key role in causing the various pathologies; it can activate clotting factors [13], it is itself amyloidogenic [14], and it may have direct protein-protein interactions with the main plasma clotting protein, fibrinogen [2,15].

presence of clotting pathology in the form of fibrinaloid microclots, hyperactivated platelets and endothelial dysfunction represents a key target for both the diagnosis and the treatment of the condition [1,8,11,12].

signals indicating the presence of microclots should be easily detectable using a conventional flow cytometer

combining cell imaging and the high-event-rate and full-sample analysis nature of a conventional flow cytometer, imaging flow cytometry can eliminate erroneous results and increase accuracy in gating and analysis beyond what pure quantitative measurements from conventional flow cytometry can provide.

we have used imaging flow cytometry for the first time to show a significantly increased concentration and size of these microclots

demonstrated a significant amyloid microclot load in Long COVID patients

One of the major pathophysiological factors contributing to Long COVID is the presence of hypercoagulability; this results in insoluble amyloid microclots that are resistant to fibrinolysis

This suggests that there may be a replicating viral reservoir remaining long term, in some cases.

Various adjuvant medications may also assist

clinicians have embarked upon clinician-initiated treatment regimens that include such treatments

Oral anticoagulants

treatments will be to prevent microclots from forming and to prevent platelet hyperactivation

easy place to break it is the microclots because they’re really the chief bad guys

got to break the cycle somewhere

due directly to hypoxia, but also ischemia reperfusion injury, which causes so-called post-exertional malaise

a lot of sequelae is caused by microclots that lead to a variety of problems

The microclots account for all the obvious symptoms like fatigue, where patients are gasping for oxygen

If you’ve got these microclots, they block up the microcapillaries, preventing red blood cells from going through so oxygen doesn’t get to the tissues. The tissues that have been blocked from getting oxygen are the ones that are going to manifest disease

hese microclots are the central element to everything,

The general principle is that if you acquire a scientific understanding of what’s gone wrong with a disease, you can use that knowledge to fix it

P-selectin on CD40L-activated platelet surfaces can form complexes with monocytes and neutrophils.

platelets express P-selectin

form a platelet-T cell complex

found that microclots and platelet pathologies were present in all 80 patients

All patients were experiencing lingering symptoms of shortness of breath, low oxygen levels, heart palpitations, constant fatigue, joint and muscle pain, brain fog, sleep disturbances, digestive problems, or kidney problems.

samples from 80 patients

Long COVID, they found that no thrombin was needed to start the fibrinogen amyloid microclot process because the SARS-CoV-2 Spike protein was capable of starting the microclot process.

when we added thrombin to a blood sample from someone with asthma, it induced clotting into the amyloid form

We found that this was happening in a variety of chronic inflammatory diseases, such as Alzheimer disease or Parkinson disease

these deposits could be induced by things like unliganded iron, and later, we discovered, also by very low concentrations of bacterial cell wall components.

University of Liverpool

Stellenbosch Universit

dense matted deposits resulting from fibrin polymerization

had been looking at clots with an electron microscope

Over 10 years ago now

help to explain why some patients experience long-term symptoms and why COVID-19 affects so many tissues and organ systems

vascular4,8 disease

However, it is now accepted that COVID-19 is primarily an endothelial4,

was thought to be a typical viral pneumonia with acute disseminated intravascular coagulopathy

known as Long COVID

persistent sequelae, typically manifesting as fatigue, shortness of beath, sleep difficulties, and central nervous system symptoms.

respiratory failure and hypoxia

multi-organ failure

Thrombotic Disorders Are Amyloid Fibrin Microclots Central to Long COVID? Jessica Nye, PhD | July 8, 2022

understanding and treatment of Long COVID

it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms

Consistent with

Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms

microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope

extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies.

result, as is strongly manifested

A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin

bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection

Biochem J. 2022 Feb 25; 479(4): 537–559. Published online 2022 Feb 23. doi: 10.1042/BCJ20220016PMCID: PMC8883497PMID: 35195253A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) Etheresia Pretorius  ORCID: orcid.org/0000-0002-9108-23841,5, Chantelle Venter1, Gert Jacobus Laubscher2, Maritha J Kotze3, Sunday O. Oladejo4, Liam R. Watson  ORCID: orcid.org/0000-0002-7016-92294, Kanshu Rajaratnam4, Bruce W. Watson  ORCID: orcid.org/0000-0003-0511-18374 & …Douglas B. Kell  ORCID: orcid.org/0000-0001-5838-79631,5,6 Show authors Cardiovascular Diabetology volume 21, Article number: 148 (2022) Cite this article

