Fda Summer Activities 2000: Fill & Download for Free

Recent surge in studies on human-associated Microbiota triggered a major transition in our understanding of human biology. Some outright inaccurate concepts such as the terms bacteria and pathogen/germs being used interchangeably are deservedly poised for erasure. Though unfortunately enshrined as a standard in biology textbooks and even more so in popular culture, increasing knowledge of human-associated microbiota renders such utterly false equivalence moot. OTOH, compared to human-associated microbiota, our knowledge of human-associated eukaryotes is even more in its infancy. Human-associated eukaryotes include fungi, Protist, and Helminths (platyhelminths/flatworms and nematodes/roundworms). Reflexively dismissed as undesirable even when routinely found in normal people, modern medicine considers human-associated protists and helminths a priori harmful/pathogenic and uses drugs to remove them (1, 2, 3, 4). Thus, protists and helminths stand practically eliminated within humans in industrialized countries even as their rates of allergies, autoimmunity and inflammatory diseases have spiraled out of control over the past half century.Just as these skyrocketing rates of dysregulated immune function forced a conversation about the need to distinguish bacteria from pathogen so too our understanding of what constitutes a beneficial/neutral eukaryotic partner versus a parasite may need similar revision. What started with microbiota is now slowly but inevitably expanding to eukaryotes. As with bacteria, far from being only harmful, research is uncovering that the diverse set of protists and helminths found in our bodies, guts in particular, may be essential forTraining and maintaining balanced immune function, a corollary of their effort to resist expulsion from the body.Helping maintain diverse, beneficial microbiota, for e.g., by influencing the amount and composition of gut-associated mucus, the substrate that's the soil for gut microbes.After all, the gut is a major niche for not just commensal bacteria but also eukaryotes. Mammals evolved with bacteria and eukaryotes as coadapted partners. Modern sanitation, lack of close contact with farm animals, and antibiotics are some of the recent major changes that profoundly disturbed these ancient relationships. Of course, it's crystal clear in hindsight that the fallout has been self-inflicted damage to human health.Some Human-Associated Protists And HelminthsBlastocystis is a common protist found in 10 to 100% of surveyed individuals, frequently in those who are healthy (5, 6, 7, 8, 9), and with a lower prevalence in inflammatory bowel diseases. For e.g., an European study found a lower prevalence of Blastocystis in active ulcerative colitis (UC) patients (10). Protists such as Blastocystis and Dientamoeba may also be beneficial for immune function (10, 11).Helminths are worms associated with humans over evolutionary time. Many of them can't replicate within their host but rather co-exist through their extensive manipulation of the host's immune function. High helminth colonization and low prevalence of allergy, autoimmunity and inflammatory diseases appear to go hand in hand among rural residents in less industrialized countries (12, 13), a cornerstone of the Hygiene hypothesis. Epidemiological studies have in fact consistently observed that IgE-mediated hypersensitivity is rare in tropical areas endemic to worms (14). Helminths such as Trichuris trichiura can transiently colonize the human colon. OTOH, Trichuris suis, a geohelminth colonizes pig colon (15). Geohelminth means fertilized eggs require several weeks of incubation in moist soil. This renders such worms incapable of direct human to human transmission, i.e. safer