The discovery of new drugs is vital to achieving the eradication of neglected tropical diseases (NTDs) in Africa and around the world. Now, researchers have identified traditional Ghanaian medicines which work in the lab against schistosomiasis, onchocerciasis and lymphatic filariasis, three diseases endemic to Ghana.
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Multiple bouts of blood feeding by mosquitoes shorten the incubation period for malaria parasites and increase malaria transmission potential, according to a new study.
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A novel computational drug screening strategy combined with lab experiments suggest that pralatrexate, a chemotherapy medication originally developed to treat lymphoma, could potentially be repurposed to treat COVID-19.
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When using social media to nudge people toward safe and healthy behaviors, it's critical to make sure the words match the pictures, according to a new study. After looking at social media posts, parents of young children were better able to recall safety messages such as how to put a baby safely to sleep when the images in the posts aligned with the messages in the text.
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Researchers report that adding a small molecule to a chimeric antigen receptor-T (CAR-T) cell therapy can help immune system T cells to effectively attack solid tumors, such as breast cancers. The boost helps recruit more immune cells into battle at the tumor site, according to the new study.
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When fat cells in the body are stuffed with excess fat, the surrounding tissue becomes inflamed. That chronic, low-level inflammation is one of the driving factors behind many of the diseases associated with obesity. Now, scientists have discovered a type of cell responsible, at least in mice, for triggering this inflammation in fat tissue. Their findings could eventually lead to new ways to treat obesity.
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A randomized clinical trial is the largest study to-date to compare thresholds for blood transfusions in premature babies, offers guidance for health care providers.
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More attention than ever is being put on your gut health, and understandably so, considering a significant proportion of your immune system resides in your gastrointestinal tract.1 As such, optimizing your gut microbiome is a worthwhile pursuit that will have far-reaching effects on your physical health and emotional well-being.
Mounting scientific evidence also continues to suggest a large component of nutrition centers on nourishing health-promoting bacteria in your gut (and elsewhere in and on your body). In doing so, you keep harmful microbes in check and shore up your protection against chronic disease.
Disease Begins in Your Gut
ADHD, autism, learning disabilities, obesity, diabetes2 and Parkinson’s disease are but a few of the conditions found to be influenced by your gut microbiome. One 2020 scientific review3 goes so far as to say that all inflammatory disease begins in the gut. Part of the blame is laid on excessive hygiene. In other words, we’re “too clean” for our own good.
But your diet also plays a crucial role. The paper specifically addresses the role of zonulin-mediated gut permeability in the pathogenesis of chronic inflammatory diseases (CIDs). According to the author, Dr. Alessio Fasano,4 a pediatric gastroenterologist, researcher and director of the Center for Celiac Research and Treatment:5
“Apart from genetic makeup and exposure to environmental triggers, inappropriate increase in intestinal permeability (which may be influenced by the composition of the gut microbiota), a ‘hyper-belligerent’ immune system responsible for the tolerance-immune response balance, and the composition of gut microbiome and its epigenetic influence on the host genomic expression have been identified as three additional elements in causing CIDs.
During the past decade, a growing number of publications have focused on human genetics, the gut microbiome, and proteomics, suggesting that loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between gut microbiome and our immune system.
This cross-talk is highly influential in shaping the host gut immune system function and ultimately shifting genetic predisposition to clinical outcome. This observation led to a re-visitation of the possible causes of CIDs epidemics, suggesting a key pathogenic role of gut permeability.
Pre-clinical and clinical studies have shown that the zonulin family, a group of proteins modulating gut permeability, is implicated in a variety of CIDs, including autoimmune, infective, metabolic, and tumoral diseases. These data offer novel therapeutic targets for a variety of CIDs in which the zonulin pathway is implicated in their pathogenesis.”
Bacteria, Not Genes, Rule Your Health Destiny
Fasano points out that we simply do not have enough genes to account for the myriad chronic diseases that can beset us. Genes also cannot explain the timing of disease onset. To solve these mysteries, we must look to the microbiome, he says, as “it is the interplay between us as individuals and the environment in which we live that dictates our clinical destiny.”
