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(PDF) Protein Structure and Function - ResearchGate
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Nutritional Lipids Market Regional Data in Terms of Value and Volume by 2024
DecResearch Inc. published a new report “Global Nutritional Lipids Market” report is inclusive of a definite aggressive standpoint that explains a summary of the entire industry and profiles of the major companies in the worldwide market. The Nutritional Lipids Market report also provides a detailed diagram of the innovations, production analysis, product specification, and product type, taking into consideration, factors such as costs, remuneration, and gross margins. About Nutritional Lipids The global Nutritional Lipids report provides a detailed outlook of this industry. It also explains the changing market dynamics, value chain, deployments, constraining factors, and market dynamic forces of the Nutritional Lipids Industry. The global Nutritional Lipids Market has depicted an appreciable progress in the last few years and is anticipated to exhibit a decent growth rate over the forecast duration. Get Instant Sample Copy of Report at:https://www.decresearch.com/request-sample/detail/2409 [This sample copy includes a market basic introduction, overview, top players, key regions, segmentation, market history and future values, CAGR and other values, table of content, etc.] Market Size USD 6 billion in 2016 Market Size USD 15 Billion in 2024 Predicted CAGR: 10% Top Players: DSM N.V., Archer Daniels Midland Company, Omega Protein Corporation, Nordic Naturals, Croda International, FMC Corporation, BASF, Pharma Marine, Neptune Wellness Solutions, Polaris Nutritional Lipids, Kerry Group, Omega , Oils, Royal Canin, Frieslandcampina, CONNOILS Major Segments of Nutritional Lipids Market Includes: "Global Nutritional Lipids Market, By Product: · Omega-3 · Alpha-Linolenic Acid (ALA) · Docosahexaenoic Acid (DHA) · Eicosapentaenoic Acid (EPA) · Omega-6 · Arachidonic Acid (AA) · Linoleic Acid (LA) · Medium Chain Triglycerides · Others (Sphingolipids, omega-7, conjugated linoleic acids) Global Nutritional Lipids Market, By Application; · Dietary supplements · Infant formula · Pharmaceuticals · Food fortification · Animal nutrition · Others Global Nutritional Lipids Market, By Form: · Liquid · Powder Global Nutritional Lipids Market, By Source: · Plant · Animal" Scope of the Report: This report completely focuses on the global Nutritional Lipids Market, spanning the regions of U.S., North America, APAC, Europe, Middle East and Africa, and South America. The market is categorized into sub-sections such as vendors, types, applications, and regions. Major Highlights of Nutritional Lipids Market report: · Nutritional Lipids Market Overview · In-depth market segmentation · Strategies of key players · Manufacturing Analysis of Nutritional Lipids · Market shares · New Project Investment Feasibility Analysis · Sales Market Forecast The content of the study subjects – enclosed in 15 chapters: 1 Nutritional Lipids Market Overview 1.1 Product Overview and Scope 1.2 Classification of Nutritional Lipids by Types 1.2.1 Global Market Revenue Comparison by Types (2019-2026) 1.2.2 Global Market Revenue Market Share by Types in 2018 1.3 Global Nutritional Lipids Market by Application 1.3.1 Global Market Size and Market Share Comparison by Applications (2014-2026) 1.4 Global Nutritional Lipids Market by Regions 2 Manufacturers Profiles 2.1 Manufacture 1 2.1.1 Business Overview 2.1.2 Nutritional Lipids Type and Applications 2.1.2.1 Product A 2.1.2.2 Product B 2.2 Manufacture 2 2.2.1 Business Overview 2.2.2 Nutritional Lipids Type and Applications 2.2.2.1 Product A 2.2.2.2 Product B More… 3 Global Market Competition, by Players 3.1 Global Nutritional Lipids Revenue and Share by Players (2014-2019) 3.2 Market Concentration Rate 3.2.1 Top 5 Nutritional Lipids Players Market Share 3.2.2 Top 10 Nutritional Lipids Players Market Share 3.3 Market Competition Trend 4 Global Market Size by Regions 4.1 Global Nutritional Lipids Revenue and Market Share by Regions 4.2 North America Revenue and Growth Rate (2014-2019) 4.3 Europe Revenue and Growth Rate (2014-2019) 4.4 Asia-Pacific Revenue and Growth Rate (2014-2019) 4.5 South America Revenue and Growth Rate (2014-2019) 4.6 Middle East and Africa Revenue and Growth Rate (2014-2019) Continued… Also, this report will provide details about short-term and long-term strategies that are adopted by the competitors of Nutritional Lipids Market. The scope of all these individual segments has been encompassed in the report and has been studied separately. This is likely to help shareholders decide where to invest in the right areas of the Nutritional Lipids Market. *If you have any special requirements about report, please let us know and we will offer you the report as you want. Thank You for reading this article. Contact Us: DEC Research, Phone: 1-302-846-7766 Toll Free: 1-888-689-0688 Email Address: [[email protected]](mailto:[email protected]) Read More Related Reports: PDF Report | Micronutrients Market Outlook, Size, Shares, CAGR From 2020-2026 Global Mulberry Leaf Extract Market Outlook, Size, Shares & Forecast From 2020-2026
Glucose supply from blood is mandatory for brain functioning and its interruption during acute hypoglycemia or cerebral ischemia leads to brain injury. Alternative substrates to glucose such as the ketone bodies (KB), acetoacetate (AcAc), and β-hydroxybutyrate (BHB), can be used as energy fuels in the brain during hypoglycemia and prevent neuronal death, but the mechanisms involved are still not well understood. During glucose deprivation adaptive cell responses can be activated such as autophagy, a lysosomal-dependent degradation process, to support cell survival. However, impaired or excessive autophagy can lead to cell dysfunction. We have previously shown that impaired autophagy contributes to neuronal death induced by glucose deprivation in cortical neurons and that D isomer of BHB (D-BHB) reestablishes the autophagic flux increasing viability. Here, we aimed to investigate autophagy dynamics in the brain of rats subjected to severe hypoglycemia (SH) without glucose infusion (GI), severe hypoglycemia followed by GI (SH GI), and a brief period of hypoglycemic coma followed by GI (Coma). The effect of D-BHB administration after the coma was also tested (Coma BHB). The transformation of LC3-I to LC3-II and the abundance of autophagy proteins, Beclin 1 (BECN1), ATG7, and ATG12-ATG5 conjugate, were analyzed as an index of autophagosome formation, and the levels of sequestrosome1/p62 (SQSTM1/p62) were determined as a hallmark of autophagic degradation. Data suggest that autophagosomes accumulate in the cortex and the hippocampus of rats after SH, likely due to impaired autophagic degradation. In the cortex, autophagosome accumulation persisted at 6 h after GI in animals exposed to SH but recovered basal levels at 24 h, while in the hippocampus no significant effect was observed. In animals subjected to coma, autophagosome accumulation was observed at 24 h after GI in both regions. D-BHB treatment reduced LC3-II and SQSTM1/p62 content and reduced ULK1 phosphorylation by AMPK, suggesting it stimulates the autophagic flux and decreases AMPK activity reducing autophagy initiation. D-BHB also reduced the number of degenerating cells. Together, data suggest different autophagy dynamics after GI in rats subjected to SH or the hypoglycemic coma and support that D-BHB treatment can modulate autophagy dynamics favoring the autophagic flux. ------------------------------------------ Info ------------------------------------------ Open Access: True Authors: Carmen Torres-Esquivel - Teresa Montiel - Marco Flores-Méndez - Lourdes Massieu - Additional links: https://www.frontiersin.org/articles/10.3389/fncel.2020.547215/pdf https://doi.org/10.3389/fncel.2020.547215 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538649
Oral versus transdermal estradiol in feminising hormone therapy for transgender individuals
Abstract
In the modern world, the oral and transdermal routes are by far the most common means to administer exogenous estradiol and are widely used as a component of gender-affirming hormone therapy. Current clinical evidence shows no difference in feminising efficacy between these formulations at equivalent doses. Although both are well tolerated in general, the oral route is unphysiological in its metabolism and is associated with a significantly greater incidence of cardiovascular and thromboembolic complications. At low adult replacement doses, transdermal forms do not have these disadvantages and may be superior to their oral counterparts in feminisng hormone therapy.
Introduction
Estrogen replacement is both an important and necessary intervention for many transgender people (Hembree et al, 2017; Cheung et al, 2019). In the past, feminising therapy in this group was done using high dose estrogen monotherapy with parenteral esters of estradiol such as estradiol valerate or estradiol undecylate (Benjamin, 1967; Hamburger, 1969). Non-bioidentical oral estrogens such as conjugated equine estrogens and ethinylestradiol were also widely used (Meyer et al, 1986; Meyer, Walker and Suplee, 1989). However, with the significant progress made in drug development, bioidentical estradiol became widely available as oral and transdermal formulations for gender-affirming hormone therapy. Today, some transgender individuals prefer to use injectable formulations of estradiol (Geffen et al, 2018). Nonetheless, the oral and transdermal routes of administration are used almost without exception for therapy in Europe and some other parts of the world and are probably most commonplace (Fisher and Maggi, 2015; Hamidi and Davidge-Pitts, 201930006-4/abstract); Seal, 2019). Many people receiving or eager to start hormone therapy may be interested to know what data exists regarding differences between oral and transdermal estradiol. As we require long-term therapy with these formulations, a discussion regarding adverse effects between these routes of administration may also be of importance. Although the focus of this review is largely on oral estradiol as compared with transdermal estradiol, a good amount of the discussion specific to transdermal estradiol can likely be extrapolated to other non-oral routes of administration when the doses have similar potency. For instance, estradiol administered by intramuscular or subcutaneous injection is a non-oral route of administration.
