Monday, November 2, 2020

I Survived Trumpworld (Barely). Will America?


For 12 years I worked as an editor at the Charles A. Dana Foundation in New York City. My office was at 745 Fifth Avenue which is significant because next door was 725 Fifth -- Trump Tower. I saw Trump himself from time to time while walking around on my lunch hour. He was always surrounded by a team of men in dark suits and dark personas being lectured by their leader. They'd gather at the nearby GM Plaza, where the men would cower and Trump would bloviate. (I hid nearby twice to get a flavor of his tone.)

I did not know then that my boss at the Dana Foundation, William Safire, had close ties to Trump and was part of the infamous "favor bank" of city power brokers. In this club, no money was  exchanged -- just deeds that advanced the interests of members. I've read that Safire's original, big favor to Trump was to help get his marginally qualified sister appointed to a federal judgeship. In the process, Safire held the young Donald's hand as he gained entry into the New York and DC Republican power elite.

Having now witnessed and experienced Trump and Trumpism for four years, I can say they mirror the experiences I had under Safire. My emotions sunk on Trump's inauguration day and fell therafter.

Through cronyism, William Safire came to be chairman of the influential Dana Foundation in 2000. Dana had a large commitment to the cause of brain research. I began work there in 1995.

Safire, who died in 2009, described himself as "the vituperative right-wing scandal monger" for the New York Times. He was probably more well-known as the Sunday language columnist for the Times Magazine. Former speech writer for President Richard Nixon (Safire was responsible for the term "nattering nabobs of negativism" -- actually delivered by Vice President Spiro Agnew), he traded in slash-and-burn, transactional relationships, just like Trump. (If you doubted Safire's loyalty to Richard Nixon, you need only stroll by the life-sized, autographed picture of the disgraced ex-president hung outside Safire's office. To Safire, Nixon did nothing wrong in the litany of scandals and crimes called Watergate. Nothing.)

Safire was hired by the Times when the paper realized it needed a right winger to counter the enlightened voices of Anthony Lewis, Russell Baker, Tom Wicker, Howell Raines, and others. 

Like Trump, Safire fabricated and inflated his public image. At the Times, by 1978 Safire was about to be fired for lack of reader interest when he reinvented himself as a "journalist" (for which he had no training…his biography said only that he "attended Syracuse University"). As a marketing pitch man for Maytag Appliances, Safire met then-Vice President Nixon at the "Kitchen Summit" with Khrushchev in the Soviet Union. 

The first victim of his "hatchet journalism" was Bert Lance, President Jimmy Carter's first budget director. Having helped push Lance out the door, as was his pattern, Safire later claimed that the two had become friends and colleagues. Safire also had a direct line to the office of the Israeli prime minister to feed and receive political dirt on world leaders. In the run up to the Iraqi War, Safire was stirring the pot of lies about Saddam Hussein's weapons program in his column. He also advocated for the discredited Times reporter Judy Miller, who promoted the theory of Iraq's Weapons of Mass Destruction, later found to be based on inaccurate information from the intelligence community.

In one memorable meeting at Dana, Safire recounted how on Meet the Press, in his avuncular tone, he tried with the help of host Tim Russert, to patch things up with Bill Clinton after having called Hillary Clinton a congenital liar. On the air, Russert offered Safire a pair of oversized boxing gloves, which if he signed, Russert said he would get Bill Clinton to sign as well, as a symbol that, again all was well. The president, an enraged Safire told us, "refused to sign the gloves and returned them unsigned to my office." Red with anger, Safire indicated that this was all you needed to know about Bill Clinton.

Like Trump, Safire was penurious and a deadbeat. My freelance writers and designers had routinely been paid upon submitting a bill when he decided to "stretch them out," needlessly, to 30-days payment. The move strained freelancers' ability to budget their finances and added extra stress on me and my fellow Dana editors. And it was needless pain because Dana was a wealthy non-profit: Safire controlled an endowment just short of $400 million.

Donald Trump has shown astonishing indifference to the deaths and suffering of Americans in the pandemic, to the massive numbers of families without jobs and income, and to the children and families at our borders, emotionally scarred for life. Similarly, his patron, Safire, was called by his own treasurer "the cheapest man in the world." In the aftermath of 9/11, Safire authorized a paltry one-time contribution of $50,000 to the Times Fund for the Neediest New Yorkers. This at a time when New York corporations and individuals were making much larger contributions, financially and in-kind, to a devastated city.

