Gingival Recession In Patients With Good Oral Hygiene - A Retrospective Analysis
Suhas Manoharan1, M. Jeevitha2*, Aravind Kumar S3
1 Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Sciences, Saveetha University, Chennai, India.
2 Senior Lecturer, Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Sciences, Saveetha University, Chennai, India.
3 Professor, Department of Orthodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Science, Saveetha University, Chennai, India.
*Corresponding Author
M. Jeevitha,
Senior Lecturer, Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Sciences, Saveetha University, Chennai, India.
Tel: +91-7904613787
E-mail: jeevitham.sdc@saveetha.com
Received: May 04, 2021; Accepted: July 09, 2021; Published: July 15, 2021
Citation:Suhas Manoharan, M. Jeevitha, Aravind Kumar S. Gingival Recession In Patients With Good Oral Hygiene - A Retrospective Analysis. Int J Dentistry Oral Sci. 2021;8(7):3174-3178.doi: dx.doi.org/10.19070/2377-8075-21000646
Copyright:M. Jeevitha©2021. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Abstract
Gingival recession is a term for apical displacement of gingival margin below the cemento enamel junction. It is a common and undesirable condition which is usually common with increase in age. Gingival recession is a common finding in most general practice. It may be indicative of poor oral hygiene. The present study aims to evaluate the prevalence of gingival recession in patients with good oral hygiene. A retrospective study was done based on data analysed from 86000 patient records collected in a dental outpatient department, out of which 2843 patient records who had presented with good oral hygiene were reviewed. Presence or absence of gingival recession was recorded. Excel tabulation was done and then imported the data to SPSS version 20 for statistical analysis. Out of the 2843, people in the age group of 36-55 years had higher gingival recession and good oral hygiene compared to other age groups that is about 33%. 64% of sample size in the age group of 56 - 80 years showed gingival recession despite having good oral hygiene status. Within the limits of the study, good oral hygiene may not be linked with gingival recession, however habits such as improper tooth brushing technique may cause recession. 18.4% of the total study group showed good oral hygiene and gingival recession.
2.Introduction
6.Conclusion
8.References
Keywords
Age; Gingiva; Gingival Recession; Oral Hygiene.
Introduction
Gingival Recession is a common problem that occurs in most
adults as they age. According to a national survey [1]. 88 % of
people above the age of 65 and 50 % of adults over 18 years
tend to have gingival recession. Recession often leads to hypersensitivity
due to exposure of underlying cementum. Recession
in anterior also leads to loss of aesthetics.[2, 3] Teeth with recession
are more prone to root caries and abrasions. Studies suggest
improper brushing techniques may also predisposed to recession
[4-7]. It is being contemplated that gingival recession is primarily
because of two etiologies frequent and improper brushing habits
and high deposits of plaque, calculus due to poor oral hygiene. [8,
9]. Forceful brushing and cervical abrasions eventually leading to
gingival recession has been strongly linked [10, 11].
Baker and Seymour in 1976 [12] described the pathogenesis of
gingival recession.According to this mechanism there are 3 stages.
First stage involves initial clinical inflammation followed by epithelial
proliferation of rete pegs.Third stage involves increased
proliferation and loss of connective tissue core leading to reduced
nutritional supply eventually leading to gingival recession.
Waerhaug [13] claimed that if free gingiva is thin, then there can
be proliferation of epithelial cells from dentogingival epithelium.
Further, the connective tissue zone depletes and both these epithelium
fuse which eventually results in gingival recession.
Previously numerous clinical trials [14-19], and literature reviews
[20-28] over the past 5 years have been done on mechanism, treatment
of gingival recession and other related fields of study. Gingival
recession is a well researched field of Periodontics. Many
studies regarding its etiology and effects have been done. However a study to analyze the prevalence of gingival recession in
patients with good oral hygiene has not been popular. Such a
study may help a practitioner in better diagnoses by understanding
the pattern of soft tissue destruction. Thereby, prepare preventive
measures to improve the patients public dental health. Most
similar earlier studies had certain limitations such as poor patient
cooperation and study group limited to certain age groups [29].