Pharmacology
Oral estradiol includes pill or tablet formulations, while transdermal estradiol is most commonly available as patches or gels (Kuhl, 2005). Oral estradiol and transdermal gel is usually administered once per day (Rohr, Volko and Schindler 2014). However, doses may be split and taken twice-daily. Theoretically, this would result in more stable estradiol levels, although is obviously less convenient. Estradiol pills may also be administered by the sublingual or buccal routes (Casper and Yen, 1981; Wren et al, 2003). Although some literature exists regarding their use for therapy in feminising hormone therapy, usage of these routes is probably still relatively rare in clinical practice (Jain, Kwan and Forcier 2019). In this review, I have used the term "oral estradiol" to refer only to the swallowing of estradiol tablets. Estradiol patches are applied and worn continuously. Different brands exist and transdermal patches are available for twice-weekly or weekly administration. A 50 μg/day dosage delivered by transdermal patch is considered to have similar potency to a 1 to 2 mg/day dosage of oral estradiol and to a 1.5 mg/day dosage of transdermal gel (Kuhl, 2005; Järvinen, Nykänen and Paasiniemi, 199900021-3)). However, as there is massive interindividual variability, these doses likely will not correspond to one another on an individual basis. Estradiol is secreted by the ovaries into systematic circulation. As a result, the liver is not disproportionately exposed to the effects of the hormone (Gravholt et al, 2017). Transdermal estradiol is effective in mimicking this behaviour. However, orally administered estradiol, owing to passage through the gastrointestinal tract, is associated with disproportionate estrogenic exposure in the liver (Bińkowska, 2014). This behaviour gives rise to a number of differences between oral and transdermal estradiol. One such difference is that about 95% of oral estradiol is metabolised, as a consequence of the first pass effect, into estrone and other clinically weak/insignificant estrogens (Kuhz, Blode and Zimmermann, 1993). The ratio of estrone to estradiol is close to 1:1 in adult women and pubertal girls and with transdermal formulations (Kuhl, 2005; Frederiksen et al, 2020). However, with a dose of oral estradiol, postmenopausal women have been found to have about 5 times the concentration of estrone as estradiol (Kuhl, 2005). In some patients, the concentration of estrone may be 20 times higher than that of estradiol (Kuhnz, Gansau and Mahler, 1993). For this reason, the metabolism of oral estradiol has been described as unphysiologic (Gravholt et al, 2017; Mauras et al, 2019).
Efficacy
A subject of great interest to many transgender people taking feminising hormone therapy seems to be concerning which regimens might be most "effective". In particular, satisfactory breast development is often sought after. However, to date, no randomised controlled trials assessing the efficacy of different gender-affirming hormone regimens have been conducted (Reisman, Goldstein and Safer, 2019; Iwamoto et al, 2019). Moreover, there are no measures of breast development or other effects of transition that are universally agreed upon by the scientific community. For this reason, it is difficult to directly compare the findings of many studies. Nonetheless, a number of observational studies have studied and quantified feminisation experienced with hormone therapy. In one prospective study, transgender women (n = 53) were treated with cyproterone acetate plus either oral or transdermal estradiol (Wierckx et al, 2014). It was noted that after 1 year, there was no apparent difference in physical measures such as breast circumference between the oral and transdermal groups. Another longitudinal and multicentre study of transgender women (n = 229) attending clinics in the Netherlands, Belgium and Italy also reported that the increase in breast-chest difference following 1 year of therapy did not differ between those using oral and transdermal formulations (de Blok et al, 2018). As a result of unsatisfactory development, many transgender women seek breast augmentation (Seal, 2016; de Blok et al, 2020). Although breast development itself was not measured, it is interesting to note that one retrospective study found no statistical difference in the rate of augmentation requests between users of different estrogen types (Seal et al, 2012). This suggests that oral estradiol valerate might be no more or less effective than the other estrogens in the study (oral conjugated estrogens and oral ethinylestradiol) in attaining a satisfying amount of breast development. Finally, it has been reported in a large cohort study of transgender women (n = 179) that percent changes in gynoid and android fat, total body fat and total lean body mass were not statistically different between the oral and transdermal estradiol groups if BMI and age were controlled for (Klaver et al, 2018). Estrogen replacement, being a necessary therapy for the vast majority of individuals with Turner syndrome, has also been studied in adolescent girls (Gravholt et al, 2017; Klein and Phillips, 201930183-4/fulltext)). Girls treated with low dose oral estradiol (n = 56) were described in one study as having "similar" breast development to the normal Dutch population (Bannink et al, 2009). Other studies of puberty induction therapy have found that patients using low doses of transdermal estradiol gel (n = 21) and low dose intramuscular estradiol cypionate (n = 14) also all achieved breast Tanner stage 4 or 5 at final follow-up (Piippo et al, 2004; Rosenfield et al, 2005). A small randomised controlled trial of hypogonadal girls (n = 12) demonstrated that the response to oral and transdermal estradiol at comparable doses was near identical (Shah et al, 2014). All the girls receiving bioidentical estrogens achieved Tanner stage 3 or greater after 18 months of treatment, irrespective of route of administration. Interestingly, a cross sectional study of breast development in women with differences of sex development (DSD), including those with Turner syndrome, reported that breast satisfaction in the sample group was much lower than in women without a DSD (van de Grift and Kreukels, 2019). Some studies have found that breast development, in addition to breast satisfaction, seems to be poorer in Turner syndrome girls than in normal cisgender girls (Guo et al, 2019). Nevertheless, a recent review concluded that all these different regimens seemed to result in similar feminising outcomes (Klein et al, 2018). In summary, current clinical evidence appears to show no difference in objectively measured outcomes between therapy with different routes of administration when the doses have comparable potency. Rather, when taken together, these findings indicate that the extent of breast development and other feminisation is independent of what route of administration is used (excerpts).
Safety and tolerability
In the past, estrogens in general have been associated with a greater overall incidence of adverse cardiovascular and thromboembolic events (Kuhl, 2005). These events can include deep vein thrombosis and myocardial infarction. Such complications of therapy have been attributed to estrogenic activity in the liver which, at sufficient exposure, causes an increased synthesis of liver proteins such as as sex-hormone binding globulin (von Schoultz et al, 1989; Ockrim, Lalani and Abel, 2006). Synthesis rates of lipids and coagulation factors have also been found to change. However, the type and route of administration of estrogen has been shown to modify risk (Olié, Canonico and Scarabin, 2011; Oliver-Williams et al, 2018). Synthetic and non-bioidentical estrogens are more resistant to enzymatic metabolism by the liver and have disproportionate estrogenic effects relative to bioidentical estrogens such as estradiol (Kuhl, 2005). Because of this behaviour, they contribute to a much greater synthesis of liver proteins and are associated with a significantly higher risk of venous thromboembolism and other cardiovascular complications (Henriksson and Edhag, 1986; Kuhl, 2005; Lycette et al, 2006). A 2015 retrospective case-control study found that venous thromboembolism was 2 to 5 times more common in young women using combined oral contraceptives containing ethinylestradiol and other synthetic progestins than in non users (Vinogradova, Coupland and Hippisley-Cox, 2015). In 2019, the same authors published another case-control study; this time investigating women receiving hormone therapy at the menopause (Vinogradova, Coupland and Hippisley-Cox, 2019). A key finding was that low doses of oral estradiol (2 mg/day or less) were associated with a slight but significant increase in the incidence of venous thromboembolism, while low transdermal doses (100 μg/day or less) were not. This has also been reported by the ESTHER case-control and E3N cohort studies (Scarabin, 2014). Therefore, a strong advantage of transdermal estradiol over oral estradiol is that the incidence of venous thromboembolism is lower (Files and Kling, 2020). As with the synthetic estrogens, this difference is thought to be attributable to the disproportionate amount of estrogenic exposure in the liver that occurs with oral administration (Olié, Canonico and Scarabin, 2011). Nevertheless, high dose polyestradiol phosphate (160 to 240 mg/month) administered by intramuscular injection has been associated with significantly increased cardiovascular and thromboembolic morbidity and mortality in at least one large study of prostate cancer patients (Mikkola et al, 2005; Mikkola et al, 2007). While the increased incidence of these adverse events is clearly much lower than with oral estradiol, it is much less clear if it may be entirely eliminated by non-oral routes of administration at higher doses (further reading). It is difficult to accurately determine the incidence of venous thromboembolism in transgender people receiving hormone therapy because of the diverse range of regimens employed in different geographical regions; which may confer different risks (Goldstein et al, 2019). Moreover, although a number of observational and retrospective studies have reported risk as low or relatively insignificant in our community, most are not adequately powered to accurately report risk (Khan et al, 2019). Based on the available evidence, we can probably safely assume that the incidence is low overall with modern regimens (Getahun et al, 2018; Ott et al, 201004661-X/fulltext); Pyra et al, 2020). It is particularly of note that these complications are, thankfully, mostly confined to people at higher baseline risk such as elderly individuals or those with inherited mutations that predispose to such toxicity (Silverstein et al, 1998; Bezgin et al, 2016). The absolute risk is likely low for most people. Nonetheless, the association between estrogens and adverse cardiovascular and thromboembolic events is of obvious importance. In the future, I intend on posting a more comprehensive evaluation of these complications with different doses and formulations of estrogens.
Summary and conclusions
In conclusion, oral and transdermal estradiol is metabolised differently. Perhaps most significantly, a dose of oral estadiol is predominantly converted by the liver into estrone and other estrogen metabolites before it enters circulation. By contrast, transdermal estradiol bypasses the liver and the conversion of the medication into these weak estrogens is mostly avoided. On average, a transdermal patch that delivers a 50 μg/day dose is thought to have similar estrogenic potency to a 1 to 2 mg/day dose of oral estradiol and to a 1.5 mg/day dose of transdermal gel. In spite of these difference, there appears to be no evidence that oral estradiol provides more effective feminisation than transdermal estradiol or vice versa if the doses are similar. Instead, the existing clinical evidence seems to show that the extent of feminising changes such as breast development and fat distribution is independent of the route that estradiol is administered by. Contrariwise, there is a good amount of epidemiological evidence that oral estradiol is associated with a higher incidence of venous thrombosis than is transdermal estradiol at a comparable dose. For this reason, transdermal estradiol at physiological doses is likely safer than oral estradiol in long term gender affirming hormone therapy. I intend to discuss, in more detail, the subject of cardiovascular and thromboembolic toxicity with different doses and types of estrogens in a future review.
The Academy of Nutrition and Dietetics was founded by Seventh-day Adventists, an evangelistic vegan religion that owns meat replacement companies. Every author of their position paper is a career vegan, one of them is selling diet books that are cited in the paper. One author and one reviewer are Adventists who work for universities that publicly state to have a religious agenda. Another author went vegan for ethical reasons. They explicitly report "no potential conflict of interest". Their claims about infants and athletes are based on complete speculation (they cite no study following vegan infants from birth to childhood) and they don't even mention potentially problematic nutrients like Vitamin K or Carnitine.
In the EU, all nutritional supplements, including B12, are by law required to state that they should not be used as a substitute for a balanced and varied diet.
In Belgium, parents can get imprisoned for imposing a vegan diet on children.
The supposed science around veganism is highly exaggerated. Nutrition science is in its infancy and the "best" studies on vegans rely on indisputably and fatally flawed food questionnaires that ask them what they eat once and then just assume they do it for several years:
Vegans aren't even vegan. They frequently cheat on their diet and lie about it.
Self-imposed dieting is linked to binge eating disorder, which makes people forget and misreport about eating the food they crave.
