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Book ; Online ; E-Book: Overtraining syndrome in athletes

Cadegiani, Flavio

a comprehensive review and novel perspectives

2020

Abstract: This book discusses major changes in our understanding of the most prevalent non-orthopedic, sports-related condition – overtraining syndrome (OTS), arguing that it should be considered as the manifestation of burnout in athletes, rather than simply the ... ...

Author's details	Flavio Cadegiani
Abstract	This book discusses major changes in our understanding of the most prevalent non-orthopedic, sports-related condition – overtraining syndrome (OTS), arguing that it should be considered as the manifestation of burnout in athletes, rather than simply the result of excessive training. While the chronic adaptations of the cardiovascular and musculoskeletal systems to exercise are well documented, those of the endocrine system are less well known, and adaptations of the hormonal ranges for athletes are yet to be determined. There is also a lack of standardized diagnostic criteria, consistent assessment methods and biomarkers. This book offers a systematic review of the hormonal aspects of overtraining syndrome, and a comparison with sports-related syndromes triggered by chronic deprivation of different sorts, including the female athlete triad (and its derivative, RED-S) and burnout syndrome of the athlete (BSA). It demonstrates that these conditions, although studied separately from each other, may all be different manifestations of the same condition, leading to ‘maladaptive’ (dysfunctional forced adaptations to a hostile environment) changes in response to chronic depletion of energy and mechanisms of repair, causing multiple dysfunctions. The author proposes that OTS/Paradoxical Deconditioning Syndrome (PDS), RED-S/TRIAD and BSA are parts of a same condition, or at least a group of similar conditions. Further, the book offers a chronological overview of OTS, based on preliminary research. Given its broad scope, this concise reference book will appeal to a range of health professionals. It allows readers, including those without a strong academic background, to gain a systematic understanding of OTS.
Keywords	Sports medicine
Subject code	617.1027
Language	English
Size	1 online resource (XXIV, 333 p. 67 illus., 28 illus. in color.)
Edition	1st ed. 2020.
Publisher	Springer
Publishing place	Cham, Switzerland
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	3-030-52628-3 ; 3-030-52627-5 ; 978-3-030-52628-3 ; 978-3-030-52627-6
DOI	10.1007/978-3-030-52628-3
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Catecholamines Are the Key Trigger of COVID-19 mRNA Vaccine-Induced Myocarditis: A Compelling Hypothesis Supported by Epidemiological, Anatomopathological, Molecular, and Physiological Findings.

