lociraju autologe CD8+ limfocite (in general ih imunski sistem koristi kao asasine) koji specifično prepoznaju neopeptide koji su se eksprimirali na malignim ćelijama kancera (i nema ih na zdravim ćelijama! ) kao posledica tzv. KRAS (Kirsten rat sarcoma viral oncogene) point mutacije (samo JEDNA (!) aminokiselina u proteinu je izmenjena a dobili smo "mašinu od proteina" koju ne možemo više da isključimo):


http://www.youtube.com/watch?v=GU-QZp5FwM8


evo i CD8+ asasina:

http://www.youtube.com/watch?v=oqI4skjr6lQ

Pa, to i ja kažem! EKSPRIMIRALI 

aj dobro, sledeći put ću biti preciznija i reći da su ti tumorski neopeptidi delovi endogeno sintetisane citoplazmatske mutirane GTPaze koji su prikazani u sklopu MHC molekula I klase i koje prepoznaju autologi tumor-infiltrirajući CD8+ T limfociti. 

CD8+. Sej nou mor. 

samo da podelim sa sagiticom kojom vakcinom bockam drage roditelje protiv gripa, odlično se pokazala za ljude preko 65 godina koji su generalno slabi responderi kad je ta vakcina u pitanju:
http://www.fluzone.com/fluzone-high-dose-vaccine.cfm

Evo, turisti nek se strpe a domoroci nek se snalaze do 2017. godine:
Successful Ebola vaccine will be fast-tracked for use

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A highly effective vaccine that guards against the deadly Ebola virus could be available by 2018, says the World Health Organization.
Trials conducted in Guinea, one of the West African countries most affected by an outbreak of Ebola that ended this year, show it offers 100% protection.
The vaccine is now being fast-tracked for regulatory approval.
Manufacturer Merck has made 300,000 doses of the rVSV-ZEBOV vaccine available for use should Ebola strike.
GAVI, the global vaccine alliance, provided $5m for the stockpile.
Results, published in The Lancet medical journal, show of nearly 6,000 people receiving the vaccine, all were free of the virus 10 days later.
In a group of the same size not vaccinated, 23 later developed Ebola.
Only one person who was vaccinated had a serious side effect that the researchers think was caused by the jab. This was a very high temperature and the patient recovered fully.
It is not known how well the vaccine might work in children since this was not tested in the trial.
Analysis - Tulip Mazumdar, Global Health CorrespondentEbola has been around for 40 years now. But it wasn't until the height of the 2014 outbreak in West Africa that the world decided to invest some serious money into finding treatments and cures.
I watched as families of those who had become infected were isolated in their homes. Often entire neighbourhoods were quarantined behind orange fencing. That was their best chance of not becoming infected and infecting others.

But as hundreds of people continued to die, and cases started being exported to Europe and the US - the world decided to act.
Now, two years later, we have a vaccine. It usually takes around 10 years.
There were some mild side effects reported in this trial, and the vaccine is only known to protect against one of the strains of Ebola, but it is the most deadly Zaire strain.
Today's news is a very welcome and much needed breakthrough. However, as the WHO points out, more lives would be saved if countries invested in vaccines before outbreaks, rather during them.

---

The director of British-based medical research institute the Wellcome Trust described the findings as "remarkable".
"Had a vaccine been available earlier in the Ebola epidemic, thousands of lives might have been saved," Jeremy Farrar said.
"We have to get ahead of the curve and make promising diagnostics, drugs and vaccines for diseases we know could be a threat in the future."
Ebola - mapping the outbreak
The trial was led by the World Health Organization (WHO), working with Guinea's health ministry and international groups.
The WHO's Marie-Paule Kieny said the results could help combat future outbreaks.
"While these compelling results come too late for those who lost their lives during West Africa's Ebola epidemic, they show that when the next Ebola outbreak hits, we will not be defenceless," said Dr Kieny, the lead author of the study.
Other drug companies are developing different Ebola vaccines that could be used in the future too.
The Ebola virus was first identified in 1976 but the recent outbreak in West Africa, which killed more than 11,000 people, highlighted the need for a vaccine.
The outbreak began in Guinea in 2013 and spread to Liberia and Sierra Leone.

well, trebalo je ranije uvesti ebolu u krajeve velikog belog čoveka...

trebao je sad veliki bijeli covjek loviti zirafe, plesati oko totema, zuriti u nebo, stancati djecu i vikati kuku, pa bi mali crni mozda razvio cjepivo...

putuješ negde? 

Quote from: Meho Krljic on 03-12-2016, 07:26:41
Prvo marihuana...

btw, ovih dana čitam studije vezane za upotrebu kanabinoid ulja (CBD) u tretmanu psihoze al nekako mi sve to nije ubedljivo. javlja mi se da je psihoterapija jedina stvar koja eventualno može pomoći, a i to samo ukoliko je osoba svesna da joj je pomoć potrebna.

U Americi:

Fewer people are dying of cancer than ever before

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The number of Americans dying of cancer has dropped to a 25-year low, equaling an estimated 2,143,200 fewer deaths in that period, says the new annual report from the American Cancer Society. In that time, the racial and gender disparities that exist in cancer rates have also narrowed somewhat, but they remain wide in many places.
Though the incidence of cancer remained stable for women and dropped slightly — by 2 percent — in men, rates remain overall 20 percent higher in men while rate of death for men is 40 percent higher than in women. The rates of both incidence and death vary wildly based on the type of cancer. The data that the ACS is using run through the end of 2014 for incidents of cancer and through 2013 for deaths.
Lung cancer remains the leading cause of cancer death in the United States for both men and women. Overall, lung cancer rates are continuing to decline faster in men than in women, as historically women took up smoking in larger numbers than men and were, according to their data, slower to quit. The ACS predicts that the largest number of new cancer diagnoses — nearly 300,000 of them — for men will be prostate cancer, while the largest number of new cancer diagnoses for women will be in the form of breast cancer.
The ACS reports that though the cancer death rate remains 15 percent higher for blacks than whites for 2014, the passing of the "Patient Protection and Affordable Care Act may expedite the narrowing racial gap." The data shows that from 2010 to 2015 the number of uninsured blacks was cut in half, from 21 percent to 11 percent, while the number of uninsured Hispanics fell from 31 percent to 16 percent.
The decline in deaths from cancer is attributed largely to the fact that fewer people smoke — from about 42 percent in 1965 to 17 percent in 2013 — as well as earlier detection for certain types of cancer.