The vast majority of studies favoring vegan diets were conducted on people who reported to consume animal products and by scientists trained at Seventh-day Adventist universities. They have contrasting results when compared other studies. The publications of researchers like Joan Sabate and Winston Craig (reviewers and authors of the AND position paper, btw) show that they have a strong bias towards confirming their religious beliefs. They brag about their global influence on diet, yet generally don't disclose this conflict of interest. They have pursued people for promoting low-carbohydrate diets.
80-100% of observational studies are proven wrong in controlled trials.
A vegan diet is not sustainable for the average person. Ex-vegans vastly outnumber current vegans, of which the majority have only been vegan for a short time. Common reasons for quitting are: concerns about health (23%), cravings (37%), social problems (63%), not seeing veganism as part of their identity (58%). 29% had health problems such as nutrient deficiencies, depression or thyroid issues, of which 82% improved after reintroducing meat. There are likely more people that quit veganism with health problems than there are vegans. Note that this is a major limitation of cohort studies on vegans as they only analyze the people who did not quit. (survivorship bias)
Vegans use appeals to authority or observational (non-causal) studies with tiny risk factors to vilify animal products. Respectable epidemiologists outside of nutrition typically reject these because they don't even reach the minimum threshold to justify a hypothesis and might compromise public health. The study findings are usually accompanied by countless paradoxes such as meat being associated with positive health outcomes in Asian cohorts:
Vegans like to say that meat causes cancer by citing the WHO's IARC. But the report actually says there's no evaluation on poultry/fish and that red meat has not been established as a cause of cancer. More importantly, Gordon Guyatt (founder of evidence-based medicine, pescetarian) criticized them for misleading the public and drawing conclusions from cherry-picked epidemiology (they chose only 56 studies out of the supposed 800+). A third of the committee voting against meat were vegetarians. Before the report was released, 23 cancer experts from eight countries looked at the same data and concluded that the evidence is inconsistent and unclear.
The idea that dietary raised cholesterol causes heart disease has never been proven.
Here's a compilation of large, government-funded clinical trials to oppose the claims made to blame meat and saturated fat for diabetes, cancer or CVD. Note that these have been ignored WHO and guidelines.
Much of the anti-meat push is coming from biased institutions like Adventist universities or Harvard School of Public Health who typically don't disclose their conflicts of interest. The latter conducted bribed studies for the sugar industry and was chaired by a highly influential supporter of vegetarianism for 26 years. He published hundreds of epidemiological anti-meat papers (e.g. the Nurses' Health Studies), tried to censor publications that oppose his views and wants to deemphasize the importance of experimental science. He has financial ties to seed oil, nut, fruit, vegetable and pharmaceutical industries and is part many plant-based movements like Blue Zones, True Health Initiative (Frank Hu, David Katz, Dean Ornish), EAT-Lancet and Lifestyle Medicine (Adventists, Michael Greger).
Popular sources that promote "plant-based diets" are actually just vegan propaganda in disguise:
Blue zones are bullshit. The longest living populations paradoxically consume the highest amount of meat. Buettner cherry-picks and ignores areas that have both high consumption of animal products and high life expectancies (Hong Kong, Switzerland, Spain, France, ... ). He praises Adventists for their health, but doesn't do the same for Mormons. Among others, he misrepresents the Okinawa diet by using data from a post WWII famine. The number of centenarians in blue zones is likely based on birth certificate fraud. The franchise also belongs to the SDA church now.
EAT-Lancet is pushing a nutrient deficient "planetary health diet" because it's essentially a global convention of vegans. Their founder and president is the Norwegian billionaire, hypocrite and animal rights activist Gunhild Stordalen. In 2017, they co-launched FReSH - a partnership of fertilizer, pesticide, processed food and flavouring companies.
The China Study, aka the Vegan Bible, has been debunked by hundreds of people including Campbell himself in his actual peer-reviewed publications on the study.
The Guardian, a pro-vegan newspaper that frequently depicts meat as bad for health and the environment, has received two grants totaling $1.78m from an investor of Impossible Foods.
A widespread lie is that the vegan diet is "clinically proven to reverse heart disease". The studies by Ornish and Esselstyn are made to sell their diet, but rely on confounding factors like exercise, medication or previous bypass surgeries (Esselstyn had nearly all of them exercise while pretending it was optional). All of them have tiny sample size, extremely poor design and have never been replicated in much larger clinical trials, which made Ornish suggest that we should discard the scientific method. Both diets included dairy.
Vegan diets are devoid of many nutrients and generally require more supplements than just B12. Some of them (Vitamin K2, EPA/DHA, Vitamin A) can only be obtained because they are converted from other sources, which is inefficient, limited or poor for a large part of the population. EPA+DHA from animal products have an anti-inflammatory effect, but converting it from ALA (plant sourced) does not seem to work the same. Taurine is essential for many people with special needs, while Creatine supplementation improves memory only in those who don't eat meat.
The US supplement industry is poorly regulated and has a history of spiking their products with drugs. Vitamin B complexes were tainted with anabolic steroids in the past, while algae supplements have been found to contain aldehydes. Supplements and fortified foods can cause poisoning, while natural products generally don't. Even vegan doctors caution and can't agree on what to supplement.
Restrictive dieting has psychological consequences including aggressive behavior, negative emotionality, loss of libido, concentration difficulties, higher anxiety measures and reduced self-esteem. There is an extremely strong link between meat abstention and mental disorders. While it's unknown what causes what, the vegan diet is low in or devoid of several important brain nutrients.
A vegan diet alone fulfills the diagnostic criteria of an eating disorder.
Patrik Baboumian, the strongest vegan on earth, lied about holding a world record that actually belongs to Brian Shaw. Patrik has never even been invited to World's Strongest Man. He dropped the weight during his "world record", which was done at a vegetarian food festival where he was the only competitor. His unofficial deadlift PR is 360kg, but the 2016 world record was 500kg. We can compare his height-relative strength with the Wilks Score and see that he is being completely dwarfed by Eddie Hall (208 vs 273). Patrik also lives on supplements. He pops about 25 pills a day to fix common vegan nutrient deficiencies and gets over 60% of his protein intake from drinking shakes.
Here's a summary on almost every pro athlete that either stopped being vegan, got injured, has only been vegan a couple of years, retired or was falsely promoted as vegan.
Historically, humans have always needed animal products and are highly adapted to meat consumption. There has never been a recorded civilization of humans that was able to survive without animal foods. Isotopic evidence shows that the first modern humans ate lots of meat and were the only natural predator of adult mammoths. Most of their historic technology and cave paintings revolved around hunting animals. Our abilities to throw and sweat likely developed for this reason. Our stomach's acidity is in the same range as obligate carnivores and its shape has changed so much from other hominids that we can't even digest cellulose anymore. The vegan diet is born out of ideology, species-inappropriate and could negatively affect future generations.
The cooked starch hypothesis that vegans use is inconsistent with many observations.
Cow farts do not cause climate change. The EPA estimates that all agriculture produces about 10% of US greenhouse emissions, while animal agriculture is less than half of that. Other developed countries, like Germany, UK and Australia all have similarly low emissions. Vegans use global estimations that are skewed by developing countries with inefficient subsistence agriculture. Their main figure is an outdated and retracted source that compared lifecycle to direct emissions.
Many environmental studies that vegans use are heavily flawed because they were made by people who have no clue about agriculture, e.g. by the SDA church. A common mistake is that they use irrational theoretical models that assume we grow crops for animals because most of the plant weight is used as feed, The reality is that 86% of livestock feed is inedible by humans. They consume forage, food-waste and crop residues that could otherwise become an environmental burden. 13% of animal feed consists of potentially edible low-quality grains, which make up a third of global cereal (not total crop) production. All US beef cattle spend the majority of their life on pasture and upcycle protein even when grain-finished (0.6 to 1). Hence, UN FAO considers livestock crucial for food security and does not endorse veganism at all.
Plant-to-animal food comparisons are deceiving because animals provide many actually usefulby-products that are needed for medicine, crop fertilization, clothing, pet food and public water safety. Vegans are in general very dishonest when comparing foods, as seen here where they compare 1kg of beef (2600 kcal, 260g protein) to 1kg of tomatoes (180 kcal, 9g protein). The claim that we could feed more people just with more calories is also wrong because the leading causes of malnutrition are deficiencies of Iron, Zinc, Folate, Iodine and Vitamin A - which are common and most bioavailable in animal products.
Vegan land use comparisons are half-truths that equate pastures with plantations. 57% of land used for feed is not even suitable for crops, while the rest is often much less productive. Grassland can sequester more carbon and has a four times lower rate of soil loss per unit area than cropland. Regenerative agriculture restores topsoil, is scalable, efficient and has high animal welfare. Big names like Kellogg are investing in it for long-term profit. On the other hand, removing livestock would create a food supply incapable of supporting the US population’s nutritional requirements due to lack of vitamin A, vitamin B12, vitamin D, calcium and fatty acids - while removing most animal by-products.
Water usage is possibly the most ridiculous way vegans deceive. The water footprint is divided into green (sourced from precipitation) and blue (sourced from the surface). Water scarcity is largely dependent on blue water use, which is why experts use lifecycle models. Vegan infographics always portray beef as a massive water hog by counting the rain that falls on the pasture. 96% of beef's water usage is green and it can even be produced without any blue water at all. The crops leading to the most depletion are wheat (22%), rice (17%), sugar (7%) and cotton (7%).
Going vegan won't do shit for the Amazon rainforest because the majority of Brazil's beef exports go to China and Hong Kong. The US or European countries each account for 2% or less. Soybean demand is driven by oil; the rest of the plant (80%) is a by-product that is exported as Chinese pig feed. Brazil is also a misrepresentative and atypical industry. Globally, cattle ranching accounts for 12%, commercial crops for 20% and subsistence farming for 48% of deforestation. The US use about half as much forest land for grazing than 70 years ago.
Livestock is not routinely supplemented with vitamin B12. Cows that consume cobalt (found in grass, which is free of B12) produce it with gut bacteria in the rumen. Gastrointestinal animals (including humans) initially can't absorb it, but instead excrete it and can then eat their own shit. B12 is in the soil because of excretions - ground bacteria exist but have never been shown to be the main source. Plants are devoid of B12 because competing bacteria consume it, not because of soil depletion. The "90% of B12 supplements go to livestock"-figure...
is bullshit that vegans keep on parroting. It originates from an article that calls humans herbivores, with no source.
ignores the fact that you can get B12 from seafood and venison. A can of sardines provides 3x the RDA.
is illogical because animals on unnatural diets can simply be given cobalt instead of the synthetic supplement that vegans rely on. Cows also destroy most of B12 in their gut before it can be absorbed.