Aside from the microbes themselves, the condition of your intestinal mucosa also plays a significant role. “Although this enormous mucosal interface (200 m2) is not apparently visible, it plays a pivotal role through its dynamic interactions with a variety of factors coming from our surrounding environment, including microorganisms, nutrients, pollutants and other materials,” Fasano explains.
While intracellular tight junctions used to be thought of as static and impermeable, we now know this is not the case. As explained by Fasano, zonulin is a powerful modulator of intestinal permeability. However, while zonulin is a biomarker of gut permeability and plays a pathogenic role in in many chronic inflammatory diseases, not all CIDs are caused by leaky gut.
Proposed Chain of Events Leading to CID
The graphic below, included in Fasano’s review but originating from an earlier paper6 titled “Zonulin, a Regulator of Epithelial and Endothelial Barrier Functions, and Its Involvement in Chronic Inflammatory Diseases,” co-written by Fasano and Craig Sturgeon, details the “proposed chain of events leading to chronic inflammatory disease.”
Under normal circumstances, a healthy homeostasis is maintained in your gut lining such that when an antigen is encountered, no excess immune reaction occurs (anergy). Under No. 2 in the graph, gut dysbiosis is setting in (i.e., an imbalance in the number and diversity of your gut microflora), causing excess production of zonulin, which in turn makes the gut lining more permeable.
According to Fasano, the two most powerful triggers of zonulin release are bacteria overgrowth and gluten. Zonulin is produced in response to bad bacteria7 — it helps flush the bacteria out by opening up the tight junctions — so bacteria overgrowth makes sense. But why does it respond to gluten?
Interestingly enough, the zonulin pathway misinterprets gluten as a potential harmful component of a microorganism. That’s why gluten triggers zonulin release. While not mentioned by Fasano, the herbicide glyphosate also triggers zonulin, and is 10 times more potent than gluten!8
The subsequent permeability allows microbiota-derived antigen and endotoxin to migrate from the lumen to the lamina propria (the connective tissue that is part of the mucous membrane lining your intestine), thereby triggering inflammation.
As the process continues to worsen (No. 3 in the graph), your adaptive immune response kicks in, triggering the production of proinflammatory cytokines, including interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). These cytokines further worsen the permeability, thus creating a vicious cycle. Eventually (No. 4), mucosal tolerance is completely broken, resulting in the onset of a chronic inflammatory disease.
Chronic Inflammatory Diseases Linked to Leaky Gut
The specific chronic inflammatory disease that ultimately emerges at the end of all this depends in part on your genetic makeup, in part on the types of exposures you’ve had, and in part on the composition of your gut microbiome. As explained by Fasano:9
“Besides genetic predisposition and exposure to environmental triggers, the pathogenesis of a variety of CIDs seems to involve mutually influenced changes in gut permeability/Ag trafficking, immune activation, and changes in composition/function of the gut microbiome.
Zonulin is a modulator of both epithelial and endothelial barrier functions … Gut dysbiosis may cause the release of zonulin leading to the passage of luminal contents across the epithelial barrier causing the release of pro-inflammatory cytokines that themselves cause increased permeability establishing a vicious loop leading to massive influx of dietary and microbial Ags triggering the activation of T cells.
Depending on the host genetic makeup, activated T cells may remain within the GI tract, causing CID of the gut … or migrate to several different organs to cause systemic CID.”
Chronic inflammatory diseases associated with dysregulation of the zonulin pathway include:
Autoimmune disorders such as Celiac disease, Type 1 diabetes, inflammatory bowel disease, multiple sclerosis and ankylosing spondylitis
Metabolic disorders such as obesity, insulin resistance, nonalcoholic fatty liver disease, gestational diabetes, hyperlipidemia and Type 2 diabetes
Intestinal diseases such as irritable bowel syndrome, non-celiac gluten sensitivity and environmental enteric dysfunction (a chronic disease affecting the proximal intestine)
Neuroinflammatory diseases such as autism spectrum disorder, schizophrenia, major depressive disorder and chronic fatigue/myalgic encephalomyelitis
Brain and liver cancers
Gut Microbes Influence Genes and Can Influence Cancer Risk
While the inclusion of cancer on that list may seem odd at first glance, some researchers believe the gut microbiome may actually end up being a game-changer for cancer prevention and treatment.