for therapeutic use. Staying confined to the GI tract producing a self-limited colonization, T. suis eggs (TSO) have been used in a number of clinical trials (16, 17).Some intestinal eukaryotes are indeed pathogenic. Examples are protists such as Cryptosporidium and Entamoeba histolytica, and helminths such as Ascaris lumbrocoides and Strongyloides stercoralis (18). However, cheek by jowl with the far more voluminous literature on how to get rid of such pathogens is a tiny but growing one on the Eukaryotome (19) or Eukaryome (11), i.e., the more commensal/benign/neutral 'normal' eukaryotic inhabitants of the human GI tract.Human Clinical Trials With Helminth Eggs: Some Successes With Autoimmune And Inflammatory DiseasesSince at least 2000, a few pioneering clinical trials have assessed whether seeding guts with live helminth eggs can reverse allergies, autoimmunities and inflammatory diseases. While such studies showed poor outcome for allergies (20, 21, 22), they've had remarkable success in autoimmunity and IBD (inflammatory bowel disease), achieving remission (23, 24) in MS (multiple sclerosis) for example, and reversal of symptoms in Crohn's (25, 26), UC (27, 28) and coeliac disease. Why then aren't such Rx becoming more mainstream? A range of factors.Convincing patients to swallow live 'parasite' eggs as Rx is understandably difficult and therefore fraught with failure.Regulatory barriers are higher for such live Rx. For e.g., the US FDA currently defines helminths as 'drugs', i.e., requiring as high and rigorous validation standard including a thorough pharmacokinetic study as for chemical agents. Contrast with leeches and maggots which the FDA considers 'medical devices', i.e., relatively low standard for approval (29).More difficult to 'manufacture' such live Rx to scale using standardized procedures and maintaining high quality control.These are some of the reasons big pharma has evinced little interest in investing effort to translate such promising preliminary trial data into large scale therapies, and only small biotechs such as Coronado Biosciences, now renamed Fortress Biotech, even invested some effort into this research. Meanwhile academic researchers have begun identifying helminth molecular entities that could recapitulate some biological outcomes of worms and their eggs (29). One of the best studied such entities is ES-62, a 62 kilo dalton excretory/secretory (ES) protein purified from the rodent filarial nematode Acanthocheilonema viteae (30). However, traveling down such a road brings another set of potential problems.Through evolutionary time, we coadapted to a wide variety of protists and helminths. We have scarcely scratched the surface of this association. How well could a purified moiety from one such organism recapitulate the whole, which is often more than the sum of its parts?Typically allergies, autoimmunities and inflammatory diseases we seek to redress through such therapies are each themselves multitudes, grouped together under one name simply for convenience when they're in fact separate diseases. A particular Helminthic therapy working in particular subsets rather than in entire groups of patients may simply reflect that unaddressed reality.Certain helminths paired with certain groups of people over evolutionary time. However, currently we are far from understanding this eukarytome/eukaryome landscape across the global human population, let alone which helminth optimally pairs as Rx for which allergy/autoimmunity/inflammatory disease. If a certain pairing fails, it may be just as likely from poor pairing choice rather than failure of the approach itself.Bibliography1. Embree, J. "Dientamoeba fragilis: a harmless commensal or a mild pathogen." Can. J. Infect. Dis 9 (1998): 69-70. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851273/pdf/pch03081.pdf2. Coyle, Christina M., et al. "Blastocystis: to treat or not to treat…." Clinical infectious diseases (2011): cir810. To Treat or Not to Treat…3. Andersen, Lee O'Brien, and Christen Rune Stensvold. "Blastocystis in Health and Disease—Are We Moving from a Clinical to a Public Health Perspective?." Journal of clinical microbiology (2015): JCM-02520.4. Kurt, Özgür, Funda Doğruman Al, and Mehmet Tanyüksel. "Eradication of blastocystis in humans: Really necessary for all?." Parasitology international (2016).5. Scanlan, Pauline D., and Christen R. Stensvold. "Blastocystis: getting to grips with our guileful guest." Trends in parasitology 29.11 (2013): 523-529.6. Scanlan, Pauline D., et al. "The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota." FEMS microbiology ecology 90.1 (2014): 326-330. http://femsec.oxfordjournals.org/content/femsec/90/1/326.full.pdf7. Parfrey, Laura Wegener, et al. "Communities of microbial eukaryotes in the mammalian gut within the context of environmental eukaryotic diversity." Roles and mechanisms of parasitism in aquatic microbial communities (2015): 126. https://www.researchgate.net/profile/Clotilde_Teiling/publication/263745070_Communities_of_microbial_eukaryotes_in_the_mammalian_gut_within_the_context_of_environmental_eukaryotic_diversity/links/54bd46050cf218da9391adad.pdf8. Scanlan, Pauline D., Christen Rune Stensvold, and Paul D. Cotter. "Development and application of a Blastocystis subtype-specific pcr assay reveals that mixed-subtype infections are common in a healthy human population." Applied and environmental microbiology 81.12 (2015): 4071-4076. Development and Application of a Blastocystis Subtype-Specific PCR Assay Reveals that Mixed-Subtype Infections Are Common in a Healthy Human Population9. Pandey, Prashant Kumar, et al. "Prevalence and subtype analysis of Blastocystis in healthy Indian individuals." Infection, Genetics and Evolution 31 (2015): 296-299. https://www.researchgate.net/profile/Nachiket_Marathe/publication/272421612_Prevalence_and_subtype_analysis_of_Blastocystis_in_healthy_Indian_individuals/links/54e5d1140cf2bff5a4f1c6ea.pdf10. Rossen, N. G., et al. "Low prevalence of Blastocystis sp. In active ulcerative colitis patients." European Journal of Clinical Microbiology & Infectious Diseases 34.5 (2015): 1039-1044. Low prevalence of Blastocystis sp. in active ulcerative colitis patients11. Lukeš, Julius, et al. "Are Human Intestinal Eukaryotes Beneficial or Commensals?." PLoS Pathog 11.8 (2015): e1005039. http://journals.plos.org/plospathogens/article/asset?id=10.1371%2Fjournal.ppat.1005039.PDF)12. Elliott, David E., and Joel V. Weinstock. "Helminth–host immunological interactions: prevention and control of immune‐mediated diseases." Annals of the New York Academy of Sciences 1247.1 (2012): 83-96. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744090/pdf/nihms492922.pdf13. Wiria, Aprilianto Eddy, et al. "Helminth infection in populations undergoing epidemiological transition: a friend or foe?." Seminars in immunopathology. Vol. 34. No. 6. Springer-Verlag, 2012. http://staff.ui.ac.id/system/files/users/aprilianto.eddy/publication/wiria2012helminthinpopulationsundergoingepidemiologicaltransition.pdf14. Versini, Mathilde, et al. "Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications." BMC medicine 13.1 (2015): 81. BMC Medicine15. Szkudlapski, D., et al. "The emering role of helminths in treatment of the inflammatory bowel disorders." J Physiol Pharmacol 65 (2014): 741-751. http://jpp.krakow.pl/journal/archive/12_14/pdf/741_12_14_article.pdf16. Jouvin, Marie-Hélène, and Jean-Pierre Kinet. "Trichuris suis ova: testing a helminth-based therapy as an extension of the hygiene hypothesis." Journal