Cadegiani, Flavio A

Cureus

2022 Volume 14, Issue 8, Page(s) e27883

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced myocarditis is a rare but well-documented complication in young males. The increased incidence of sudden death among athletes following vaccination has been reported and ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced myocarditis is a rare but well-documented complication in young males. The increased incidence of sudden death among athletes following vaccination has been reported and requires further investigation. Whether the risk of myocarditis, a known major cause of sudden death in young male athletes, also increases after coronavirus disease 2019 (COVID-19) infection is unknown. The severity and implications of these critical adverse effects require a thorough analysis to elucidate their key triggering mechanisms. The present review aimed to evaluate whether there is a justification to hypothesize that catecholamines in a "hypercatecholaminergic" state are the key trigger of SARS-CoV-2 mRNA vaccine-induced myocarditis and related outcomes and whether similar risks are also present following COVID-19 infection. A thorough, structured scoping review of the literature was performed to build the hypothesis through three pillars: detection of myocarditis risk, potential alterations and abnormalities identified after SARS-CoV-2 mRNA vaccination or COVID-19 infection and consequent events, and physiological characteristics of the most affected population. The following terms were searched in indexed and non-indexed peer review articles and recent preprints (<12 months): agent, "SARS-CoV-2" or "COVID-19"; event, "myocarditis" or "sudden death(s)" or "myocarditis+sudden death(s)" or "cardiac event(s)"; underlying cause, "mRNA" or "spike protein" or "infection" or "vaccine"; proposed trigger, "catecholamine(s)" or "adrenaline" or "epinephrine" or "noradrenaline" or "norepinephrine" or "testosterone"; and affected population, "young male(s)" or "athlete(s)." The rationale and data that supported the hypothesis were as follows: SARS-CoV-2 mRNA vaccine-induced myocarditis primarily affected young males, while the risk was not observed following COVID-19 infection; independent autopsies or biopsies of patients who presented post-SARS-CoV-2 mRNA vaccine myocarditis in different geographical regions enabled the conclusion that a primary hypercatecholaminergic state was the key trigger of these events; SARS-CoV-2 mRNA was densely present, and SARS-CoV-2 spike protein was progressively produced in adrenal medulla chromaffin cells, which are responsible for catecholamine production; the dihydroxyphenylalanine decarboxylase enzyme that converts dopamine into noradrenaline was overexpressed in the presence of SARS-CoV-2 mRNA, leading to enhanced noradrenaline activity; catecholamine responses were physiologically higher in young adults and males than in other populations; catecholamine responses and resting catecholamine production were higher in male athletes than in non-athletes; catecholamine responses to stress and its sensitivity were enhanced in the presence of androgens; and catecholamine expressions in young male athletes were already high at baseline, were higher following vaccination, and were higher than those in non-vaccinated athletes. The epidemiological, autopsy, molecular, and physiological findings unanimously and strongly suggest that a hypercatecholaminergic state is the critical trigger of the rare cases of myocarditis due to components from SARS-CoV-2, potentially increasing sudden deaths among elite male athletes.
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.27883
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Article ; Online: Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension?

Cadegiani, Flávio A

American journal of physiology. Endocrinology and metabolism

2020 Volume 318, Issue 5, Page(s) E587–E588

MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Humans ; Hypertension/complications ; Pandemics ; Peptidyl-Dipeptidase A/blood ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Respiratory Distress Syndrome/drug therapy ; Respiratory Distress Syndrome/virology ; SARS-CoV-2 ; Spironolactone/therapeutic use
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Spironolactone (27O7W4T232) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-04-28
Publishing country	United States
Document type	Letter
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00136.2020
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Article ; Online: Repurposing existing drugs for COVID-19: an endocrinology perspective.

Cadegiani, Flavio A

BMC endocrine disorders

2020 Volume 20, Issue 1, Page(s) 149

Abstract: Background: Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry ... ...

Abstract	Background: Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text: While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion: While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Betacoronavirus/drug effects ; Betacoronavirus/isolation & purification ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Coronavirus Infections/virology ; Dexamethasone/therapeutic use ; Drug Repositioning/methods ; Endocrine System ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/virology ; Prognosis ; SARS-CoV-2
Chemical Substances	Anti-Inflammatory Agents ; Dexamethasone (7S5I7G3JQL)
Keywords	covid19
Language	English
Publishing date	2020-09-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2091323-0
ISSN	1472-6823 ; 1472-6823
ISSN (online)	1472-6823
ISSN	1472-6823
DOI	10.1186/s12902-020-00626-0
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Article: Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension?

Cadegiani, Flávio A

Am J Physiol Endocrinol Metab

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #66476
Database	COVID19

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Article ; Online: Nonpharmacological Interventions for the Management of Testosterone and Sperm Parameters: A Scoping Review.

Santos, Heitor O / Cadegiani, Flávio A / Forbes, Scott C

Clinical therapeutics

2022 Volume 44, Issue 8, Page(s) 1129–1149

Abstract: Purpose: Testosterone replacement and associated pharmacologic agents are effective strategies to treat male hypogonadism; however, nutraceutical agents and lifestyle modification approaches have gained medical interest. The purpose of this scoping ... ...