Previously our team has a rich experience in working on various
research projects across multiple disciplines [30-44]. The aim of
the present study is to evaluate the prevalence of gingival recession
in patients with good oral hygiene.
Materials and Methods
Study design and setting
The study was carried out after obtaining approval from the Institutional
Ethical Committee (Ethical approval number: SDC/
SIHEC/2020/DIASDATA/0619-0320). In this retrospective
study, records of 86000 patients who had visited Saveetha dental
College and hospitals from June 2019 to March 2020 were analysed
and the study population included all patients with good oral
hygiene. A total of 2843 case sheets of patients who had good
oral hygiene were reviewed.
Data collection
The inclusion criteria was all patients who reported with good
oral hygiene. The exclusion criteria was any incomplete data that
wasn't recorded properly. All available data were included in the
study to minimise sampling bias. Patients of 7-80 years of age
were included in this study. Collected data was cross verified using
photos and case sheets. Data collected was then tabulated. Inclusion
criteria consisted of all patients with good oral hygiene from
7- 80 years of age. Patients with good oral hygiene and other adverse
habits such as smoking were excluded. All data was collected
and tabulated using MS Excel.
Statistical Analysis
After tabulation using MS Excel, the data was exported to IBM
SPSS software [Version 20: IBM Corporation NY USA] for statistical analysis. Descriptive statistics
was done to assess the prevalence of gingival recession in patients
with good oral hygiene. Chi-square test was done to statistically
analyze the data to identify any significant level of variation
of association. The significance level was set at 0.05.
Results
From the study it was evident that the patients in the age group of
36-55 years had a high prevalence of gingival recession (9.64%)
and patients in the age group of 19-35 years had comparatively
lesser prevalence of gingival recession compared to other groups
(Figure I). It was also seen that males had a higher prevalence
of gingival recession compared to females (Figure 2). Using IBM
SPSS software the association between age and gender was analysed (Table I). Out of the 2843, people in the age group of 36-55
years had higher prevalence of gingival recession and good oral
hygiene compared to other age groups (33%). However, in general
only 18.47% of patients showed good oral hygiene and gingival
recession. 64% of patients in the age group of 56-80 years of age
showed gingival recession despite having good oral hygiene status.
Figure 1. Preoperative clinical frontal picture with Gingival inflammation in relation to 13-23 with supra-eruption of 11.
Figure 2. Intraoperative clinical picture of flap surgery with the use of provisional splints, PRF membrane and tetracycline root conditioning.
Table 1. Table showing age distribution of patients with good oral hygiene and gingival recession. Gingival recession is more commonly seen in the age group of 36-55 years despite maintaining good oral hygiene. [IBM SPSS software Version 20: IBM Corporation NY USA].
Discussion
From the results it was clear that gingival recession can occur in
patients with good oral hygiene. Factors such as improper brushing
technique involving forceful brushing or low quality dental
abrasive may lead to gingival recession despite the patients have
good oral hygiene [45].
In the present study, males showed higher prevalence of gingival
recession.This consensus was similar to Munghamba et al [46]
which showed females had better oral hygiene than males and less
evidence of gingival recession [46].
Despite having good oral hygiene gingival recession was more
commonly seen in 36-55 years of age.This association of age and
gingival recession doesn't mean this is due to physiological reasons
[45, 47]. Gingival recession may occur with increase in age
due to prolonged periods of exposure to toxic agents that lead
to recession [48, 49]. There is also a lot of controversy regarding
the etiology of gingival recession, early root exposure or gingival
margin recession. Studies have reported physical, chemical or bacterial
toxins as etiological factors for gingival recession [12, 50].
Previous literature showed that the primary precipitating factors
of gingival recession are plaque, trauma due to improper brushing
habits, frequent brushing, orthodontic treatment, smoking and
other chemical irritants [12, 51-53]. Predisposing factors are primarily
local anatomic variations such as improper tooth position
such as buccal tipping, bone dehiscence, poor quality of attached
gingiva, high frenal attachment and trauma from occlusion [54].
Localized gingival enlargement is usually seen in younger patients
due to certain etiological factors whereas generalised gingival recession
is seen in older patients due to accumulation of factors
over a prolonged period of time [54].