Not only have gut bacteria been shown to influence gene expression,10,11 turning some genes on and others off, research12 published in 2018 found gut microbes actually control antitumor immune responses in your liver, and that antibiotics can alter the composition of immune cells in your liver, triggering tumor growth.
Certain gut bacteria also promote inflammation, which is an underlying factor in virtually all cancers, whereas other bacteria quell it.13 The presence of certain gut bacteria has even been shown to boost the patient’s response to anticancer drugs.14
One way in which gut bacteria improve the effectiveness of cancer treatment is by activating your immune system and allowing it to function more efficiently. Researchers have actually found that when these specific microbes are absent, certain anticancer drugs may not work at all.
Gut Bacteria Are Part of Your Antiviral Defense
Gut bacteria are also involved in your antiviral defense, recent research15 shows. As reported by Harvard Medical School November 18, 2020:16
“For the first time, Harvard Medical School researchers have … identified the specific population of gut microbes that modulates both localized and systemic immune response to ward off viral invaders. The work … pinpoints a group of gut microbes, and a specific species within it, that causes immune cells to release virus-repelling chemicals known as type 1 interferons.
The researchers further identified the precise molecule — shared by many gut bacteria within that group — that unlocks the immune-protective cascade. That molecule, the researchers noted, is not difficult to isolate and could become the basis for drugs that boost antiviral immunity in humans.”
While the findings still need to be replicated and confirmed, they point to the possibility that you might be able to enhance your antiviral immunity by reseeding your gut with Bacteroides fragilis and other bacteria in the Bacteroides family.17
These bacteria initiate a signaling cascade that induces the release of interferon-beta that protect against viral invasion by stimulating immune cells to attack the virus and causing virus-infected cells to self-destruct.
“Specifically, … a molecule that resides on the bacterium’s surface triggers the release of interferon-beta by activating the so-called TLR4-TRIF signaling pathway,” Harvard explains.18“This bacterial molecule stimulates an immune-signaling pathway initiated by one of the nine toll-like receptors (TLR) that are part of the innate immune system.”
The Role of Vitamin D
Recent research also highlights the role of vitamin D in gut health and systemic autoimmunity. The review article, published January 21, 2020, in Frontiers in Immunology, notes:19
“Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier.
In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.”
As noted in this review, vitamin D has several direct and indirect regulatory effects on your immune system, including promoting regulatory T cells (Tregs), inhibiting differentiation of Th1 and Th17 cells, impairing development and function of B cells, reducing monocyte activation and stimulating antimicrobial peptides from immune cells.
That said, the relationship between vitamin D and autoimmunity is complicated. Aside from immunosuppression, vitamin D also appears to improve autoimmune disorders by the way it affects your microbiota composition and gut barrier.
The review cites research showing that your vitamin D status alters the composition of your gut microbiome. Generally speaking, vitamin D deficiency tends to increase Bacteriodetes and Proteobacteria while higher vitamin D intake tends to increase prevalence of Prevotella and reduce certain types of Proteobacteria and Firmicutes.
While research is still slim when it comes to vitamin D’s impact on gut bacteria, especially in patients with autoimmune disease, vitamin D deficiency and autoimmune diseases are known comorbidities and vitamin D supplementation is often recommended for these patients.
Vitamin D Required for Tight Junction Maintenance
Better known is how vitamin D supports intestinal and immune cell defenses in the gut. In fact, vitamin D is one of the crucial components required for maintaining tight junctions. As explained in this review:20
“The intestinal epithelium is in constant interaction with the external environment. Adequate barrier integrity and antimicrobial function at epithelial surfaces are critical in maintaining homeostasis and preventing invasion or overcolonization of particular microbial species.
A healthy intestinal epithelium and intact mucus layer are critical to protect against invasion by pathogenic organisms, and vitamin D helps to maintain this barrier function … Multiple studies found that vitamin D3/VDR signaling modulates tight junction protein quantity and distribution …
As a ‘leaky’ protein that allows movement of ions into the intestinal lumen, claudin-2 expression in the setting of functional vitamin D deficiency may contribute to colitis pathology …
Vitamin D upregulates antimicrobial peptide mRNA and protein expression including cathelicidin, defensins, and lysozyme … Antimicrobial peptides, primarily secreted by Paneth cells in the gut, are important mediators of microbiome composition … Defensins are secreted by epithelial cells, Paneth cells, and immune cells, and are important components of the innate immune response in the gut.”