Doduše, možda je to zato jer umiru od drugih bolesti više nego što bi trebalo:

Life Expectancy In U.S. Drops For First Time In Decades, Report Finds

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One of the fundamental ways scientists measure the well-being of a nation is tracking the rate at which its citizens die and how long they can be expected to live.
So the news out of the federal government Thursday is disturbing: The overall U.S. death rate has increased for the first time in a decade, according to an analysis of the latest data. And that led to a drop in overall life expectancy for the first time since 1993, particularly among people younger than 65.
"This is a big deal," says Philip Morgan, a demographer at the University of North Carolina, Chapel Hill who was not involved in the new analysis.
"There's not a better indicator of well-being than life expectancy," he says. "The fact that it's leveling off in the U.S. is a striking finding."
Now, there's a chance that the latest data, from 2015, could be just a one-time blip. In fact, a preliminary analysis from the first two quarters of 2016 suggests that may be the case, says Robert Anderson, chief of the mortality statistics branch at the National Center for Health Statistics, which released the new report.  Anderson says government analysts are awaiting more data before reaching any definitive conclusions.
"We'll have to see what happens in the second half of 2016," he says.
Still, he believes the data from 2015 are worth paying attention to. Over that year, the overall death rate increased from 724.6 per 100,000 people to 733.1 per 100,000.
While that's not a lot, it was enough to cause the overall life expectancy to fall slightly. That's only happened a few times in the past 50 years. The dip in 1993, for example, was due to high death rates from AIDS, flu, homicide and accidental deaths that year.
On average, the overall life expectancy, for someone born in 2015, fell from 78.9 years to 78.8 years. The life expectancy for the average American man fell two-tenths of a year — from 76.5 to 76.3. For women, it dropped one-tenth — from 81.3 to 81.2 years.
"It's remarkable," Morgan says. "There are lots of things about this that are unexpected."
Most notably, the overall death rate for Americans increased because mortality from heart disease and stroke increased after declining for years. Deaths were also up from Alzheimer's disease, respiratory disease, kidney disease and diabetes. More Americans also died from unintentional injuries and suicide. In all, the decline was driven by increases in deaths from eight of the top 10 leading causes of death in the U.S.
"When you see increases in so many of the leading causes of death, it's difficult to pinpoint one particular cause as the culprit," Anderson says.
The obesity epidemic could be playing a role in the increase in deaths from heart disease, strokes, diabetes and possibly Alzheimer's. It could also be that doctors have reached the limit of what they can do to fight heart disease with current treatments.
The epidemic of prescription opioid painkillers and heroin abuse is probably fueling the increase in unintentional injuries, Arun Hendi, a demographer at Duke University, wrote in an email. The rise in drug abuse and suicide could be due to economic factors causing despair.
"Clearly, that could be related to the economic circumstances that many Americans have experienced in the last eight years, or so, since the recession," says Irma Elo, a sociologist at the University of Pennsylvania.
Whatever the cause, the trend is concerning, especially when the death rate is continuing to drop and life expectancy is still on the rise in most other industrialized countries.
"It's pretty grim," says Anne Case, an economist at Princeton University studying the relationship between economics and health.

The Tiny Robots Revolutionizing Eye Surgery

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Machines that are capable of making precise operations inside the human eye will make it possible to perform entirely new procedures.


Last September, Robert MacLaren, an ophthalmologist and professor at Oxford University, plunged a tiny robotic arm into William Beaver's eye. A membrane had recently contracted on the 70-year-old priest's retina, pinching it into an uneven shape and causing him to see the world as if reflected in a hall of mirrors.
Using a joystick and a camera feed, MacLaren guided the arm of the Robotic Retinal Dissection Device, or R2D2 for short, through a tiny incision in the eye, before lifting the wrinkled membrane, no more than a hundredth of a millimeter thick, from the retina, and reversing Beaver's vision problems.
It was the first operation performed inside the human eye using a robot. Since September, five more patients have undergone robot-assisted operations at Oxford's John Radcliffe Hospital in England, including one in which a virus, used in gene therapy to halt the effects of retinal degeneration, was planted on the retina itself, a procedure only made possible by R2D2's unprecedented precision.
"My movements were improved and finessed by the robot," MacLaren says. "I could even let go and the robot would hold everything securely in place."
In the past decade the use of robots in surgery has become commonplace. Da Vinci, an American-made surgical robot that is used to repair heart valves, among other things, has operated on more than three million patients around the world. Robotic surgery provides numerous benefits, offering surgeons a greater degree of control while simultaneously reducing a patient's trauma and risk of infection. The market for medical robotic systems will exceed $17 billion by 2020, according to some estimates. But until now surgical robots have been too bulky to be used in certain procedures at small scale (da Vinci, for example, is around the size of an elephant, its bulk necessary to push against the forces of the body wall).
R2D2, which was developed by Preceyes BV, a Dutch medical robotics firm established by the University of Eindhoven, is not the only robot targeting the human eye. Chris Wagner, head of advanced surgical systems at Cambridge Consultants, has led a team in the development of Axsis—one of the smallest known robots for surgical use, its external body is the size of a can of soda.
"Building a surgical robot that can work on the size scale of the lens of an eye, which is less than 10 millimeters across, is difficult," says Wagner, whose team began work on Axsis last April. For example, the cables that enable the robot to navigate are each 110 microns across, a little over the diameter of a human hair.
Both R2D2, which, according to MacLaren's estimates, will cost around $1 million, and Axsis are prototype robots currently unavailable on the market. Cambridge Consultants hopes that future versions of its Axsis robot will prove affordable for smaller hospitals, thereby lowering the barrier to entry for less experienced robotic surgeons.
"With this system, we're trying to expand the range of procedures that should be considered candidates for robotic technology, in terms of the size of the manipulations and the size of the access," says Wagner. He hopes that Axsis could, for example, be used to operate on cataracts, the most commonly performed surgery in developed countries. Oxford's MacLaren, however, is skeptical of the need for robotic support in this kind of routine eye operation. To meet the demand, "thousands of machines" would have to be manufactured, he says. "It's clearly not necessary. But these robots do open up a new chapter of operations that are currently impossible."
MacLaren believes that R2D2 and other robots like it will enable surgeons to, for the first time, operate underneath the retina and interact with blood vessels in the eye. "Undoubtedly this will lead to improvements in quality of eye surgery that require highly technical procedures," he says. "But most significantly they will open the door to new operations for which the human hand does not have the necessary control and precision."

Jako lepo za nas bogate i matore!

First human-pig chimeras spark hopes for transplantable organs — and debate

http://www.pbs.org/newshour/rundown/first-human-pig-chimeras-spark-hopes-transplantable-organs-debate/

Spiderpig, spiderpig!

