List of chronic diseases linked to infectious pathogens
Introduction[edit | edit source]
Many chronic diseases are linked to infectious pathogens (meaning the pathogens are found in patients with the disease much more frequently than in healthy controls).[1][2] When a pathogen such as a virus, bacterium, fungus or protozoan is linked to a disease, researchers will start to investigate whether the pathogen might be the cause the disease, or might be playing a causal role.
There are several explanations for why a pathogen is found associated with a disease:
- The pathogen is an "innocent bystander" that plays no causal role in the disease, but is more prevalent in patients with the disease (for example because the disease compromises the immune response).
- The pathogen increases the risk of getting the disease, but does not actually cause the disease. For example, genital herpes increases the risk of catching HIV, but does not cause AIDS.[3]
- The pathogen causes the disease, but only combined with other causal factors (such as host genetic factors, or toxic exposure).
- The pathogen is a singular cause of the disease.
Determining whether a pathogen plays a causal role in a given chronic disease is difficult for the following reasons:
- The time between contracting the infectious pathogen and the appearance of the first chronic disease symptoms can be lengthy, sometimes decades.
- An infection may be asymptomatic when first contracted and go unnoticed.
- An infectious pathogen may not cause its associated disease in every person.
- Only specific strains of a pathogen may be linked to a disease; other strains may not be so harmful (for example, multiple sclerosis is strongly associated with certain genetic variants of Epstein-Barr virus).[4]
- A given disease may be precipitated by more than one pathogen.
- A pathogen may precipitate the disease only in combination with one or more other causal factors.
- A pathogenic microbe may only precipitate the disease when it breaches into and infects specific organs. When it infects different organs, a different disease (or no disease) may be precipitated.
- Some pathogens are not easily detectable, and it is difficult to link hard-to-detect pathogens to a disease.
- For obvious ethical reasons, you cannot inoculate pathogenic microbes into humans to see if they do cause the disease.
- A pathogen may cause disease by indirectly, such as via autoimmune processes induced by the pathogen.
In spite of the difficulties in obtaining proof of causality, investigation into the link between pathogenic microbes and chronic disease is ongoing, and there is a large volume of published studies which demonstrate these associations.
One champion of the theory that pathogens are the likely cause of many chronic diseases is evolutionary biologist Professor Paul W. Ewald, who is one of an increasing number of researchers who believe that many chronic diseases of presently unknown etiology will probably turn out to be caused by persistent low-level microbial infections.[5][6]
Professor Ewald supports his thesis with an argument from evolutionary biology, explaining that "chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them".[7] In other words, a disease-causing gene which reduces an animal's survival and its creation of offspring will tend to eliminate itself over a number of generations. Therefore such genetic diseases are self-extinguishing.
Professor Ewald explains that the only genetic diseases which are likely to persist are those that provide a compensating benefit. For example, genes that encode for sickle cell anemia disease are maintained and persist down the generations, as these genes also protect against malaria, which kills millions worldwide each year.
One large meta-analysis found that the vast majority of diseases have a very small genetic contribution of only 5% to 10% at most. Though notable exceptions include Crohn's disease, celiac disease and macular degeneration, which have a genetic contribution of about 40% to 50%.[8]
Infectious pathogens are one of several potential causes of disease; other causal factors include environmental toxins (naturally-occurring and man-made), radiation, genetics, epigenetics, events during pregnancy, stress, diet and lifestyle factors. More than one causal factor may be involved in the development of a disease, and an illness may only manifest when several causal factors are present at the same time.
For example, in a mouse model, Crohn's disease can be precipitated by a norovirus, but only when both a specific gene variant is present and a certain toxin has damaged the gut.[9] Thus a pathogen's ability to cause a disease may be contingent upon several other causal factors.
Pathogen-associated diseases include many of the most common and costly chronic illnesses.[10] About 70% of all deaths in the United States result from chronic diseases, with the treatment of chronic diseases accounting for 75% of all US healthcare costs.[11]
List of Diseases Associated With Infectious Pathogens[edit | edit source]
In the following list of diseases linked to infectious pathogens, there is a good possibility that the pathogens might cause the disease, but further research is need to work out whether these pathogens do play a causal role.
This list covers some of the most common human diseases linked to infectious pathogens, but it is not intended to be a comprehensive list of pathogen-associated diseases.