Abstract	Purpose: Testosterone replacement and associated pharmacologic agents are effective strategies to treat male hypogonadism; however, nutraceutical agents and lifestyle modification approaches have gained medical interest. The purpose of this scoping review is to highlight the evidence (or lack thereof) of nutraceuticals and lifestyle modification approaches in the management of testosterone levels and sperm parameters. Methods: A scoping review of nonpharmacologic interventions (supplements, herbal medicines, diets, sleep, and exercise) with the potential to improve male health was undertaken to elucidate changes in testosterone levels and sperm parameters in men with hypogonadism or infertility compared with healthy patients. Findings: A multitude of nutraceuticals and functional nutrients are purported to stimulate testosterone production; however, only a select few have had promising results, such as zinc, vitamin D (in case of hypovitaminosis D), l-arginine, mucuna, and ashwagandha, based on well-controlled randomized clinical trials of men with low testosterone levels and related problems. Except for l-arginine, these natural agents, as well as tribulus and ω3 fatty acids, can improve some degree of sperm parameters in infertile men. Before implementing these nutraceutical agents, adequate sleep, exercise, and weight loss in patients with obesity are imperative. The effects of nonpharmacologic interventions on testosterone levels are modest and hence do not directly translate into clinical benefits. Correspondingly, androgen receptor content, but not endogenous androgens, has been regarded as the principal factor in muscle hypertrophy. Implications: A limited number of supplements and herbal medicines can be considered as adjunctive approaches in the management of testosterone levels and sperm parameters, primarily in men with low testosterone levels and infertility, whereas most nonpharmacologic supplements appear to lack evidence. Although proper physical exercise, sleep, and diet are indisputable approaches because of the general benefits to health, the use of nutraceuticals, if considered, must be personalized by physicians and/or registered dietitians.
MeSH term(s)	Arginine/therapeutic use ; Fatty Acids/therapeutic use ; Humans ; Hypogonadism/drug therapy ; Infertility/drug therapy ; Male ; Receptors, Androgen ; Semen ; Spermatozoa ; Testosterone/therapeutic use ; Vitamin D/therapeutic use ; Zinc
Chemical Substances	Fatty Acids ; Receptors, Androgen ; Vitamin D (1406-16-2) ; Testosterone (3XMK78S47O) ; Arginine (94ZLA3W45F) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	603113-4
ISSN	1879-114X ; 0149-2918
ISSN (online)	1879-114X
ISSN	0149-2918
DOI	10.1016/j.clinthera.2022.06.006
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Article ; Online: Repurposing existing drugs for COVID-19

Cadegiani, Flavio A.

BMC Endocrine Disorders

an endocrinology perspective

2020 Volume 20, Issue 1

Abstract: Abstract Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, ...

Abstract	Abstract Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
Keywords	Endocrinology, Diabetes and Metabolism ; General Medicine ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ISSN	1472-6823
DOI	10.1186/s12902-020-00626-0
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani, Flavio A

BMC Endocr Disord

Abstract: BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry ... ...

Abstract	BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. MAIN TEXT: While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. CONCLUSION: While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #800840
Database	COVID19

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Article ; Online: Repurposing existing drugs for COVID-19

Flavio A. Cadegiani

BMC Endocrine Disorders, Vol 20, Iss 1, Pp 1-

an endocrinology perspective

2020 Volume 19

Abstract	Abstract Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
Keywords	COVID-19 ; SARS-CoV-2 ; ACE2 ; TMPRSS2 ; Pandemic ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665 ; covid19
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Eating, Sleep, and Social Patterns as Independent Predictors of Clinical, Metabolic, and Biochemical Behaviors Among Elite Male Athletes: The EROS-PREDICTORS Study.

Cadegiani, Flavio A / Kater, Claudio E

Frontiers in endocrinology

2020 Volume 11, Page(s) 414

Abstract: Objectives: ...

Abstract	Objectives:
MeSH term(s)	Adaptation, Physiological ; Adolescent ; Adult ; Athletes/psychology ; Body Composition ; Cumulative Trauma Disorders/physiopathology ; Cumulative Trauma Disorders/psychology ; Energy Intake ; Exercise ; Fatigue/physiopathology ; Fatigue/psychology ; Feeding Behavior ; Humans ; Male ; Middle Aged ; Sleep ; Social Behavior ; Sports ; Sports Nutritional Physiological Phenomena ; Young Adult
Language	English
Publishing date	2020-06-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2020.00414
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