How Vitamin D May Contribute to Autoimmune Disease
According to the authors, vitamin D deficiency may contribute to autoimmune disease by affecting the microbiome and the immune system in the following manner:
Vitamin D deficiency or supplementation changes the microbiome, and manipulation of bacterial abundance or composition impacts disease manifestation.
Lack of vitamin D signaling due to dietary deficiency can impair physical and functional barrier integrity of the gut, thereby allowing bacterial interactions to either stimulate or inhibit immune responses.
Your innate immunologic defenses may be compromised if you are deficient in vitamin D.
How to Optimize Your Gut Microbiome
All of this information should really drive home the point that optimizing your gut flora and vitamin D level is of crucial importance for good health. By reseeding your gut with beneficial bacteria, you can keep pathogenic microbes and fungi in check and prevent them from taking over, and optimizing your vitamin D will help avoid leaky gut.
Regularly eating traditionally fermented and cultured foods is the easiest, most effective and least expensive way to make a significant impact on your gut microbiome. Healthy choices include lassi (an Indian yogurt drink), cultured grass fed organic milk products such as kefir and yogurt, natto (fermented soy) and fermented vegetables of all kinds.
Although I'm not a major proponent of taking many supplements (as I believe the majority of your nutrients need to come from food), probiotics are an exception if you don’t eat fermented foods on a regular basis. Spore-based probiotics, or sporebiotics, can be particularly helpful when you’re taking antibiotics. They’re also an excellent complement to regular probiotics.
Sporebiotics, which consist of the cell wall of bacillus spores, will help boost your immune tolerance, and because they do not contain any live bacillus strains, only its spores — the protective shell around the DNA and the working mechanism of that DNA — they are unaffected by antibiotics.
Antibiotics, as you may know, indiscriminately kill your gut bacteria, both good and bad. This is why secondary infections and lowered immune function are common side effects of taking antibiotics. Chronic low-dose exposure to antibiotics through your food also takes a toll on your gut microbiome, which can result in chronic ill health and increased risk of drug resistance. Last but not least, you also need to avoid things that disrupt or kill your microbiome, and this includes:
Antibiotics, unless absolutely necessary
Conventionally-raised meats and other animal products, as these animals are routinely fed low-dose antibiotics, plus genetically engineered and/or glyphosate-treated grains
Processed foods (as the excessive sugars feed pathogenic bacteria)
Chlorinated and/or fluoridated water
Antibacterial soap and products containing triclosan
A spate of studies has called into question the effectiveness of mask mandates and other nonpharmaceutical interventions (NPIs) — such as lockdowns, curfews and stay-at-home orders — in controlling COVID-19 and lowering death rates.
Researchers from Rational Ground, which is providing resources, including data analysis, related to COVID-19, specifically looked into mask mandates and whether or not they're effective, with results suggesting widespread mask usage has been virtually useless.1The fact is, mask mandates were rolled out despite a lack of solid evidence to support their use among the general population. On the contrary, the evidence against them continues to mount.
COVID Cases Higher With Mask Mandates Than Without
The computer scientists, actuaries and data analysts that make up Rational Ground2 looked at COVID-19 cases from May 1, 2020, to December 15, 2020, in all 50 U.S. states. They calculated how many cases per day occurred by population with and without mask mandates.3
Non-mandate data included states that had mask mandates at some point but not others, with the data including only days the mask mandates were not in place. The states without mask mandates for the entire study period included:
Alaska
Arizona
Florida
Georgia
Idaho
Iowa
Missouri
North Dakota
Nebraska
New Hampshire
Oklahoma
South Carolina
South Dakota
Tennessee
Wyoming
An important point: the researchers waited 14 days from the start of mask mandates to begin counting COVID-19 cases. This ensured cases from spread that occurred before the mandate weren't counted against them. The results found 9,605,256 confirmed COVID-19 cases over 5,907 days in the mask mandate states. Among states without a mask mandate, 5,781,716 cases were counted over 5,772 days. This works out to:4
No mask mandates — 17 cases per 100,000 people per day
Mask mandates — 27 cases per 100,000 people per day
No Evidence of Masks Reducing Virus Spread
In response to critics suggesting the cases were higher with mandates because they were implemented in areas that had higher spread to begin with, Hart posted on Twitter, "Team Apocalypse will object and say: 'well, states which put mandates in place were seeing surges in cases!' Perhaps … but our data shows that even AFTER the mandates went up … it did nothing."5
The data holds true even when population density is taken into account. Among the 12 counties with the greatest population density in Florida, eight had mask mandates at some point, during which 24 cases per 100,000 people per day were counted.