Socioeconomics
Voluntary veganism is a privilege that is enabled by globalization and concentrated in first-world societies. Less than 1% of Indians are vegan. Jains, who are similar to vegans, are the wealthiest Indian community and even they still drink milk. In fact, India is a great example of why veganism doesn't work because they've religiously pursued it for thousands of years and still couldn't do it. Even Gandhi was an ex-vegan that had to warn them how dangerous the diet is.
Ethics
Veganism is a harmful ideology that promotes the abstinence from any "optional" animal suffering inflicted to support human health. For example, vaccines are not vegan. And just like meat, some people have already considered themunnecessary. Likewise, popular vegan communities also encourage people to put their carnivorous pets on a vegan diet to "avoid" cruelty. Hence, promoting animal rights is fundamentally anti-human because it will restrict or remove access to even the most basic needs, such as food or clothes. The only reason vegans are able to deny this is because they are pretending that the people who had to suffer for their ideology don't exist.
Vegan diets are more dependent on slavery because they rely on global food supply. Many crops, especially cotton, nuts, oils and seeds that they have to include in higher quantities to make up for animal products are to a large extent child labor products from developing countries. 108 million children work in agriculture. Cheese replacements (guess who's responsible for that) are usually made with cashews, which burn the fingers of the women who have to remove the shells. A larger list of examples can be found here.
Vegans have never been able to define or measure that their diet causes less deaths/suffering than an omnivorous one. They are ignorantly contributing to an absolute bloodbath of trillions of zooplankton, mites, worms, crickets, grasshoppers, snails, frogs, turtles, rats, squirrels, possum, raccoons, moles, rabbits, boars, deer, 75% of insect biomass, half of all bird species and 20,000 humans per year. Two grass-fed cows are enough to feed someone for a year and, if managed properly, can restore biodiversity. The textbook vegan excuse where they try to blame plant agriculture on animals and use only mice deaths, fabricated feed conversion ratios of 20:1 and a coincidentally favourable per-calorie metric is nonsense because:
The majority of animal feed is either low-maintenance forage or a by-product that only exists because of human food harvest.
It literally shows that grass-fed beef kills fewer animals.
Vegans likely exploit more animals than the average person. The Vegan Society officially rejects beekeeping, but many commercial crops require to be pollinated by domestic bees that are forced to breed, shipped around and then worked to death. It's principally impossible to have a nutritionally complete vegan diet without forced pollination, but fodder crops do not exploit bees. As a result, human food crops kill five times as many bees as all livestock slaughter combined and directly support honey production (taking excess honey is necessary for colony health). Vegans should also call around and make sure that their seasonally changing food exporters don't rely on insects, terriers, sheep, ducks, organic fertilizers or anything from developing countries where animal labor is still common.
The ethical framework around veganism (negative utilitarianism) is so insane that its logical conclusion is to prevent as much life and biodiversity as possible in order to reduce suffering, which means it also favors Brazilian rainforest beef over crop cultivation. This line of thought is already followed by organizations like PETA who proudly state it to be their goal and will steal and euthanize other people's pets. Vegans reject appeals to nature when they are used to defend omnivorism, yet falsely assume that animals are more happy under the stress of natural selection. In contrast to livestock, wild animals are never guaranteed to receive shelter, protection, food, medical care, low stress or a quick death. Animal rights conflict with welfare because their goal is not to increase happiness, but just to oppose animal husbandry. Put differently, vegans pretend to support the wellbeing of animals, but can hardly even do so with their consumer power. What they are doing is more likely to kill off local ranchers and ensure a monopoly for Tyson/JBS, who are spearheading fake meat btw.
The average vegan is, based on their demographic, a New York hipster that has never seen a farm in their live. Animals are not being abused (This is one of the "factory farms" where 99% of animals come from). Undercover videos have often been staged by agenda-driven activists who get paid to apply for farm jobs and encourage animal abuse. The real industry has government-inspected welfare regulations. (Dominion straight up lies about pigs in slaugherhouses getting no water - it's required by law). Here's some actual industrial slaughterhouse footage of Beef, Turkey and Pork. For comparison, rodenticides are intentionally made to drain the life out of rats over three days so that they can't figure out what killed them.
Vegans love to misportray farm practises and anthropomorphize animals by giving them concepts that they don't care about, or even enjoy. Sexual coercion ("rape") is normal procreation and cows don't see a problem with it. They will even milk themselves when given the possibility. Pigs don't mind eating their own babies or getting shot. Even the myth that they are as intelligent as dogs comes from a questionable study made by animal rights advocates.
The reputation of vegans is based exactly on how they present themselves in public. Humans evolved to have predatory behaviour and as a result many people enjoy homesteading, hunting or fishing. Vegan activists frequently bother society and disrespect human biology - with thousands of years of history - for their arbitrarily chosen set of morals. There are actualanimal rights terrorist groups that have sent bombs and stalked children, which they justify with it being done "in the name of veganism". Therefore, a very good reason to stay away from veganism is simply because someone doesn't want to be associated with a cult-like ideology.
Philosophy
The definition that vegans pride themselves with is a laughing stock because not only is it so loosely defined that it can be used to call everyone vegan, but it also shamelessly co-opts all the belief systems that have existed for much longer. According to this definition, Hindu, Buddhists, the Inuit and carnivores can all be called vegan, but are not following the diet and therefore considered impure (apparently caring about animals was invented by some British guy in 1944). Vegans are nothing more than people who abstain from animal products, in fact veganism was originally defined as a diet.
The misanthropic idea of "speciecism" was popularized by a nutjob philosopher who argues in favour of bestiality and belittles disabled people, but makes exceptions when it affects himself. Ironically, he eats animal products and calls consistent veganism fanatical. When it comes to the misanthropic aspect, animal rights activists themselves are the best example because they frequently insult minorities and crime victims by equating them to livestock with analogies to rape, murder, slavery or holocaust. The best part is that vegans are speciecists themselves because they justify their killing as "necessary for human survival" and still won't equate a cow to an insect.
Since vegans somehow manage to justify systematically poisoning and torturing insects by arbitrarily declaring that they can't suffer ("sentience"), they might aswell consider eating them. The same goes for bivalves, since there's about as much evidence that they feel pain as there is for plants.
A vegan diet itself is not even vegan under its own premises because it's not "practicable" to follow. It demands an opportunity cost of time, research and money that could be utilized in a better way and even then is not guaranteed to be efficient because it emphasizes purity. The entire following around veganism represents a Nirvana Fallacy and is the reason why the majority of people quit: Perfect is the enemy of good. A vegan diet makes it harder, and for many people impossible, to follow productive consumer approaches such as buying local, seasonal or supporting regenerative agriculture.
List of known nutrients that vegan diets either can't get at all or are typically low in, especially when uninformed and for people with special needs. Vegans will always say that "you can get X nutrient from Y specific source", but a full meal plan with sufficient quantities will essentially highlight how absurd a "well-planned" vegan diet is.
Nirvana fallacy: "There's no point in eating animal products because everything can be solved with a perfect vegan diet, supplements and genetic predisposition."
Proof by example: "Some people say they are vegan. Therefore, animal products are unnecessary."
Appeal to authority: Pointing to opinion papers written by vegan shills as proof that their diet is adequate.
No true Scotsman: "Everyone who failed veganism didn't do enough research. Properly planned vegan diets are healthy!" (aka not real Socialism)
Narcissist's prayer: "Everything bad that came out of veganism is fault of the world, not veganism itself."
No true Scotsman: "Veganism is not a diet, it's an ethical philosophy. No true vegan eats almonds, avocados or bananas ..."
Definist fallacy: "... as far as is possible and practicable." (Can be used to defend any case of hypocrisy)
Special pleading: "It's never ethical to harm animals for food, except when we 'accidentally' hire planes to rain poison from the sky." (You can trigger their cognitive dissonance by pointing that out.)
Special pleading: "Anyone who doesn't agree with my ideology has cognitive dissonance."
Appeal to emotion: Usage of words exclusive to humans (rape, murder, slavery, ... ) in the context of animals.
Fallacy fallacy: "Evolution is a fallacy because it's natural."
Texas sharpshooter fallacy: "A third of grains are fed to livestock. Therefore, a third of all crops are grown as animal feed."
False dilemma: "Producing only livestock is less sustainable than producing only crops, so we should only produce crops."
False cause: Asserting that association infers causation because it's the best data they have. ("Let's get rid of firefighters because they correlate to forest fires")
Faulty generalization: Highlighting mediocre athletes to refute the fact that vegans are underrepresented in elite sports.
JAQing off: This is how vegans convert other people. They always want them to justify eating meat by asking tons of loaded questions, presumably because nobody would care about their logically inconsistent arguments otherwise. Cults often employ this tactic to recruit new members. (They mistakenly call it the Socratic method)
Argument from ignorance: NameTheTrait aka "vegans are right unless you prove their nonsensical premises wrong". (It's essentially asking "When is a human not a human?")
Moving the goalposts: Whenever a vegan is cornered, they will dodge and change the subject to one of their other pillars (Ethics, Health, Environment or Sustainability) as seen here.
Ad hominem: Nit-picking statements out of context, attacking them in an arrogant manner, and then proclaiming everything someone says is wrong while not being able to refute the actual point. (see Kresser vs Wilks debate)
They are a late-stage company developing fusion protein medicines. Their fusion protein approach tethers a tumor-targeting antibody fragment to a protein cytotoxic payload to form a single protein molecule designed to selectively and broadly kill cancer cells while minimizing toxicity to healthy cells and to activate the body’s innate immune response system.
In other words, they work to make a better treatment, one that kills cancer effectively in a way that does not harm normal healthy cells the same way traditional chemotherapy does.
Vicinium, also known as VB4-845, is an antibody-drug conjugate (ADC), developed for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells.
According to another medical publication posted on the same gov website, [the article states that Nearly three-fourths of patients](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773281) diagnosed with high-risk bladder cancer will recur, progress, or die within ten years of their diagnosis.
according to the preliminary findings of phase 3 of Vicinium trials, it goes to show that at the end of the 12month study:
40% of participants showed complete response rate to Vicinium
71% were recurrence free
Overall survival rate at 12 months for those participating in the study is 98% (this just shows that currently on Vicinium, at the 12month mark, survival rate is at 98%. At the two year mark it could be the same or much lower, that statistic is unknown as of right now)
Here are links on what i have mentioned regarding phase 3 preliminary results
In November 2019, SESN met with the FDA for a Type C meeting to discuss the details of a post-marketing confirmatory trial for Vicinium for the treatment of high-risk NMIBC.