Research Article| August 20 2021 SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19 In Collection Coronavirus Lize M. Grobbelaar; Lize M. Grobbelaar Sample analysis, Visualization, Writing—original draft 1Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland 7602, South Africa Search for other works by this author on: This Site PubMed Google Scholar Chantelle Venter; Chantelle Venter Data curation, Project administration 1Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland 7602, South Africa Search for other works by this author on: This Site PubMed Google Scholar Mare Vlok; Mare Vlok Software, Formal analysis, Investigation 2Central Analytical Facility: Mass Spectrometry Stellenbosch University, Tygerberg Campus, Room 6054, Clinical Building, Francie van Zijl Drive, Tygerberg, Cape Town 7505, South Africa Search for other works by this author on: This Site PubMed Google Scholar Malebogo Ngoepe 0000-0002-3639-9063 ; Malebogo Ngoepe Methodology 3Department of Mechanical Engineering, Faculty of Engineering and the Built Environment, University of Cape Town, Cape Town, Rondebosch 7701, South Africa4Stellenbosch Institute for Advanced Study, Wallenberg Research Centre, Stellenbosch University, Stellenbosch, South Africa Search for other works by this author on: This Site PubMed Google Scholar Gert Jacobus Laubscher; Gert Jacobus Laubscher Writing—review and editing 5Private practice clinician, Mediclinic Stellenbosch, Stellenbosch 7600, South Africa Search for other works by this author on: This Site PubMed Google Scholar Petrus Johannes Lourens; Petrus Johannes Lourens Writing—review and editing 5Private practice clinician, Mediclinic Stellenbosch, Stellenbosch 7600, South Africa Search for other works by this author on: This Site PubMed Google Scholar Janami Steenkamp; Janami Steenkamp Project administration, Writing—review and editing 1Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland 7602, South Africa6PathCare Laboratories, PathCare Business Centre, PathCare Park, Neels Bothma Street, N1 City 7460, South Africa Search for other works by this author on: This Site PubMed Google Scholar Douglas B. Kell 0000-0001-5838-7963 ; Douglas B. Kell Writing—review and editing 1Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland 7602, South Africa7Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K.8The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, Kgs Lyngby 2800, Denmark Correspondence: Etheresia Pretorius (resiap@sun.ac.za) or Douglas B. Kell (dbk@liv.ac.uk) Search for other works by this author on: This Site PubMed Google Scholar Etheresia Pretorius

However, there was a complete failure to dislodge or disturb COVID-19 PPP clots from the channels.

COVID-19 clots, on the contrary, could not be displaced or dislodged and remained intact, even with the force of high-speed water flow in a small flow channel.

Clots also formed with the PPP with the addition of the spike protein, but not as disruptive as the COVID-19 PPP clots

Interestingly, these clots did not propagate much after the initial burst, indicating that most of the thrombin was consumed in a short period of time

reaction between thrombin and PPP occurred rapidly, resulting in large clots after approximately 90 s

disorderly clots that cover the bulk of the channel and often protruding into the center of the flow channel and disrupting flow

PPP with added spike protein showed a combination of a fibrous laminar clot and disorderly clotted mass

clot formation was also less frequent

clot had orderly layers that did not disrupt flow through the centre of the channel

Clots formed in healthy PPP were relatively small and were limited to the walls of the flow channel

In healthy plasma, clot formation was a relatively slow and gradual process, resulting in the formation of a modest clot

anomalous deposits that is amyloid in nature

spontaneously formed fibrin network

Whole blood sample of healthy volunteers, before and after exposure to spike protein

formation of spontaneous and anomalous fibrin(ogen) deposits with an amyloid nature, were prominent in all the samples incubated with spike protein, without the addition of thrombin

An increase in platelet hyperactivation, membrane spreading

WB incubated with spike protein showed erythrocyte agglutination, despite the very low concentration of the spike protein

targeting it directly, whether via vaccines or antibodies, is likely to be of therapeutic benefit.