Krejzi:

Nicotine shown to reduce symptoms of schizophrenia

A s druge strane i srodno ovom splajsovanju čoveka i svinje iz Batinog posta, kod miševa izlečen dijabetes pomoću ćelija koje su uzgojene u pacovima:

Scientists have discovered a process that could transform human organ transplants

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Hundreds of people die every day while waiting for an organ transplant. A solution to this horrible reality is to make human organs readily available—by growing them on-demand in labs or even other animals.
Scientists in Japan and the US have taken a huge step in that direction. In a study published in Nature, they report to have cured mice of diabetes by transplanting mouse cells grown in rats.
To achieve this feat, researchers injected mouse pluripotent stem cells into a rat embryo. As the name suggests, these pluripotent stem cells are able to transform themselves into all types of cells. The mouse cells intermingled with rat cells, and created a chimera whose organs and tissues were almost all created from a mix of mouse and rat cells.
Crucially, however, they had modified the rat to not produce pancreatic cells. They achieved this by knocking out a gene called Pdx1. The upshot was that the pancreas in the chimera was almost completely made of mouse cells.
When the rat-mouse chimeras became adults, the researchers removed the animals' pancreases and from them, isolated endocrine islets, which contain β-cells that produce insulin. The β-cells were then transplanted to diabetic mice that had lost all their native β-cells.
Every human-to-human organ transplant requires the use of drugs that suppress the immune system. Though these drugs have severe side effects, without them, the body would consider the transplanted object foreign and unleash the immune system on it. Often a transplant patient has to take these drugs for life.
Anticipating a similar reaction, the mice that received the transplant were put on mild immunosuppressant drugs. However, the scientists found they only needed to administer the drugs for five days after transplantation. Surprisingly, the few rat cells that came along during the transplant (mostly in the blood vessels in the islets) had been destroyed and replaced by the mouse's own cells.
Scientists don't know yet how this happened. Qiao Zhou of Harvard University, who was not involved in the research, thinks that one way this could have occurred is that, despite the mild immunosuppressant drugs, the mouse's immune system recognized the few rat cells present in the transplantation, and destroyed them. At the same time, native mouse cells started building blood vessels to replace them.
The β-cells in mice that got the transplants functioned just as they would in a healthy mouse for more than a year, which was the complete observation period. These lab mice only live for two to three years, which makes a one-year observation fairly long. The research opens up the door for growing human organs inside, say, a pig, using the patient's own stem cells and then transplanting the organ when it's mature and ready.
There are, of course, many obstacles before we achieve that feat. For instance, the pancreas is a relatively uncomplicated organ, genetically speaking. Scientists only had to knock out one gene to ensure that rat cells didn't participate in creating the organ and mouse cells could monopolize the construction. Creation of more complex organs like the heart or kidney are controlled by many more genes, which often have multiple purposes in the body, and thus will require a more complicated genetic modification technique—or some other workaround to ensure that the changes made won't destroy some other part of the body.
In addition, mice and rats, though separate species, are close cousins. Transplanting from a pig to a human would be a bigger leap, and it will come with its own challenges. (Pigs have some organs that are roughly the same size as humans, which is why they are good candidates for future organ transplant techniques).
And maybe we won't even have to do all that. Researchers are also trying a different tack: xenotransplantations, where organs from a different species are used without the need to create a chimera. In 2013, researchers at Northwestern University showed that endocrine islets from rats could survive and thrive in mice without the use of immunosuppressant drugs.

Naravno da bi miš ozdravio, pacov mora da strada... tako da...

Quote from: Meho Krljic on 28-01-2017, 08:56:50
Krejzi:

Nicotine shown to reduce symptoms of schizophrenia

nije krejzi nimalo, vrlo je logično.
vrlo sličan mehanizam kao kod parkinsona, a za sve je naravno kriv dopamin!!!
(naravno, pojednostavljeno do bola jer svaka šiza ima svoje različitosti, a i parkinsoni nisu svi isti)

https://www.ncbi.nlm.nih.gov/pubmed/25925389

u stvari, ljudi se "self medicate" cigaretama 

Quote from: Meho Krljic on 28-01-2017, 09:09:25
A s druge strane i srodno ovom splajsovanju čoveka i svinje iz Batinog posta, kod miševa izlečen dijabetes pomoću ćelija koje su uzgojene u pacovima:

imunski sistem svinja je toliko sličan čovekovom i jedina njihova sreća da su relativno komplikovane za hendlovanje (milion aspekata) pa miševe ipak nećemo menjati. 
trenutno radimo neki tretman okularne hlamidijalne infekcije baš na svinjama, neverovatno je koliko nam je konjunktiva ista.

Predviđam budućnost u kojoj vegani i vegetarijanci poput mene odbijaju transplantaciju organa jer su uzgojeni na svinji.

Ma dobro, neće tebi ništa da otkaže, praktično bez mesa i alkohola jedva i da si živ!

Prava dilema je dal ti prasići s hlamidijom mogu poslije da se jedu, misim da spojimo lijepo i korisno!

LSD je svakako droga budućnosti pošto se još uvek proučava kako i šta on to tačno radi. U najnovijim vestima:

Why an LSD high lasts for so long

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One drop of LSD can erase your entire sense of being until—interminable hours later—you recapitulate your identity, one puzzle piece at a time. Beyond that and the iconic kaleidoscope visual effects, lysergic acid diethylamide has supposedly inspired revolutionary ideas, too. It has been famously (and controversially) credited, in part, for the creation of the iPhone and the polymerase chain reaction, the tool used to clone DNA.
And all it takes is 100 micrograms of the drug, roughly the weight of two and a half eyelashes. By contrast, a common dose of dimethyltryptamine (DMT)—the main psychedelic ingredient in the increasingly popular and purportedly therapeutic plant brew ayahuasca—is 20,000 to 40,000 micrograms. The mechanism that makes a tiny, diaphanous strip of acid-flecked paper exert such power over the brain and behavior, and for such a long time, is only just coming to light.
A new study published this week in Cell examines LSD's peculiar way of binding to brain receptor proteins—and may be a key step toward unraveling the inner workings of the drug.



"There's always been confusion about why it lasts the duration it does, and why it seems to be extraordinarily potent," says Adam Halberstadt, a pharmacologist at the University of California, San Diego, who was not involved in the new study. "So this is pretty impressive."
LSD and other psychoactive drugs work by binding to specialized proteins called receptors on the surfaces of neural cells. On the receptor protein is a sculpted "pocket," into which molecules with the right shape can fit and thus stick to the cell, where they initiate changes in the brain. But different substances can often fit into the same receptor. Many receptors that bind LSD and DMT, for example, also fit the natural chemical messenger serotonin—which is produced in the body and helps regulate mood. Figuring out how each drug interacts with the same receptor in a different way is key to understanding why an LSD trip lasts all day whereas an experience with extracted DMT is often over in 15 minutes or less.
By freezing an LSD molecule bound to a single brain cell receptor as a crystal in a lab, researchers were able to get a 3-D x-ray image of the drug and the protein locked together.
"My lab has been trying to do this since the early 1990s," says Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper. "I remember Dan Wacker [a co-author, also at U.N.C.] showing the image. It was basically a moment of silence. I started to fight back tears of gratitude that we had finally gotten it."
It is the first 3-D image of a psychedelic bound to a brain receptor, Roth says.


The image showed Roth and his co-authors something strange about the way LSD fit inside this receptor. Drugs typically come and go from receptor proteins like ships pulling in and out of a port. But when an LSD molecule lands on the receptor, the molecule snags onto a portion of the protein and folds it over itself as the molecule binds to the receptor.
"There was this lid that came over the molecule. It looked like it trapped LSD in the receptor," Roth says. "That immediately suggested to us why LSD lasts so long."