On days without mandates, which includes four counties that never had them, 17 cases per 100,000 people per day occurred.6 As noted by Daniel Horowitz, a senior editor of The Blaze:7
"We can turn the numbers upside down and inside out, but no matter how we examine them, there is no evidence of masks correlating with reduced spread. If anything, the opposite is true … It's self-evident that the virus does what it does naturally and follows a very mechanical pattern regardless of state policies …
The phony 'fact checkers' will always find ways to show that we can't prove beyond a shadow of doubt that masks will never work. But while they force us to prove 100% that they don't work, mandaters don't have to prove any efficacy at all, even as 2-year-olds are forced to have their faces covered on planes."
Rational Ground's data compilations also include charts that break down daily COVID-19 cases in a wide variety of regions, from Hawaii to Los Angeles, Orange, Ventura, and San Diego counties in California to Kansas, West Virginia, France and Peru, marking the dates mask mandates were put in place. The charts show no correlation between the implementation of mask mandates and reduced cases.
There is one chart that shows a steady decline of COVID-19 deaths after a mask mandate — New York City. But the mandate occurred as the death rate was already falling, following a similar pattern of a peak followed by a decline seen in many areas, with or without mask usage.8
Four Facts Suggest Importance of NPIs May Be Overstated
NPIs, including not only mask mandates but also travel restrictions, stay-at-home orders, quarantines and lockdowns, do not reduce COVID-19 transmission and death rates, according to a working paper released by the National Bureau of Economic Research (NBER).9
They present four stylized facts that call into question conclusions by health agencies claiming that social distancing and other NPI mandates have been essential in lowering COVID-19 transmission rates and deaths:10
For all the countries and U.S. states studied, once the region experienced 25 cumulative COVID-19 deaths, the growth rates of daily COVID-19 deaths fell from initially high levels to close to zero within 20 to 30 days
After this initial period, growth rates of daily COVID-19 deaths have "hovered around zero or below everywhere in the world"
A cross-section standard deviation of growth rates of daily COVID-19 deaths across the studied locations "fell very rapidly in the first 10 days of the epidemic and has remained at a relatively low level since then"
"These first three facts about the growth rate of COVID deaths imply that both the effective reproduction numbers and transmission rates of COVID-19 fell from widely dispersed initial levels and the effective reproduction number has hovered around one after the first 30 days of the epidemic virtually everywhere in the world"
In other words, virus transmission and death rates appear to follow a similar pattern throughout the world, regardless of what type of NPIs were put in place. "[T]hose policies have varied in their timing and implementation across countries and states, but the trends in outcomes do not," the American Institute for Economic Research reported.11
The working paper notes that considering transmission rates for COVID-19 fell during the early days of the pandemic worldwide, "we are concerned that these studies may substantially overstate the role of government-mandated NPI's in reducing disease transmission …"12
Further, they add that since disease transmission rates have remained low worldwide even as NPIs have been lifted, "we are concerned that estimates of the effectiveness of NPI's in reducing disease transmission from the earlier period may not be relevant for forecasting the impact of the relaxation of those NPI's in the current period:"13
"Many of the regions in our sample that instated lockdown policies early on in their local epidemic, removed them later on in our estimation period, or have not relied on mandated NPI's much at all. Yet, effective reproduction numbers in all regions have continued to remain low relative to initial levels indicating that the removal of lockdown policies has had little effect on transmission rates."14
Study Praising Mask Mandates Retracted
A study that found COVID-19 hospitalizations decreased after mask mandates were put in place in 1,083 U.S. counties was withdrawn in November 2020, after changes in the number of cases caused researchers to second-guess their conclusions:
"The authors have withdrawn this manuscript because there are increased rates of SARS- CoV-2 cases in the areas that we originally analyzed in this study. New analyses in the context of the third surge in the United States are therefore needed …"15
Meanwhile, the first randomized controlled trial of more than 6,000 individuals to assess the effectiveness of surgical face masks against SARS-CoV-2 infection found masks did not statistically significantly reduce the incidence of infection.16 Among mask wearers, 1.8% ended up testing positive for SARS-CoV-2, compared to 2.1% among controls.