conclude that the spike protein may have pathological effects directly, without being taken up by cells

comparing naïve healthy platelet-poor plasma (PPP) samples, with and without added spike protein

also determine if the spike protein may interfere with blood flow

directly interact with platelets and fibrin(ogen) to cause fibrin(ogen) protein changes and blood hypercoagulation

infected cells liberates free receptor binding domain-containing S1 particles

Free spike protein can potentially be released due to spontaneous ‘firing’ of the S protein trimers on the surface of virions

Free S1 particles may also play a role in the pathogenesis of the disease

S1 proteins can also cross the blood–brain barrier

Spike protein, can however be shed

spike proteins are the key factors for virus attachment

inflammatory biomarkers

platelets

numerous reports of damage to erythrocytes

Plasma of COVID-19 patients also carries a massive load of preformed amyloid clots

substantial deposition of microclots in the lungs

Endotheliopathies are therefore a key clinical feature of the condition

directly bind to endothelial receptors

dysregulated inflammatory coagulation biomarkers,

hypercoagulation and thrombosis

Phenotypic vascular characteristics are strongly associated with various coagulopathies

important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.

lytic impairment may result in the persistent large microclots

cause substantial impairment of fibrinolysis

we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19

roteins were substantially resistant to trypsinization, in the presence of spike protein S1

prothrombin

complement 3

β and γ fibrin(ogen)

Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes

we show that spike protein may interfere with blood flow

directly

cause blood hypercoagulation

investigate the potential of this inflammagen to interact with platelets and fibrin(ogen)

effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen

One of the most important pathologies, is hypercoagulation and microclots

there is a significant difference in peptide structure before and after spike protein addition

less resistant to trypsinization

Is the Child’s Therapist Part of the Problem? What Judges, Attorneys, and Mental HealthProfessionals Need to Know About Court-related Treatment for ChildrenLYN R. GREENBERG, PH.D.*, JONATHAN W. GOULD,PH.D.**, DIANNA J. GOULD-SALTMAN, ESQ.***,PHILIP M. STAHL, PH.D.****I.

parents are provided legal representation to address a range of civil legal problems that could create family instability

There is an increased likelihood of psychotic symptoms with lifetime PTSD diagnoses

nTrauma exposure leads to various psychiatric disorders including depression, anxiety, bipolar disorders, personality disorders, psychotic disorders, and trauma related disorders, especially posttraumatic stress disorder (PTSD

person with delusional disorder may be high functioning in daily life

Apart from their delusion or delusions, people with delusional disorder may continue to socialize and function in a normal manner and their behavior does not necessarily generally seem odd.[

Delusional disorder, traditionally synonymous with paranoia, is a mental illness in which a person has delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect.[7][8] Delusions are a specific symptom of psychosis. Delusions can be bizarre or non-bizarre in content;[8] non-bizarre delusions are fixed false beliefs that involve situations that could occur in real life, such as being harmed

bullied?TRAUMA TRIggERS In cURREnT PlAcEMEnT

some children do not recover on their own.

Explain to the child that he or she is not responsible for what happened. Children often blame themselves for events

impact of child traumatic stress can last well beyond childhood.

self-harming behaviors

signs of traumatic stress are different in each child

important to learn how traumatic events affect children

reported experiencing multiple and repeated traumatic events

violent loss of a loved one

life-threatening illnes

events overwhelm a child’s or adolescent’s ability to cope

InvestigationReportDearMr.Furman:Asyouareaware,ourlawfirmservesasCountyAttorneyforWashingtonCounty,Colorado.Thisletterissenttoyouinyourcapacityas

Andrea Marsh

Alicia told me that the Bernhardts “can be victims, too.” Once the system “put this idea in their heads that adoption could be an achievable goal for them, it damaged our family, and my son, and the foster parents’ family.”

We didn’t do any of this for any reason other than to make sure that Carter has the best life,” J’Lyn told me later. “He deserves that.”

they’d paid around thirty-two thousand dollars to Eirich’s firm.

he is on target developmentally, and even “potentially gifted.” When I mentioned to Baird that there is little sign of the attachment trauma she predicted, she said this just demonstrates that Carter knows he has to “hero on.”

Can we tell Dad I slept so good?” he asked his mom with excitement one morning, and Alicia wondered if he knew or sensed that his sleep problems had been debated for years.

could do anything about it.

