The Gary Null Show

The Gary Null Show - 08.03.21

August 3, 2021

When stressed, people are quicker to jump to the worst conclusion

University College London, July 29, 2021

When under stress, people reach undesirable conclusions based on weaker evidence than when they are relaxed, finds a new study led by UCL researchers.

The findings, published today in the Journal of Neuroscience, show that stress can make people more likely to conclude the worst scenario is true.

Senior author Professor Tali Sharot (UCL Psychology & Language Sciences and Max Planck UCL Centre for Computational Psychiatry and Ageing Research) said: "Many of the most significant choices you will make, from financial decisions to medical and professional ones, will happen while you feel stressed. Often these decisions require you to first gather information and weigh the evidence. For example, you may consult multiple physicians before deciding on a best course of medical treatment. We wanted to find out: does feeling stressed change how you process and use the information you gather?

"Our research suggests that under stress, people weight each piece of evidence that supports undesirable conclusions more than when they are relaxed. In contrast, how they weigh evidence that supports desirable conclusions is not affected by stress. As a result, people are more likely to conclude the worst is true when they are stressed."

For the study, 91 volunteers played a categorisation game, in which they could gather as much evidence as they wanted to decide whether they were in a desirable environment (which was associated with rewards) or an undesirable environment (which was associated with losses). They were incentivised for accuracy. Prior to playing the game, 40 of the volunteers were told that they had to give a surprise public speech, which would be judged by a panel of experts. This caused them to feel stressed and anxious.

The researchers found that under stress, the volunteers needed weaker evidence to reach the conclusion that they were in the undesirable environment. By contrast, stress did not change the strength of the evidence needed to reach the conclusion that they were in the desirable environment.

Lead author, PhD student Laura Globig (UCL Psychology & Language Sciences and Max Planck UCL Centre for Computational Psychiatry and Ageing Research) said that "we usually think of stressful situations as a hindrance to our decision-making process. But the pattern of learning we have uncovered may counterintuitively be adaptive, because negative beliefs may drive people to be extra cautious when in threatening environments."


Thai Cabinet Approves Use of Fah Talai Jone (green chiretta) to Treat Asymptomatic COVID-19 Cases

Bangkok Post, July 22, 2021

Prime Minister Prayut Chan-o-cha has instructed authorities to set up a committee to study the use of green chiretta (Andrographis paniculata) extracts to treat Covid-19 patients with mild symptoms.

The announcement was made at a cabinet meeting on Tuesday, which was convened to discuss additional measures to help curb the Covid-19 outbreak, the premier said on Wednesday.

Deputy Prime Minister and Public Health Minister Anutin Charnvirakul was appointed head of the committee.

It will coordinate studies on the safety and efficacy of green chiretta extracts on Covid-19 patients, as well as draft a strategic plan to promote Thai traditional medicine in general.

The decision was taken in response to a proposal from Justice Minister Somsak Thepsutin, who urged the government to scale up the use of traditional medicines on Covid-19 patients with mild symptoms. This comes amid a vaccine shortage which has led to criticism for the government.

His proposal came with evidence showing the Department of Corrections' success in treating 12,376 inmates who were infected with Covid-19 with green chiretta extracts.

Of this number, 5,045 inmates were in Chiang Mai Central Prison, 2,100 in Nonthaburi Provincial Prison and 5,231 in Bang Kwang Central Prison also in Nonthaburi, said Mr Somsak.

Before prescribing the herbal medicine to infected inmates, Mr Somsak said he had studied information by the Department of Thai Traditional and Alternative Medicine, which recommended a dosage of 180mg of andrographolides from green chiretta for five consecutive days to patients with mild symptoms.

Citing the same research, the minister said each rai of land can yield up to 600kg of green chirettas, which can be turned into roughly 375,000 herbal extract capsules, he said.

A total of 3.1 billion such capsules will be needed to cover all Thais, which means 8,400 rai of land will need to be planted with the herb, he said.

The Department of Corrections now plans to produce about 50 million capsules of the herbal medicine in the next four months, which it aims to prescribe to about 50% of the prison population, he said.

Due to its medical benefits, green chiretta has become a cash crop which is now in high demand in the export sector, he said.

