New Evidence COVID-19 Invades the Brain – Medscape

January 4, 2021 medical

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests.

Investigators injected spike 1 (S1), which is found on the tufts of the "red spikes" of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs specifically, the lungs, spleen, liver, and kidneys.

"We found that the S1 protein, which is the protein COVID-19 uses to 'grab onto' cells, crosses the BBB and is a good model of what the virus does when it enters the brain," lead author William A. Banks, MD, professor of medicine, the University of Washington School of Medicine, Seattle, Washington, told Medscape Medical News.

"When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity," said Banks, who is also associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online December 16 in Nature Neuroscience.

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators note.

Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus' action at the site of the lungs.

The researchers set out to assess whether a particular viral protein S1, which is a subunit of the viral spike protein could cross the BBB or enter other organs when injected into mice.

They found that when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, "suggesting that this protein is cleared from the blood predominantly by the liver," Banks said. In addition, uptake by the lungs is "important, because that's where many of the effects of the virus are," he added.

The researchers found that I-S1 in the brains of the mice was "mostly degraded" 30 minutes following injection. "This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain," they write.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%).

"These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake," the authors suggest. Moreover, inflammation also increased the entry of I-S1 into the brain, "likely due to BBB disruption."

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors note. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the "fastest I-S1 uptake" was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

"This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes," coauthor Jacob Raber, PhD, professor, Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Oregon Health and Science University, Portland, Oregon, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.

Banks said his laboratory has studied the BBB in conditions such as Alzheimer's disease, obesity, diabetes, and HIV.

"Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks," he said. In this case, "the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB."

Conversely, "the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines," he added.

An additional finding of the study is that whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

"When an antibody locks onto something, it prevents it from crossing the BBB," Banks noted.

Commenting on the study for Medscape Medical News, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, said the study is confirmatory.

"What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems," he said.

"So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding," added Gendelman, who is also the director of the Center for Neurodegenerative Disorders. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Gendelman have disclosed no relevant financial relationships.

Nat Neurosci. Published online December 16, 2020. Full text

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New Evidence COVID-19 Invades the Brain - Medscape

Neuroscience

Cormac the Llama Yields Antibodies That May Prove Effective Against COVID-19 – Department of Defense

January 4, 2021 medical

Researchers at the Uniformed Services University of the Health Sciences recently identified pint-sized antibodies, or "nanobodies," that could protect against COVID-19. At least one of these nanobodies produced by a llama named Cormacalso appears to work well in either liquid or aerosol form, suggesting it could also help protect a person's lungs from infections.

The study was led by Dr. David Brody, director of USU's Center for Neuroscience and Regenerative Medicine, along with Thomas J. "T.J." Esparza, a Henry M. Jackson Foundation for the Advancement of Military Medicine employee working in support of CNRM. Both Esparza and Brody also work in the National Institutes of Health's National Institute of Neurological Disorders and Stroke .

Nanobodies are a type of antibody naturally produced by the immune systems of camelids, such as camels, alpacas and llamas. These proteins are about a tenth of the weight of most human antibodies on average. They can be isolated in the lab and essentially free-floating versions of the tips of the arms of heavy chain proteins, which form the backbone of a typical Y-shaped human immunoglobulin antibody found in the blood. These tips recognize proteins on viruses, bacteria and other invaders, also known as antigens. Therefore, they play a vital role in the immune system's defenses.

Nanobodies are also more stable, less expensive to produce and easier to engineer than typical antibodies. Therefore, they have been increasingly used for medical research. A few years ago, for example, scientists showed humanized nanobodies may be more effective at treating an autoimmune form of thrombotic thrombocytopenic purpura, a rare blood disorder, than current treatments.

Since the pandemic broke, several researchers have produced llama nanobodies against the SARS-CoV-2 spike protein, which is believed to be effective at preventing infections. In this study, published in Scientific Reports, the researchers used a slightly different strategy to find nanobodies that may work especially well.

"For years, TJ and I had been testing out how to use nanobodies to improve brain imaging. When the pandemic broke, we thought this was a once in a lifetime, all-hands-on-deck situation and joined the fight,"Brody, the senior author of the study, said. "We hope that these anti-COVID-19 nanobodies may be highly effective and versatile in combating the coronavirus pandemic."

The researchers found that at least one of these nanobodies, called NIH-CoVnb-112, may be highly effective at preventing infections or detecting virus particles by grabbing hold of SARS-CoV-2 spike proteins. These "spike proteins" act like a key by "opening the door to infections" when they bind to a protein found on the surface of certain cells, called the angiotensin converting enzyme 2 receptor, the researchers explained. They then found a way to isolate these nanobodies that block infections by covering the "teeth" of the spike protein, which bind to and unlock the ACE2 receptor. This was done by immunizing the llama, Cormac, five times over the course of 28 days with a purified version of the SARS-CoV-2 spike protein.

After testing hundreds of nanobodies, they found Cormac produced 13 nanobodies that could potentially be strong candidates, including one they refer to as NIH-CoVnB-112. The researchers then showed that the NIH-COVnB-112 nanobody could be effective at preventing infections.