LSD seems to stimulate the receptor for the entire time it is trapped underneath the protein "lid," Roth says. Proteins are in constant motion, so he thinks the lid eventually flops open, allowing the drug to fly out and the effects to wear off. But the team ran computer models that suggest it could take hours for that to happen. Until then, the trip goes on.
Roth's experiments also suggest that the longer LSD stimulates the receptor, the more powerful the effects become. "What we show in the paper is that LSD becomes a hundred times to a thousand times more potent [after a few hours]," Roth says. "It begins to explain not only why standard recreational doses have this profound effect, but also why microdoses (about 10 micrograms of LSD) might have an effect."
So-called microdoses are minute amounts of LSD—usually about 10 times smaller than a typical recreational dose. LSD is outlawed around the world and is a Schedule I drug in the U.S. (putting it in a category with heroin and ecstasy). But microdosing has gained some traction among Silicon Valley technology workers as a creativity-boosting "smart drug." The practice has become more popular since psychologist James Fadiman wrote about it in his book The Psychedelic Explorer's Guide in 2011.
Scientists have suggested LSD might have some broad clinical use for conditions such as anxiety or addiction, and there is early evidence that it could treat cluster headaches. Roth says more research needs to be done on all of these applications, however.



"In terms of microdosing, what we really need are controlled clinical trials, and we don't have any," he explains. Some microdosers claim the practice can enhance productivity, focus and mood. Ayelet Waldman, who recently published A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life, asserts that microdosing on LSD helped her overcome depression and bipolar disorder. "I was suicidal, and now I'm not dead," Waldman says.
Roth says he had initially believed the effects of microdosing, which users say are nearly imperceptible, could be attributed to a placebo phenomenon. "Previously, I thought these are just 'homeopathic' doses—not doing anything," he says. But "these low doses, it's clear now, really can have significant effects at these receptors."
Halberstadt thinks that idea is interesting. "This could be a reason why LSD is so potent," he says. "If it has a really long dissociation rate that would magnify the effect of even very small concentrations."
But it is still unclear exactly how, once bound to LSD, these receptor proteins go on to create the specific, often bizarre effects of LSD—like the frequently reported destruction of one's sense of self, or careening uncontrollably into one's deepest, most personal memories and emotions. The work only studied two of 40 known receptors that LSD touches in the brain, says Nicholas Cozzi, a pharmacologist at the University of Wisconsin–Madison who was not involved with the study.
Any combination of those receptors working in concert, and the different ways LSD might interact with each one, may be contributing to the feeling of oneness with the universe, shifting reality or generally elevated mood often attributed to the drug.
"It's like a musical chord formed by notes," Cozzi says.
This article is reproduced with permission from Scientific American. It was first published on Jan. 27, 2017. Find the original story here.

mehane, prijaviću nas za clinical trial.

a ovo je zašto se research toliko voli 

Quote
"My lab has been trying to do this since the early 1990s," says Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper. "I remember Dan Wacker [a co-author, also at U.N.C.] showing the image. It was basically a moment of silence. I started to fight back tears of gratitude that we had finally gotten it."

Ja sam poznati strejter, ali mogu da shvatim zašto ljude toliko fascinira esid. A vidimo da su i istraživači emotivna bića 

možda je u esidu budućnost, al ima nešto i u starenju. leonard hayflick je uvek tu kad nam je najviše potreban.

QuoteThe future of ageing

Leonard Hayflick

Advances in our knowledge of age-associated diseases have far outpaced advances in our understanding of the fundamental ageing processes that underlie the vulnerability to these pathologies. If we are to increase human life expectancy beyond the fifteen-year limit that would result if today's leading causes of death were resolved, more attention must be paid to basic research on ageing. Determination of longevity must be distinguished from ageing to take us from the common question of why we age to a more revealing question that is rarely posed: why do we live as long as we do? But if the ability to intervene in ageing ever becomes a reality, it will be rife with unintended and undesirable consequences.

savršeno i jednostavno napisano, vredi pročitati: http://www.nature.com/nature/journal/v408/n6809/full/408267a0.html

Može li negde integralna verzija tog teksta za nas koji ne plaćamo pretplatu a čita nam se?



U drugim vestima, ako se ignoriše klikbejtaški naslov, ovo je vrlo zanimljivo:

Reached Via a Mind-Reading Device, Deeply Paralyzed Patients Say They Want to Live

Quote
A brain-computer interface records "yes" and "no" answers in patients who lack any voluntary muscle movement.


In 1995, Jean-Dominique Bauby suffered a massive stroke that left him paralyzed and speechless, with only the ability to blink his left eyelid. Using just that eye, he silently dictated his memoir, The Diving Bell and the Butterfly, later adapted into a film.
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Bauby suffered from "locked-in syndrome," in which patients are completely paralyzed except for some eye movement. Some patients eventually lose even the ability to blink, cutting off all contact with the world and raising questions of whether they are still fully conscious and, if so, whether they still wish to live.
Now researchers in Europe say they've found out the answer after using a brain-computer interface to communicate with four people completely locked in after losing all voluntary movement due to Lou Gehrig's disease, or amyotrophic lateral sclerosis.
In response to the statement "I love to live" three of the four replied yes. They also said yes when asked "Are you happy?" The fourth patient, a 23-year-old woman, wasn't asked open-ended questions because her parents feared she was in a fragile emotional state.
Designed by neuroscientist Niels Birbaumer, now at the Wyss Center for Bio and Neuroengineering in Geneva, the brain-computer interface fits on a person's head like a swimming cap and measures changes in electrical waves emanating from the brain and also blood flow using a technique known as near-infrared spectroscopy.
To verify the four could communicate, Birbaumer's team asked patients, over the course of about 10 days of testing, to respond yes or no to statements such as "You were born in Berlin" or "Paris is the capital of Germany" by modulating their thoughts and altering the blood-flow pattern. The answers relayed through the system were consistent about 70 percent of the time, substantially better than chance.
Birbaumer says "the relief was enormous" for family members who were able to communicate with their loved ones after as many as four years of total silence, and to learn they wished to remain alive on ventilators. They detail their experiments in a study appearing today in the journal PLOS Biology.
In 2010, British neuroscientist Adrian Owen first reported that changes in blood flow in certain parts of the brain showed that a patient previously written off as being in a vegetative state was actually conscious.
No one has a clear idea of how many locked-in patients there are, says Jane Huggins, who runs the Direct Brain Interface Laboratory at the University of Michigan, although an estimate by Dutch researchers puts it at less than one in 150,000 in that country.
Some may be misdiagnosed as being comatose because they lack eye movement or it's so subtle. Birbaumer and his team say their system could be used as a diagnostic to determine who actually remains conscious and aware, and he hopes to develop a technology to allow people with complete locked-in syndrome to select letters so they can communicate beyond answering yes-or-no questions.

Izvinjavam se, meni ga otvara, a uvek zaboravim na privilegije. 
Evo ga: https://www.dropbox.com/s/ztxqyys8u7t4lnz/the%20future%20of%20ageing.pdf?dl=0
Javi ako ima problema s linkom. I kako ti deluje Leonard. Mnogo volim da ga čitam, ima tu neku crtu u pisanju koju volim.