Mr Somsak added that the medicinal herb costs about 450 baht per kg 


Taking breaks while learning improves memory


Max Planck Institute of Neurobiology (Germany), July 29, 2021

We remember things longer if we take breaks during learning, referred to as the spacing effect. Scientists at the Max Planck Institute of Neurobiology gained deeper insight into the neuronal basis for this phenomenon in mice. With longer intervals between learning repetitions, mice reuse more of the same neurons as before—instead of activating different ones. Possibly, this allows the neuronal connections to strengthen with each learning event, such that knowledge is stored for a longer time.

Many of us have experienced the following: the day before an exam, we try to cram a huge amount of information into our brain. But just as quickly as we acquired it, the knowledge we have painstakingly gained is gone again. The good news is that we can counteract this forgetting. With expanded time intervals between individual learning events, we retain the knowledge for a longer time.

But what happens in the brain during the spacing effect, and why is taking breaks so beneficial for our memory? It is generally thought that during learning, neurons are activated and form new connections. In this way, the learned knowledge is stored and can be retrieved by reactivating the same set of neurons. However, we still know very little about how pauses positively influence this process—even though the spacing effect was described more than a century ago and occurs in almost all animals.

Learning in a maze

Annet Glas and Pieter Goltstein, neurobiologists in the team of Mark Hübener and Tobias Bonhoeffer, investigated this phenomenon in mice. To do this, the animals had to remember the position of a hidden chocolate piece in a maze. On three consecutive opportunities, they were allowed to explore the maze and find their reward—including pauses of varying lengths. "Mice that were trained with the longer intervals between learning phases were not able to remember the position of the chocolate as quickly," explains Annet Glas. "But on the next day, the longer the pauses, the better was the mice's memory."

During the maze test, the researchers additionally measured the activity of neurons in the prefrontal cortex. This brain region is of particular interest for learning processes, as it is known for its role in complex thinking tasks. Accordingly, the scientists showed that inactivation of the prefrontal cortex impaired the mice's performance in the maze.

"If three learning phases follow each other very quickly, we intuitively expected the same neurons to be activated," Pieter Goltstein says. "After all, it is the same experiment with the same information. However, after a long break, it would be conceivable that the brain interprets the following learning phase as a new event and processes it with different neurons." However, the researchers found exactly the opposite when they compared the neuronal activity during different learning phases. After short pauses, the activation pattern in the brain fluctuated more than compared to long pauses: In fast successive learning phases, the mice activated mostly different neurons. When taking longer breaks, the same neurons active during the first learning phase were used again later.

Memory benefits from longer breaks

Reactivating the same neurons could allow the brain to strengthen the connections between these cells in each learning phase—there is no need to start from scratch and establish the contacts first. "That's why we believe that memory benefits from longer breaks," says Pieter Goltstein.

Thus, after more than a century, the study provides the first insights into the neuronal processes that explain the positive effect of learning breaks. With spaced learning, we may reach our goal more slowly, but we benefit from our knowledge for much longer. Hopefully, we won't have forgotten this by the time we take our next exam!



The flavonoid epicatechin inhibits progressive tau pathology in Alzheimer's

University of Bath (UK), July 23, 2021

According to news reporting originating in Avon, United Kingdom, by NewsRx journalists, research stated, “Aggregation of the microtubule-associated protein tau into paired helical filaments (PHFs) and neurofibrillary tangles is a defining characteristic of Alzheimer’s Disease. Various plant polyphenols disrupt tau aggregation in vitro but display poor bioavailability and low potency, challenging their therapeutic translation.”  Green tea, cocoa, blackberries and blueberries are high in epicatechin.

The news reporters obtained a quote from the research from the University of Bath, “We previously reported that oral administration of the flavonoid (-)-epicatechin (EC) reduced Amyloid-beta (A beta) plaque pathology in APP/PS1 transgenic mice. Here, we investigated whether EC impacts on tau pathology, independent of actions on A beta, using rTg4510 mice expressing P301L mutant tau. 4 and 6.5 months old rTg4510 mice received EC (similar to 18 mg/day) or vehicle (ethanol) via drinking water for 21 days and the levels of total and phosphorylated tau were assessed. At 4 months, tau appeared as two bands of similar to 55 kDa, phosphorylated at Ser262 and Ser396 and was unaffected by exposure to EC. At 6.5 months an additional higher molecular weight form of tau was detected at similar to 64 kDa which was phosphorylated at Ser262, Ser396 and additionally at the AT8 sites, indicative of the presence of PHFs. EC consumption reduced the levels of the similar to 64 kDa tau species and inhibited phosphorylation at Ser262 and AT8 phosphoepitopes. Regulation of the key tau kinase glycogen synthase kinase 3 beta (GSK3 beta) by phosphorylation at Ser9 was not altered by exposure to EC in mice or primary neurons. Furthermore, EC did not significantly inhibit GSK3 beta activity at physiologically-relevant concentrations in a cell free assay.”