of Allergy and Clinical Immunology 130.1 (2012): 3-10. https://parasitology.cvm.ncsu.edu/vmp930/supplement/trichuris_treatment_allergies.pdf17. Loke, P., and Y. A. L. Lim. "Helminths and the microbiota: parts of the hygiene hypothesis." Parasite immunology 37.6 (2015): 314-323. https://www.researchgate.net/profile/Png_Loke/publication/274965905_Helminths_and_the_microbiota_parts_of_the_hygiene_hypothesis/links/55898a6308ae9076016f9ad9.pdf18. Girgis, Natasha M., Uma Mahesh Gundra, and P'ng Loke. "Immune regulation during helminth infections." PLoS Pathog 9.4 (2013): e1003250. http://journals.plos.org/plospathogens/article/asset?id=10.1371%2Fjournal.ppat.1003250.PDF19. Andersen, Lee O'Brien, Henrik Vedel Nielsen, and Christen Rune Stensvold. "Waiting for the human intestinal Eukaryotome." The ISME journal 7.7 (2013): 1253. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695289/pdf/ismej201321a.pdf20. Bager, Peter, et al. "Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial." Journal of allergy and clinical immunology 125.1 (2010): 123-130. https://www.researchgate.net/profile/Lars_Poulsen/publication/26866959_Trichuris_suis_ova_therapy_for_allergic_rhinitis_a_randomized_double-blind_placebo-controlled_clinical_trial/links/00b4952a7f6c89aaa2000000.pdf21. Croft, Ashley M., Peter Bager, and Sushil Kumar. "Helminth therapy (worms) for allergic rhinitis." Cochrane Database Syst Rev 4 (2012). https://www.researchgate.net/profile/Ashley_Croft/publication/224708548_Helminth_therapy_%28worms%29_for_allergic_rhinitis/links/09e4150b0b21ddf09b000000.pdf22. Feary, J. R., et al. "Experimental hookworm infection: a randomized placebo‐controlled trial in asthma." Clinical & Experimental Allergy 40.2 (2010): 299-306. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2009.03433.x/epdf23. Fleming, J. O., et al. "Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study." Multiple Sclerosis Journal 17.6 (2011): 743-754. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894910/pdf/nihms536054.pdf24. Correale, Jorge, Mauricio Farez, and Gabriela Razzitte. "Helminth infections associated with multiple sclerosis induce regulatory B cells." Annals of neurology 64.2 (2008): 187-199.25. Summers, Robert W., et al. "Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease." The American journal of gastroenterology 98.9 (2003): 2034-2041. https://www.researchgate.net/profile/Robert_Summers2/publication/9088450_Trichuris_suis_seems_to_be_safe_and_possibly_effective_in_the_treatment_of_inflammatory_bowel_disease/links/0deec51a656df20723000000.pdf26. Summers, Robert W., et al. "Trichuris suis therapy in Crohn’s disease." Gut 54.1 (2005): 87-90. http://www.lumen.luc.edu/lumen/MedEd/hostdef/ARTICLES1/worms%20to%20the%20rescue.pdf27. Summers, Robert W., et al. "Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial." Gastroenterology 128.4 (2005): 825-832. http://tropicalhealthsolutions.com/documents/worms/Summers-2005.pdf28. Broadhurst, Mara J., et al. "IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient." Science translational medicine 2.60 (2010): 60ra88-60ra88. https://www.researchgate.net/profile/Png_Loke/publication/49650965_IL-22_CD4_T_Cells_Are_Associated_with_Therapeutic_Trichuris_trichiura_Infection_in_an_Ulcerative_Colitis_Patient/links/00b7d535585b829413000000.pdf29. Shepherd, C., et al. "Identifying the immunomodulatory components of helminths." Parasite immunology 37.6 (2015): 293-303.30. Pineda, M. A., et al. "From the worm to the pill, the parasitic worm product ES-62 raises new horizons in the treatment of rheumatoid arthritis." Lupus 24.4-5 (2015): 400-411. From the worm to the pill, the parasitic worm product ES-62 raises new horizons in the treatment of rheumatoid arthritisThanks for the A2A, Alecia Li Morgan.

