Introduction: Exceedingly high levels of the chemokine CCL5/RANTES have been found in fatty degenerated osteonecrotic alveolar bone cavities (FDOJ) and aseptic ischemic osteolysis of the jaw (AIOJ) from toothless regions. Because CCL5/RANTES seems to have a prominent role in creating the COVID-19 “cytokine storm”, some researchers have used the monoclonal antibody Leronlimab to block the CCR5 on inflammatory cells. Objective: Is preexisting FDOJ/AIOJ jaw marrow pathology a “hidden” co-morbidity affecting some COVID-19 infections? To what extent does the chronic CCL5/RANTES expression from preexisting FDOJ/AIOJ areas contribute to the progression of the acute cytokine storm in COVID-19 patients? Methods: Authors report on reducing the COVID-19 “cytokine storm” by treating infected patients through targeting the chemokine receptor 5 (CCR5) with Leronlimab and interrupting the activation of CCR5 by high CCL5/RANTES signaling, thus dysregulating the inflammatory phase of the viremia. Surgical removal of FDOJ/AIOJ lesions with high CCL5/RANTES from patients with inflammatory diseases may be classified as a co-morbid disease. Results: Both multiplex analysis of 249 FDOJ/AIOJ bone tissue samples as well as serum levels of CCL5/RANTES displayed exceedingly high levels in both specimens. Discussion: By the results the authors hypothesize that chronic CCL5/RANTES induction from FDOJ/AIOJ areas may sensitize CCR5 throughout the immune system, thus, enabling it to amplify its response when confronted with the virus. As conventional intraoral radiography does little to assess the quality of the alveolar bone, ultrasonography units are available to help dentists locate the FDOJ/AIOJ lesions in an office setting. Conclusion: The authors propose a new approach to containment of the COVID-19 cytokine storm by a prophylactic focus for future viral-related pandemics, which may be early surgical clean-up of CCL5/RANTES expression sources in the FDOJ/AIOJ areas, thus diminishing a possible pre-sensitization of CCR5. A more complete dental examination includes trans-alveolar ultrasono-graphy (TAU) for hidden FDOJ/AIOJ lesions.