According to the news reporters, the research concluded: “Therefore, a 21-day intervention with EC inhibits or reverses the development of tau pathology in rTg4510 mice independently of direct inhibition of GSK3 beta.”



Fruit compound may have potential to prevent and treat Parkinson's disease


Johns Hopkins University, July 29, 2021

Johns Hopkins Medicine researchers say they have added to evidence that the compound farnesol, found naturally in herbs, and berries and other fruits, prevents and reverses brain damage linked to Parkinson's disease in mouse studies.

he compound, used in flavorings and perfume-making, can prevent the loss of neurons that produce dopamine in the brains of mice by deactivating PARIS, a key proteininvolved in the disease's progression. Loss of such neurons affects movement and cognition, leading to hallmark symptoms of Parkinson's disease such as tremors, muscle rigidity, confusion and dementia. Farnesol's ability to block PARIS, say the researchers, could guide development of new Parkinson's disease interventions that specifically target this protein.

"Our experiments showed that farnesol both significantly prevented the loss of dopamine neurons and reversed behavioral deficits in mice, indicating its promise as a potential drug treatment to prevent Parkinson's disease," says Ted Dawson, M.D., Ph.D., director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Results of the new study, published July 28, in Science Translational Medicine, detail how the researchers identified farnesol's potential by screening a large library of drugs to find those that inhibited PARIS.

In the brains of people with Parkinson's disease, a buildup of PARIS slows down the manufacture of the protective protein PGC-1alpha. The protein shields brain cells from damaging reactive oxygen molecules that accumulate in the brain. Without PGC-1alpha, dopamine neurons die off, leading to the cognitive and physical changes associated with Parkinson's disease.

To study whether farnesol could protect brains from the effects of PARIS accumulation, the researchers fed mice either a farnesol-supplemented diet or a regular mouse diet for one week. Then, the researchers administered pre-formed fibrils of the protein alpha-synuclein, which is associated with the effects of Parkinson's disease in the brain.

The researchers found that the mice fed the farnesol diet performed better on a strength and coordination test designed to detect advancement of Parkinson's disease symptoms. On average, the mice performed 100% better than mice injected with alpha-synuclein, but fed a regular diet.

When the researchers later studied brain tissue of mice in the two groups, they found that the mice fed a farnesol-supplemented diet had twice as many healthy dopamine neurons than mice not fed the farnesol-enriched diet. The farnesol-fed mice also had approximately 55% more of the protective protein PGC-1alpha in their brains than the untreated mice.

In chemical experiments, the researchers confirmed that farnesol binds to PARIS, changing the protein's shape so that it can no longer interfere with PGC-1alpha production.

While farnesol is naturally produced, synthetic versions are used in commerce, and the amounts people get through diet is unclear. The researchers caution that safe doses of farnesol for humans have not yet been determined, and that only carefully controlled clinical trials can do so.

Though more research is needed, Dawson and his team hope farnesol can someday be used to create treatments that prevent or reverse brain damage caused by Parkinson's disease.


Plant compounds reveal anticancer mechanisms

Russian Academy of Sciences, July 28 2021. 

Research published on June 9, 2021 in Scientific Reportsexplored mechanisms involved in the cancer protective effects of 30 compounds derived from fruits and vegetables. The researchers hope that their findings will contribute to the formulation of new drugs that will have fewer side effects than drugs currently in use.  

“To create potent new drugs that will target only the tumor, it was necessary to determine how dietary compounds affect cell proteins in the prevention and treatment of cancer,” explained coauthor Grigory Zyryanov, who is a professor at the Russian Academy of Sciences. “Therefore, by modeling molecular mechanisms, we figured out how substances bind to proteins. This allowed us to determine the pool of therapeutic targets that the drugs will subsequently target. For example, these are anti-apoptotic (prevent apoptosis) and pro-apoptotic (induce apoptosis) proteins, protein kinases, and others. But a key drug target is phosphatidylinositol-3-kinase . . . This enzyme influences mutations in cancer, rearrangement, and amplification of genes.”