To mimic the COVID-19 virus, the researchers genetically mutated a harmless 'pseudovirus' so that it could use the SARS-CoV-2 spike protein to infect cells that produce human ACE2 receptors. The researchers saw that relatively low levels of the NIH-CoVnb-112 nanobodies prevented the pseudovirus from infecting these cells in petri dishes.

Additionally, the researchers showed that the nanobody was just as effective in preventing the infections in petri dishes when it was sprayed through a nebulizer, or inhaler, often used to help treat patients with asthma.

"One of the exciting things about nanobodies is that, unlike most regular antibodies, they can be aerosolized and inhaled to coat the lungs and airways," Brody said. "This is promising in that it could potentially be used to protect the lungs from infections."

This study was supported by NIH Intramural Research Programs at the National Institute of Neurological Disorders and Stroke and National Institute of Environmental Health Sciences.

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Cormac the Llama Yields Antibodies That May Prove Effective Against COVID-19 - Department of Defense

Genetics

Common Brain Malformation Affecting About 1 in 100 Children Traced to Its Genetic Roots – SciTechDaily

January 4, 2021 medical

The lowest part of a childs brain is visible below the bottom of the skull in this MRI scan and shows evidence of a Chiari 1 malformation. Researchers at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes linked to brain development, and that children with large heads are at increased risk of developing the condition. Credit: David Limbrick

Discovery could aid early screening, shed light on how Chiari malformation arises.

About one in 100 children has a common brain disorder called Chiari 1 malformation, but most of the time such children grow up normally and no one suspects a problem. But in about one in 10 of those children, the condition causes headaches, neck pain, hearing, vision and balance disturbances, or other neurological symptoms.

In some cases, the disorder may run in families, but scientists have understood little about the genetic alterations that contribute to the condition. In new research, scientists at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes involved in brain development.

The condition occurs when the lowest parts of the brain are found below the base of the skull. The study also revealed that children with unusually large heads are four times more likely to be diagnosed with Chiari 1 malformation than their peers with normal head circumference.

The findings, published Dec. 21 in the American Journal of Human Genetics, could lead to new ways to identify people at risk of developing Chiari 1 malformation before the most serious symptoms arise. It also sheds light on the development of the common but poorly understood condition.

A lot of times people have recurrent headaches, but they dont realize a Chiari malformation is the cause of their headaches, said senior author Gabriel Haller, PhD, an assistant professor of neurosurgery, of neurology and of genetics. And even if they do, not everyone is willing to have brain surgery to fix it. We need better treatments, and the first step to better treatments is a better understanding of the underlying causes.

If people start experiencing severe symptoms like chronic headaches, pain, abnormal sensations or loss of sensation, or weakness, the malformation is treated with surgery to decompress the Chiari malformation.

Theres an increased risk for Chiari malformations within families, which suggests a genetic underpinning, but nobody had really identified a causal gene, Haller said. We were able to identify two causal genes, and we also discovered that people with Chiari have larger head circumference than expected. Its a significant factor, and easy to measure. If you have a child with an enlarged head, it might be worth checking with your pediatrician.

To identify genes that cause Chiari 1 malformation, Haller and colleagues sequenced all the genes of 668 people with the condition, as well as 232 of their relatives. Of these relatives, 76 also had Chiari 1 malformation and 156 were unaffected. The research team included first author Brooke Sadler, PhD, an instructor in pediatrics, and co-authors David D. Limbrick, Jr., MD, PhD, a professor of neurosurgery and director of the Division of Pediatric Neurosurgery, and Christina Gurnett, MD, PhD, a professor of neurologyand director of the Division of Pediatric and Developmental Neurology, among others.

Sequencing revealed that people with Chiari 1 malformation were significantly more likely to carry mutations in a family of genes known as chromodomain genes. Several of the mutations were de novo, meaning the mutation had occurred in the affected person during fetal development and was not present in his or her relatives. In particular, the chromodomain genes CHD3 and CHD8 included numerous variants associated with the malformation.

Further experiments in tiny, transparent zebrafish showed that the gene CHD8 is involved in regulating brain size. When the researchers inactivated one copy of the fishs chd8 gene, the animals developed unusually large brains, with no change in their overall body size.

Chromodomain genes help control access to long stretches of DNA, thereby regulating expression of whole sets of genes. Since appropriate gene expression is crucial for normal brain development, variations in chromodomain genes have been linked to neurodevelopmental conditions such as autism spectrum disorders, developmental delays, and unusually large or small heads.

Its not well known how chromodomain genes function since they have such a wide scope of activity and they are affecting so many things at once, Haller said. But they are very intriguing candidates for molecular studies, to understand how specific mutations lead to autism or developmental delay or, as in many of our Chiari patients, just to increased brain size without cognitive or intellectual symptoms. Wed like to figure out the effects of each of these mutations so that in the future, if we know a child has a specific mutation, well be able to predict whether that variant is going to have a harmful effect and what kind.