Oral DiseasesEarly View LETTER TO THE EDITOROpen Access Challenging NICO again? Robert E. McMahon, Corresponding Author Robert E. McMahon vosg@aol.com orcid.org/0000-0003-3307-122X Oral Surgery Group, Inc., Merrillville, Indiana, USA Correspondence Robert E. McMahon, Oral Surgery Group, Inc., Merrillville, Indiana 46410, USA. Email: vosg@aol.comSearch for more papers by this author Robert E. McMahon, Corresponding Author Robert E. McMahon vosg@aol.com orcid.org/0000-0003-3307-122X Oral Surgery Group, Inc., Merrillville, Indiana, USA Correspondence Robert E. McMahon, Oral Surgery Group, Inc., Merrillville, Indiana 46410, USA. Email: vosg@aol.comSearch for more papers by this author First published: 06 October 2021 https://doi.org/10.1111/odi.14041AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Despite all their negative comments, it was encouraging that Sekundo et al. (2021) recognized the many contributions of Glueck, Mcmahon, et al. (1997), who were so instrumental in applying to NICO lesions the same blood panels used to identify underlying systemic hypercoagulability conditions in idiopathic hip and knee necrosis (Jones, 1997). Considering that Factor V Leiden mutation, a heritable prothrombotic disorder causing resistance to activated protein C (APCR), is relatively common in Europeans (as high as 15% in Greeks and Scandinavian populations), it is ironic that European dentists and oral surgeons are not taking this discovery more seriously (Dahlback, 2002). APCR is associated with premature life-threatening thrombotic events: deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke (Rosendaal et al., 1997). The osseous tissues most affected by this disorder have long included the cancellous bone of the femoral heads, knees, and jaws (Cheras, 1997, Glueck et al., 1997). Glueck et al demonstrated, in a cohort of chronic facial pain patients with biopsy-proven chronic osteomyelitis of the jaw (NICO), a pathogenetic link with the mutant Factor V Leiden gene and thrombophilia. This is a common (24% vs. 3%), significant (p = .001) underlying cause of the chronic ischemia, alveolar bone necrosis and jaw pain of NICO, and coagulation panels often reveal other vascular risk factors in such patients (Gruppo et al., (1996)). See Figure 1. FIGURE 1Open in figure viewerPowerPoint Fibrosed medullary space with arteriovascular bundle showing greatly dilated veins and two less dilated arterioles in chronic facial pain patient with NICO. One arteriole is completely occluded by a thrombus (white arrow), as is a smaller vein (yellow arrow) It is ironic that the editors of Oral Diseases chose to publish a systematic review of NICO written by professionals who have never published anything on their experience with chronic facial pain disorders. The editors may not have realized that this particular review so far underrepresented the world literature on ischemic bone disorders, their multiple etiologies, diagnoses, and treatments, or that they were so underqualified to make opinions regarding the well-documented histopathology and pathophysiological mechanisms operating to maintain the health of alveolar and other bones. Surely the research of Wannfors and Gazelius (1991), Mauer et al. (2006) and others long ago proved there was significant reduction in blood flow and oxygenation within affected jaws, including the vaso nervosa of the alveolar nerves. These phenomena were not even discussed in this systematic review. It is the author's opinion that a proper NICO assessment should include pathologists well versed in the histopathology and pathophysiology of chronic osteomyelitis and ischemic osteonecrosis, as well as dentists and oral surgeons with great experience in the treatment of chronic facial pain. An epidemiologist and radiologist would also be beneficial. The editors of Oral Diseases, of course, should never shy away from controversial reviews simply because they are controversial. However, debate should be a strong part of such reviews and that is grievously lacking in the Sekundo et al paper. I challenge the journal, therefore, to provide a more science-based, less-biased review and update of NICO in a future issue, especially one utilizing pathologists and others who have made the incredibly painstaking effort to understand the underlying pathophysiology of this fascinating and so often devastating bone entity. Sekundo et al have shown us how not to do it and so have provided a wonderful primer on mistakes to avoid. ACKNOWLEDGEMENTS This manuscript is my work entirely and I have received. No funding for it nor do I have any conflicts of interest to disclose. PEER REVIEW The peer review history for this article is available at https://publons.com/publon/10.1111/odi.14041. Open Research PEER REVIEW The peer review history for this article is available at https://publons.com/publon/10.1111/odi.14041. REFERENCES Cheras, P. A. (1997) Role of hyperlipidemia, hypercoagulability, and hypofibrinolysis in osteo- necrosis and osteoarthritis. In J. R. Urbaniak & J. P. Jones. OSTEONECROSIS—Etiology, diagnosis, and treatment (pp. 97- 104). American Academy of Orthopaedic Surgeons. Google Scholar Dahlback, B. (2002). Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood, 112(1), 19– 27. CrossrefGoogle Scholar Glueck, C. J., Brandt, G., Gruppo, R., Crawford, A., Roy, D., Tracy, T., & Becker, A. (1997). Resistance to activated protein C and legg-perthes disease. Clinical Orthopaedics, 336, 1– 14. Google Scholar Glueck, C. J., Mcmahon, R. E., Bouquot, J. E., Triplett, D., Gruppo, R., & Wang, P. (1997). Heterozygosity for the Leiden mutation V gene, a common pathoetiology for osteonecrosis of the jaw with thrombophilia augmented by exogenous estrogens. Journal of Laboratory and Clinical Medicine, 130, 540– 543. CrossrefCASPubMedWeb of Science®Google Scholar Gruppo, R., Glueck, C. J., Mcmahon, R. E., Bouquot, J., Rabinovich, B. A., Becker, A., & Wang, P. (1996). The pathophysiology of osteonecrosis of the jaw: Anticardiolipin antibodies, thrombophilia and hypofibrinolysis. Journal of Laboratory and Clinical Medicine, 127, 481– 488. CrossrefCASPubMedWeb of Science®Google Scholar Jones, J. P. Jr. (1997). Risk factors potentially activating intravascular coagulation and causing non- traumatic osteonecrosis. In J. R. Urbaniak & J. P. Jones (Eds.), OSTEONECROSIS—Etiology, diagnosis, and treatment (pp. 89- 96). American Academy of Orthopaedic Surgeons. Google Scholar Mauer, P., Meyer, L., Eckert, A. W., Berginski, M., & Schubert, J. (2006). Measurement of oxygen partial pressure in the mandibular bone using a polarographic fine needle probe. International Journal of Oral and Maxillofacial Surgery, 35, 231– 236. https://doi.org/10.1016/j.ijom.2005.07.016CrossrefPubMedWeb of Science®Google Scholar Rosendaal, F. R., Siscovick, D. S., Schwartz, S. M., Beverly, R. K., Psaty, B. M., Longstreth, W. T. Jr, Reitsma, P. H. (1997). Factor V Leiden (resistance to activated protein C) increase the risk of myocardial infarction in young women. Blood, 89, 2817– 2821. CrossrefCASPubMedWeb of Science®Google Scholar Sekundo, C., Wiltfang, J., Schliephake, H., Al-Nawas, B., Rückschloß, T., Moratin, J., & Ristow, O. (2021). Neuralgia-inducing cavitational osteonecrosis–A systematic review. Oral Diseases, 1– 20. https://doi.org/10.1111/odi.13886Web of Science®Google Scholar Wannfors, K., & Gazelius, B. (1991). Blood flow in jaw bone affected by chronic osteomyelitis. British Journal of Oral and Maxillofacial Surgery, 29, 147– 153. 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Objective. We hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO).Design: In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender.Results. Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender-matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13).Conclusions. The eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 548-553)