Disease | Pathogens Linked to the Disease |
Alzheimer's disease | Alzheimer's disease is associated with the bacteria Porphyromonas gingivalis,[12] Chlamydia pneumoniae[13] and Helicobacter pylori,[14] and with the protozoan parasite Toxoplasma gondii.[15] Herpes simplex virus 1 is associated with Alzheimer's disease in individuals who possess the APOE-4 form of the APOE gene (APOE-4 enables the herpes virus to enter the brain).[16] |
Amyotrophic lateral sclerosis | Amyotrophic lateral sclerosis, the most common of five forms of motor neuron disease, is associated with echovirus (an enterovirus) infection of the central nervous system,[19] and with retrovirus[20] activity (it is not known whether this retrovirus activity arises from a human endogenous retrovirus, or from an exogenous retrovirus). |
Anorexia nervosa | Infection with Borrelia[21] species bacteria is associated with anorexia nervosa. In rare cases, anorexia nervosa may arise after infection with Streptococcus[22] species bacteria. Anorexia (which is distinct from anorexia nervosa) is associated with the protozoan parasite Dientamoeba fragilis.[23] |
Anxiety disorder | Anxiety is associated with cytomegalovirus,[24][25] and the bacterium Helicobacter pylori.[26] Anxiety is associated with Toxoplasma gondii,[27] or at least associated with higher levels of IgG antibodies to this parasite.[28] Anxiety as a personality trait is associated with higher antibody titers to Epstein-Barr virus.[29] |
Asthma | Asthma is associated with rhinovirus, human respiratory syncytial virus,[30] and the bacterium Chlamydia pneumoniae.[31] Chlamydia pneumoniae is particularly associated with adult-onset asthma.[32] |
Atherosclerosis | Atherosclerosis is associated with cytomegalovirus,[33] and the bacteria Helicobacter pylori[34] and Chlamydia pneumoniae.[35] |
Attention deficit hyperactivity disorder | Attention deficit hyperactivity disorder (ADHD) and learning disorders are associated with the bacteria Borrelia burgdorferi and Streptococcus, and with HIV and enterovirus 71. Febrile seizures due to human herpesvirus 6 or influenza A are a risk factor for ADHD. Viral infections during pregnancy, at birth, and in early childhood are risk factors for ADHD.[36] |
Autism | Autism is linked to congenital infection with rubella virus or cytomegalovirus.[37][38] Clostridia bacterial species are associated with autism (these bacteria are present in greater numbers in the guts of autistic children).[39] |
Autoimmune diseases | Autoimmune diseases are strongly associated with enteroviruses such as Coxsackie B virus.[40] Autoimmune diseases are also associated with Epstein-Barr virus,[41] cytomegalovirus,[42] parvovirus B19,[43] and HIV,[44] and the bacterium Mycobacterium tuberculosis.[45] Autoimmune thyroid disease is associated with Epstein-Barr virus,[46] and Helicobacter pylori.[47] |
Bipolar disorder | Bipolar disorder is associated with bornavirus,[48] and with Borrelia species bacteria.[49] The level of cognitive impairment in bipolar disorder is associated with herpes simplex virus 1.[50] |
Cancer |
Some estimates currently attribute 15% to 20% of all cancers to infectious pathogen causes.[51][52] In future, this percentage may be revised upwards if the pathogens currently associated with cancers (such as those listed below) are proven to actually cause those cancers. (For the sake of completeness, some pathogens proven to cause cancers are included in the list, in addition to pathogens that have been linked to cancers, but are not yet proven to cause the cancer.) Adrenal tumor is associated with BK virus and simian virus 40.[53] |
Chronic fatigue syndrome | Chronic fatigue syndrome (also known as myalgic encephalomyelitis) is associated with enteroviruses (such as Coxsackie B virus),[85][86] partial reactivation of Epstein-Barr virus,[87] human herpesvirus 6 variant A,[88] human herpesvirus 7,[89] and parvovirus B19.[90][91] The intracellular bacterium Chlamydia pneumoniae[92] is also linked chronic fatigue syndrome. |
Chronic myocarditis | Chronic myocarditis is associated with the enterovirus coxsackievirus B.[93] |
Chronic obstructive pulmonary disease | Chronic obstructive pulmonary disease (which includes both chronic bronchitis and emphysema) is associated with Chlamydia pneumoniae[94] and Epstein-Barr virus.[95] |
