I have not been sick once since the pandemic. I started wearing N95 masks and continue to do so when around others (even after assaults by fucker truckers trying to rip my masks off). I will wear an N95 in public for the rest of my days. No flu, no cold, no COVID, no weeks wasted in bed miserable. I love not getting sick.
Masks are an easy, excellent economical health protection that I control, no one else. Freedom!
Masks protect community, especially the vulnerable, and me. Win. Win. Win.
Masks keep the sun off my face, keep it warm on walks in -30C and make breathing in extreme cold easier.
And, best, masks protect my privacy when I am out in public. I love hiding my face from people I don’t know.
I’d much rather wear a mask, than get sick and lose my mind and or my immune system.
Daniel Brittain Dugger@dbdugger:
Kenneth Podell predicted folks would have the brain of an AIDS Dementia Complex patient.
Here we are, Lewy Body Dementia.
SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms by Joanna Agata Motyl , Grazyna Gromadzka, Grzegorz Arkadiusz Czapski and Agata Adamczyk, Nov 10, 2024
Int. J. Mol. Sci.2024, 25(22), 12079; https://doi.org/10.3390/ijms252212079
Submission received: 23 September 2024 / Revised: 30 October 2024 / Accepted: 8 November 2024 / Published: 10 November 2024
(This article belongs to the Special Issue Cross-Talk between Mitochondrial Dysfunction and Neuroinflammation in Central Nervous System Disorders)
Abstract
Alpha-synuclein (Ɑ-syn) is a 140-amino-acid, intrinsically disordered, soluble protein that is abundantly present in the brain. It plays a crucial role in maintaining cellular structures and organelle functions, particularly in supporting synaptic plasticity and regulating neurotransmitter turnover. However, for reasons not yet fully understood, Ɑ-syn can lose its physiological role and begin to aggregate. This altered Ɑ-syn disrupts dopaminergic transmission and causes both presynaptic and postsynaptic dysfunction, ultimately leading to cell death. A group of neurodegenerative diseases known as Ɑ-synucleinopathies is characterized by the intracellular accumulation of Ɑ-syn deposits in specific neuronal and glial cells within certain brain regions. In addition to Parkinson’s disease (PD), these conditions include dementia with Lewy bodies (DLBs), multiple system atrophy (MSA), pure autonomic failure (PAF), and REM sleep behavior disorder (RBD). Given that these disorders are associated with Ɑ-syn-related neuroinflammation—and considering that SARS-CoV-2 infection has been shown to affect the nervous system, with COVID-19 patients experiencing neurological symptoms—it has been proposed that COVID-19 may contribute to neurodegeneration in PD and other Ɑ-synucleinopathies by promoting Ɑ-syn misfolding and aggregation. In this review, we focus on whether SARS-CoV-2 could act as an environmental trigger that facilitates the onset or progression of Ɑ-synucleinopathies. Specifically, we present new evidence on the potential role of SARS-CoV-2 in modulating Ɑ-syn function and discuss the causal relationship between SARS-CoV-2 infection and the development of parkinsonism-like symptoms.
…
Testosterone may not only increase men’s susceptibility to SARS-CoV-2 infection but also weaken antiviral immunity. Several studies [219] confirm that testosterone reduces immune responses in men. By suppressing T helper (Th) 2 and Th17 cells, testosterone decreases antibody production and impairs B cell proliferation, thus compromising adaptive immunity [220]. In dendritic cells, testosterone reduces interleukin levels (IL-10, IL-13, and IL-4) and lowers the expression of the MHC-II receptor on antigen-presenting cells [221]. These effects are linked to delayed antibody responses in severe COVID-19 cases and lower IgG production in men compared with women, which may correlate with worse prognoses [222]. Interestingly, testosterone also increases anti-inflammatory cytokine levels in vivo, challenging the idea that it solely suppresses inflammation. It has been shown to enhance IL-10 expression while decreasing levels of IL-6, IL-1, and TNF-Ɑ [223]. Thus, at younger ages, elevated testosterone levels may render men more susceptible to SARS-CoV-2 infection and weaken their antiviral immunity, potentially leading to more severe infections compared with women. Simultaneously, the reduced inflammatory response in men may protect them from cytokine storms and associated complications.
In turn, estradiol has been shown to reduce ACE2 levels in the kidneys of women, while ovariectomy, which removes estrogen, increases ACE2 activity and expression in kidneys and adipose tissue in mice [213]. Additionally, recent studies suggest that increased estrogens can also enhance antiviral immunity [224]. Estradiol stimulates the production of interferon type 1 by T lymphocytes after binding to ER [225]. Increased levels of interferon I and III are associated with a milder course of COVID-19 [226]. Additionally, estrogen increases the expression of T cell chemokine receptor 5 (CCR5) and influences the increased adhesion of blood lymphocytes to endothelial cells [218,227], increases the production of IL-4 and the development of T helper type 2 cells [228] as well as stimulates T helper cell type 1 differentiation by reducing T helper cell type 17 and IL-17 cytokines [229].