On December 6, 2019, SESN initiated their BLA submission for Vicinium to the FDA under Rolling Review The submission consisted of Modules 1, 2, 4 and 5, with information amendments to be submitted to these modules throughout 2020. They anticipate completing Module 3 to finalize the BLA submission in the second half of 2020 (Q2).
Recent Financials (Q1 of 2020)
Their estimated EPS for the quarter according to the NASDAQ website was at -0.1 but they beat expectations and reported an EPS of 0.31
Net income was $41.6 million, or $0.31 per basic share and $0.31 per diluted share, for the three months ended March 31, 2020, compared to a net loss of $6.5 million, or $0.08 per basic and diluted share, for the same period in 2019
As stated in their most recent SEC Filings: "Based on our current operating plan, we anticipate having sufficient cash to fund our operations into 2021".
In April 2019, the first full, commercial-scale cGMP run was completed at Fujifilm and all quality acceptance criteria were met. This supports Fujifilm’s ability to produce the bulk drug substance form of Vicinium for commercial purposes if we receive regulatory approval to market Vicinium for the treatment of high-risk NMIBC. Link
In February 2020, manufacturing of the pre-process performance qualification batch was completed at Fujifilm Full quality release testing of the drug substance has been completed and all quality acceptance criteria were met. In addition, the bulk drug substance from the Fujifilm pre-PPQ batch has been used to manufacture the first drug product PPQ batch by Baxter Oncology GmbH. Full quality release testing of the first drug product process performance qualification batch is currently underway.
Target Price & Forecasts
CNN money sets a median target price of $3, a low of $2.25 and a high estimate of $5
TipRanks sets a median target price at $3.63, a low of $2.25 and a high of $5
as requested, I will be providing a risks portion to my DDs
As stated in their recent SEC FIlings:
"On March 2, 2020, we received written notice (the “Notice”) from The Nasdaq Stock Market, LLC (“Nasdaq”) indicating that we are not in compliance with the $1.00 minimum bid price requirement for continued listing on The Nasdaq Global Market, as set forth in Nasdaq Listing Rule 5450(a)(1). In accordance with Nasdaq Listing Rule 5810(c)(3)(A), we had a period of 180 calendar days, or until August 31, 2020, to regain compliance with the minimum bid price requirement. To regain compliance, the closing bid price of our common stock must meet or exceed $1.00 per share for a minimum of ten consecutive business days during this 180-day period." Link for this
Sesen Bio Received an extension and they have until November 12 2020 to reach compliance, if they do not they run the risk of delisting and would have to reapply to be listed on the Nasdaq market. If they do not come to compliance by then, they will "consider implementing available options to regain compliance with the minimum bid price requirement under the Nasdaq Listing Rules, including effecting a reverse stock split."
** Final thoughts and comments**
I believe that they will be approved by the FDA in the foreseeable future. Especially with the fact that they have been granted a fast track designation to approval of vicinium.
Not only that, but during their first quarter market research, data shows that Uruologists prefer Vicinium over Keytruda and traditional treatments. As stated by SESEN bio on their website: " The research revealed that, when prescribing a branded agent, Urologists would prescribe Vicinium to 83% of their patients compared to 17% for Keytruda" Link
I have personally invested 100 shares of SESN at the price of .78
I firmly believe they will reach to their low estimated price target due to all the science behind their work and the fact that they are currently debt free and have enough funds to last them through 2021.
As i always tell everyone, dont blindly buy stocks without doing your own research. I highly recommend that you do your own DD alongside reading all the material and links i have provided.
I do this so you, the reader, can have the best knowledge/information on a stock so you can , make a well informed decision before purchasing a stock.
Always remember, do not go all in on any stock, if you do, thats on you. Always purchase any stocks youre interested in with what you are comfortable spending
I hope this DD can help you make a well informed decision to either purchase or stay away from.
EDIT: I FORGOT TO MENTION THIS: Another reason why I believe in this stock & their flagship product is because there currently is a shortage of BCG. This shortage, alongside the fact Vicinium is expected to be approved sooner due to their fast track designation & successful manufacturing with partner Fujifilm, is why I truly do believe in this stock.
Photosynthesis boosted in plants, a musician makes music with artificial cells, and other things that happened This Week in Synthetic Biology
Every week, I compile the latest peer-reviewed research, preprints, and other news on genetic engineering and synthetic biology. This is the third week, and the response has been positive so far, so I will keep going! ***
Listening to the Music of a Cell Eduardo Reck Miranda is a professor of computer music at the University of Plymouth. In his latest paper, he introduces “a system for music composition informed by synthetic biology”, in which music is generated via simulations of various cellular processes, including transcription and protein folding. The study was published in Artificial Life. E. coli30875-8#articleInformation)Engineered to Grow Solely on Methanol30875-8#articleInformation) (They must be starving!) At UCLA, the Liao lab has engineered E. coli to utilize methanol as its sole carbon source. With a paltry doubling time of 8.5 hours, the team began by using “metabolic robustness criteria” to engineer the strain, followed by laboratory evolution, and found that the final organism carefully balanced metabolic flux by tuning gene copy numbers and mutating key enzymes. The work was published in Cell. Going Deeeep on the SARS-CoV-2 Receptor Binding Domain31003-5) (Open Access) Researchers at the University of Washington and the Fred Hutchinson Cancer Research Center, in Seattle, have performed a deep-mutational scan on the SARS-CoV-2 receptor binding domain (RBD), the bit that binds to ACE2 on human cells. They created every single amino-acid substitution in the RBD, and show that, while most mutations are deleterious, some mutations enhance affinity for ACE2. The work was published in Cell. Boosting Photosynthesis in Plants At the University of Essex, the Raines lab inserted multiple genes, from red algae and cyanobacteria, into Nicotiana tabacum (tobacco) to stimulate both electron transport and Ribulose 1,5-bisphosphate turnover, increasing photosynthesis. The engineered plants also had an increase in above-ground biomass of up to 52% compared to controls. The study was published in Nature Plants. Read the press release. E. Coli30363-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929420303636%3Fshowall%3Dtrue)Gets a 21st Amino Acid30363-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929420303636%3Fshowall%3Dtrue) (Open Access) The Xiao lab at Rice University has engineered E. coli to both synthesize a 21st amino acid (5-hydroxyl-tryptophan, or 5HTP) and then site-specifically incorporate it into proteins. The team then used the engineered cell to “serve as a living indicator for reactive oxygen species”, as stated by Xiao in a Rice press release. The work was published in Chem.
The Next Pandemic: Confronting Emerging Disease and Antibiotic Resistance
Two problems not commonly discussed prior to the novel Coronavirus outbreak are the emergence of infectious disease and the related increasing prevalence of antimicrobial resistance. Here, I will explain the science behind these problems and some solutions that can be driven by legislation. My background is more squarely rooted in the science, so I apologize if I lean too heavily in this area as opposed to the economics and policy focus of this subreddit. I frequent this sub and enjoy the discourse here, and in my area this is one topic that overlaps with public health policy that I am passionate about. To understand emerging disease and antimicrobial resistance, it’s important to understand evolution The novel coronavirus, SARS-CoV2, is an example of an emerging infectious disease. SARS-CoV2 is a disease that, prior to 2019, had not to the best of our knowledge infected a human being. The genetic makeup of the virus indicates that the virus is natural, originating likely as a bat or pangolin Coronavirus that acquired the ability to infect humans, and that it is not man-made (1). Why do new diseases come into existence? Why haven’t humans encountered all the diseases capable of infecting us? Furthermore, why do diseases that we had previously thought conquered have the newfound ability to harm us again, in spite of our advancements in antibiotic development? The answer to these questions is partially answered by evolution. Several novel viruses, like SARS-CoV1, MERS, and SARS-CoV2, began as zoonosis: infection by a pathogen with an animal source. Viruses, though generally considered non-living, contain nucleic acid genomes (either RNA or DNA) similar to every other organism in the tree of life. This genome is subject to selective pressures, just as with every other nucleic-acid containing being, and mutates non-specifically (that is, an organism develops a mutation, then selective pressures have a positive, negative, or neutral effect on retaining or discarding the mutation). An animal coronavirus that recognizes surface molecules on animal cells that have some similarity to human cell surface molecules may only be a few small genome changes away from being capable of infecting humans. It is likely that SARS-CoV2 emerged in one of two ways: as either an animal virus that mutated within an animal that gained the ability to infect humans, or as an animal virus that jumped to humans, and within the human host was selected for the ability to infect humans (1). The advent of novel viruses is also facilitated by the horizontal transfer of genetic material between distinct viral lineages. In Influenza viruses, this can take the form of segments of genome being transferred wholesale between viruses. Influenza viruses contain a genome composed entirely of RNA in multiple segments of sequence. Segments “re-assort” when flu viruses of distinct lineage infect the same cell, and viral genomes are mixed during the process of producing new viruses. Alternatively, as would be the case in coronaviruses, recombination occurs through a mechanism not fully understood, where whole portions of genome are exchanged between viruses (2). The problem of antimicrobial resistance is also best understood through evolution. To explain this phenomenon, I will describe mainly how resistance manifests in bacteria, but similar processes drive resistance to anti-virals, anti-fungals, and anti-parasitics. Antibiotics are largely derived from natural sources: as microbes compete for resources, there is a drive to reduce competitors numbers by killing them or inhibiting their growth. Antibiotics are typically small molecules that target essential processes for bacterial growth; commonly cell wall biosynthesis (preventing growth and division of the cell, an example being penicillin), protein synthesis (blocks the process of translation, an example being erythromycin), production of RNA (blocks the process of transcription, an example being rifampin) or production of DNA (blocks the process of replication, an example being fluoroquinolone). These antibiotics arose through selective pressures, and in response bacteria have developed systems to circumvent the deleterious effects of antibiotics. These include: rapidly excreting the antibiotic before it is capable of inhibiting growth (efflux pumps, a notable offender being Pseudomonas aeruginosa, a common pathogen in patients with cystic fibrosis), degrading the antibiotic (beta-lactamases are a class of enzyme that degrade beta-lactam family antibiotics, such as penicillin), modifying the antibiotic (the most common mechanism for aminoglycoside resistance is to chemically modify the antibiotic so it doesn’t work), or simply modifying the target (Streptococcus pneumoniae is a microbe that causes multiple diseases that is naturally resistant to beta-lactams by modification of the drug target, the aptly-named Penicilin-binding protein) (3). As humans, it has been beneficial to identify these natural compounds and use them medically to treat infection. Bacteria have incredible genome plasticity, engaging in a process known as horizontal gene transfer (HGT; sometimes referred to as lateral gene transfer) that increases the prevalence of resistant microbes. Not all bacteria are capable of this