Crohn's disease | Crohn's disease is linked to a thin layer of infection on the intestinal lining with the fungus Candida tropicalis, in tandem with the bacteria Escherichia coli and Serratia marcescens.[96] One study found ileocecal Crohn's disease is associated with viral species from the enterovirus genus (but note that all the study cohort with ileocecal Crohn's disease had disease-associated mutations in either their NOD2 or ATG16L1 genes).[97] Crohn's disease is associated with Mycobacterium avium subspecies paratuberculosis.[98] In a murine model, Crohn's disease is precipitated by the norovirus CR6 strain,[99][100] but only in combination with a variant of the Crohn's susceptibility gene ATG16L1, and chemical toxic damage to the gut. In other words, in this mouse model, Crohn's is precipitated only when these three causal factors (virus, gene, and toxin) act in combination. |
Coronary heart disease | Coronary heart disease is associated with herpes simplex virus 1 and the bacterium Chlamydia pneumoniae.[101] |
Dementia | Dementia is associated with herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, West Nile virus, bornavirus, and HIV. Dementia is also associated with the helminth Taenia solium (pork tapeworm), and with Borrelia[102] species bacteria. |
Depression |
Depression is associated with cytomegalovirus[103] and West Nile virus,[104] and the protozoan parasite Toxoplasma gondii.[105] It is thought that depression may be precipitated by the effect of immune signals (such as pro-inflammatory cytokines) reaching the brain from infections located in the peripheries of the body.[106][107] Major depressive disorder is associated with bornavirus,[108] as well as Bartonella[109] and Borrelia[110] species bacteria. |
Diabetes mellitus type 1 | Type 1 diabetes is associated with viral species from the enterovirus genus,[112][113] such as echovirus 4,[114] echovirus 16,[115] and Coxsackie B4 virus.[116][117] Coxsackie B virus can infect and destroy the insulin-producing beta cells in the pancreas, and also damage these cells via indirect autoimmune mechanisms).[118] Coxsackie B1 virus is associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes, whereas Coxsackie B3 and B6 viruses is associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus).[119] |
Diabetes mellitus type 2 | Type 2 diabetes is associated with cytomegalovirus,[121] hepatitis C virus,[122] enteroviruses[123] and Ljungan virus,[124] In rabbits, exposure to toxic shock syndrome toxin-1 from a Staphylococcus aureus infection leads to impaired glucose tolerance, the hallmark of type 2 diabetes in humans.[125] |
Dilated cardiomyopathy | Dilated cardiomyopathy is associated with enteroviruses such as Coxsackie B virus.[126] |
Epilepsy | Mesial temporal lobe epilepsy is associated with infection by the B variant of human herpesvirus 6 virus (HHV-6B) of the astrocyte cells of the brain.[127][128] Epilepsy is associated with human papillomavirus infection of the brain.[129] |
Guillain-Barré syndrome | Guillain-Barré syndrome is associated with the bacterium Campylobacter jejuni,[130] and with the viruses cytomegalovirus[131] and enterovirus.[132] |
Hypertension | Hypertension (high blood pressure) is associated with enteroviruses such as coxsackievirus B5 and echovirus.[133] |
Infertility | Infertility is associated with an infection of the endometrium with the A variant of human herpesvirus 6 virus (HHV-6A ).[134] |
Interstitial cystitis | The ulcerative form of interstitial cystitis is associated with an infection of the bladder tissues with polyomavirus, and in particular BK virus.[135] Interstitial cystitis is associated with an infection of the bladder tissues with Epstein-Barr virus.[136] |
Irritable bowel syndrome | Irritable bowel syndrome (IBS) is associated with the bacteria enteroaggregative Escherichia coli[137] and Mycobacterium avium subspecies paratuberculosis,[138] the protozoan parasite Giardia lamblia,[139] and pathogenic strains of the protozoan parasite Blastocystis hominis.[140] Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis.[141] |
Low back pain | Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Propionibacterium acnes.[142][143] |
Lupus | Lupus is associated with the viruses parvovirus B19,[144] Epstein-Barr virus,[145] and cytomegalovirus.[146] |
Macular degeneration | Neovascular (wet) macular degeneration is associated with high titers of cytomegalovirus.[147][148] |