It may be suggested that dentition in old people has been subjected
to prolonged force of brushing and other irritants such as
plaque and calculus [45, 55]. It was also seen that the males tend
to have more recession on the buccal aspect compared to females
[45, 50].
Recession management is thoroughly based on the assessment of
the causative factors and the condition of the soft tissue. Any
therapeutic treatment will be compromised if the etiological factors
are not removed or eliminated. A treatment plan should be
formulated only when the causative factor has been addressed.
In any treatment plan, the initial phase should involve preventive
therapy which involves balanced diet and oral hygiene instructions.
Along with this, preventive phase can be supplemented with
scaling and root planing at regular intervals or whenever needed.
Surgical treatment due to their invasive nature which leads to both
physical and mental stress to the patient must be resorted to only
as a last option of treatment. Root coverage procedures to be
done only in cases of severe recession, sensitivity or aesthetic reasons.
Case selection, patient awareness and surgical methodologies
of treatment together can be used to treat gingival recession
successfully.
Other factors such as immunological profile, hematology profile,
position of teeth, diet, prosthetics, orthodontics or any periodontal
surgery may affect gingival recession. The general consensus is
that oral good hygiene shows reduced incidents of gingival recession.
A future study on diverse populations taking into account,
forceful brushing technique, physiological status and also dental
status can provide a more accurate result.Our institution is passionate
about high quality evidence based research and has excelled
in various fields [56-66].
However, the drawback of this study is that there were geographic
limitations and the people involved in the study were from an
isolated population and belonged to the same ethnic group. The
causative factors for the gingival recession to occur were not studied.
Conclusion
Within the limits of the study, It was observed that gingival recession
was more common in 36-55 years of age even if good oral hygiene is maintained. Other factors such as improper oral
hygiene methods, tooth malposition and anatomical factors can
predispose to gingival recession even at a young age. Hence, preventive
therapeutic measures are needed along with good oral hygiene
aids which can greatly reduce the development of gingival
recession among all age groups.
References
- Periodontology RSATC of TAA of, Research, Science and Therapy Committee of the American Academy of Periodontology. Position Paper: Periodontal Diseases of Children and Adolescents. J. Periodontol. 2003;74.1696–704.
- Tonetti MS, Mombelli A. Early-onset periodontitis. Ann. Periodontol. 1999 Dec;4(1):39-52.
- Ramesh A, Varghese SS, Doraiswamy JN, Malaiappan S. Herbs as an antioxidant arsenal for periodontal diseases. J Intercult Ethnopharmacol. 2016 Jan 27;5(1):92-6.Pubmed PMID: 27069730.
- Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann. Periodontol. 1999 Dec;4(1):1-6.
- Varghese SS, Thomas H, Jayakumar ND, Sankari M, Lakshmanan R. Estimation of salivary tumor necrosis factor-alpha in chronic and aggressive periodontitis patients. Contemp Clin Dent. 2015 Sep;6(Suppl 1):S152-6. Pubmed PMID: 26604566.
- Lenggogeny P, Masulili SL, Tadjoedin FM, Radi B. Levels of interleukin-1ß in gingival crevicular fluid in patients with coronary heart disease and its relationship to periodontal status. In AIP Conference Proceedings. 2017 Feb 21;1817(1):030004.
- Ramesh A, Varghese SS, Jayakumar ND, Malaiappan S. Chronic obstructive pulmonary disease and periodontitis–unwinding their linking mechanisms. J. Oral Biosci. 2016 Feb 1;58(1):23-6.
- Mittal S, Dani N, Abullais SS, Al-Qahtani NA, Shah K. Effect of Smoking and Tobacco Chewing on Periodontal Disease and Non-Surgical Treatment Outcome: A Clinical and Biochemical Study. J Int Acad Periodontol.. 2017 Dec 24;20(1):12-8.
- Verma SK, Kumar BD, Singh S, Kumari P, Agarwal A, Singh TK, et al. Effect of gutkha chewing on periodontal health and oral hygiene of peoples in Delhi NCR region of North India: A cross-sectional multicentered study. J Family Med Prim Care. 2019 Feb;8(2):564-567.Pubmed PMID: 30984673.