set of processes, but importantly several medically important pathogens, such as E. coli, Salmonella, Yersinia pestis, Acinetobacter baumannii engage in processes that facilitate the transfer of genetic material between bacteria. There are several molecular mechanisms for HGT: bacteria-infecting viruses can transmit pieces of genetic material between similar bacteria (transduction), bacteria can form a bridge that transfers plasmids (conjugation; plasmids are typically circular pieces of DNA, and are typically maintained independently of the bacterial chromosome and commonly encode antibiotic resistance genes), or bacteria can simply pick up naked DNA in the environment and integrate that DNA into their chromosomes (natural transformation) (3). The effect of these processes is that, when a gene that imparts resistance to a particular antibiotic is introduced into a population, it may spread between members of the population, not just within the progeny of the cells that encode the resistance gene. This is especially true when a gene that imparts resistance is on a plasmid or is otherwise mobilizable (transposons, or jumping genes, are also common perpetrators of transmission in that they move somewhat readily and often encode drug resistance). The key point to understand here is that while genes are present in bacteria, either on a chromosome or on a mobilizable element, these genes are capable of moving to many other members of the same population. To understand this in more practical terms, many people have undergone a course of antibiotics and experienced gastrointestinal distress or stomach pains. This can be attributed to disturbing your normal intestinal microbiome, as you kill off non-resistant bacteria. Now assume you have an infection of some sort, it could be anywhere in your body accessible to an orally administered antibiotic, and your doctor prescribes you an antibiotic. It is possible, and possibly probable, that within your gut are bacteria that harbor resistance genes. In the absence of the antibiotic, these are likely to have a neutral or possibly deleterious effect; think of this like a welder that is unable to remove his welding mask: it certainly helps when he is welding, but is cumbersome at other times of the day. Taking the antibiotic results in high selection for resistant microbes to grow and prosper. This allows the resistant bugs to soon outnumber the non-resistant bugs. Ultimately, this increases the concentration of the resistance genes in the population of microbes in your gut. Subsequent to this, you may encounter an infection of a gastrointestinal pathogen that, in infecting your gut, acquires the resistance genes that you selected for. In disseminating this pathogen, you are also disseminating this resistance gene. Additionally, and perhaps more importantly, in taking antibiotics you select for drug resistance in the opportunistic pathogens of your body, notably Clostridium dificile and Staphylococcus epidermidis. These microbes are capable of causing disease, but reside in you or on you and cause infection when conditions are optimal for their growth. The problem of antimicrobial resistance is convergent with emerging pathogens, as many pathogens “re-emerge” as they develop resistance to antimicrobials. While TB cannot be said to be an emerging pathogen as the world has been experiencing a TB pandemic since at least the early 1800’s, TB is re-emerging in the since that increased drug resistance has led to strains of TB that are not treatable via the traditional course of antibiotics (4). Similarly, common pathogens such as E. coli, Klebsiella, and Clostridium dificile are bugs that have become increasingly resistant to the antibitoics used to treat them (5). Acinetobacter baumanii, a soil microbe with resistance to a spectrum of antibiotics, became a common Gulf and Iraq War wound infection. Many of these pathogens find a home in hospitals, where the use of antibiotics is prevalent and potential hosts are abundant. Furthermore, the recently emerged pathogen HIV, the causal agent of AIDS, is intersectional with that of antibiotic resistance, as infection with HIV increases susceptibility to bacterial infections due to reduced immune cell numbers; increased infection rates of Both issues, antibiotic resistance and emerging pathogens, pose a threat to human health the world over, and I will attempt to address both of these issues in this post. The problem of emerging disease and antibiotic resistance is exacerbated by humans To what extent do emerging diseases and antibiotic resistance affect humans? SARS-CoV2 has had an extensive impact on human health and living, and the response to shut down to stop the spread of the virus has had a large economic impact. It is impossible to accurately predict the threat posed by non-discovered viruses, so the next threat could be relatively benign, or truly horrific. This is not to fearmonger, there is no reason to suspect that such a virus is bound to steamroll us soon, but to say that the next plague may be brewing inside a pig in a Chinese farm or outside our homes in the bodies of ticks, and we would not know it. The US Center for Disease Control and Prevention (CDC) has published two Antibiotic Resistance Threat reports on the subject, in 2013 and 2019. In the 2013 edition, it was reported that 2 million people in the United States will acquire an antibiotic resistant infection, and that 23,000 will die as a direct result of that infection (5). While by 2019 this was realized to be an underestimation of the drug-resistant cases, new approaches had determined that the true value had lowered from 2013 to 2019, with an updated estimate of 2.8 million cases and 35,000 fatalities in 2019 (6). An excellent illustration of the problem can be found on page 28 of the 2013 report, which reports the introduction date (left) and the date at which resistance was observed on the right for crucial antibiotic groups. Commonly, within a decade of the introduction of an antibiotic, resistance emerges. This problem cannot be expected to go away on its own, and more than likely pathogens commonly thought vanquished will re-emerge with drug-resistant characteristics. There are human processes that contribute to the emergence of disease and spread of antibiotic resistance. In China, Wet Markets bring together livestock from all over the country, creating an environment that is diverse in the microbial life that live commensally and parasitically in and on these animals. The proximity of these animals allows for the exchange of these microbes; these microbes are then capable of exchanging genetic material. As I described for Flu and Coronaviruses, viruses that come into contact within cells are capable of genetic recombination, a process that can result in viruses that are capable of infecting humans. This is not to say this is a common phenomenon, just that 1) the process is accelerated by live animal markets and 2) this practice and resulting genetic recombination of zoonotic viruses is thought to have contributed to both the original and novel SARS-CoV outbreaks. In the United States, a textbook example of an emerging disease is Lyme Disease (7). Named for the town of Lyme, Connecticut, Lyme Disease is caused by the peculiar bacterium known as Borellia burgdorferi. Borellia is a corkscrew-shaped bacteria that is interesting for its ability to grow without iron (a key component of the immune response is the sequestration of iron away from pathogens). Lyme Disease is spread through ticks, and the number of infectious cases is exacerbated by reforestation and settlement close to wooded areas in suburban environments. As building projects move closer to forested areas, exposure to arthropod-borne illnesses will be expected to rise. Beyond settlement and the wet market practice, the emergence of new infectious disease is complicated by global warming and healthcare practices. Global warming is hypothesized to drive heat resistance in fungi, potentially improving their capacity to grow within the human body (8). The pathogenic potential of fungi is hypothesized to be limited by the heat of the human body, and there is some speculation that global warming is a contributing factor to the emergence of the notorious fungal pathogen Candida auris (8). These claims should be taken with a grain of salt and evaluated critically, but it is possible that human-caused climate change will disturb the ecology of our planet with as of yet unforeseen consequences, among them the generation novel and resurgent diseases. In healthcare, over-prescription of and a lack of regulation on antibiotics has caused the problem to worsen (5,6). When a patient receives an antibiotic, the drug has an effect on all microbes where the drug is bioavailable. This includes the intestines, which contain a resident population of microbes, and the skin, which contains Staphylococci resident species that prevent colonization by pathogenic strains of similar bacteria. These residents are then selected for their ability to resist the drug, causing an increase in resistance among the healthy microbiota. These resistance genes, as I have described, can then move between dissimilar bacteria in the same environment. If a harmful strain of E. coli is introduced into such an environment, for example, it has a higher likelihood of encountering and assimilating the genetic potential to resist antibiotics than in an environment that is naïve to the antibiotic. Patients are commonly prescribed antibiotics for infections that are more likely to be caused by a virus, or in instances where an infection is likely to run course without medical intervention. The increased exposure to antibiotics causes the microbiota to increase the concentration of resistance genes. Additionally, in places like India, the regulations on antibiotics are much more laxed than even the United States, where one is able to purchase over-the-counter antibiotics. This allows anyone to give themselves an incomplete course of antibiotics for any condition, even if the symptoms are not caused by an infection of any kind. Additionally, prescription antibiotics that have deteriorated with time, or are manufactured with subpar quality control resulting in lower concentrations, that remain in circulation exacerbate the problem by establishing sub-inhibitory concentrations of the antibiotic in the body and resulting in selection for resistance. Furthermore, environmental pollution of antibiotics into natural water sources and sewage results in increased environmental concentrations of resistance genes. These genes can spill into humans by exposure to microbes in these environments (9). Agriculture provides another increase in the concentration of resistance genes (10). Livestock are fed antibiotics, which increase the weight of animals in an as-of-yet not understood mechanism. A deleterious consequence of this increase in yield with antibiotic usage is the increase in resistance in response to this widespread antibiotic usage. These resistance genes then find their way into humans, whether through ingestion of food contaminated with resistant microbes. Science and technology can solve the problem, but face institutional and biological challenges There are both institutional and scientific challenges to combating emerging disease and antibiotic resistance. Some of these problems are easily apparent as I have described above: countries with laxed restrictions on who can obtain antibiotics, countries where the drugs are used often over-prescribed, suburbanization, and global warming all contribute to the problem. Scientifically, there are challenges in that novel diseases are difficult to combat. The novel Coronavirus had the precedent of other coronaviruses (i.e. SARS and MERS) that had been studied and their virology dissected, but that won’t necessarily be the case everytime a novel pathogen infects a human. A technological benefit to this problem is the use of meta-genomics, which allows for DNA/RNA sequencing without prior knowledge of the nucleic acid sequence of the genome. Within weeks of the first identification of the virus, its sequence was available to researchers. This was not the case during the outbreak of SARS-CoV1, when meta-genomics approaches such as Illumina Sequencing, NanoPore Sequencing, and Pacific Biosciences Sequencing were not available. In the event of a novel disease emergence, this information would be vital to combating the pathogen. Despite not knowing necessarily what the next threat will be, expanding the human knowledge base on microbes is an essential component of any plan to fight emerging diseases. Any emerging disease is likely to be similar to other microbes that we have encountered, and knowledge of the physiology of these organisms helps to understand weaknesses, transmission, and potential therapeutic targets. The study of all microorganisms therefore benefits the effort to combat