The association between chromodomain genes and head size inspired Haller and colleagues to measure the heads of children with Chiari malformations, comparing them to age-matched controls and to population averages provided by the Centers for Disease Control and Prevention. Children with Chiari tended to have larger than average heads. Those children with the largest heads bigger than 95% of children of the same age were four times more likely to be diagnosed with the malformation.

The findings suggest that children with larger heads or people with other neurodevelopmental disorders linked to chromodomain genes may benefit from screening for Chiari malformation.

A lot of kids that have autism or developmental disorders associated with chromodomain genes may have undiscovered Chiari malformations, Haller said. The only treatment right now is surgery. Discovering the condition early would allow us to watch, knowing the potential for serious symptoms is there, and perform that surgery as soon as its necessary.

Reference: Rare and de novo coding variants in chromodomain genes in Chiari I malformation by Brooke Sadler, Jackson Wilborn, Lilian Antunes, Timothy Kuensting, Andrew T. Hale, Stephen R. Gannon, Kevin McCall, Carlos Cruchaga, Matthew Harms, Norine Voisin, Alexandre Reymond, Gerarda Cappuccio, Nicola Burnetti-Pierri, Marco Tartaglia, Marcello Niceta, Chiara Leoni, Giuseppe Zampino, Allison Ashley-Koch, Aintzane Urbizu, Melanie E. Garrett, Karen Soldano, Alfons Macaya, Donald Conrad, Jennifer Strahle, Matthew B. Dobbs, Tychele N. Turner, Chevis N. Shannon, Douglas Brockmeyer, David D. Limbrick, Christina A. Gurnett and Gabe Haller, 21 December 2020, American Journal of Human Genetics.DOI: 10.1016/j.ajhg.2020.12.001

This study was funded by Sam and Betsy Reeves and the Park-Reeves Syringomyelia Research Consortium; the University of Missouri Spinal Cord Injury Research Program; the Childrens Discovery Institute of St. Louis Childrens Hospital and Washington University; the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number U54HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University; the Swiss National Science Foundation, grant number 31003A_182632; and the Jrme Lejeune Foundation.

Genetics

Global Genetic Testing Market Forecasts for Applications and Technologies to 2025 – ResearchAndMarkets.com – Yahoo Finance

January 4, 2021 medical

The "Genetic Testing. Global Market Forecasts for Applications and Technologies. Updated for COVID-19 Pandemic Impact with Executive and Consultant Guides 2021 to 2025" report has been added to ResearchAndMarkets.com's offering.

The role of genetics in health and disease is just now being understood. This new knowledge, combined with lower pricing is driving the Genetic Testing industry to record growth. New drugs may only work for people with a certain genetic makeup, and this too is driving the Genetic Testing Industry.

The traditional genetic testing market is growing in volume and growing in the breadth of tests creating a new life for the industry. The report forecasts the market size out to 2025. The report includes detailed breakouts for 14 countries and 5 regions.

Predictive Diagnostics? Pharmacogenomic Testing? Direct to Consumer? Find out about the technology in readily understood terms that explain the jargon. What are the issues? Find the opportunities and the pitfalls. Understand growth expectations and the ultimate market forecasts for the next five years.

Companies Mentioned

10x Genomics, Inc

23andME Inc

Abbott Diagnostics

AccuraGen Inc

Adaptive Biotechnologies

Admera Health, LLC

Agena Bioscience, Inc

Agilent

Akonni Biosystems

Ancestry.com LLC

Anchor Dx

ArcherDx, Inc

ARUP Laboratories

Asuragen

Baylor Miraca Genetics Laboratories

Beckman Coulter, Inc

Becton, Dickinson and Company

BGI Genomics Co. Ltd

Bio-Rad Laboratories, Inc

Bio-Techne

Bioarray Genetics

Biocept, Inc

Biodesix Inc

BioFluidica

BioGenex

Biolidics Ltd

bioMerieux Diagnostics

Bioneer Corporation

Cancer Genetics

Caris Molecular Diagnostics

CellMax Life

Centogene

Chronix Biomedical

Circulogene

Clinical Genomics

And Many More Companies!