Safire and Trump created desultory, mean environments where women were objects to be used in sexual relationships. Aside from being morally objectionable, these arrangements (in Safire's case with women on staff) created favoritism and distrust among the staff as we tried to figure who was in favor and who wasn't. I was ordered to spy on one such woman by another who had become my boss.

Finally, Trump and Safire shared a total lack of pathos, or empathy. Instead they valued loyalty, especially blind loyalty. Safire told us directly that we were to be available to him at any time. He asked for and received our cell phone numbers. He threatened to fire staff not willing to sacrifice themselves and their family life to his irrational, erratic needs. One colleague, the intensely smart and capable Barbara Rich, saw no other option but to surrender to monstrously long hours and work demands. Each year, I watched as she managed to get only four days away of her four-weeks of vacation time (which usually included a three-day holiday weekend). A proud liberal and one-time campaigner for Robert F. Kennedy, she felt it necessary to accede to Safire's views by reading far right-wing Web sites such as the dreadful Drudge Report. Barbara was the only experienced journalist at the Foundation and she admitted she felt debased as Safire called her his chief "flak."

A breast cancer survivor, Barbara resumed smoking to deal with the stress. I winced as she kept adding projects and travel to her workload. One day, I watched her, ashen, break up with her partner by phone. She died of a stroke far too young a few years ago.

I resisted his work demands as long as I could, but when asked to write and edit a book on an insanely short schedule of six weeks, I knew I couldn't pull all-nighters and give up my personal life. My partner, Fred, and I had just built a weekend house and I couldn't bear the thought of him there alone while I stayed in the city indefinitely.

The worlds that Trump and Safire created were harsh and heartless. When I quit the Dana Foundation in 2006, it was very painful and career-damaging. I left a job that as a gay man I felt comfortable in because of the access I had to smart, intellectually, and sociably able colleagues. My work, despite the stresses, had a high "psychic reward" I never was able to replace.

The consequences of Trumpism, so similar to "Safireism," cut deep. They derailed lives, and ruined the health of workers. We used to joke that we wrote about the stress hormone cortisol as oceans of it flowed past our offices. If you wanted to maintain your relationship with him, or your job, the key was being able to call him "Bill." It signaled an obeisance, a surrender to his views and world, at least superficially. I could and would not do it.

How did Safire ultimately gain and maintain his power and influence? Much in the same way that Trump does it. Safire exploited a very basic principal of human behavior, something I learned from the brain scientists at the Dana Foundation: Fear is our most powerful emotion. Anybody in the advertising world knows this basic fact and exploits it to the maximum extent. Those who abhorred Safire's right-wing views, nevertheless glommed on to him to avoid his wrath, which could be terrifying. He could offer a word of slight praise and then five minutes later be in your face physically shaking with rage, irrationally and often misguidedly. Much like other men on the high-end of the corporate ladder, Safire had an imposing physical presence: he was quite tall and physically intimidating. He was another arrogant CEO, who in the words of my colleague Barbara Rich,  was "looking for redemption from this world and not going to get it."

The "boss," as one especially maltreated secretary called him, also exploited another biological principle, phototropism, the basic tendency of plants...and humans...to bend toward a light source. He preyed on anyone's desire to be near power. He name-dropped his celebrity connections, (one being Monica Lewinsky) to remind you of the access he had created and to those who wanted to get that access (or a gift from the money he controlled) he readily offered a carrot. Oblivious to his audience, he once announced in a meeting that he was going to tell us everything we were dying to know about Monica. He had no clue that he was speaking to New York liberals and we did not want to hear his tawdry details, including information about the blue dress. I began to hate Amtrak trips to his office in Washington and I literally got depressed from the city and the atmosphere I experienced there.

Under Donald Trump, our country has gone down the same life-draining path. Particularly during the isolation induced by the COVID-19 pandemic, caused by Trump's incompetence and indifference, rates of depression, isolation and despair are now sky-high across America. 

We won't fully realize how bad it's been until it ends -- both Trump's rule and the pandemic.

It took me years to recover from my traumatic experience on the periphery of America's power center. It eroded my self-confidence and self-image. It ended a writing career in which I took great pride.