- Locker D, Slade GD, Murray H. Epidemiology of periodontal disease among older adults: a review. Periodontology 2000. 1998 Feb 1;16:16-33.
- Nanaiah KP, Nagarathna DV, Manjunath N. Prevalence of periodontitis among the adolescents aged 15-18 years in Mangalore City: An epidemiological and microbiological study. J Indian Soc Periodontol. 2013 Nov;17(6):784-9.Pubmed PMID: 24554891.
- Hafeez N. Accessory foramen in the middle cranial fossa. Res J Pharm Technol. 2016;9(11):1880-2.
- Krishnan RP, Ramani P, Sherlin HJ, Sukumaran G, Ramasubramanian A, Jayaraj G, et al. Surgical Specimen Handover from Operation Theater to Laboratory: A Survey. Ann Maxillofac Surg. 2018 Jul-Dec;8(2):234-238. Pubmed PMID: 30693238.
- Somasundaram S, Ravi K, Rajapandian K, Gurunathan D. Fluoride Content of Bottled Drinking Water in Chennai, Tamilnadu. J Clin Diagn Res. 2015 Oct;9(10):ZC32-4.Pubmed PMID: 26557612.
- Felicita AS. Orthodontic extrusion of Ellis Class VIII fracture of maxillary lateral incisor - The sling shot method. Saudi Dent J. 2018 Jul;30(3):265- 269.Pubmed PMID: 29942113.
- Kumar S, Rahman R. Knowledge, awareness, and practices regarding biomedical waste management among undergraduate dental students. Asian J. Pharm. Clin. Res. 2017;10(8):341.
- Gurunathan D, Shanmugaavel AK. Dental neglect among children in Chennai. J Indian Soc Pedod Prev Dent. 2016 Oct 1;34(4):364.
- Sneha S. Knowledge and awareness regarding antibiotic prophylaxis for infective endocarditis among undergraduate dental students. Asian J. Pharm. Clin. Res. 2016 Oct 1:154-9.
- Dhinesh B, Lalvani JI, Parthasarathy M, Annamalai K. An assessment on performance, emission and combustion characteristics of single cylinder diesel engine powered by Cymbopogon flexuosus biofuel. Energy Convers Manage. 2016 Jun 1;117:466-74.
- Choudhari S, Thenmozhi MS. Occurrence and Importance of Posterior Condylar Foramen. Res J Pharm Technol. 2016;9(8):11-43.
- Paramasivam A, Vijayashree Priyadharsini J, Raghunandhakumar S. N6- adenosine methylation (m6A): a promising new molecular target in hypertension and cardiovascular diseases. Hypertens Res. 2020 Feb;43(2):153-154.Pubmed PMID: 31578458.
- Wu F, Zhu J, Li G, Wang J, Veeraraghavan VP, Krishna Mohan S, et al. Biologically synthesized green gold nanoparticles from Siberian ginseng induce growth-inhibitory effect on melanoma cells (B16). Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3297-3305.Pubmed PMID: 31379212.
- Palati S, Ramani P, Shrelin HJ, Sukumaran G, Ramasubramanian A, Don KR, et al. Knowledge, Attitude and practice survey on the perspective of oral lesions and dental health in geriatric patients residing in old age homes. Indian J Dent Res. 2020 Jan-Feb;31(1):22-25.Pubmed PMID: 32246676.
- Saravanan M, Arokiyaraj S, Lakshmi T, Pugazhendhi A. Synthesis of silver nanoparticles from Phenerochaete chrysosporium (MTCC-787) and their antibacterial activity against human pathogenic bacteria. Microb Pathog. 2018 Apr;117:68-72.Pubmed PMID: 29427709.
- Govindaraju L, Gurunathan D. Effectiveness of Chewable Tooth Brush in Children-A Prospective Clinical Study. J Clin Diagn Res. 2017 Mar;11(3):ZC31-ZC34.Pubmed PMID: 28511505.
- Vijayakumar Jain S, Muthusekhar MR, Baig MF, Senthilnathan P, Loganathan S, Abdul Wahab PU, et al. Evaluation of Three-Dimensional Changes in Pharyngeal Airway Following Isolated Lefort One Osteotomy for the Correction of Vertical Maxillary Excess: A Prospective Study. J Maxillofac Oral Surg. 2019 Mar;18(1):139-146.Pubmed PMID: 30728705.