1. Introduction and Market Definition

1.1 Genetic Testing Definition in This Report

1.2 The Genomics Revolution

1.3 Market Definition

1.3.1 Revenue Market Size

1.3.1 Newborn Screening

1.3.2 Non Invasise Pregnancy Testing

1.3.3 Predictive

1.3.4 Oncology

Story continues

1.3.5 Direct to Consumer

1.3.6 Other Application

1.3.7 PCR

1.3.4 NGS

1.3.5 Cytogenetic

1.3.6 Other Technology

1.4 U.S. Medical Market and laboratory Testing - Perspective

1.4.1 U.S. Medicare Expenditures for Laboratory Testing

2. Market Overview

2.1 Market Participants Play Different Roles

2.1.1 Supplier/pharmaceutical

2.1.2 Independent lab specialized/esoteric

2.1.3 Independent lab national/regional

2.1.4 Independent lab analytical

2.1.5 Public National/regional lab

2.1.6 Hospital lab

2.1.7 Physician lab

2.1.8 DTC Lab

2.1.9 Independent Genetic Testing Lab

2.1.10 Audit Body

2.2 Genetic Tests -Types, Examples and Discussion

2.2.1 Preimplantation Genetic Diagnosis- An Emerging Market

2.2.2 Prenatal Diagnosis - New Technologies Create Opportunity

2.2.3 Newborn Screening

2.2.2 Diagnostic Testing

2.2.3 Carrier Testing

2.2.6 Predictive and Presymptomatic Testing

2.2.7 Pharmacogenomics

2.2.8 Forensic Testing

2.2.9 Parental Testing

2.2.10 Ancestral Testing

2.3 Industry Structure

2.3.1 Hospital's Testing Share

2.3.2 Economies of Scale

2.3.2.1 Hospital vs. Central Lab

2.3.3 Physician Office Lab's

2.3.4 Physician's and POCT

2.4 Market Shares of Key Genetics Players - Analysis

3. Market Trends

3.1 Factors Driving Growth

3.1.1 Genetic Discoveries Creating New Diagnostic Markets

3.1.2 Aging Population a Boon for Diagnostics

3.1.3 Pharmacogenomics Drives Further Growth

3.1.4 Oncology and Liquid Biopsy Enter New Era

3.1.5 Fertility Practice Growth drives market

3.1.6 Direct to Consumer begins to break out

3.2 Factors Limiting Growth

3.2.1 Increased Competition Lowers Price

3.2.2 Lower Costs

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Global Genetic Testing Market Forecasts for Applications and Technologies to 2025 - ResearchAndMarkets.com - Yahoo Finance

Genetics

Rare Genetic Variants in Immune Genes and Neonatal Herpes Simplex Viral Infections – American Academy of Pediatrics

January 4, 2021 medical

Neonatal herpes simplex virus (HSV) infection is a devastating disease with high mortality, particularly when disseminated. Studies in adults and children suggest that susceptibility to herpes simplex encephalitis (HSE) may represent phenotypes for inborn errors in toll-like receptor 3 (TLR3) signaling. However, the genetic basis of susceptibility to neonatal HSV including disseminated disease remains unknown. To test the hypothesis that variants in known HSE-susceptible genes as well as genes mediating HSV immunity will be identified in neonatal HSV, we performed an unbiased exome sequencing study in 10 newborns with disseminated, HSE, and skin, eyes, and mouth disease. Determination of potential impact on function was determined by following American College of Medical Genetics and Genomics guidelines. We identified deleterious and potentially deleterious, rare variants in known HSE-related genes including a stop IRF3 variant (disseminated), nonsynonymous variants in TLR3 and TRAF3 (HSE), STAT1 (skin, eyes, and mouth), and DBR1 (disseminated) in our cohort. Novel and rare variants in other immunodeficiency genes or HSV-related immune genes GRB2, RAG2, PRF1, C6, C7, and MSR1 were found in 4 infants. The variant in GRB2, essential for T-lymphocyte cell responses to HSV, is a novel stop variant not found in public databases. In this pilot study, we identified deleterious or potentially deleterious variants in TLR3 pathway and genes that regulate anti-HSV immunity in neonates with HSV including disseminated disease. Larger, definitive studies incorporating functional analysis of genetic variants are required to validate these data and determine the role of immune genetic variants in neonatal HSV susceptibility.

Human Behavior

Richard Foley, a GOP chief who taunted the FBI, dies at 71 – The CT Mirror

January 4, 2021 medical

Marty Heiser Show

From left, J.R. Romano, Dave Mathus, Matt OBrien and Richard Foley during the 2019 campaign for GOP chair.

On his way to prison in January 1994, the 44-year Richard Foley said he knew how his obituary would begin: There would be a mention of his service as a state lawmaker and Republican state chairman, followed by the fact he was convicted of taking a bribe.

Dick Foley wasnt known for flinching. He was the blue-collar guy who led the state GOP from 1989 to 1992, when Connecticut was a presidential swing state and the party struggled to decide if its future was in Fairfield County or the post-industrial Naugatuck Valley.

When it became clear in late 1992 that he was in the crosshairs of the FBI, Foley called a press conference to call the feds bumblers and bureaucrats. Were going on offense. Put up or shut up, Foley said. They picked on the wrong mick.

The quote ended up on the wall of a semi-secret office the FBI kept for a time in Waterbury, a corruption target. Foley was convicted of four felonies in connection with $25,000 he accepted from two corrupt businessmen, a developer and a banker.

When asked for an interview before he left for prison, Foley said, Yeah, why not?

Foley, 71, was found dead at his condominium in Danbury on Saturday. His friend, Ben F. Proto, said Foleys daughter called with news of his death. No cause was immediately evident.

He came head-on at pretty much everything, from politics to prison. He had an Irish memory, forever remembering friends and foes. He was a state representative, a salesman and a student of human behavior.

His conviction was overturned on appeal, and Foley managed a second act in political life as a lobbyist and campaign consultant. He attempted a comeback last year, challenging J.R. Romano for state chair of the GOP.