the next pandemic, as any one piece of information could be critical. Surveillance is perhaps the most important tool to fight emerging infectious disease; knowing the problem exists is a crucial step to curbing spread. A recent example of successful surveillance can be seen in a recent PNAS publication regarding the presence of potential pandemic influenza in hogs, and the presence of antibodies against this particular class of flu viruses in swine workers (11). While at present it does not appear that the virus has acquired the ability to cause a pandemic, this knowledge allows for immunologists to potentially include viral antigens specific to this particular viral class in seasonal vaccines. Surveillance is critical in controlling both emerging diseases and antibiotic resistance: knowledge of what potential pathogens emerge where, and what microbes are exhibiting resistance to what drugs, can drive containment and treatment efforts. To combat antibiotic resistance, new drugs must be developed, but there are hurdles in identification, validation, and production of new antibiotics. First, potential new antibiotics have to be either identified or designed. This often involves looking through filtered environmental samples to determine the presence of small molecules that inhibit bacterial growth, or chemically altering known drugs to circumvent drug resistance. This is not necessarily difficult, as there are microbes in the soil and water that produce potential therapeutics, but this does require both time and money, as well as the consideration that it is likely that resistance to that novel therapeutic exists in the environment from which it was pulled. New drugs must be safe, but due to the abundance of antibiotics presently in use and their historic efficacy, the standard for antibiotics to pass safety regulations is extremely high. As drug resistance becomes more common, it will become apparent that more and more side effects may have to be tolerated to prevent death due to bacterial infection. Finally, and the most important challenge to developing antibiotics is that the profit margin on antibiotics is low for drug companies in the present market, disincentivizing research and production of novel drugs. In addition to stand-alone antibiotics, new inhibitors of resistance must be developed as well. Clavulanic acid is one such inhibitor, and is administered with the beta-lactam drug amoxicillin to improve its ability to kill bacteria. Bacteria that are resistant beta-lactams often encode enzymes called beta-lactamases. Beta-lactamases break open the active portion of the beta-lactam molecule, rendering it ineffective in attacking its target. Clavulanic acid is a beta-lactam itself, and is a target for the beta-lactamase enzyme; however, when the enzyme begins to degrade clavulanic acid, the enzyme becomes stuck at an intermediate step in the reaction, rendering the beta-lactamase enzyme useless. These drugs must also be explored and screened for in environmental samples, as well as developed. It is possible to take a rational approach to drug design, with increasing knowledge of how resistance mechanisms work. This means that scientists specifically look at, say, a beta-lactamase enzyme at the molecular level, and design a small molecule that will fit into the enzyme and block its function. Chemists then design the molecule to test its efficacy. Ultimately, scientists either know how to solve the problem, or know how to get the tools they need to solve the problem. It is the institutional challenges that make the problem more difficult to solve. How legislation can improve the ability of scientists to combat emerging disease and drug resistance In discussing emerging diseases and antibiotic resistance, I try to draw parallels to the problem of global warming: a global problem with global solutions. I don’t have a novel solution to climate change to discuss here, other than to parrot this subreddit’s typical ideas, so I will omit that discussion here. That is to say, global warming is a driver for emerging infectious disease, and fighting global warming is important to combat the potential rise of fungal pathogens. I will, however, discuss some ideas for combating emerging disease and drug resistance. These ideas are mostly derived from scientists familiar with the problem, Funding for research, basic and applied, is crucial. No bit of knowledge hurts in the fight against human disease. Learning how Alphaviruses replicate, determining the structure of E. coli outer membrane proteins, and examining the life cycle of the non-pathogen Caulobacter crescentus all contribute to the fight against the next disease. The more we know, the more powerful our vision is in understanding the inner machinations of disease. Every immune response, every molecular mechanism, and every aspect of microbial physiology is potentially a drug or vaccine target, a clue into pathogenesis, or an indication of how a bug is likely to spread. The Trump administration has not been kind to science funding (12). Science that does not appear to have benefit at first glance often does in the long run, and for this reason I will stress the importance of funding research of this sort, as well as funding applied research. Knowing is half the battle. In combating emerging diseases, it is important to know they exist. As I have mentioned the example of recent viral surveillance with regard to the novel reassortment influenza viruses, I would like to stress the importance of funding surveillance programs in fighting emerging disease and drug resistance. There are currently US governmental surveillance programs that provide valuable information about the spread of drug resistance, such as NARMS in the United States (13). In the United States, there is a need for greater accountability in using antibiotics. Resistance is unlikely to completely go away, even when the use of an antibiotic is discontinued, but the levels of resistant bacteria dwindle when the selective pressure is reduced. For this reason, several medical practitioners have proposed a rotating schedule of prescription antibiotics, that includes the retention of some new antibiotics from use. The reasoning for this is that, in the years following the halted use of a particular antibiotic, it is expected that the concentration of resistant bacteria will decrease. As I discussed with the example of always wearing a welding helmet, carrying resistance genes often imparts some form of growth defect on the resistant bacteria (for example, altering an essential gene targeted by an antibiotic may render the bacteria resistant, but there is a reason such a gene is essential, in that it’s required for growth; changing the gene in a substantive way may negatively impact its performance and by extension make these resistant bacteria less fit). A rotating cycle of what antibiotics are allowed to be prescribed, informed by surveillance data, would buy time for the development of new antibiotics as well. Additionally, higher standards should be required for the prescription of antibiotics, to increase accountability of physicians; these standards could involve clinically verifying the presence of susceptible bacteria prior to administering a drug in situations where the disease in not life-threatening. There is a need to reduce the environmental pollution of drugs into sewage and natural bodies of water as well. This will require research into cost-effective methods for reducing the population of resistant bugs and drugs in these environments. In the case of natural bodies of water, a source of contamination is often factories where drugs are produced. Often, waters near these factories have high levels of antibiotics that select for resistance to develop and spread. This may require legislation to improve environmental outcomes, as well as surveillance of drug resistance gene levels and the levels of antibiotics in these waters to ensure compliance. There is also a need to halt the use of antibiotics in treating livestock (14). Halting the use of antibiotics typically results in reductions of antibiotic resistant bug populations within a year or two (10). I don’t know of studies that estimate the economic cost of halting use of antibiotics in American meat, but in the case of Denmark, livestock production does not appear to have been significantly impacted. I think that the most challenging problem will be for drug companies to develop new antibiotics when there is not presently a financial incentive to do so. Because antibiotics are still largely effective, and the financial benefit to adding an antibiotic to the market does not outweigh the cost to put a drug to market, there is not currently a large incentive to produce new drugs (15). To address this negative externality, it is necessary to generate financial incentives of some form for the production of new antibiotics. This may take the form of subsidizing antibiotic discovery efforts and drug safety trials; additionally, applied research with the goal of specifically finding new antibiotics should see increased funding. To combat the problem overseas, it is obvious that obtaining an antibiotic course must occur through a doctor. This eliminates false self-diagnoses of bacterial infections. The problem of wet markets may be partially resolved by preventing animals that do not regularly contact each other from being traded and stored in the same vicinity as animals that are not typically encountered. This may involve limiting a particular wet market to the trade of animals that come from a particular geographic area, preventing geographically diverse microbes from encountering each other. It's on all of us to stop the next pandemic: If you made it this far, thank you reading this post and I hope that I have convinced you of the importance of this issue! There are simple steps that we can all take as consumers to reduce antimicrobial resistance: don’t take antibiotics unless prescribed by a doctor and buy meat that was produced without antibiotics. I welcome any and all criticism, and would love to hear people's ideas! Please let me know of any errors as well, or any missed concepts that I glossed over. I've been excited to give my two cents to this sub, and I don't want to mislead in any way. Sources: 1: Andersen, KG, et al. 2020. The Proximal Origin of Sars-CoV-2. Nature Medicine 26: 450-452. 2: Su, Shou, et al. 2016. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Cell Trends in Microbiology 24(6): 490-502. https://doi.org/10.1016/j.tim.2016.03.003 3: Munita, JM; Arias, CA. 2016. Mechanisms of Antibiotic Resistance. Microbiology Spectrum VMBF-0016-2015. doi:10.1128 /microbiolspec.VMBF-0016-2015. 4: Shah, NS; et al. 2007. Worldwide Emergence of Extensively Drug-resistant Tuberculosis. Emerging Infectious Diseases 13(3): 380-387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725916/ 5: CDC Antibiotic Threats Report, 2013. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf 6: CDC Antibiotic Threats Report, 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf 7: Barbour, AG; Fish, D. 1993. The Biological and Social Phenomenon of Lyme Disease. Science 260(5114):1610-1616. https://pubmed.ncbi.nlm.nih.gov/8503006/ 8: Casadevall, A; Kontoyiannis, DP; Robert, V. 2019. On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds. mBio 10.1128/mBio.01397-19. https://mbio.asm.org/content/10/4/e01397-19 9: Kraemer, SA; Ramachandran, A; Perron, GG. 2019. Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy. Microorgansims 7(6): 180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616856/ 10: Levy, S. 2014. Reduced Antibiotic Use in Livestock: How Denmark Tackled Resistance. Environmental Health Perspectives 122(6): A160-A165. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050507/ 11: Sun, H, et al. 2020. Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. Proceedings of the National Academy of Sciencehttps://doi.org/10.1073/pnas.1921186117. 12: Kaiser, J. 2020. National Institutes of Health would see 7% cut in 2021 under White House plan. Science Magazine. https://www.sciencemag.org/news/2020/02/national-institutes-health-would-see-7-cut-2021-under-white-house-plan 13: About NARMS: National Antimicrobial Resistance Monitoring System for Enteric Bacteria. https://www.cdc.gov/narms/about/index.html 14: Khachatourians, GG. 1998. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. CMAJ 159(9):1129-1136 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1229782/ 15: Jacobs, Andrew. 2019. Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. The New York Times. https://nyti.ms/366f7it
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CDC Admits 98 Million Americans Received Polio Vaccines Contaminated With Cancer Virus
by Dave MihalovicJuly 17, 2013 fromPreventDiseaseWebsite
Dave Mihalovicis a Naturopathic Doctor who specializes in vaccine research, cancer prevention and a natural approach to treatment.