- Avinash K, Malaippan S, Dooraiswamy JN. Methods of Isolation and Characterization of Stem Cells from Different Regions of Oral Cavity Using Markers: A Systematic Review. Int J Stem Cells. 2017 May 30;10(1):12-20. Pubmed PMID: 28531913.
- Panda S, Jayakumar ND, Sankari M, Varghese SS, Kumar DS. Platelet rich fibrin and xenograft in treatment of intrabony defect. Contemp Clin Dent. 2014 Oct;5(4):550-4.
- Mootha A, Malaiappan S, Jayakumar ND, Varghese SS, Toby Thomas J. The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review. Int J Inflam. 2016;2016:1-8.Pubmed PMID: 26998377.
- Ravi S, Malaiappan S, Varghese S, Jayakumar ND, Prakasam G. Additive effect of plasma rich in growth factors with guided tissue regeneration in treatment of intrabony defects in patients with chronic periodontitis: a split-mouth randomized controlled clinical trial. J. Periodontol.. 2017 Sep;88(9):839-45.
- Khalid W, Varghese SS, Sankari M, Jayakumar ND. Comparison of Serum Levels of Endothelin-1 in Chronic Periodontitis Patients Before and After Treatment. J Clin Diagn Res. 2017 Apr;11(4):ZC78-ZC81.Pubmed PMID: 28571268.
- Khalid W, Vargheese SS, Lakshmanan R, Sankari M, Jayakumar ND. Role of endothelin-1 in periodontal diseases: A structured review. Indian J Dent Res. 2016 May-Jun;27(3):323-33.Pubmed PMID: 27411664.
- Kavarthapu A, Thamaraiselvan M. Assessing the variation in course and position of inferior alveolar nerve among south Indian population: A cone beam computed tomographic study. Indian J Dent Res. 2018 Jul- Aug;29(4):405-409.Pubmed PMID: 30127186.
- Ramesh A, Ravi S, Kaarthikeyan G. Comprehensive rehabilitation using dental implants in generalized aggressive periodontitis. J. Indian Soc. Periodontol. 2017 Mar;21(2):160.
- Ramesh A, Vellayappan R, Ravi S, Gurumoorthy K. Esthetic lip repositioning: A cosmetic approach for correction of gummy smile - A case series. J Indian Soc Periodontol. 2019 May-Jun;23(3):290-294.Pubmed PMID: 31143013.
- Priyanka S, Kaarthikeyan G, Nadathur JD, Mohanraj A, Kavarthapu A. Detection of cytomegalovirus, Epstein-Barr virus, and Torque Teno virus in subgingival and atheromatous plaques of cardiac patients with chronic periodontitis. J Indian Soc Periodontol. 2017 Nov-Dec;21(6):456-460.Pubmed PMID: 29551863.
- Thamaraiselvan M, Elavarasu S, Thangakumaran S, Gadagi JS, Arthie T. Comparative clinical evaluation of coronally advanced flap with or without platelet rich fibrin membrane in the treatment of isolated gingival recession. J Indian Soc Periodontol. 2015 Jan;19(1):66-71.
- Peeran SW, Singh AJ, Alagamuthu G, Peeran SA, Naveen Kumar PG. Periodontal status and risk factors among adults of Sebha City (Libya). Int. J. Dent.. 2012 Nov 14;2012:1-5.
- Ioannidou E. The Sex and Gender Intersection in Chronic Periodontitis. Front Public Health. 2017 Aug 4;5:189.Pubmed PMID: 28824898.
- Borojevic T. Smoking and periodontal disease. Mater Sociomed. 2012;24(4):274-6.
- Hayman L, Steffen MJ, Stevens J, Badger E, Tempro P, Fuller B, et al. Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria. Clin Exp Immunol. 2011 Apr;164(1):118-26.Pubmed PMID: 21303363.