I hope America fares better after Trump and recovers much more quickly. Joe Biden and Kamala Harris, I'm pulling for you.



Wednesday, September 2, 2020

New hope for Alzheimer's disease, spinal cord injury, more

Date:

August 27, 2020



Source:

DZNE - German Center for Neurodegenerative Diseases


Summary:

Researchers have developed a neurologically acting protein and tested it in laboratory studies. In mice, the experimental compound ameliorated symptoms of certain neurological injuries and diseases, while on the microscopic level it was able to establish and repair connections between neurons. This proof-of-principle study suggests that biologics, which act on neuronal connectivity, could be of clinical use in the long term.


    

FULL STORY

Researchers from the German Center for Neurodegenerative Diseases (DZNE), UK and Japan have developed a neurologically acting protein and tested it in laboratory studies. In mice, the experimental compound ameliorated symptoms of certain neurological injuries and diseases, while on the microscopic level it was able to establish and repair connections between neurons. This proof-of-principle study suggests that biologics, which act on neuronal connectivity, could be of clinical use in the long term. The results are published in the journal Science.


Brain essentials in plain language. Click here.


The human brain's neuronal network undergoes life-long changes in order to be able to assimilate information and store it in a suitable manner. This applies in particular to the generation and recalling of memories. So-called synapses play a central role in the brain's ability to adapt. They are junctions through which nerve signals are passed from one cell to the next. A number of specific molecules -- known as "synaptic organizing proteins" -- make sure that synapses are formed and reconfigured whenever necessary.


An artificial protein


An international team of researchers has now combined various structural elements of such naturally occurring molecules into an artificial protein called CPTX and tested its effect in different disease models. To this end, the compound was administered to mice with neurological deficits that occur in similar fashion in humans. Specifically, the tests focused on Alzheimer's disease, spinal cord injury and cerebellar ataxia -- a disease that is characterized primarily by a failure of muscle coordination. All these conditions are associated with damage to the synapses or their loss. The study was a collaborative effort by experts from several research institutions, including the DZNE's Magdeburg site, MRC Laboratory of Molecular Biology in UK, Keio University School of Medicine in Tokyo, and, also in Japan, Aichi Medical University.


Easing symptoms of disease


"In our lab we studied the effect of CPTX on mice that exhibited certain symptoms of Alzheimer's disease," said Prof. Alexander Dityatev, a senior researcher at the DZNE, who has been investigating synaptic proteins for many years. "We found that application of CPTX improved the mice's memory performance." The researchers also observed normalization of several important neuronal parameters that are compromised in Alzheimer's disease, as well as in the studied animal model. Namely, CPTX increased the ability of synapses to change, which is considered as a cellular process associated with memory formation. Furthermore, CPTX was shown to elevate what is called "excitatory transmission." This is to say that the protein acted specifically on synapses that promoted activity of the contacted cell. And finally, CPTX increased the density of so-called dendritic spines. These are tiny bulges in the cell's membrane that are essential for establishing excitatory synaptic connections.


Brain essentials in plain language. Click here.


Further research by the study partners in the UK and Japan revealed that application of CPTX to mice with motor dysfunction -- caused either by spinal cord injury or pathological conditions similar to cerebellar ataxia -- improved the rodent's mobility. And at the cellular level, the drug was shown to repair and promote excitatory synaptic connections.


A molecular connector


CPTX combines functional domains present in natural synaptic organizing proteins in a unique way. The compound was designed to act as a universal bridge builder for excitatory connections between nerve cells. Where two neurons meet, either in adhesive contact or actually in synaptic connection, CPTX links to specific molecules on the surfaces of both involved cells, and thereby either triggers the formation of new synapses or strengthens already existing ones.



"At present, this drug is experimental and its synthesis, the credit for which goes to our UK partners, is quite demanding. We are far off from application in humans," Dityatev emphasized, who in addition to his research at the DZNE is also a member of the Medical Faculty of the University Magdeburg. "However, our study suggests that CPTX can even do better than some of its natural analogs in building and strengthening nerve connections. Thus, CPTX could be the prototype for a new class of drugs with clinical potential." Application would be in disorders that are associated with impaired neuronal connectivity. "Much of the current therapeutic effort against neurodegeneration focuses on stopping disease progression and offers little prospect of restoring lost cognitive abilities. Our approach could help to change this and possibly lead to treatments that actually regenerate neurological functions. Based on the principles we have used in designing CPTX, we thus intend to develop further compounds. In future studies, we want to refine their properties and explore possible therapeutic applications."