Metabolic syndrome | Metabolic syndrome is associated with the bacteria Chlamydia pneumoniae[149] and Helicobacter pylori, as well as the viruses cytomegalovirus and herpes simplex virus 1.[150] |
Multiple sclerosis | Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus[151] (and strongly associated with certain genetic variants of this virus)[152] which is found in the brain tissues of most ME patients,[153] human herpesvirus 6,[154] human herpesvirus 6 variant A,[155] varicella zoster virus,[156] and the bacterium Chlamydia pneumoniae.[157] |
Myocardial infarction | Myocardial infarction (heart attack) is associated with Chlamydia pneumoniae,[158] cytomegalovirus[159] and Coxsackie B virus (an enterovirus).[160] Coxsackie B virus and enterovirus are also associated with sudden unexpected death due to myocarditis.[161] An autopsy study found 40% of those who died of sudden heart attack had enterovirus markers in their endomyocardial tissues, compared to 8% in controls.[162] |
Myopia | Myopia (short-sightedness) is associated with childhood febrile illnesses of measles, rubella, pertussis and mumps.[163] |
Obesity |
Obesity is associated with adenovirus 36, which is found in 30% of obese people, but only in 11% of non-obese people.[164][165] It has further been demonstrated that animals experimentally infected with adenovirus 36 (and likewise adenovirus 5 or adenovirus 37) will develop increased obesity.[166] And it is known adenovirus 36 causes a proliferation of fat cells (adipocytes).[167] |
Obsessive-compulsive disorder | Obsessive-compulsive disorder is associated with Streptococcus[171] and Borrelia[172] species bacteria. |
Panic disorder | Panic disorder is associated with Borrelia[173] and Bartonella[174] species bacteria.[175] |
Parkinson's disease | Parkinson's disease is associated with enterovirus,[176] influenza A virus,[177] as well as the protozoan parasite Toxoplasma gondii.[178] |
Psoriasis | Psoriasis is associated with a Helicobacter pylori trigger.[179] |
Rheumatoid arthritis | Rheumatoid arthritis is linked to the bacterium Porphyromonas gingivalis,[180] and the bacterium Proteus mirabilis.[181] Rheumatoid arthritis is associated with parvovirus B19.[182] Antibodies to Borrelia outer surface protein A are associated with rheumatoid arthritis.[183] |
Sarcoidosis | Sarcoidosis is associated with Mycobacteria[184] species and the bacterium Helicobacter pylori.[185] |
Schizophrenia | Schizophrenia is linked to an aberrant immune response to Epstein-Barr virus.[186] Schizophrenia is associated with bornavirus,[187] the bacterium Chlamydia trachomatis,[188] as well as Borrelia species bacteria.[189]
Schizophrenia is also linked to neonatal infection with Coxsackie B virus (an enterovirus), which one study found carries an increased risk of adult onset schizophrenia.[190] Prenatal exposure to influenza virus in the first trimester of pregnancy increases the risk of schizophrenia by 7-fold.[191] |
Sjögren's syndrome | Primary Sjögren's syndrome is associated with the enterovirus Coxsackie B virus.[192] |
Stroke | Persistent enterovirus infection (Coxsackie B virus or echovirus) is linked to the development of acute stroke.[193] Stroke is associated with the bacteria Chlamydia pneumoniae,[194] Helicobacter pylori,[195] Mycobacterium tuberculosis,[196] and Mycoplasma pneumoniae,[197] as well as the virus varicella zoster virus[198] and the fungus Histoplasma.[199] |
Tourette syndrome | Tourette syndrome is associated with the bacterium Streptococcus.[200] Aggravating or contributory microbes in Tourette's may include the bacteria Mycoplasma pneumoniae,[201] Chlamydia pneumoniae, Chlamydia trachomatis, and the protozoan parasite Toxoplasma gondii.[202] |
Vasculitis | Vasculitis is associated with HIV, parvovirus B19,[203] and hepatitis B virus. The hepatitis C virus is an established and proven cause of vasculitis. |
Further Reading[edit | edit source]
Popular Science Articles and Books[edit | edit source]
- Plague Time: The New Germ Theory of Disease by Paul W. Ewald, Anchor, 2002
- Interview With Evolutionary Biologist Paul Ewald by Amy Proal, Feb 2008
- Stealth Germs in Your Body by Erno Daniel, Sterling Publishing Company, 2008
- Infections can affect your IQ, Science Daily, May 2015
- A New Germ Theory: Part 1 by Judith Hooper, The Atlantic Monthly Magazine, Feb 1999
- A New Germ Theory: Part 2: Antibiotics Against Heart Disease?