A serious weakness of all bisphosphonate-associated jaw osteonecrosis cases reported to date is a lack of histopathologic evaluation of alveolar bone and marrow some distance beyond the acutely inflamed exposed cortex. 1 Wang E.P. Kaban L.B. Strewler G.J. et al. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg. 2007; 65: 1328 Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar , 2 Freiberger J.J. Padilla-Burgos R. Chhoeu A. et al. Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: A case series. J Oral Maxillofac Surg. 2007; 65: 1321 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar , 3 Marx R.E. Sawatari Y. Fortin M. et al. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005; 63: 1567 Abstract Full Text Full Text PDF PubMed Scopus (1261) Google Scholar , 4 Migliorati C.A. Casiglia J. Epstein J. et al. Managing the care of patients with bisphosphonate-associated osteonecrosis. J Am Dent Assoc. 2005; 136: 1658 Crossref PubMed Scopus (354) Google Scholar , 5 Kumar V. Pass B. Guttenberg S.A. et al. Bisphosphonate-related osteonecrosis of the jaws: A report of three cases demonstrating variability in outcomes and morbidity. J Am Dent Assoc. 2007; 138: 602 Crossref PubMed Scopus (23) Google Scholar Ischemic osteonecrosis has evolved recently into a consolidation of dozens of orthopedic diseases that have certain microscopic alterations in common but differ widely in terms of clinical manifestations and etiologic associations. 6 Kenzora J.E. Glimcher M.J. Accumulative cell stress: The multifactorial etiology of idiopathic osteonecrosis. Orthop Clin North Am. 1985; 16: 669 PubMed Google Scholar , 7 Cruess R.L. Osteonecrosis of bone. Clin Orthop. 1986; 208: 30 PubMed Google Scholar , 8 Jones J.P. Intravascular coagulation and osteonecrosis. Clin Orthop. 1992; 277: 41 PubMed Google Scholar , 9 Jones J.P. Evidence for progressive intraosseous fat overload causing osteoarthritis, osteoporosis, and osteonecrosis. J Jpn Orthop Assoc. 1992; 66: 16 Google Scholar , 10 Mankin J.H. Non-traumatic necrosis of bone (osteonecrosis). N Engl J Med. 1992; 326: 1473 Crossref PubMed Scopus (718) Google Scholar , 11 Chang C.C. Greenspan A. Gershwin M.E. Osteonecrosis: Current perspectives on pathogenesis and treatment. Semin Arthritis Rheum. 1993; 23: 47 Abstract Full Text PDF PubMed Scopus (154) Google Scholar , 12 Urbaniak J.R. Jones Jr, J.P. Osteonecrosis: Etiology, Diagnosis, and Treatment. American Academy of Orthopaedic Surgeons, Rosemont, IL1997 Google Scholar We do not doubt that bisphosphonate-associated jawbone disease is another in the long list of osteonecrotic disorders, but none of the microscopic descriptions and photos of jawbone cases has demonstrated ischemic marrow damage. They illustrate dead bone, certainly, but only as one of the classic features of acute osteomyelitis— a sequestrum covered by pus, bacteria, and necrotic granulation tissue 13 Neville B. Damm D. Allen C. et al. Oral and Maxillofacial Pathology. (ed 2). Saunders, Philadelphia, PA2002 Google Scholar (Fig 1). No evidence has been demonstrated of underlying marrow disease, which is the normal foundation of a diagnosis of ischemic osteonecrosis (Fig 2).