Brain essentials in plain language. Click here.




Saturday, August 15, 2020

Hope for chronic pain



Science News
from research organizations

Potential treatment for chronic pain

Date:
April 30, 2020
Source:
University of Copenhagen The Faculty of Health and Medical Sciences
Summary:
Researchers have developed a new way to treat chronic pain which has been tested in mice. With a compound designed and developed by the researchers themselves, they can achieve complete pain relief.
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FULL STORY

Researchers from the University of Copenhagen have developed a new way to treat chronic pain which has been tested in mice. With a compound designed and developed by the researchers themselves, they can achieve complete pain relief.

The treatment has been tested in mice, and the new results have been published in the scientific journal EMBO Molecular Medicine. For more than a decade, the researchers have been working to design, develop and test a drug that shall provide complete pain relief.

"We have developed a new way to treat chronic pain. It is a targeted treatment. That is, it does not affect the general neuronal signalling, but only affects the nerve changes that are caused by the disease," says co-author Kenneth Lindegaard Madsen, Associate Professor at the Department of Neuroscience, University of Copenhagen.

"We have been working on this for more than ten years. We have taken the process all the way from understanding the biology, inventing and designing the compound to describing how it works in animals, affects their behaviour and removes the pain," says Kenneth Lindegaard Madsen.

Chronic pain can occur, among other things, after surgery, in people with diabetes, after a blood clot and after an amputation in the form of phantom pain.

Clinical trials as the next step

The compound developed by the researchers is a so-called peptide named Tat-P4-(C5)2. The peptide is targeted and only affects the nerve changes that pose a problem and cause the pain.

In a previous study, the researchers have shown in an animal model that use of the peptide can also reduce addiction. Therefore, the researchers hope that the compound may potentially help pain patients who have become addicted to, for example, opioid pain relievers in particular.

"The compound works very efficiently, and we do not see any side effects. We can administer this peptide and obtain complete pain relief in the mouse model we have used, without the lethargic effect that characterises existing pain-relieving drugs," says Kenneth Lindegaard Madsen, adding:

"Now, our next step is to work towards testing the treatment on people. The goal, for us, is to develop a drug, therefore the plan is to establish a biotech company as soon as possible so we can focus on this."

The researchers are now working towards clinical trials in collaboration with, among others, pain researcher Nanna Brix Finnerup, Professor at Aarhus University.



Brain essentials in plain language. Click here


Story Source:

Materials provided by University of Copenhagen The Faculty of Health and Medical SciencesNote: Content may be edited for style and length.



 


Brain essentials in plain language. Click here

Wednesday, July 29, 2020

Breakthrough Test for Alzheimer's

New blood test shows great promise in the diagnosis of Alzheimer's disease



Date:

July 29, 2020

Source:

Lund University


Summary:

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study.



Brain essentials in plain language. Click here!

    

FULL STORY


A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer's Association International Conference.


For many years, the diagnosis of Alzheimer's has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer's research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles -- corresponding to the diagnosis of Alzheimer's -- in living people.


"The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting."




Brain essentials in plain language. Click here!



Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute's Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer's disease (ADAD)-causing mutation carriers and non-carriers from the world's largest ADAD cohort.


In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of "intermediate or high likelihood Alzheimer's" (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of "high likelihood Alzheimer's" with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.


In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer's and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.


In each of these analyses, p-tau217 (a major component of Alzheimer's disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer's) and several other studied blood tests.


In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer's. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer's. It has the potential to advance the disease's research and care in other important ways.


"Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author on the study.


"While there's more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years."


Alzheimer's is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.




Brain essentials in plain language. Click here!




Thursday, July 23, 2020

Covid-19 and the Brain

July 8, 2020

Source:

University of Liverpool


Summary:

Cases of brain complications linked to COVID-19 are occurring across the globe, a new review has shown. The research found that strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease.





    

FULL STORY

Cases of brain complications linked to COVID-19 are occurring across the globe, a new review by University of Liverpool researchers has shown.



Published in The Lancet Neurology, the study found that strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease.