If you were unable to exercise much at all, doing it MORE could be life-changing. Many seniors and people who are wheelchair bound get tremendous benefits in cardiovascular health and energy from doing exercises that other people might consider very light exertion. On the other hand, if you already exercise and are active, then doing even more than that isn’t a priority.Same with food. The extreme diets popular today could lead to obsessive behavior towards food, avoiding whole food groups for as long as possible, then binge eating and repeating the whole process over and over again. If your diet includes fruits, vegetables, complex carbohydrates and protein, you have a healthy diet already. Chances are, if you’re including these things, the small pleasure you get from an ice cream cone on a summer day does more for your mental health than eliminating would do for physical health. If you’ve been taking your daily calories lower and lower in the name of healthy eating, while feeling depressed and suffering fatigue and a sedentary lifestyle, prioritizing an increase in exercise could be a good idea(while also making sure you’re not having an obsessive relationship with food and diet.) In a nutshell, your diet changes or exercise changes should be about tweaking your existing patterns. Change the behaviors most in need of change FOR YOU. If you eat junk food and nothing else all day long, changing that can be a priority. Good luck!Also, consider this article:Why Does the FDA Recommend 2,000 Calories Per Day?And this:The "Women Burn 2000 Calories A Day" Myth Debunked

I’d love to answer this question for you, but unfortunately, the statistics in your link don’t bear out to the actual facts, something the CDC has only recently admitted to. The CDC Quietly Admits It Screwed Up Counting Opioid PillsSo much hype has been put out about this opioid crisis, by the CDC, government, DEA, and countless news agencies, that they never bothered to distinguish, or share with anyone, what each addict actually overdoses on. They didn’t bother to distinguish between non-pharmaceutical opioids (illegal), or the pharmaceutical ones (legal), nor whether the individual mixed legal opioids with illegal ones, whether alcohol was involved in that mix, or if other drugs like benzodiazepines, gabapentin, and any number of other prescription drugs might be included in there as well.As a result of this fudging of numbers, be it as a result of laziness, inconvenience, profits, or who knows what else, on the part of those in our government, Department of Health & Human Services, DEA, certain individuals, etc., Joe Public has been fed nothing but a regular diet of hysteria and misinformation. As a result of this, years mind you, the real costs to countless patients, have yet to be reported on, factored in, or to receive even an iota of the compassion, sympathy, funding, or focus that those who suffer from addiction have received.News agencies, doctors, and other federal regulators and agencies, have done nothing but report, at a frantic rate mind you, that there’s a crisis, and addicts are dying every day. What has that resulted in, what are the only measures being taken to quell this crisis, is mandating that doctors stop prescribing opioids to chronic pain patients, even those suffering through cancer, or they’ll lose their licenses, and possibly be arrested. Is Joe Public concerned about these patients, obviously not, otherwise they’d be an outcry, demanding to know why the government, and DEA, even have a say in what goes on between a patient and their doctor, or how the CDC can possibly mandate draconian policies to the AMA, without ever considering how these policies will, and continue to, affect patients suffering in pain.Since the Centers for Disease Control and Prevention published its guideline for prescribing opioids for chronic pain in March 2016, pain patients have experienced increasing difficulty getting needed opioid medication due to denials by pharmacists and insurance providers.More troubling are recent press reports, blog posts, and journal articles that describe patients being refused necessary medication or those dismissed by their treating physicians, who practice in fear of regulatory reprisal. At the interim meeting, the AMA responded to these developments, passing several resolutionsagainst the rash of laws and mandatory policies that limit or prevent patient access to opioid painkillers.Related: Tapered to zero: In radical move, Oregon’s Medicaid program weighs cutting off chronic pain patients from opioidsThe CDC designed its guideline as non-mandatory guidance for primary care physicians. But legislators, pharmacy chains, insurers, and others have seized on certain parts of its dosage and supply recommendations and translated them into blanket limits in law and mandatory policy. Today, in more than half of U.S. states, patients in acute pain from surgery or an injury may not by law fill an opioid prescription for more than three to seven days, regardless of the severity of their surgery or injury.How the CDC's opioid prescribing guideline is harming pain patients - STATThe opinion now in the minds of the general public, is that all opioids are bad, and that we’ve got to stop the opioid crisis, even if it means stopping doctors from prescribing pharmaceutical opioids to all chronic pain patients.Because of this