- Ramamurthy JA, Mg V. Comparison of effect of Hiora mouthwash versus Chlorhexidine mouthwash in gingivitis patients: A clinical trial. Asian J Pharm Clin Res. 2018 Jul 7;11(7):84-8.
- Giri DK, Kundapur P, Bhat KM, Maharjan IK. Betel Nut Chewing Associated With Severe Periodontitis . Health Renaissance. 2015;12:57–60.
- Al Qahtani NA, Joseph B, Deepthi A, Vijayakumari BK. Prevalence of chronic periodontitis and its risk determinants among female patients in the Aseer Region of KSA. J Taibah Univ Med Sci. 2017 Mar 3;12(3):241-248. Pubmed PMID: 31435246.
- Susin C, Albandar JM. Aggressive periodontitis in an urban population in southern Brazil. J Periodontol. 2005 Mar;76(3):468-75.Pubmed PMID: 15857083.
- Demmer R, Papapanou PN. Epidemiologic patterns of chronic and aggressive periodontitis. Periodontol 2000. 2010 Jun;53:28-44.
- Balaji SK, Lavu V, Rao S. Chronic periodontitis prevalence and the inflammatory burden in a sample population from South India. Indian J Dent Res. 2018 Mar-Apr;29(2):254-259.Pubmed PMID: 29652025.
- Albandar JM. Periodontal diseases in north america. Periodontol 2000. 2002 Apr;29(1):31-69.
- Vijayashree Priyadharsini J. In silico validation of the non-antibiotic drugs acetaminophen and ibuprofen as antibacterial agents against red complex pathogens. J Periodontol. 2019 Dec;90(12):1441-1448.Pubmed PMID: 31257588.
- Pc J, Marimuthu T, Devadoss P, Kumar SM. Prevalence and measurement of anterior loop of the mandibular canal using CBCT: A cross sectional study. Clin Implant Dent Relat Res. 2018 Apr 6;20(4):531-4.
- Ramesh A, Varghese S, Jayakumar ND, Malaiappan S. Comparative estimation of sulfiredoxin levels between chronic periodontitis and healthy patients - A case-control study. J Periodontol. 2018 Oct;89(10):1241-1248.Pubmed PMID: 30044495.
- Ramadurai N, Gurunathan D, Samuel AV, Subramanian E, Rodrigues SJ. Effectiveness of 2% Articaine as an anesthetic agent in children: randomized controlled trial. Clin Oral Investig. 2019 Sep;23(9):3543-50.
- Sridharan G, Ramani P, Patankar S, Vijayaraghavan R. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma. J Oral Pathol Med. 2019 Apr;48(4):299-306.
- Ezhilarasan D, Apoorva VS, Ashok Vardhan N. Syzygium cumini extract induced reactive oxygen species-mediated apoptosis in human oral squamous carcinoma cells. J Oral Pathol Med. 2019 Feb;48(2):115-121.Pubmed PMID: 30451321.
- Mathew MG, Samuel SR, Soni AJ, Roopa KB. Evaluation of adhesion of Streptococcus mutans, plaque accumulation on zirconia and stainless steel crowns, and surrounding gingival inflammation in primary molars: randomized controlled trial. Clin Oral Investig. 2020 Sep;24(9):1-6.Pubmed PMID: 31955271.
- Samuel SR. Can 5-year-olds sensibly self-report the impact of developmental enamel defects on their quality of life? Int J Paediatr Dent. 2021 Mar;31(2):285-286.Pubmed PMID: 32416620.
- R H, Ramani P, Ramanathan A, R JM, S G, Ramasubramanian A, et al. CYP2 C9 polymorphism among patients with oral squamous cell carcinoma and its role in altering the metabolism of benzo[a]pyrene. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 Sep;130(3):306-312.Pubmed PMID: 32773350.
- Chandrasekar R, Chandrasekhar S, Sundari KKS, Ravi P. Development and validation of a formula for objective assessment of cervical vertebral bone age. Prog Orthod. 2020 Oct 12;21(1):38.Pubmed PMID: 33043408.
- Priyadharsini JV, Girija AS, Paramasivam A. In silico analysis of virulence genes in an emerging dental pathogen A. baumannii and related species. Arch. Oral Biol. 2018 Oct 1;94:93-8.