A ovo drugo videh juče. Fascinira koliko toga može biti omogućeno, a opet verovatno nikad neće biti dostupno širokim narodnim masama.

Quote...their system could be used as a diagnostic to determine who actually remains conscious and aware, and he hopes to develop a technology to allow people with complete locked-in syndrome to select letters so they can communicate beyond answering yes-or-no questions.

Hvala puno, ovo je za celu našu kancelariju zanimljiv tekst.

 GM Salmonella destroys cancer

Quote
A genetically modified bacterium destroys tumors by provoking an immune response, according to a study published Wednesday.

Using mice and cultures of human cancer cells, a South Korean-led scientific team demonstrated that Salmonella typhimurium engineered to make a foreign protein caused immune cells called macrophages and neutrophils to mobilize against the cancer.
The bacterium came from an attenuated strain that has little infectious potential. Such strains have been tested as vaccines. The protein, called FlaB, is made by a gene in the estuarine bacterium Vibrio vulnificus, a close relative of the cholera bacterium, Vibrio cholerae.
  Tumors shrank below detectable levels in 11 out of 20 mice injected with the modified Salmonella, said the study, published in Science Translational Medicine.
Go to j.mp/salcancer for the study. The first author was Jin Hai Zheng of Chonnam National University Hwasun Hospital, in Jeonnam, South Korea.
The engineered Salmonella provoke a sustained immune response, in addition to preventing the spread of a human colon cancer implanted in a mouse. The bacterium also were found to be nontoxic, multiplying almost exclusively inside tumors.
Sandip Patel, MD, of UC San Diego Moores Cancer Center, praised the study's "very novel strategy."
"The importance of the host bacteria (the microbiome) on immune responses against tumor is increasingly appreciated and a very active area of research," Patel said by email. "To utilize bacteria as a delivery system builds on this concept."
"The immune effects induced by Salmonella here are an important first step in stimulating an immune environment that is primed to kill tumors. Further research looking into this therapeutic strategy, as well alternative means of modulating the tumor microenvironment (toll-like receptor agonists), will be needed to help our patients have the most effective options to fight their cancer."
Researchers have explored the use of Salmonella against cancer for years, because it grows in the low-oxygen environment inside solid tumors. This environment is hard for the immune system to reach.
UC San Diego researcher Jeff Hasty has developed engineered Salmonella that deliver cancer-killing toxins inside the tumor. This bacterium periodically self-destructs when it reaches a certain population density, releasing the toxins. Some of the engineered Salmonella survive, rebuilding the population until it reaches the self-destruct density. So the tumor receives periodic doses of targeted chemotherapy.
Bacterial immunotherapy itself began more than 100 years ago, with experiments by bone surgeon and cancer researcher William Coley. But the results were inconsistent, and the method was abandoned in favor of advances in radiation, chemotherapy and surgery.

Fasting diet 'regenerates diabetic pancreas'

Quote
The pancreas can be triggered to regenerate itself through a type of fasting diet, say US researchers.
Restoring the function of the organ - which helps control blood sugar levels - reversed symptoms of diabetes in animal experiments.
The study, published in the journal Cell, says the diet reboots the body.
Experts said the findings were "potentially very exciting" as they could become a new treatment for the disease.
People are advised not to try this without medical advice.
In the experiments, mice were put on a modified form of the "fasting-mimicking diet".
It is like the human form of the diet when people spend five days on a low-calorie, low-protein, low-carbohydrate but high unsaturated-fat diet.
It resembles a vegan diet with nuts and soups, but with around 800 to 1,100 calories a day.
Then they have 25 days eating what they want - so overall it mimics periods of feast and famine.
Previous research has suggested it can slow the pace of ageing.Diabetes therapy?But animal experiments showed the diet regenerated a special type of cell in the pancreas called a beta cell.
These are the cells that detect sugar in the blood and release the hormone insulin if it gets too high.
Dr Valter Longo, from the University of Southern California, said: "Our conclusion is that by pushing the mice into an extreme state and then bringing them back - by starving them and then feeding them again - the cells in the pancreas are triggered to use some kind of developmental reprogramming that rebuilds the part of the organ that's no longer functioning."
There were benefits in both type 1 and type 2 diabetes in the mouse experiments.
Type 1 is caused by the immune system destroying beta cells and type 2 is largely caused by lifestyle and the body no longer responding to insulin.
Further tests on tissue samples from people with type 1 diabetes produced similar effects.
Dr Longo said: "Medically, these findings have the potential to be very important because we've shown - at least in mouse models - that you can use diet to reverse the symptoms of diabetes.
"Scientifically, the findings are perhaps even more important because we've shown that you can use diet to reprogramme cells without having to make any genetic alterations."

What's it like?

BBC reporter Peter Bowes took part in a separate trial with Dr Valter Longo.
He said: "During each five-day fasting cycle, when I ate about a quarter of the average person's diet, I lost between 2kg and 4kg (4.4-8.8lbs).
"But before the next cycle came round, 25 days of eating normally had returned me almost to my original weight.
"But not all consequences of the diet faded so quickly."
His blood pressure was lower as was a hormone called IGF-1, which is linked to some cancers.
He said: "The very small meals I was given during the five-day fast were far from gourmet cooking, but I was glad to have something to eat."
Peter Bowes: Fasting for science
Peter Bowes: Intermittent fasting and the good things it did to my body

---

Separate trials of the diet in people have been shown to improve blood sugar levels. The latest findings help to explain why.
However, Dr Longo said people should not rush off and crash diet.
He told the BBC: "It boils down to do not try this at home, this is so much more sophisticated than people realise."
He said people could "get into trouble" with their health if it was done without medical guidance.
Dr Emily Burns, research communications manager at Diabetes UK, said: "This is potentially very exciting news, but we need to see if the results hold true in humans before we'll know more about what it means for people with diabetes.
"People with type 1 and type 2 diabetes would benefit immensely from treatments that can repair or regenerate insulin-producing cells in the pancreas."

 Scientists Have Found a Way to Rapidly Thaw Cryopreserved Tissue Without Damage


https://youtu.be/cVfTQMh-Wd0

DARPA's Brain Chip Implants Could Be the Next Big Mental Health Breakthrough—Or a Total Disaster

Malo o bioinformatici i upotrebi data mininga u medicini:



https://startit.rs/bioinformatika-saveti-programiranje/

našli ljudi marker da se u ranim fazama bolesti vidi da li je šizofrenija il depresija, a samim tim tretman prilagodi pre nego se situacija pogorša i lekari krenu s predlozima da je klozapin iz raja izašao.

QuoteFirst physiological test for schizophrenia and depression
March 13, 2017

Researchers have found a new way of using proteins in nerve cells to identify people with depression and schizophrenia. The method, reported in Experimental Physiology, will help identify people whose depression or schizophrenia involves signalling via a receptor called NMDAR, and differentiate between the two diseases. At present, there are no diagnostic tests to help distinguish them.