Without addressing the established multicausal medical model of osteonecrosis, 1 Kenzora J.E. Glimcher M.J. Accumulative cell stress: The multifactorial etiology of idiopathic osteonecrosis. Orthop Clin North Am. 1985; 16: 669 PubMed Google Scholar , 2 Cruess R.L. Osteonecrosis of bone. Clin Orthop Relat Res. 1986; 208: 30 PubMed Google Scholar , 3 Jones J.P. Intravascular coagulation and osteonecrosis. Clin Orthop Relat Res. 1992; 277: 41 PubMed Google Scholar , 4 Mankin J.H. Non-traumatic necrosis of bone (osteonecrosis). N Engl J Med. 1992; 326: 1473 Crossref PubMed Scopus (728) Google Scholar , 5 Urbaniak J.R. Jones Jr, J.P. Osteonecrosis: Etiology, Diagnosis, and Treatment. American Academy of Orthopaedic Surgeons, Rosemont, IL1997 Google Scholar your editorial leaves the reader with an oversimplified understanding of what “co-factors” may be contributing to the progression of jaw necrosis in the multiple myeloma patient taking bisphosphonates. 6 Assael L.A. A time for perspective on bisphosphonates. J Oral Maxillofac Surg. 2006; 64: 877 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar This greatly limits our ability to make informed decisions about prevention, treatment, and prognosis. Heritable disorders of coagulation that increase the likelihood of thrombosis (thrombophilia and hypofibrinolysis) are not uncommon, with an estimated 10% of the United States affected. 7 Hemostasis and coagulative disorders. in: Beers M.H. Berkow R. Merck Manual of Diagnosis and Treatment. Merck Research Laboratories, Whitehouse Station, NJ1999: 906 Google Scholar A Time for Perspective on BisphosphonatesJournal of Oral and Maxillofacial SurgeryVol. 64Issue 6PreviewCommunication on the use of bisphosphonates has become skewed toward the risk of osteonecrosis of the jaws (ONJ). While this is an important clinical problem, it should not be allowed to deny patients the important benefits of these drugs or prevent researchers from investigating the potential benefits yet to be gained from bisphosphonates. Full-Text PDF

The scientific and diagnostic status of neuralgia-inducing cavitational osteonecrosis, NICO, has not been definitively established. A case is presented in favor of this diagnosis based on published literature. It is argued that the case against NICO has been made largely based on personal experiences, by innuendo, and through personal attacks rather than in scientific debate.

Ischemic osteonecrosis (IO) is not so much a disease in its own right as it is the natural consequence of a wide variety of systemic and local factors capable of compromising marrow blood flow (Table 1).1-9It is the condition for which the term cavitation was coined in the orthopedic literature, and it is one of a select group of interrelated diseases able to deteriorate and hollow out medullary spaces (Fig 1)1-10: First described in 1794 in a case of septic necrosis of the femoral head, this enigmatic disease is as old as the dinosaurs, but it has been poorly understood and has such subtle radiographic changes that until recently it was seldom diagnosed before end-stage damage.