thinking, the pendulum has swung the other way, so now there needs to be a separation between what’s going on the street, and illegal/illicit drugs, because that’s tragic, and to what’s going on with chronic pain patients and their access to opioids, which is equally tragic, especially when you factor in the number of chronic pain patients committing suicide, and those who are losing their livelihood, because they can no longer work.Two very different issues, requiring very different approaches, but nowhere in there should patients be made to suffer, while the FDA, CDC, DEA, AMA, and whatever other governmental agency waits to decide on what they’re going to do to address them.Thanks to the opioid crisis in the United States, Canada, and the regulatory bodies up here, have had their realities twisted, much to the detriment of chronic patients.North of the border, many people believe that the opioid crisis is playing out the same as in the U.S. That's because Canadians watch CNN and read American newspapers, and the effect has been for important regional variations in the crisis to be glossed over and confused. In response to media reports that focus on the U.S., Canadian doctors have received increasingly intense criticism and pressure to scale back opioid prescriptions. This has left patients like Reid—people with real pain who just want to get through a hard day’s work—with nowhere to turn for the medicine they need, except maybe to the streets.This patient profile has become so common that in the United States that it has a name: “opioid refugee”.Unintended consequencesThere might be no one in B.C. with a better sense of the crisis here than the province’s chief coroner, Lisa Lapointe. She told the Straight that although the overdose epidemic in the United States is driven by a combination of prescription opioids like OxyContin plus heroin, and, more recently, fentanyl, B.C’s opioid crisis is largely the result of just one drug: fentanyl.According to the B.C. Coroners Service, illicit-drug overdose deaths in B.C. increased from 333 in 2013 to 518 two years later, then to 1,436 in 2017. The portion of these deaths that involved fentanyl during those years increased from 15 percent to 29 percent—then to 83 percent last year.“It’s really clear that fentanyl is the root of the problem,” Lapointe said.She noted that B.C. does not have statistics on fentanyl-associated deaths that also look back at a deceased individual’s history with prescription opioids (although some U.S. jurisdictions do and have used that information to establish a link). But Lapointe said her coroners are on the ground, interviewing the families of drug-overdose victims, and what they’re hearing is that a majority of deaths in B.C. involve people who struggled with addictions to illicit drugs for some time.Dr. Patricia Daly is chief medical health officer and vice president of public health for Vancouver Coastal Health and executive director of the province’s new Overdose Emergency Response Centre. In a separate interview, she emphasized the same point as the coroner: “There is not a causal link between prescription opioids and the opioid crisis here,” Daly said.She expressed concern for a false perception that unfairly paints B.C. doctors as reckless.“I think it arises from a lot of media reports from the U.S., where there are communities where there was significant overprescribing of oral-prescription opioids,” Daly said. “Most of our crisis here concerns people who have a long-term heroin addiction and the contamination of the heroin supply.”Opioid refugees: How the fentanyl crisis led to a backlash against doctors that's leaving people in painSo, as a chronic pain patient in Canada, this opioid crisis has had a direct effect on me, namely by having my doctor taper, and then cut me off of all my opioid medication 2 years ago. As a result of that, my livelihood has been directly affected, as has my health. My activity level for the past 2 years has been markedly decreased, so much so, that my weight has gone up, my cholesterol has gone up, as has my blood pressure, and as it turns out, even my blood sugar, but hey, pump me full of medications to control all that, forget about the intolerable side effects, rather than prescribing me something that can enable me to stay healthy on my own. I’ve refused the statins, any sort of medication for my Type 2 diabetes, and I will see how things go. Let’s hope I don’t pop a blood vessel in my head, or have a heartache any time soon, or I’ll miss summer.Has this opioid crisis affected me in other ways, yes, people I know who have been cut off of opioids, have ended their lives, and no one, not one person in any regulatory body or government agency, has even batted an eye lid over it. A dear friends husband had his opioids cut drastically down to meet with the new guidelines, and all I can say about him, is he’s barely a ghost of his former self.As doctors taper or end opioid prescriptions, many patients driven to despair, suicideThey said patients are living with unnecessary pain, have turned to illegal drugs, sometimes with fatal consequences, and committed suicide.Opinion: There’s a chronic pain crisis in Canada, and governments must address itOpioid-Related Suicides and Overdose Deaths Have More Than Doubled Since 2000I’ll stop here or this will turn into a bloody novel, but you get my point.