COVID-19 has been associated mostly with problems like difficulty breathing, fever and cough. However, as the pandemic has continued, it has become increasingly clear that other problems can occur in patients. These include confusion, stroke, inflammation of the brain, spinal cord, and other kinds of nerve disease.


A recent Liverpool-led study of COVID-19 patients hospitalised in the UK found a range of neurological and psychiatric complications that may be linked to the disease.




To get a sense of the wider picture, the researchers brought together and analysed findings from COVID-19 studies across the globe that reported on neurological complications. The review, which included studies from China, Italy and the USA among others, found almost 1000 patients with COVID-19-associated brain, spinal cord and nerve disease.


Research Fellow, Dr Suzannah Lant, who was working on the project, said: "While these complications are relatively uncommon, the huge numbers of COVID-19 cases globally mean the overall number of patients with neurological problems is likely to be quite large."


One of the complications found to be linked to COVID-19 is encephalitis, which is inflammation and swelling of the brain.


Dr Ava Easton, CEO of the Encephalitis Society, and co-author on the paper said: "It is really important that doctors around the world recognise that COVID-19 can cause encephalitis and other brain problems, which often have potentially devastating, life-changing consequences for patients."


Professor Tom Solomon, senior author on the paper and Director of the Global COVID-Neuro Network, added: "Although such patients are being seen everywhere the virus occurs, many of the reports are lacking in detail. We are currently pooling data from individual patients all around the world, so that we can get a more complete picture. Doctors who would like to contribute patients to this analysis can contact us via the Global COVID-Neuro Network

website."






Wednesday, June 10, 2020

Unexpected uncertainty can breed paranoia



Date:
June 9, 2020
Source:
Yale University
Summary:
In times of unexpected uncertainty, such as the sudden appearance of a global pandemic, people may be more prone to paranoia, say researchers.

    
Silhouette of person, | Credit: © lassedesignen / stock.adobe.com
Silhouette of person, photo concept (stock image).
Credit: © lassedesignen / stock.adobe.com

In times of unexpected uncertainty, such as the sudden appearance of a global pandemic, people may be more prone to paranoia, Yale University researchers suggest in a new study published in the journal eLife.

Paranoia is a key symptom of serious mental illness, marked by the belief that other people have malicious intentions. But it also manifests in varying degrees in the general population. For instance, one previous survey found that 20% of the population believed people were against them at some time during the past year; 8% believed that others were actively out to harm them.

The prevailing theory is that paranoia stems from an inability to accurately assess social threats. But Corlett and lead author Erin Reed of Yale hypothesized that paranoia is instead rooted in a more basic learning mechanism that is triggered by uncertainty, even in the absence of social threat.

"We think of the brain as a prediction machine; unexpected change, whether social or not, may constitute a type of threat -- it limits the brain's ability to make predictions," Reed said. "Paranoia may be a response to uncertainty in general, and social interactions can be particularly complex and difficult to predict."



In a series of experiments, they asked subjects with different degrees of paranoia to play a card game in which the best choices for success were changed secretly. People with little or no paranoia were slow to assume that the best choice had changed. However, those with paranoia expected even more volatility in the game. They changed their choices capriciously -- even after a win. The researchers then increased the levels of uncertainty by changing the chances of winning halfway through the game without telling the participants. This sudden change made even the low-paranoia participants behave like those with paranoia, learning less from the consequences of their choices.

In a related experiment, Yale collaborators Jane Taylor and Stephanie Groman trained rats, a relatively asocial species, to complete a similar task where best choices of success changed. Rats who were administered methamphetamine -- known to induce paranoia in humans -- behaved just like paranoid humans. They, too, anticipated high volatility and relied more on their expectations than learning from the task.

Reed, Corlett and their team then used a mathematical model to compare choices made by rats and humans while performing these similar tasks. The results from the rats that received methamphetamine resembled those of humans with paranoia, researchers found.

"Our hope is that this work will facilitate a mechanistic explanation of paranoia, a first step in the development of new treatments that target those underlying mechanisms," Corlett said.

"The benefit of seeing paranoia through a non-social lens is that we can study these mechanisms in simpler systems, without needing to recapitulate the richness of human social interaction," Reed said.




Source:

Materials provided by Yale University. Original written by Bill Hathaway.