An additional hypothesis explains the superior immunity of females against SARS-CoV-2 infection, linked to their double dose of the X chromosome, which houses several immunity-related genes such as Fork-head box P3 (FOXP3), CD40 ligand (CD40L), Toll-like receptor 7 (TLR-7), and Toll-like receptor 8 (TLR-8) [230]. Although X chromosome inactivation occurs during female embryogenesis, some proteins encoded on the X chromosome can still be produced in a biallelic manner. This biallelic expression of X-linked genes in immune cells may lead to heightened immunity or unfavorable inflammatory responses [231]. One key protein is TLR-7, crucial for pathogen recognition and the activation of innate immunity and predominantly found in monocytes, plasmacytoid dendritic cells (PDCs), and B cells [232]. Women may exhibit overexpression of TLR-7 due to biallelic expression compared with men [233,234]. Consequently, this increased expression may enhance women’s immune response, offering a protective advantage against COVID-19 infection and its severe outcomes. This protection may persist even after menopause, despite the decline in estrogen synthesis.
Results from various studies involving humans and rodents indicate that estrogen may provide protection to females against cytokine storms and inflammation. At physiologically elevated levels, estrogen appears to inhibit the production of several pro-inflammatory cytokines, such as IL-6, IFN-Ɑ, IL-1, and chemokine (C-C motif) ligand 2 (CCL2), from monocytes and macrophages. This action helps to prevent the migration of neutrophils and monocytes to inflammatory sites [235].
The data suggest that younger men may be at a higher risk of COVID-19 infection and severe illness compared with women. In this age group, both men and women appear to have a lower risk of developing a cytokine storm, a factor that could otherwise promote Ɑ-synuclein aggregation. This protective effect may stem from testosterone and estradiol, which help to reduce the production of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-Ɑ [236].
However, these dynamics may shift with age as sex hormone levels decline. Among older adults, both men and women may experience similar risks of SARS-CoV-2 infection, cytokine storm development, and related complications affecting the central nervous system. The interplay between sex, SARS-CoV-2 infection, and Ɑ-synucleinopathy is thus complex, shaped by age and hormonal status. Further research is needed to clarify these relationships and their broader implications.
- Conclusions
The emerging evidence suggests that COVID-19 may have lasting effects on the nervous system and brain function, with a potential link between Ɑ-synucleinopathies and SARS-CoV-2 infection. However, the nature of this relationship and its direct causality remain poorly understood. Several mechanisms could explain how SARS-CoV-2 infection might contribute to the onset or progression of neurodegenerative diseases such as PD and other Ɑ-synucleinopathies, involving both direct and indirect alterations of Ɑ-syn.
These mechanisms include the viral-induced dysfunction of Ɑ-syn resulting from direct protein–protein interactions that accelerate the conversion of Ɑ-syn into pathological multimeric forms, such as oligomers and protofibrils, promoting its spread and leading to widespread neurodegeneration. Additionally, chronic neuroinflammation triggered by SARS-CoV-2 may cause pathological changes in Ɑ-syn, further supporting a potential connection between these disorders.
Interestingly, in the context of SARS-CoV-2 infection, Ɑ-syn may play a “Janus-faced” role, potentially acting protectively through upregulation as part of the immune response to viral infections. Understanding the interplay between SARS-CoV-2 infection and the dual nature of Ɑ-syn is crucial for managing and treating patients with pre-existing neurological conditions who contract COVID-19, as well as for exploring the role of long COVID in the development of Ɑ-synucleinopathies.
To date, several potential therapies have been proposed, targeting pro-inflammatory processes, ACE2 receptors, ERK1/2 activity, and intracellular Ca2+ homeostasis (Table 3). However, the search for effective treatments for long COVID is ongoing, necessitating more in-depth studies and subsequent clinical trials to identify promising therapeutic targets and develop successful interventions.
If Premier Danielle Smith criminalizes masks in Alberta, I’ll continue wearing mine regardless and will avoid being indoors with others as much as possible until the public health-hating mega douche gets her evil oily ass voted out.
Fucker Trucker organizer/lead Pat King in court. Hideously evil selfish piece of shit. I hate to think how many he sickened and or killed via COVID.
Visual showing risk reductions wearing masks to protect against pathogens like COVID which spreads in the air:
Two humans, no mask, one infected = 90% risk of transmission
Two humans, infected one not wearing a mask = 30% risk of transmission
Two humans, infected one wearing a mask = 5% risk of transmission
Two humans, one infected, both wearing mask = 1.5% risk of transmission.
***
PS Canadian health officials like social mass murderer Dr. Bonnie Henry still lie about COVID being spread by hands and not our breath, to keep people out in public mask-less in church, pubs and restaurants, at parties, travelling, spending money like there’s no pandemic making billionaires richer. Quadruple douche doctor.