Compounds investigated in the study included emodin, eugenol, gingerol, sulforaphane, linalool, catechin, oleanolic acid, ursolic acid, curcumin, yakuchinone-A, pinusolide, alpha-boswellic acid, oleandrin, sesquiterpene lactone-326, resveratrol, triterpenoid, beta-boswellic acid, anethole, capsaicin, glycolic acid, quercetin, genistein, ellagic acid, flavopiridol, zerumbone, garcinol, guggulsterone, parthenolide, halogenated monoterpenes and silibinin. Of these compounds, silibinin, flavopiridol, oleandrin, ursolic acid, alpha-boswellic acid, beta-boswellic acid, triterpenoid, guggulsterone and oleanolic acid had the greatest binding affinity with phosphatidylinositol-3-kinase alpha (P13K), which is involved in functions that can contribute to cancer. Other targets identified as binding with various compounds included PKC-η, Ras and H-Ras. 

“We assumed that the foods we selected for the study had anti-cancer properties, but this needed to be verified,” Dr Zyryanov noted. “As a result, we found out that diseased cells stop development under the influence of certain combinations of food compounds.”



Meta-analysis supports potential of omega-3s for ADHD

Kings College London, July 31, 2021

Omega-3s fatty acid supplements may improve symptoms and cognitive performance in children and adolescents with attention deficit hyperactivity disorder (ADHD), according to a meta-analysis of gold standard clinical trials.

Data from seven clinical trials involving over 500 children and adolescents indicated that omega-3s were associated with improvements in clinical symptoms of ADHD, while data from three clinical trials involving over 200 children and adolescents indicated a positive impact on cognitive measures associated with attention.

“[W]e provide strong evidence supporting a role for n3-PUFAs deficiency in ADHD, and for advocating n-3 PUFAs supplementation as a clinically relevant intervention in this group, especially if guided by a biomarker-based personalization approach,” wrote the authors, led by Jane Pei-Chen Chang from King’s College London, in Neuropsychopharmacology .

Boosting EPA/DHA intakes

Commenting independently on the meta-analysis, Harry Rice, PhD, VP of regulatory & scientific affairs for the Global Organization for EPA and DHA Omega-3s (GOED): “In the past, I've been lukewarm on whether or not increasing EPA/DHA intake benefits children with ADHD. Results from this meta-analysis put me a little closer to believing.

“Minimally, given the low side effect profile of omega-3s versus the drugs of choice to treat ADHD, I would highly recommend first increasing intake of EPA/DHA. This is particularly true if a child doesn't eat at least two servings of fatty fish a week or doesn't take an omega-3 supplement on a regular basis.”

Meta-analysis details

The new meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and used established scientific literature databases to identify appropriate studies for inclusion.

Data from seven randomized controlled trials (RCTs) with 534 young people indicated that that omega-s3 supplementation significantly improved inattention and hyperactivity symptoms, according to parental reports.

Additional analysis revealed that the improvements in hyperactivity were only observed when doses of EPA (eicosapentaenoic acid) of 500 mg/day or more were used.

Interesting, the researchers did not find improvements in hyperactivity and inattention when they looked at teacher’s reports, unlike what was reported by parents.

Omega-3 supplements were associated with improvements in select measures of cognitive performance, said the researchers.

“N-3 PUFAs are crucial for optimal neurotransmitter function: for example, incorporating more EPA and DHA in the cell membrane can increase cholesterol efflux, modulate lipid raft clustering and disruption, and affect the function of the dopamine transporter (DAT), which in turn may affect attention and executive function by regulating synaptic dopamine levels,” wrote the researchers.

Omega-3 levels

Data from case-control studies were also collected to assess if omega-3 levels were also associated with ADHD, with results indicating that children and adolescents with ADHD had lower levels of EPA, DHA (docosahexaenoic acid),and total omega-3s.

“In the context of ‘personalised medicine’, it is tempting to speculate that a subpopulation of youth with ADHD and with low levels of n-3 PUFAs may respond better to n-3 PUFAs supplementation, but there are no studies to date attempting this stratification approach,” wrote the researchers. “However, we have [previously] shown that individuals at genetic risk of developing depression in the context of the immune challenge, interferon-alpha (IFN-alpha), have lower levels of RBCs n3-PUFAs, and that n-3 PUFAs supplementation prevents the onset of IFN-alpha-induced depression, arguably by replenishing the endogenously low anti-inflammatory PUFAs in the ‘at risk’ individuals.”

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