February, the judge asked for an explanation of what, exactly, was still unfit about Alicia and Fred as parents

Two days later, a letter from an attorney representing Washington County revealed that an internal investigation had found improprieties in the handling of Carter’s case. (The investigative report is under a gag order, and neither Smith nor the new director would elaborate on the resignation.) The trial was cancelled

director of the Department of Human Services, Grant Smith, resigned.

Washington County had spent more than three hundred and ten thousand dollars on Carter’s case: on his brain-mapping and medical exams, on the many expert evaluations, on Baird’s travel to and from Denver, on payments to the Bernhardts, and so on

They filed a Colorado Open Records Act request, and soon received dozens of invoices.

Last year, the Kempe Center’s director asked Baird in an e-mail to stop using the Kempe name to describe her protocol an

Baird has long called her technique for evaluating

had again brought in an expert—Diane Baird—to assess

the judge did little but say that he would await responses to a motion and schedule another hearing

judge, for his part, lamented all the medical tests. “We’re going to turn this kid into a lab rat,” he said

they couldn’t hear, let alone counter, much of what the county’s lawyer was saying about them

sitting cross-legged on their living-room floor,

Janina Fariñas, another clinical psychologist who evaluated him for the county, told me, “There was almost a need for Carter to not be O.K.”

therapist

A clinical psychologist found that he had normal social functioning for his age but that the fuzz-eating could be attributed to pica, a condition marked by eating non-food items, and that other signs of distress might be caused by “upbringing away from parents.”

experts

tests

Paul Spragg, a Colorado forensic psychologist

Foster Source

veteran nurse practitioner

What is the process at this point?” she wrote. “Will I hear from you or should I expect to hear from someone else? Is there anything else I can/should be doing to be prepared for baby and court? Should I plan a visit to Colorado to meet [the child] or to meet persons involved?”

She has significant experience,” the judge said,

only a preference under state laws. The judge rule

, as Eirich underlined to me, though parents have a constitutional right to their child until such right is terminated

but you’re also being blamed

in reality, children may be dysregulated for any number of reasons—perhaps they miss their parent, feel confused, or are simply behaving as toddlers do.” Green used to employ the dysregulation claim in her own cases, she said. She now regrets it.

Allison Green, the legal director of the National Association of Counsel for Children,

gave his foster parents more time to make their central argument

remained in foster care, with no transition home planned.

social worker had explained that Eirich and Baird “went around the state together,” arguing for the termination of birth-parents’ rights

Another judge, recognizing Fred’s transformation, had recently granted him full custody of his other son, Robert, who was twelve years old.

The problem was that Alicia and Fred would not give up.

A healthy attachment trumps biology in the first three years of life, period,”

an attachment expert whom she has trained.

intervenor-training sessions for judges and foster parents

When the American Academy of Pediatrics reviewed

foster children were becoming a “hot commodity,” he said

prominent local ranching family

expert

saying that their visits with him were threatening his primary attachment and causing “a biologic hyperarousal that not only burns calories but self-perpetuates”—a state that becomes worrisome when a child spends “twenty-five to fifty-seven per cent of their time, or whatever,” in it. Rupturing a primary attachment could ultimately cause “sociopathy” in a child, she said.

judge

without having met them.

hundreds

as an expert

Although hired as a consultant by Washington County in this case, Baird had a long-standing independent agenda: helping foster parents across Colorado succeed in intervening and permanently claiming the children they care for. Often working hand in hand with Tim Eirich

Did Baird not understand how hard it is to bond with a baby you’ve been allowed to see for only a few hours a week, while masked, or in fifteen-minute stints on Zoom

social worker named Diane Baird

the sentence under this section for such offense shall include imprisonment for not less than 20 years

Special Rule for Certain Offenses Involving Children

c) If two or more persons conspire to violate this section and one or more of such persons do any overt act to effect the object of the conspiracy, each shall be punished by imprisonment for any term of years or for life.

shall be punished by imprisonment for any term of years or for life

any person

kidnaps

) Whoever unlawfully

Kidnapping

Kidnapping -- 18 U.S.C. § 1201

Section 1201(d) prohibits attempts to kidnap

Section 241 makes it unlawful for two or more persons to agree to injure, threaten, or intimidate a person in the United States in the free exercise or enjoyment of any right or privilege secured by the Constitution or laws of the United States

penalties up to and including life in prison or death

kidnapping

A violation of the statute is a misdemeanor, unless prosecutors prove one of the statutory aggravating factors such as