NMDA receptor signalling may be decreased in schizophrenia patients and increased in those with depression. The authors hope that this research is the first step towards producing a test to identify certain forms of depression and schizophrenia. Distinguishing this specific form of these diseases could allow for earlier and more accurate diagnoses as well as more targeted treatment.

Depression is thought to affect over 300 million people worldwide1 and schizophrenia affects as many as 51 million people2. Both diseases have severe impacts on sufferers' lives3.

The researchers infused patients with a high concentration salt solution to induce the release of the hormone arginine-vasopressin (AVP), and then measured the level of the hormone in their blood. Previously, animal studies had shown that the release of AVP in response to the salt solution depends on NMDA receptor signalling. In this study, they found that AVP release can distinguish schizophrenia from depression.

Depressed patients showed an increased release of the hormone, while patients with schizophrenia showed a decreased response. Clinically, it is difficult to distinguish between these two diseases in their early phases, because symptoms are non-specific and relatively mild. This hormone test may be a simple way to distinguish and identify patients with NMDA receptor malfunction in each disorder. The study was a collaboration among Yale University, The John B. Pierce Laboratory, New Haven and the VA Medical Center, West Haven, Connecticut.

Handan Gunduz-Bruce, co-author of the paper, said, "This is the first objective, physiological marker for two major psychiatric disorders that, once fully developed into a clinical test, can allow for earlier and more accurate diagnosis, and selection of more appropriate medications for patients."

https://medicalxpress.com/news/2017-03-physiological-schizophrenia-depression.html

http://onlinelibrary.wiley.com/doi/10.1113/EP086212/epdf

Molecule kills elderly cells, reduces signs of aging in mice

Quote

Even if you aren't elderly, your body is home to agents of senility—frail and damaged cells that age us and promote disease. Now, researchers have developed a molecule that selectively destroys these so-called senescent cells. The compound makes old mice act and appear more youthful, providing hope that it may do the same for us.

"It's definitely a landmark advance in the field," says cell and molecular biologist Francis Rodier of the University of Montreal in Canada who wasn't connected to the study. "This is the first time that somebody has shown that you can get rid of senescent cells without having any obvious side effects."

As we get older, senescent cells build up in our tissues, where researchers think they contribute to illnesses such as heart disease, arthritis, and diabetes. In the past, scientists have genetically modified mice to dispatch their senescent cells, allowing the rodents to live longer and reducing plaque buildup in their arteries. Such genetic alterations aren't practical for people, but researchers have reported at least seven compounds, known as senolytics, that kill senescent cells. A clinical trial is testing two of the drugs in patients with kidney disease, and other trials are in the works.

However, current senolytic compounds, many of which are cancer drugs, come with downsides. They can kill healthy cells or trigger side effects such as a drop in the number of platelets, the cellular chunks that help our blood clot.

Cell biologist Peter de Keizer of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues were investigating how senescent cells stay alive when they uncovered a different strategy for attacking them. Senescent cells carry the type of DNA damage that should spur a protective protein, called p53, to put them down. Instead, the researchers found that a different protein, FOXO4, latches onto p53 and prevents it from doing its duty.

To counteract this effect, De Keizer and colleagues designed a molecule, known as a peptide, that carries a shortened version of the segment of FOXO4 that attaches to p53. In a petri dish, this peptide prevented FOXO4 and p53 from hooking up, prompting senescent cells to commit suicide. But it spared healthy cells. 

The researchers then injected the molecule into mutant mice that age rapidly. These rodents live about half as long as normal mice, and when they are only a few months old, their fur starts to fall out, their kidneys begin to falter, and they become sluggish. However, the peptide boosted the density of their fur, reversed the kidney damage, and increased the amount of time they could scurry in a running wheel, the scientists report online today in Cell. When the researchers tested the molecule in normal, elderly mice, they saw a similar picture: In addition to helping their kidneys and fur, the molecule also increased their willingness to explore their surroundings.

"The paper adds a potentially new way to target senescent cells," says diabetes researcher James Kirkland of the Mayo Clinic in Rochester, Minnesota. He cautions, however, that peptides like the one De Keizer and colleagues developed have their own limitations. The digestive system destroys them, so they can only be delivered through inhalation or an injection–you can't just swallow a pill, he notes.

Although the molecule did not reduce the number of platelets in either mouse group, killing off large numbers of senescent cells could still trigger a potentially fatal complication sometimes suffered by cancer patients. Moreover, senescent cells foster wound healing, and destroying the cells could impair this ability.

That's why De Keizer says he and his colleagues plan to move cautiously with their molecule. "I don't think you should start treating frail people in their 90s." Instead, he says, they want to determine whether the molecule kills cancer cells, which share some similarities with senescent cells, starting with the brain tumor glioblastoma. If the compound continues to prove safe, they can think about testing the peptide against age-related diseases or even aging itself.

The Hunt for Undiscovered Drugs at the Bottom of the Sea

'Exercise-in-a-pill' boosts athletic endurance by 70 percent

Quote

Every week, there seems to be another story about the health benefits of running. That's great -- but what if you can't run? For the elderly, obese or otherwise mobility-limited, the rewards of aerobic exercise have long been out of reach.
  Salk Institute scientists, building on earlier work that identified a gene pathway triggered by running, have discovered how to fully activate that pathway in sedentary mice with a chemical compound, mimicking the beneficial effects of exercise, including increased fat burning and stamina. The study, which appears in Cell Metabolism on May 2, 2017, not only deepens our understanding of aerobic endurance, but also offers people with heart conditions, pulmonary disease, type 2 diabetes or other health limitations the hope of achieving those benefits pharmacologically.
"It's well known that people can improve their aerobic endurance through training," says senior author Ronald Evans, Howard Hughes Medical Institute investigator and holder of Salk's March of Dimes Chair in Molecular and Developmental Biology. "The question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?"
Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. So researchers assumed that endurance is a function of the body's increasing ability to burn fat, though details of the process have been murky. Previous work by the Evans lab into a gene called PPAR delta (PPARD) offered intriguing clues: mice genetically engineered to have permanently activated PPARD became long-distance runners who were resistant to weight gain and highly responsive to insulin -- all qualities associated with physical fitness. The team found that a chemical compound called GW1516 (GW) similarly activated PPARD, replicating the weight control and insulin responsiveness in normal mice that had been seen in the engineered ones. However, GW did not affect endurance (how long the mice could run) unless coupled with daily exercise, which defeated the purpose of using it to replace exercise.
In the current study, the Salk team gave normal mice a higher dose of GW, for a longer period of time (8 weeks instead of 4). Both the mice that received the compound and mice that did not were typically sedentary, but all were subjected to treadmill tests to see how long they could run until exhausted.
Mice in the control group could run about 160 minutes before exhaustion. Mice on the drug, however, could run about 270 minutes -- about 70 percent longer. For both groups, exhaustion set in when blood sugar (glucose) dropped to around 70 mg/dl, suggesting that low glucose levels (hypoglycemia) are responsible for fatigue.
To understand what was happening at the molecular level, the team compared gene expression in a major muscle of mice. They found 975 genes whose expression changed in response to the drug, either becoming suppressed or increased. Genes whose expression increased were ones that regulate breaking down and burning fat. Surprisingly, genes that were suppressed were related to breaking down carbohydrates for energy. This means that the PPARD pathway prevents sugar from being an energy source in muscle during exercise, possibly to preserve sugar for the brain. Activating fat-burning takes longer than burning sugar, which is why the body generally uses glucose unless it has a compelling reason not to -- like maintaining brain function during periods of high energy expenditure. Although muscles can burn either sugar or fat, the brain prefers sugar, which explains why runners who "hit the wall" experience both physical and mental fatigue when they use up their supply of glucose.
"This study suggests that burning fat is less a driver of endurance than a compensatory mechanism to conserve glucose," says Michael Downes, a Salk senior scientist and co-senior author of the paper. "PPARD is suppressing all the points that are involved in sugar metabolism in the muscle so glucose can be redirected to the brain, thereby preserving brain function."
Interestingly, the muscles of mice that took the exercise drug did not exhibit the kinds of physiological changes that typically accompany aerobic fitness: additional mitochondria, more blood vessels and a shift toward the type of muscle fibers that burn fat rather than sugar. This shows that these changes are not exclusively driving aerobic endurance; it can also be accomplished by chemically activating a genetic pathway. In addition to having increased endurance, mice who were given the drug were also resistant to weight gain and more responsive to insulin than the mice who were not on the drug.
"Exercise activates PPARD, but we're showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort," says Weiwei Fan, a Salk research associate and the paper's first author.
Although the lab's studies have been in mice, pharmaceutical companies are interested in using the research to develop clinical trials for humans. The team can envision a number of therapeutic applications for a prescription drug based on GW, from increasing fat burning in people suffering from obesity or type 2 diabetes to improving patients' fitness before and after surgery.
 