The CDC has quickly removed a page from their website, which WAS cached here (since removed by Google so you can view an image of the cache below), admitting that more than 98 million Americans received one or more doses of polio vaccine within an 8-year span from 1955-1963 when a proportion of the vaccine was contaminated with a cancer causing polyomavirus called SV40. https://preview.redd.it/b9x1h3p686b41.jpg?width=360&format=pjpg&auto=webp&s=c903ed47f79c1c1e6fc4f0985304d8950430d4cd SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has been found to cause tumors and cancer. SV40 is believed to suppress the transcriptional properties of the tumor-suppressing genes in humans through the SV40 Large T-antigen and SV40 Small T-antigen. Mutated genes may contribute to uncontrolled cellular proliferation, leading to cancer. Michele Carbone, Assistant Professor of Pathology at Loyola University in Chicago, has recently isolated fragments of the SV-40 virus in human bone cancers and in a lethal form of lung cancer called mesothelioma. He found SV-40 in 33% of the osteosarcoma bone cancers studied, in 40% of other bone cancers, and in 60% of the mesotheliomas lung cancers, writes Geraldo Fuentes. Dr. Michele Carbone openly acknowledged HIV/AIDS was spread by the hepatitis B vaccine produced by Merck & Co. during the early 1970s. It was the first time since the initial transmissions took place in 1972-74, that a leading expert in the field of vaccine manufacturing and testing has openly admitted the Merck & Co. liability for AIDS (below video): VIDEO The matter-of-fact disclosure came during discussions of polio vaccines contaminated with SV40 virus which caused cancer in nearly every species infected by injection. Many authorities now admit much, possibly most, of the world's cancers came from the Salk and Sabin polio vaccines, and hepatitis B vaccines, produced in monkeys and chimps. It is said mesothelioma is a result of asbestos exposure, but research reveals that 50% of the current mesotheliomas being treated no longer occurs due to asbestos but rather the SV-40 virus contained in the polio vaccination (See Asbestos, Mesothelioma Claims and Lawsuit Case Examples.) In addition, according to researchers from the Institute of Histology and General Embryology of the University of Ferrara, SV-40 has turned up in a variety other tumors. By the end of 1996, dozens of scientists reported finding SV40 in a variety of bone cancers and a wide range of brain cancers, which had risen 30 percent over the previous 20 years. The SV-40 virus is now being detected in tumors removed from people never inoculated with the contaminated vaccine, leading some to conclude that those infected by the vaccine might be spreading SV40. Soon after its discovery, SV40 was identified in the oral form of the polio vaccine produced between 1955 and 1961 produced by American Home Products (dba Lederle). Both the oral, live virus and injectable inactive virus were affected. It was found later that the technique used to inactivate the polio virus in the injectable vaccine, by means of formaldehyde, did not reliably kill SV40. Just two years ago, the U.S. government finally added formaldehyde to a list of known carcinogens and and admitted that the chemical styrene might cause cancer. Yet, the substance is still found in almost every vaccine. According to the Australian National Research Council, fewer than 20% but perhaps more than 10% of the general population may be susceptible to formaldehyde and may react acutely at any exposure level. More hazardous than most chemicals in 5 out of 12 ranking systems, on at least 8 federal regulatory lists, it is ranked as one of the most hazardous compounds (worst 10%) to ecosystems and human health (Environmental Defense Fund). In the body, formaldehyde can cause proteins to irreversibly bind to DNA. Laboratory animals exposed to doses of inhaled formaldehyde over their lifetimes have developed more cancers of the nose and throat than are usual. Facts Listed on The CDC Website about SV40
SV40 is a virus found in some species of monkey. SV40 was discovered in 1960. Soon afterward, the virus was found in polio vaccine. SV40 virus has been found in certain types of cancer in humans.
Additional Facts
In the 1950s, rhesus monkey kidney cells, which contain SV40 if the animal is infected, were used in preparing polio vaccines. Not all doses of IPV were contaminated. It has been estimated that 10-30 million people actually received a vaccine that contained SV40. Some evidence suggests that receipt of SV40-contaminated polio vaccine may increase risk of cancer.
A Greater Perspective on Aerial Spraying and SV40 The Defense Sciences Office of the Pathogen Countermeasures Program, in September 23, 1998 funded the University of Michigan's principal investigator, Dr. James Baker, Jr. Dr. Baker, Director of Michigan Nanotechnology Institute for Medicine and Biological Sciences under several DARPA grants. Dr. Baker developed and focused on preventing pathogens from entering the human body, which is a major goal in the development of counter measures to Biological Warfare. This research project sought to develop a composite material that will serve as a pathogen avoidance barrier and post-exposure therapeutic agent to be applied in a topical manner to the skin and mucous membranes. The composite is modeled after the immune system in that it involves redundant, non-specific and specific forms of pathogen defense and inactivation. This composite material is now utilized in many nasal vaccines and vector control through the use of hydro-gel, nanosilicon gels and actuator materials in vaccines. Through Dr. Baker's research at the University of Michigan; he developed dendritic polymers and their application to medical and biological science. He co-developed a new vector system for gene transfer using synthetic polymers. These studies have produced striking results and have the potential to change the basis of gene transfer therapy. Dendrimers are nanometer-sized water soluble polymers that can conjugate to peptides or arbohydrates to act as decoy molecules to inhibit the binding of toxins and viruses to cells. They can act also as complex and stabilize genetic material for prolonged periods of time, as in a "time released or delayed gene transfer". Through Dr. Baker's ground breaking research many pharmaceutical and biological pesticide manufacturers can use these principles in DNA vaccines specific applications that incorporate the Simian Monkey Virus SV40. WEST NILE VIRUS SPRAYING In 2006 Michael Greenwood wrote an article for the Yale School of Public Health entitled, "Aerial Spraying Effectively Reduces Incidence of West Nile Virus (WNV) in Humans." The article stated that the incidence of human West Nile virus cases can be significantly reduced through large scale aerial spraying that targets adult mosquitoes, according to research by the Yale School of Public Health and the California Department of Public Health. Under the mandate for aerial spraying for specific vectors that pose a threat to human health, aerial vaccines known as DNA Vaccine Enhancements and Recombinant Vaccine against WNV may be tested or used to "protect" the people from vector infection exposures. DNA vaccine enhancements specifically use Epstein-Barr viral capside's with multi human complement class II activators to neutralize antibodies. The recombinant vaccines against WNV use Rabbit Beta-globulin or the poly (A) signal of the SV40 virus. In early studies of DNA vaccines it was found that the negative result studies would go into the category of future developmental research projects in gene therapy. During the studies of poly (A) signaling of the SV40 for WNV vaccines, it was observed that WNV will lie dormant in individuals who were exposed to chicken pox, thus upon exposure to WNV aerial vaccines the potential for the release of chicken pox virus would cause a greater risk to having adult onset Shingles. CALIFORNIA AERIAL SPRAYING for WNV and SV40 In February 2009 to present date, aerial spraying for the WNV occurred in major cities within the State of California. During spraying of Anaheim, CA a Caucasian female (age 50) was exposed to heavy spraying, while doing her daily exercise of walking several miles. Heavy helicopter activity occurred for several days in this area. After spraying, she experienced light headedness, nausea, muscle aches and increased low back pain. She was evaluated for toxicological mechanisms that were associated with pesticide exposure due to aerial spraying utilizing advanced biological monitoring testing. The test results which included protein band testing utilizing Protein Coupled Response (PCR) methods were positive for KD-45. KD-45 is the protein band for SV-40 Simian Green Monkey virus. Additional tests were performed for Epstein-Barr virus capside and Cytomeglia virus which are used in bioengineering for gene delivery systems through viral protein envelope and adenoviral protein envelope technology. The individual was positive for both; indicating a highly probable exposure to a DNA vaccination delivery system through nasal inhalation. The question of the century is, how many other viruses and toxins are within current day vaccines that we'll only find out about in a few decades? Sources
Section 5.1: The structure of the protein may be described as follows: < type of protein> is conjugated with <name of polymer contained in conjugate> at a degree of substitution of <n moles of polymer/mole of protein>. The average molecular mass is approximately <Y> of which the protein moiety constitutes approximately <X>. Acrolein is a ubiquitous environmental pollutant. Whey protein and conjugated linoleic acid are widely used weight-loss supplements. We aimed to evaluate blood lipid profiles, oxidative stress and mitochondrial bioenergetics function in hearts of rats treated with acrolein and/or the weight-loss supplements. ADVERTISEMENTS: Conjugated proteins are proteins that contain non-protein constituents or prosthetic groups. The prosthetic groups are permanently associated with the molecule, usually through covalent and/or non-covalent linkages with the side chains of certain amino acids. Conjugated proteins can be divided into three major classes: (1) Chromo proteins ADVERTISEMENTS: (2) Glycoproteins ... conjugated antibodies to their targets, the protein levels can be converted to oligonucleotide levels. In this report we describe a simple method for preparing oligonucleotide-conjugated antibodies and discuss this method’s application in oligonucleotide extension reaction (OER) for multiplex protein detection. Conjugation Polymeric Chains of SUMO-2 and SUMO-3 Are Conjugated to Protein Substrates by SAE1/SAE2 and Ubc9* Received for publication, May 9, 2001, and in revised form, July 9, 2001 Published, JBC Papers in Press, July 12, 2001, DOI 10.1074/jbc.M104214200 Michael H. Tatham‡, Ellis Jaffray, Owen A. Vaughan, Joana M. P. Desterro§, Antonio Blanco, Gustavo Blanco, in Medical Biochemistry, 2017. Hemoglobin. Hemoglobin is a conjugated protein whose prosthetic group, heme, gives it its typical intense red color.Among the heme proteins are the cytochromes, which are substances that act as electron carriers and enzymes, such as catalase and peroxidase; myoglobin, a molecule that carries and stores oxygen in muscle; and ... These are proteins conjugated with lipids such as neutral fat, phospholipids and cholesterol Metalloproteins These are metal-binding proteins. A ˜-globulin, termed transferrin is capable of combining with iron, copper and zinc. This protein constitutes 3% of the total plasma protein. PDF Proteins are made ... There are 20 different kinds of amino acids that are linked together by peptide bond to make a protein molecule. ... The non-amino acid moiety of the conjugated protein ...
The four levels of protein structure are primary, secondary, tertiary, and quaternary. It is helpful to understand the nature and function of each level of p... About Press Copyright Contact us Creators Advertise Developers Terms Privacy Policy & Safety How YouTube works Test new features Press Copyright Contact us Creators ... About Press Copyright Contact us Creators Advertise Developers Terms Privacy Policy & Safety How YouTube works Test new features Press Copyright Contact us Creators ... The Amoeba Sisters explain enzymes and how they interact with their substrates. Vocabulary covered includes active site, induced fit, coenzyme, and cofactor.... Nick Gee, the CEO and CSO of Innova Biosciences, explains the benefits of using directly conjugated antibodies and the various approaches and techniques that... Developed and produced by http://www.MechanismsinMedicine.comAnimation Description: The DNA is shown as a circular double strand within the bacterial cell. ... Paul Andersen explains the structure and importance of proteins. He describes how proteins are created from amino acids connected by dehydration synthesis. ... Matt Wenning has a masters in biomechanics- and has broken multiple all time world records in powerlifting . He has had major contacts with armed forces units such as US Army rangers - 82nd ... After a polypeptide is produced in protein synthesis, it's not necessarily a functional protein yet! Explore protein folding that occurs within levels of pro... Do you remember tripping over as a kid and cutting your knee? And then like magic the bleeding suddenly stops? Have you ever wondered why this happens?Our bo...