- A New Germ Theory: Part 3: The Great Synthesizer
- The Big Idea That Might Beat Cancer and Cut Health-Care Costs by 80 Percent by Andrew Grant, Discover Magazine, Sept 2009
- The Infection Connection by Harriet Washington, Psychology Today, July 1999
- Can Infections Result in Mental Illness? by Dr Jeff Szymanski, Psychology Today, Feb 2012
- Do Germs Cause Cancer? by Philip E. Ross, Forbes, Nov 1999
- The Emerging Role Of Infection In Alzheimer's Disease, Science Daily, May 2008
- People Hospitalized For Infections Are 62% More Likely To Develop A Mood Disorder by Anoopa Singh, Medical Daily, June 2013
- Chronic Infections Linked with Memory Problems Later in Life, by Christopher Wanjek, Live Science, Feb 2014
Academic Articles[edit | edit source]
- Toward a unified, evolutionary theory of cancer, presentation by Paul Ewald.
- Infection Eyed as Culprit In Chronic Disease, Susan J. Landers, American Medical News, Jul 2004
- Emerging Infectious Determinants of Chronic Diseases, Siobhán M O'Connor, Christopher E Taylor, James M Hughes, Emerging Infectious Diseases, 2006
- The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary, Stacey L Knobler, Siobhán O'Connor, Stanley M Lemon, et al, Forum on Microbial Threats, 2004
- Infectious Causes of Chronic Inflammatory Diseases and Cancer, Gail H. Cassell, Lilly Research Laboratories, 2004
- Causal Inference Regarding Infectious Aetiology of Chronic Conditions: A Systematic Review, Sofia Orrskog, Emma Medin, Svetla Tsolova, Jan C Semenza, PLoS One, July 2013
- Equations that Spell Disaster: Researchers are Pinpointing the Factors that Combine to Produce Complex Diseases, Cristina Luiggi, The Scientist, Dec 2010
- The infection connection: Helicobacter pylori is more than just the cause of gastric ulcers: it offers an unprecedented opportunity to study changes in human micro ecology and the nature of chronic disease, Caroline Hadley, EMBO Reports, May 2006
- Evidence That Chronic Disease is Caused by Pathogens Autoimmunity Research Foundation, 2012
- Challenging the Primacy of Genetics in Late-Onset Alzheimer Disease, Brian J. Balin, Alzheimer Research Forum, Dec 2005
- Can an Infection Suddenly Cause OCD?, Jeff Szymanski, Harvard Health Blog, Feb 2012
- Mechanisms of Viral Pathogenicity, Gerald Tritz (Lecture Notes)
- Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1, Garth L. Nicolson and Jörg Haier, British Journal of Medical Practitioners, Dec 2009
- Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 2, Garth L. Nicolson and Jörg Haier, British Journal of Medical Practitioners, Mar 2010
References[edit | edit source]
- ↑ Threats, Institute of Medicine (US) Forum on Microbial; Knobler, Stacey L.; O'Connor, Siobhán; Lemon, Stanley M.; Najafi, Marjan (2004). Preface. National Academies Press (US).
- ↑ O'Connor, Siobhán M.; Taylor, Christopher E.; Hughes, James M. (2006-07). "Emerging infectious determinants of chronic diseases". Emerging Infectious Diseases. 12 (7): 1051–1057. doi:10.3201/eid1207.060037. ISSN 1080-6040. PMC 3291059. PMID 16836820. Check date values in:
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(help) - ↑ Freeman, Esther E.; Weiss, Helen A.; Glynn, Judith R.; Cross, Pamela L.; Whitworth, James A.; Hayes, Richard J. (January 2, 2006). "Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies". AIDS (London, England). 20 (1): 73–83. doi:10.1097/01.aids.0000198081.09337.a7. ISSN 0269-9370. PMID 16327322.