Annals of the New York Academy of SciencesVolume 349, Issue 1 p. 46-56 THE METABOLISM OF DRUGS AND OTHER FOREIGN COMPOUNDS IN SUSPENSIONS OF ISOLATED RAT HEPATOCYTES Robert E. McMahon, Robert E. McMahon Lilly Research Laboratories Indianapolis, Indiana 46206Search for more papers by this author Robert E. McMahon, Robert E. McMahon Lilly Research Laboratories Indianapolis, Indiana 46206Search for more papers by this author First published: September 1980 https://doi.org/10.1111/j.1749-6632.1980.tb29513.xCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Vlndesine(VDS; deacetyl vinblastineamide sulfate) giveni.p. dailycompletelyinhibitedthe growthof boththe Ridgewayosteogenic sarcomaat 0.4mg/kgandthe Gard ncrIymphosarcóma at 0.25mg/kg.Incontrast,the parent alkaloid, vinbbastine (VLB), at 0.5 mg/kg was inactive againstthesetwotumors.VDScausedinhibition ofgrowth of the Meccalymphosarcoma thatwascomparableto the inhibitionby vincristine(VCR),(60versus68%)whileVLB caused 41% inhibition.The Ca115 Shlonogimammary carcinomadidnotrespondto VDS,butbothVLBandVCR causedinhibitions of 62and67%,respectively. TheCa755 mammaryadenocarcinoma showeda moderateresponse to VDS (46%)and VCR (39%),and no responseto VLB. The Sarcoma180 ascitestumor(solid,s.c.), the X5563 myeloma,and the C3H mammarycarcinomawere not responsive to VDS,VLB,or VCR. VDScauseda 113%prolongation of life in micewiththe B16melanoma(i.p.), and there were three of ten 45-day survivorsin one study,andten of ten 45-daysurvivorsin anotherstudy.VLBhadtwoof ten andeightof ten 45-day survivorsin the same studies.Animalsinoculatedwith the P388leukemiaandthe Walker256andEhrlichascites tumorshad greater than 100% prolongation of life with manyindefinitesurvivorswhentreatedwithVDS,VLB,or VCR. The L1210, AKR, L5178Y,and C1498 leukemias showsdnoresponseto VDSgivendailyat I.0 mg/kg. In tissueculturesof Chinesehamsterovarycells, the minimum effectiveconcentration of VDSthatcaused10to 15%accumulation of cellsin mitosiswas2.3 x 1O@N, for VLBit was 2.2 x 1O@M,andfor VCRft was 7.3 x 1O@M. The concentration of VDSneededfor 40 to 50%accumu lationof cells in mitosiswas 2.8 x 1O@M;for VLBit was 8.3 x 1O-@ M; and for VCR ft was 2.4 x 1O@N.

Publisher Summary This chapter presents an overview of different studies that focus on drug metabolism. The initial discovery that arene oxides play an important role in hydroxylation of aromatic compounds was expanded from the naphthalene series to include various alkyl benzene derivatives and polycyclic hydrocarbons. Although the alkyl benzene arene oxides were not stable enough to be isolated from enzyme incubations, the breakdown of chemically prepared arene oxides strongly supports their intermediate role in the formation of phenols and mercapturic acids. The production of cyclohexadiene diols from benzenoid drugs such as dilantin, phenobarbital, and diphenoxylate was consistent with the intermediary formation of arene oxides. Phenylacetone oxime was identified as a metabolite of amphetamine in vitro and in vivo . Isotope studies using 18 O 2 suggested that this oxime and carbinolamine are intermediates in the deamination of amphetamine. N -oxides were identified as metabolites of a variety of tertiary amines including nicotine, cotinine, methadone, and orphenadrine. Another study reported the enzymatic conversion of an aziridine to an alpha amino alcohol. Phosphines readily metabolized to phosphine oxides. Metabolic cleavage of the furan ring of 2-(furyl) benzimidazole gave (S)(-)4-(2-benzimidazoyl)-4-hydroxy butyric acid as a urinary metabolite in five species.

Chemischer InformationsdienstVolume 3, Issue 33 Preparative Organic Chemistry ChemInform Abstract: IDENTIFIZIERUNG DREIER NEUER METABOLITEN VON METHADON IM MENSCHEN UND IN DER RATTE HUGH R. SULLIVAN, HUGH R. SULLIVANSearch for more papers by this authorSUSAN L. DUE, SUSAN L. DUESearch for more papers by this authorROBERT E. MCMAHON, ROBERT E. MCMAHONSearch for more papers by this author HUGH R. SULLIVAN, HUGH R. SULLIVANSearch for more papers by this authorSUSAN L. DUE, SUSAN L. DUESearch for more papers by this authorROBERT E. MCMAHON, ROBERT E. MCMAHONSearch for more papers by this author First published: August 15, 1972 https://doi.org/10.1002/chin.197233460AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume3, Issue33August 15, 1972 RelatedInformation

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIn vivo hydroxylation of the alkaloid acronine, an experimental antitumor agentHugh Richard Sullivan, Billings Ruth E., John L. Occolowitz, Harold E. Boaz, Frederick J. Marshall, and Robert E. McMahonCite this: J. Med. Chem. 1970, 13, 5, 904–909Publication Date (Print):September 1, 1970Publication History Published online1 May 2002Published inissue 1 September 1970https://doi.org/10.1021/jm00299a025RIGHTS & PERMISSIONSArticle Views58Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (749 KB) Get e-Alerts Get e-Alerts