He won and lost plenty of political bets. In 1991, he was convinced that passage of the income tax by a Democratic legislature and an independent governor, Lowell P. Weicker Jr., would be the GOPs ticket to the majority. It wasnt.

I talked with him earlier in the week, said Proto, who joined Foley in the 2018 floor fight at the GOP state convention that led to Steve Obsitnik of Westport obtaining enough delegate support to join the party primary for governor. We were going to have lunch next week. He was a dear friend. He was the kind of guy you wanted to have as a friend.

Proto said that Foley was steeped in Connecticuts political history and was among the very young Republicans who, in the early 1970s, made up Gov. Thomas Meskills kiddie corps.

Chris Healy, a former GOP state chairman, said Foley prized and exuded loyalty.

He was the most-loyal, steadfast person you could find, Healy said Saturday. I am grief-stricken because I lost one of my best friends. You either loved him or hated him, and those of us who loved him, we would have done anything for him. He loved to have fun, and he loved to laugh at the absurdity of things. You always ended up laughing during a conversation with Dick Foley, at some point.

MSNBC

Richard Foley

Foley was blunt, often coarse. He had no patience for the timid or cautious. To them, he would say, If you want a guarantee, then buy a f refrigerator.

He could be flippant, but his advice to candidates seeking counsel on issues of morality was not: figure out where you stand; dont be cute; your constituents will tolerate a principled difference.

He offered himself as an example. For 10 years, he represented a conservative and largely Catholic district, but he was more pro-choice than pro-life in his voting.

His legal troubles came from an association with Richard D. Barbieri Sr. and John A. Corpaci, key figures in a Waterbury corruption scandal. They told the FBI they had built a favor bank with politicians as they established a real estate and banking business.

To curry favor with a bigger banking chain, they said they paid Foley $25,000 to help pass a bill liberalizing state banking laws. The story had some holes: Foley, for one, was in the minority. Second, he voted against the bill and urged its defeat.

Foley never denied accepting ten $2,500 payments, but he insisted they were a consulting fee in return for seeking tenants for a commercial property. He was convicted and sentenced to 40 months in prison.

He went to prison uncertain about winning his appeal.

Over coffee at an Abdows Big Boy on the Silas Deane Highway in Wethersfield, Foley talked for three hours about prison and his expectation he might have to serve three years before qualifying for a good-behavior release.

He smoked a cigar, one that he promised would be among his last. He was loud. An elderly woman in the next booth gave him a long sideward glance, mouth agape.

Foley talked about quitting tobacco, losing weight. If he was going to lose three years going in, perhaps he could gain five more on the back end by clean living.

But he had no illusions about how he would be remembered, even if he won his appeal.

In most situations, death pays the debt. Not in this one, he said. This one you pay after you die. Thats hard. Thats hard. But thats one you gotta accept. Thats the way its going to be.

A federal appeals court voted 2-1 in January 1996 to overturn his conviction, concluding he had been improperly charged under statutes that covered the illegal acceptance of federal funds.

Foley served four months in prison, then was freed on bond during his appeal.

Ken Dixon of Hearst Media contributed to this report.

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Richard Foley, a GOP chief who taunted the FBI, dies at 71 - The CT Mirror

Human Behavior

Alexandra Ziesler: Trump was the right president at the right time – Salt Lake Tribune

January 4, 2021 medical

(Susan Walsh | AP photo)In this Nov. 20 photo, President Donald Trump listens during an event in the briefing room of the White House in Washington.

By Alexandra Ziesler | Special to The Tribune

| Jan. 3, 2021, 1:00 p.m.

It takes courage to face the onslaught of daggers and arrows that come as people are forced to leave behind whats familiar, no matter how dysfunctional. Yet familiar patterns, established ways, even traditions can evoke complacency, ingratitude, boredom, sluggishness. It can take the force of immense moral courage to break these holds to awaken to new freedom.

At the eve of a new presidential administration, I want to thank President Trump for his example of morally courageous leadership. He forced a fresh look at everything from news gathering practices to domestic policy, from business practices to foreign relations. His fearless defense of our country and insistence that we use a new type of logic one that questions the rationale of past decisions brought purpose to many.

Beyond policy reform, he enlivened the human spirit to reengage in the national discourse and fight for Americas well-being. He stirred things up enough to allow us to see societal problems and begin conversations we had avoided for years. His brazenness gave us space to be less afraid of the ugliest of human behavior in ourselves and others we couldnt escape confrontation with it and that made larger issues less intimidating.

He was the right president at the right time. Withstanding hate and fear, he helped us leave old ways of doing things. When waking people from complacency, apathy and depression, kind words arent always effective. His election seemed a call to the spirit of those who were ready to recognize their own power, ask questions and employ the moral requirement of being an alert, engaged and informed citizen.

With freedom comes responsibility. During his presidency, he demonstrated this responsibility, following words up with actions. He engaged dialog with foreign dignitaries, who many called enemies. Somehow, they dont feel like enemies anymore.