---

   Story Source:
Materials provided by Salk Institute. Note: Content may be edited for style and length.
 

---

Journal Reference:

   
• Weiwei Fan, Wanda Waizenegger, Chun Shi Lin, Vincenzo Sorrentino, Ming-Xiao He, Christopher E. Wall, Hao Li, Christopher Liddle, Ruth T. Yu, Annette R. Atkins, Johan Auwerx, Michael Downes, Ronald M. Evans. PPARδ Promotes Running Endurance by Preserving Glucose. Cell Metabolism, 2017; 25 (5): 1186 DOI: 10.1016/j.cmet.2017.04.006

Eto ti ga sad:


The older the doctor, the higher the patient mortality rate, study finds

Without action on antibiotics, medicine will return to the dark ages  

Ne znamo kako će biti u budućnosti ali u sadašnjost, američki zdravstveni sistem ispašta zbog nestašice - sode bikarbone:

Baking soda shortage has hospitals frantic, delaying treatments and surgeries

ovo je američki zdravstveni sistem (bez preterivanja)

https://www.youtube.com/watch?v=yw_nqzVfxFQ

Ancient Chinese Medicine Outright Blocks Sperm From Egg

Quote
What if there was a birth control that was hormone-free, 100 percent natural, resulted in no side effects, didn't harm either eggs nor sperm, could be used in the long-term or short-term, and — perhaps the best part of all — could be used either before or after conception?
Thanks to ancient Chinese folk medicine, that's not a far-out dream.
Research published Monday in the journal Proceedings of the National Academy of Sciences by scientists at the University of California, Berkeley, identified two plant compounds that could hold the secret to preventing conception.
Here's how it works: In order to actually penetrate the egg, sperm need to whip their tails faster to pick up momentum. But there are two plant compounds that can prevent sperm from doing this, no matter how valiantly they may try — lupeol, found in mango and dandelion root, and pristimerin, from a plant called the "thunder god vine," the leaves of which had been used as birth control in traditional Chinese medicine. The sperm and egg are never actually harmed; they're just never able to meet.


"Because these two plant compounds block fertilization at very, very low concentrations — about 10 times lower than levels of levonorgestrel in Plan B — they could be a new generation of emergency contraceptive we nicknamed 'molecular condoms,'" team leader Polina Lishko, an assistant professor of molecular and cell biology, said in a press release. "If one can use a plant-derived, non-toxic, non-hormonal compound in lesser concentration to prevent fertilization in the first place, it could potentially be a better option."


In previous research, the team had identified progesterone as a key hormone in triggering the sperm tail-whipping, which it facilitates by binding to a protein called ABHD2. While reading up on folk medicines and indigenous methods of natural contraception, they found the lupeol and pristimerin and eventually determined that both work by keeping progesterone and ABHD2 apart. The concentrations of the two substances that exist naturally in plants aren't high enough for cost-effective commercial birth control, so the researchers are now looking for alternative sources.
Hormone-based birth control methods are generally well-tolerated by most people who take them, but they can also bring accompanying side effects that a lupeol- or pristimerin-based method would not. And even though they could also be used as emergency contraception taken after conception, like Plan B, it's possible this would be a more palatable option to some who disapprove of Plan B because it can stop fertilized eggs from being implanted and prevent the egg from being fertilized in the first place.

>Abstract

The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

Često kažu da je malo crnog vina dobro za kardiovaskularni sistem, antioksidansi, ovoono, ali evo sad ovo:

Even moderate drinking can damage the brain, claim researchers

New frontier in cancer care: Turning blood into living drugs

Quote
SEATTLE (AP) -- Ken Shefveland's body was swollen with cancer, treatment after treatment failing until doctors gambled on a radical approach: They removed some of his immune cells, engineered them into cancer assassins and unleashed them into his bloodstream.
Immune therapy is the hottest trend in cancer care and this is its next frontier — creating "living drugs" that grow inside the body into an army that seeks and destroys tumors.
Looking in the mirror, Shefveland saw "the cancer was just melting away." A month later doctors at the Fred Hutchinson Cancer Research Center couldn't find any signs of lymphoma in the Vancouver, Washington, man's body.
"Today I find out I'm in full remission — how wonderful is that?" said Shefveland with a wide grin, giving his physician a quick embrace.
This experimental therapy marks an entirely new way to treat cancer — if scientists can make it work, safely. Early-stage studies are stirring hope as one-time infusions of supercharged immune cells help a remarkable number of patients with intractable leukemia or lymphoma.
"It shows the unbelievable power of your immune system," said Dr. David Maloney, Fred Hutch's medical director for cellular immunotherapy who treated Shefveland with a type called CAR-T cells.
"We're talking, really, patients who have no other options, and we're seeing tumors and leukemias disappear over weeks," added immunotherapy scientific director Dr. Stanley Riddell. But, "there's still lots to learn."
T cells are key immune system soldiers. But cancer can be hard for them to spot, and can put the brakes on an immune attack. Today's popular immunotherapy drugs called "checkpoint inhibitors" release one brake so nearby T cells can strike. The new cellular immunotherapy approach aims to be more potent: Give patients stronger T cells to begin with.
Currently available only in studies at major cancer centers, the first CAR-T cell therapies for a few blood cancers could hit the market later this year. The Food and Drug Administration is evaluating one version developed by the University of Pennsylvania and licensed to Novartis, and another created by the National Cancer Institute and licensed to Kite Pharma.
CAR-T therapy "feels very much like it's ready for prime time" for advanced blood cancers, said Dr. Nick Haining of the Dana-Farber Cancer Institute and Broad Institute of MIT and Harvard, who isn't involved in the development.
Now scientists are tackling a tougher next step, what Haining calls "the acid test": Making T cells target far more common cancers — solid tumors like lung, breast or brain cancer. Cancer kills about 600,000 Americans a year, including nearly 45,000 from leukemia and lymphoma.
"There's a desperate need," said NCI immunotherapy pioneer Dr. Steven Rosenberg, pointing to queries from hundreds of patients for studies that accept only a few.
For all the excitement, there are formidable challenges.
Scientists still are unraveling why these living cancer drugs work for some people and not others.
Doctors must learn to manage potentially life-threatening side effects from an overstimulated immune system. Also concerning is a small number of deaths from brain swelling, an unexplained complication that forced another company, Juno Therapeutics, to halt development of one CAR-T in its pipeline; Kite recently reported a death, too.
And, made from scratch for every patient using their own blood, this is one of the most customized therapies ever and could cost hundreds of thousands of dollars.
"It's a Model A Ford and we need a Lamborghini," said CAR-T researcher Dr. Renier Brentjens of New York's Memorial Sloan Kettering Cancer Center, which, like Hutch, has a partnership with Juno.
In Seattle, Fred Hutch offered a behind-the-scenes peek at research underway to tackle those challenges. At a recently opened immunotherapy clinic, scientists are taking newly designed T cells from the lab to the patient and back again to tease out what works best.
"We can essentially make a cell do things it wasn't programmed to do naturally," explained immunology chief Dr. Philip Greenberg. "Your imagination can run wild with how you can engineer cells to function better."
TWO LONG WEEKS TO BREW A DOSE
The first step is much like donating blood. When leukemia patient Claude Bannick entered a Hutch CAR-T study in 2014, nurses hooked him to a machine that filtered out his white blood cells, including the T cells.
Technicians raced his bag of cells to a factory-like facility that's kept so sterile they must pull on germ-deflecting suits, booties and masks just to enter. Then came 14 days of wait and worry, as his cells were reprogrammed.
Bannick, 67, says he "was almost dead." Chemotherapy, experimental drugs, even a bone marrow transplant had failed, and "I was willing to try anything."
GENETICALLY ENGINEERING CELLS
The goal: Arm T cells with an artificial receptor, a tracking system that can zero in on identifying markers of cancer cells, known as antigens. For many leukemias and lymphomas, that's an antigen named CD19.
Every research group has its own recipe but generally, scientists infect T cells with an inactive virus carrying genetic instructions to grow the desired "chimeric antigen receptor." That CAR will bind to its target cancer cells and rev up for attack.
Millions of copies of engineered cells are grown in incubators, Hutch technicians pulling out precious batches to monitor if they're ready for waiting patients.
If they work, those cells will keep multiplying in the body. If they don't, the doctors send blood and other samples back to researchers like Riddell to figure out why.
WHAT'S THE DATA?
Small, early studies in the U.S. made headlines as 60 percent to 90 percent of patients trying CAR-Ts as a last resort for leukemia or lymphoma saw their cancer rapidly decrease or even become undetectable. Last week, Chinese researchers reported similar early findings as 33 of 35 patients with another blood cancer, multiple myeloma, reached some degree of remission within two months.
Too few people have been studied so far to know how long such responses will last. A recent review reported up to half of leukemia and lymphoma patients may relapse.
There are long-term survivors. Doug Olson in 2010 received the University of Pennsylvania's CAR-T version for leukemia. The researchers were frank — it had worked in mice but they didn't know what would happen to him.
"Sitting here almost seven years later, I can tell you it works," Olson, now 70, told a recent meeting of the Leukemia and Lymphoma Society.
Bannick, the Hutch patient treated in 2014, recalls Maloney calling him "the miracle man." He had some lingering side effects that required blood-boosting infusions but says CAR-T is "giving me a second life."
SCARY SIDE EFFECTS
"The more side effects you have, that sort of tells everybody it's working," said Shefveland, who was hospitalized soon after his treatment at Hutch when his blood pressure collapsed. His last clear memory for days: "I was having a conversation with a nurse and all of a sudden it was gibberish."
As CAR-T cells swarm the cancer, an immune overreaction called "cytokine release syndrome" can trigger high fevers and plummeting blood pressure and in severe cases organ damage. Some patients also experience confusion, hallucinations or other neurologic symptoms.
Treatment is a balancing act to control those symptoms without shutting down the cancer attack.
Experienced cancer centers have learned to expect and watch for these problems. "And, most importantly, we've learned how to treat them," said Dr. Len Lichtenfeld of the American Cancer Society, who is watching CAR-T's development.
FIGHTING SOLID TUMORS WILL BE HARDER
CAR-Ts cause collateral damage, killing some healthy white blood cells, called B cells, along with cancerous ones because both harbor the same marker. Finding the right target to kill solid tumors but not healthy organ tissue will be even more complicated.
"You can live without some normal B cells. You can't live without your lungs," Riddell explained.
Early studies against solid tumors are beginning, targeting different antigens. Time-lapse photos taken through a microscope in Riddell's lab show those new CAR-T cells crawling over aggressive breast cancer, releasing toxic chemicals until tumor cells shrivel and die.
CARs aren't the only approach. Researchers also are trying to target markers inside tumor cells rather than on the surface, or even gene mutations that don't form in healthy tissue.
"It's ironic that the very mutations that cause the cancer are very likely to be the Achilles heel," NCI's Rosenberg said.
And studies are beginning to test CAR-Ts in combination with older immunotherapy drugs, in hopes of overcoming tumor defenses.
HOW WILL PATIENTS GET THE FIRST CAR-T THERAPIES?
If the FDA approves Novartis' or Kite's versions, eligible leukemia and lymphoma patients would be treated at cancer centers experienced with this tricky therapy. Their T cells would be shipped to company factories, engineered, and shipped back. Gradually, more hospitals could offer it.
Because only certain patients would qualify for the first drugs, others would have to search for CAR-T studies to try the treatment. A drug industry report lists 21 CAR-T therapies in development by a dozen companies.
"This is the hope of any cancer patient, that if you stay in the game long enough, the next treatment's going to be just around the corner," said Shefveland, the Hutch patient.
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This Associated Press series was produced in partnership with the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content

quite big paper izašao juče, ljudi izneli dokaze da parkinson ima autoimunsku etiologiju (naš imunski sistem nas vidi kao neprijatelja i kreće da nas napada kao što napada bakterije i viruse). ako se potvrdi, ugasili smo.

https://www.nature.com/nature/journal/vaop/ncurrent/full/nature22815.html?sf90794231=1

Ugasili smo u smislu "do sada neizlečiva bolest nastavlja da bude neizlečiva ali na nov način"?