When they removed the people who did not adhere to proper mask use, the results remained the same — 1.8%, which suggests adherence makes no significant difference. Among those who reported wearing their face mask "exactly as instructed," 2% tested positive for SARS-CoV-2 compared to 2.1% of the controls.
The findings further call into question the effectiveness of mandated masks for preventing COVID-19, as does a case-control investigation of people with COVID-19 who visited 11 U.S. health care facilities. The U.S. Centers for Disease Control and Prevention report revealed factors associated with getting the disease,17 including the use of cloth face coverings or masks in the 14 days before becoming ill.
The majority of them — 70.6% — reported that they "always" wore a mask, but they still got sick. Among the interview respondents who became ill, 108, or 70.6%, said they always wore a mask, compared to six, or 3.9%, who said they "never" did, and six more, or 3.9%, who said they "rarely" did.
Taken together, this shows that, of the symptomatic adults with COVID-19, 70.6% always wore a mask and still got sick, compared to 7.8% for those who rarely or never did.18
Is Wearing Something Better Than Nothing?
Some may suggest that in the case of wearing cloth masks, even if they're not incredibly effective, "something is better than nothing." This may not be the case, however, as wearing a mask isn't innocuous.
Dr. Jim Meehan, an ophthalmologist and preventive medicine specialist who has performed more than 10,000 surgical procedures and is also a former editor of the medical journal Ocular Immunology and Inflammation, has peer-reviewed thousands of medical research studies. He used this expertise to conduct an evidence-based scientific analysis on masks, which shows that not only should healthy people not be wearing masks but they could be harmed as a result.19
Meehan suggests that the notion of mask-wearing defies common sense and reason, considering that most of the population is at very low or almost no risk of becoming severely ill from COVID-19. He also compiled 17 ways that masks can cause harm:20
Medical masks adversely affect respiratory physiology and function
Medical masks lower oxygen levels in the blood
Medical masks raise carbon dioxide levels in the blood
SAR-CoV-2 has a "furin cleavage" site that makes it more pathogenic, and the virus enters cells more easily when arterial oxygen levels decline, which means wearing a mask could increase COVID-19 severity
Medical masks trap exhaled virus in the mouth/mask, increasing viral/infectious load and increasing disease severity
SARS-CoV-2 becomes more dangerous when blood oxygen levels decline
The furin cleavage site of SARS-CoV-2 increases cellular invasion, especially during low blood oxygen levels
Cloth masks may increase the risk of contracting COVID-19 and other respiratory infections
Wearing a face mask may give a false sense of security
Masks compromise communications and reduce social distancing
Untrained and inappropriate management of face masks is common
Masks worn imperfectly are dangerous
Masks collect and colonize viruses, bacteria and mold
Wearing a face mask makes the exhaled air go into the eyes
Contact tracing studies show that asymptomatic carrier transmission is very rare
Face masks and stay at home orders prevent the development of herd immunity
Face masks are dangerous and contraindicated for a large number of people with pre-existing medical conditions and disabilities
Considering the lack of evidence for their use, and the potential harms, it's no wonder that calls for peaceful civil disobedience against mandatory masking are growing. The U.S. nonprofit Stand for Health Freedom is among those calling for civil disobedience, and has a widget you can use to contact your government representatives to let them know wearing a mask must be a personal choice.
If you live in an area without a mask mandate, remember that wearing one, or not, is a highly personal choice. For those in areas with mask mandates, keep in mind that most rules state you must wear a mask "unless you can maintain a 6-foot distance," which means in many cases you can forgo wearing a mask and still be in compliance with the mandate.