Under Trumps administration, subversive tactics from North Korea and Russia lessened. Looking at his approach, Trumps genuine discourse with those countries leaders people who need love and attention just like the rest of us seemed to meet the spiritual needs and still historical patterns of aggressiveness.

What if, beyond the torrent of Trumps mean-sounding words and brash bravado, we could have recognized his use of moral courage, bringing healing between nations?

The highlight of his presidency, for me, was the refusal to engage in military action against Iran. In late 2018, there were provocations and his advisors advocated a strong military response. Yet, Trump had the discipline to counsel with his sense of moral justice and drew a line that would only be crossed if there had been a direct hit to an American. There was a response, but no war.

While the legacy of Trump may be long-debated, we may all be cheering if we were to look at Americas progress from a psychological perspective. To me, a quake-like wrenching has taken place, replacing complacency with vigor. What if Trump has led us through a national re-awakening? Even media pundit George Stephanopoulos acknowledged on election night 2020, that Trumps legacy is a more engaged electorate.

Trump incited us to care again, to engage, to consider how and where to take action. Care, action, engagement are tools of love. He brought national focus back to ourselves, allowed us to build from within, strengthen Americas sense of self. Any psychologist would applaud this approach for a patient.

Our country is maturing. No matter who the president is, each of us has the moral duty to engage with each other productively, purposefully, and harmoniously. We have a long way to go, but there is new momentum now.

Thank you, President Trump.

Alexandra Ziesler, Park City, studies the Science of Spirit and practices through her business, The Truth of Being.

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Alexandra Ziesler: Trump was the right president at the right time - Salt Lake Tribune

Human Behavior

Welcome To Hyperreality: Where The Physical And Virtual Worlds Converge – Forbes

January 4, 2021 medical

getty

For more than 200,000 years, we humans only had access to the physical world, full of objects we could touch, taste, hear, smell and see. In the 1980s the internet gave birth to cyberspace: a virtual computer world designed to facilitate online communication. Then in 1991, the Web became publicly available; a new technology that would fundamentally change human behavior.

For kids growing up today, its hard to imagine a time without computers, smartphones, Google, Netflix or Instagram. A time when boredom existed, where we needed to memorize phone numbers and ask complete strangers for directions.Today, the ubiquitous use of social media and digital devices has made the web look and feel like the real world. The division between reality and imagery has collapsed.

We now live in hyperreality, a world where simulations of reality seem more real than reality itself. The concept of hyperreality was first coined by French sociologist Jean Baudrillard in Simulacra and Simulation. Baudrillard defined Hyperreality as, "the generation by models of a real without origin. When Baudrillard first posited the theory of hyperreality in 1981, it was seen as a highly provocative and controversial idea. Today, hyperreality is a permanent fixture of modern life.

In many ways, the current lockdown is the largest social and psychological experiment ever conducted. At the height of the pandemic, more than half of the worlds population4.2 billion peoplewere subject to a partial or complete lockdown. Our way of life has been upended. Human interaction has been replaced by digital pixels beamed across the internet each day. Predictably, people have been spending a record amount of time online. Zoom now has 300 million daily participants, compared to just 10 million in December 2019. Twitch has seen viewership increase by 56% per quarter. And Amazons profits have tripled as the pandemic accelerates the shift to e-commerce.

Perhaps more importantly, digital platforms like Zoom, Twitch and Amazon have been around for years. The technology hasnt changed, but rather our relationship with technology. Clearly, the global lockdown has been a catalyst for the mass adoption of e-commerce, online payments and video conferencing. For the first time in history, we have managed to move society or at least a large chunk online. Many people have established new-found habits built around the digital world. Under these conditions, the virtual world begins to compete with the physical world for time, resources and attention.

The rise of virtual propositions

Most of our time online is spent on devices, while remaining in the physical world. The next level is the virtual world, a fully immersive computer-simulated environment where people are represented by digital avatars. Currently, the virtual world is most visible in the gaming industry. Already, games like Fortnite, Minecraft and Roblox have built complex worlds, where people can create new identities, explore new possibilities and spend time with friends. The explosive growth of gaming is powering major developments in the virtual world.

The virtual world even has its own economy, with 2.5 billion people spending $100 billion on virtual goods. Contrary to popular opinion, gaming is not a form of escapism, but a chance for people to connect with friends and strangers on a deeper level. From a commercial perspective, global brands are scrambling to enter the virtual world. Recent attempts include Nikes League of Legends partnership, Guccis $10,000 virtual dress and Balenciagas runway show in a video game. For corporations with global reach and physical distributionthe virtual world represents an untapped opportunity to 10x revenuewithout having to manufacture physical products. The brands that build compelling virtual propositionsnot digital adswill undoubtedly shape society in the 21st century.

Welcome to the hyperreal

At the final level, we enter hyperreality, a state where the physical and virtual worlds converge. Where we can no longer distinguish between the two realities. But more importantly, the distinction wouldnt matter because people derive equal meaning and value from the simulated world. Early examples include virtual influencer Lil Miquela who has 2.9 million followers on Instagram. AI-powered Soundcloud rapper Fnmeka with 8 million followers on TikTok. And Genies, an avatar company that believes every human will need an avatar to represent themselves.