- ↑ Mechelli, Rosella; Manzari, Caterina; Policano, Claudia; Annese, Anita; Picardi, Ernesto; Umeton, Renato; Fornasiero, Arianna; D'Erchia, Anna Maria; Buscarinu, Maria Chiara (March 31, 2015). "Epstein-Barr virus genetic variants are associated with multiple sclerosis". Neurology. 84 (13): 1362–1368. doi:10.1212/WNL.0000000000001420. ISSN 1526-632X. PMC 4388746. PMID 25740864.
- ↑ Ewald, Paul W. (2002). Plague Time: The New Germ Theory of Disease. Anchor Books. ISBN 978-0-385-72184-4.
- ↑ Cochran, G. M.; Ewald, P. W.; Cochran, K. D. (2000). "Infectious causation of disease: an evolutionary perspective". Perspectives in Biology and Medicine. 43 (3): 406–448. doi:10.1353/pbm.2000.0016. ISSN 0031-5982. PMID 10893730.
- ↑ Ewald, Paul W. (2002). Plague Time: The New Germ Theory of Disease. Anchor Books. ISBN 978-0-385-72184-4.
- ↑ Patron, Jonas; Serra-Cayuela, Arnau; Han, Beomsoo; Li, Carin; Wishart, David Scott (2019). "Assessing the performance of genome-wide association studies for predicting disease risk". PloS One. 14 (12): e0220215. doi:10.1371/journal.pone.0220215. ISSN 1932-6203. PMC 6894795. PMID 31805043.
- ↑ Cadwell, Ken; Patel, Khushbu K.; Maloney, Nicole S.; Liu, Ta-Chiang; Ng, Aylwin C. Y.; Storer, Chad E.; Head, Richard D.; Xavier, Ramnik; Stappenbeck, Thaddeus S. (June 25, 2010). "Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine". Cell. 141 (7): 1135–1145. doi:10.1016/j.cell.2010.05.009. ISSN 1097-4172. PMC 2908380. PMID 20602997.
- ↑ Kockaya, Guvenc; Wertheimer, Albert (October 26, 2010). "What are the top most costly diseases for USA? The alignment of burden of illness with prevention and screening expenditures". Health. 2 (10): 1174–1178. doi:10.4236/health.2010.210172.
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(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/21278394. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/11919208. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/22009989. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18990738. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20704754. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20167111. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20539059. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19017178. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15788203. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19339934. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15907199. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7510038. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20501758. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20699096. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18520265. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15202523. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/445337. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19840258. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/21206097. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/26699530. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/30508006/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12873884. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/24629358/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/26171139/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12574230. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17872383. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19828908. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23155374. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7650209. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17276369. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18277075. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/11911112. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/10476765. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18357775. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/9129592. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18287127. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/27651359. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23804031. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20857526. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20602997. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ http://www.the-scientist.com/?articles.view/articleNo/29384/title/Equations-that-Spell-Disaster/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/10645920. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7943444. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17703915. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17552106. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15018628. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18073775. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19389580. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12857781. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18092060. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7943444. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/8308519. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/21292721. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19266182. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/11905853. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12898016. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18951821. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17360338. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15236922. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23974921. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23852688. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/16108236. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19340895. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19266182. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19780970. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/25714716. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12015932. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17535102. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/25840441. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23280839. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/24000328/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/8797462. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/10815319. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/24940338/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/27367597. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/26325074/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/29653163. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17359324. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17913930. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19821794. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19393117. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15258093. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23404353. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/23397187. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18549931. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/16896283. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/9272302. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15364212. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/22570607. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20016424. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17140429. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/16927411. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/25740864. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/29394264/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20926836. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/32038605. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18306233. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12606878. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15791511. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/14618212. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18061067. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/22966951. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18061067. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/26846593. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15611785. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19593728. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19960394. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/26184280/. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17420782. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17908526. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17183309. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15995031. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7943444. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7943444. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18092060. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18092060. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/29899977. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/10507986. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20350582. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17642857. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/27605245. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17206398. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18549931. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/17881508. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/16926652. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15068230. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/30462333. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12857781. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20602604. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/7943444. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/9279617. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15289276. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15457458. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/28511156. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/9472881. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/12063957. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/20035070. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/16148858. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19815828. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18755412. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15995031. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/15590039. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/19890596. Cite journal requires
|journal=
(help); Missing or empty|title=
(help) - ↑ https://pubmed.ncbi.nlm.nih.gov/18549931. Cite journal requires
|journal=
(help); Missing or empty|title=
(help)