In a different realm, pornography has long been at the frontline of technological innovation. Unsurprisingly, porn is one of the only industries where virtual reality (VR) has reached widespread adoption. An estimated60%of the top virtual reality websites are porn sites. Psychologists warn that VR porn can disconnect people from reality. Hyperreality allows individuals to avoid the hardship of life, replacing it with a world perfectly calibrated to their own tastes. Similarly, we are beginning to see the emergence ofsex doll brothelsaround the world. Despite sounding like an excerpt from a cyberpunk novel, sex dolls are threatening the future of sex workers. In many instances customers choose dolls over humans to satisfy their fantasies. A recent study from Finlandsuggests that people view sex with a robot more kindly than they view with a human sex worker.

The global pandemic has further blurred the lines between the physical and digital world. We are now seeing the virtual world compete with the physical for resources. In the next decade, the two worlds will converge, creating a state of hyperreality: a simulation of reality without origin. Although it can be easy to dismiss hyperreality as some kind of sci-fi fantasy. We only have to look at the radical changes in human behavior and technological adoption during the current lockdown. In truth, elements of the hyperreal have already entered mainstream culture. This point takes on extra significance considering the leaders of the new worldGen-Zare equally, if not more comfortable living online. To quote Marshall McLuhan, We shape our tools and then our tools shape us.

Human Behavior

New Year’s Eve Parties in Los Angeles: It’s Happening – The New York Times

January 4, 2021 medical

Prohibition in the United States, a short-lived experiment that began 100 years ago, popularized the speakeasy: an illicit establishment designed to sell alcoholic beverages during the years they were legally banned.

Now, people are developing clandestine social clubs all over again and even styling their parties after the era of speakeasies.

Thats true even in Los Angeles, where more than 14,000 positive coronavirus tests are being reported in a day, and where the public health risks of going to a party seem too obvious to let partygoers remain in denial.

For the record: The Centers for Disease Control and Prevention recommends celebrating at home, wearing a mask around others and definitely avoiding crowds.

Throughout the pandemic, well-attended parties have mostly been shut down across Los Angeles, which has led to a culture of secrecy on social media. At the same time, underground party hosts are choosing to appeal to the truth of human behavior. They know that they can capitalize on the innate desire to socialize; for all those who cant imagine leaving their homes right now, there are others who are fully ready to celebrate the arrival of 2021 in the company of near strangers, as they would any other year.

These New Years Eve parties in Los Angeles include Spankys, which promises a laid-back affair at an indoor/outdoor venue downtown. The price of admission includes a 10 min Covid-19 antigen test, according to the invite. (While testing may weed out some people with coronavirus, it isnt a foolproof method. For one thing, rapid tests have a higher potential for false positives, according to the F.D.A.)

Chloe Chappe, 26 and a private chef in Los Angeles, has been getting Spankys emails since July and doesnt know how she ended up on their mailing list. I find it funny and frustrating that people are trying to justify partying right now, she said. Why are you trying to party when theres such a severe level of infection rates?

In many cases, revelry has been traded for discretion. People are not posting things because they know how much backlash theyll get, Ms. Chappe said. Being deprived of that kind of interaction for almost a year, I completely understand why people would want to finally celebrate this year being over, but were not at that point safety-wise, so theres such a dissonance there.

Cherrelle Moore, 28 and a freelance creative from New York celebrating New Years Eve in Los Angeles, has been visiting California for about a month. She said she has been to four or five house parties, and one strip club during that time. Ms. Moore plans to see people on the eve of 2021 but to limit her night to a low-key house party.

People think you going out is just being irresponsible, but it feels good and warm and good for your mental health too sometimes to be around people you love and even meet new people too you just have to be responsible, she said. She estimated shed been tested more than 15 times almost every other week, especially because I was in big gatherings.

Ms. Moore said she has never had coronavirus Thank God and that she believes theres a line of communication and trust required to socialize safely during the pandemic. And while she does post about it on social media, she noticed that it seemed like people were shading me and her friends as well, so she started posting only to her private Instagram network of close friends instead.

The reason why I even left New York was because I felt like I was about to go into a deep hole of depression again. I came out here for friends. I just didnt feel like staying in New York for the new year to come, Ms. Moore said. We can agree to disagree, but life is so short. It may sound irresponsible, but Im just going to live my life. Ive been super cautious and responsible this whole time, so Im going to try to turn up and manifest for 2021 and hopefully its way better than this year.

She is not alone.

An iOS app called Vybe Together encouraged users to Get your rebel on and Get your party on, and was designed to organize and promote underground parties to its audience. It seemed particularly well designed to facilitate parties that would violate current restrictions.

After it received attention this week, its website went down and Apple pulled the app from its store on Tuesday. (Business Insider reported that TikTok also removed the companys account.) We kinda blew up over night, said someone who answered Vybe Togethers phone. (The owners declined to speak further.)

The app had only a few thousand users, though there were thousands more waiting for their access to be approved.

Vybe Together updated its Instagram bio amid the trouble: App Store took us down!!! We will be back!!! Follow to stay updated!!! A minimal text post appeared on the accounts Instagram story: blown out of proportion by the media. We DO NOT CONDONE LARGE GATHERINGS!!!

Eventbrite, an event management and ticketing platform, has also been a popular option for people hosting parties. A recent Maskerade at a Los Angeles mansion ($80, open bar, round-trip party-bus ride) was advertised there. The invite, which drew ire on social media, has been removed from Eventbrites website.

Several other parties to be held at popular Los Angeles nightlife venues (such as Bootsy Bellows and Harriets Rooftop) were also listed on Eventbrite but are now marked as canceled. Blind Dragon, a venue listed as closed on OpenTable, promised a premium open bar beginning at 9 p.m. Gatsbys House NYE in Huntington Beach had tickets starting at $99 and topping out at $3,795. An event at Skybar, on the roof of the Mondrian in West Hollywood, promised a special live D.J. performance.

Our Community Guidelines have always prohibited events that promote or contain illegal behavior and our community plays an essential role in reporting any concerning event listings or content, a spokesperson for Eventbrite said in a statement. The company investigates complaints and says it wants to foster digital gatherings during the pandemic.

In the absence of our ability to bring people together for in-person experiences, we moved fast to help creators take their experiences online, said Julia Hartz, a founder and the chief executive of Eventbrite.

Those who wish to party anyway will return to finding celebrations the retro way: through private Instagrams, DMs and invites with no downloadable details, just an address thatll be texted out before midnight along with a request to wear a mask.

Earlier this month, the Los Angeles city attorneys office filed a lawsuit against the manager of LA Party Society, a nightclub in Downtowns Fashion District, and others associated with the venue for holding crowded events amid a surging pandemic, said Mike Feuer, the Los Angeles city attorney, in a virtual news conference.

As of now, the citys revised targeted safer at home order is clear. It states that all public and private gatherings and events with people from more than one household are not permitted except for outdoor faith-based services and outdoor political expression and that all lounges and nightclubs are to be closed.

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New Year's Eve Parties in Los Angeles: It's Happening - The New York Times

Human Behavior

Borne the Battle: Top 8 Most Popular Interviews of 2020 – VAntage Point – VAntage Point Blog

January 4, 2021 medical

2020 has come and gone, and this year,Borne the Battle has hosted many great Veterans and their stories. This year-end bonus episode of Borne the Battle features clips from the eight most downloaded episodes of 2020.

The following list explains how the top 8 episodes were calculated:

It was definitely a close call: the top 4 15 episodes were separated by less than 1,000 downloads.

2020s Top 8 most popular interviews:

Marine Veteran Ben Killoy struggled with the challenges of being a father. He found online communities of other men going through the same struggle, connected with them and, in doing so, was able to better connect as a husband and as a dad. He spent years learning to blog, write, and connect with other people. Killoy then founded the Military Veteran Dad Podcast in 2018. He shares stories and helps Veteran fathers be more present for their families.

Army Veteran Josh Strickland is a family man, the lead singer of the Phoenix-based band the Bayou Bandits, and a registered nurse who has worked through the COVID-19 pandemic in some of the hardest-hit areas of the United States.

Marine Corps Veteran, former police officer, MMA champion, bestselling author, and founder of the Mighty Oaks Foundation, Chad Robichaux turned his passion and greatest struggles into a foundation that helps his fellow Veterans who suffer from PTSD.

This 200th episode of Borne the Battle features Air Force Veteran Aerial Johnson, better known by her wrestling name Big Swole. Johnson shares stories from her time in the military and how she transitioned into civilian life, eventually becoming a professional wrestler.

While most events and clubs arent functioning as normal, Army Veteran Luke Wade and the KC Crew have found ways to keep people and communities connected during the COVID-19 pandemic.

Bigfoot, Aliens, Vampires: Do paranormal creatures really exist or are they all products of our imagination? Navy Veteran and private investigator, Jennifer Marshall, started her own show to investigate and solve these mysteries. Marshall believes she has some answers and joins this Halloween episode of Borne the Battle to share her perspective.

Marine Corps Veteran and sniper Brian Marren is an expert in Human Behavior Pattern Recognition and Analysis. He has trained Tier One military units, Fortune 500 companies, schools, churches, as well as local, state and federal law enforcement agencies. Marren explains how Human Behavior Pattern Recognition and Analysis is a scientific form of human behavior profiling and is not based on race or religion but rather on how all humans behave.

And the most downloaded interview of 2020 is

Navy Veteran Bryan Bergjans is brings a unique perspective on VA Home Loan Program by educating future Veteran homeowners and realtors.

Michaela Yesis is a podcast volunteer who recently graduated from George Mason University with a BA in English.

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Borne the Battle: Top 8 Most Popular Interviews of 2020 - VAntage Point - VAntage Point Blog