• Users Online: 382
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 211-216

Influence of Helicobacter pylori infection on periodontitis: A meta-analysis


Department of Stomatology, Oral Medicine Unit, Faculty of Dentistry, University of Granada, Granada, Spain

Date of Submission16-Jul-2022
Date of Acceptance11-Aug-2022
Date of Web Publication14-Nov-2022

Correspondence Address:
Alberto Rodriguez-Archilla
Department of Stomatology, Oral Medicine Unit, Faculty of Dentistry, University of Granada, Colegio Maximo, s/n. Campus de Cartuja, 18071.Granada
Spain
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdrr.jdrr_103_22

Rights and Permissions
  Abstract 


Background: Helicobacter pylori detection in dental plaque, saliva, or oral mucosa would allow to include this bacteria as a member of the normal oral microbiota and have an etiological role in periodontitis. Objective: The objective of this study is to assess the possible relationship of H. pylori with periodontitis. Methods: A search for studies on H. pylori and periodontitis was conducted in the following databases: PubMed (MEDLINE, Cochrane Library), Web of Science, and Scopus. The pooled prevalence was calculated according to DerSimonian and Laird method. For dichotomous outcomes, the estimates of effects of the intervention were expressed as odds ratios using Mantel–Haenszel method, and for continuous outcomes, the estimates of effects of the intervention were expressed as mean differences using the inverse-variance method, all with 95% confidence intervals. Results: Twenty-six studies with 4072 participants were included in this meta-analysis. Among periodontitis patients, the estimated prevalence of H. pylori detection was 47.93%. Periodontitis patients had 1.89 times more likely to be infected with H. pylori (P < 0.001) and also, an increase of 2.78 times the probability of H. pylori detection on dental plaque (P < 0.001). Similarly, H. pylori was 2.32 times more likely in the oral microbiota than in the gastric one (P < 0.001). Some periodontal parameters (plaque index, probing depth, and clinical attachment level) were significantly worse in positive H. pylori patients. Conclusions: H. pylori infection seems to aggravate periodontitis.

Keywords: Helicobacter infections, Helicobacter pylori, periodontitis, risk factors


How to cite this article:
Rodriguez-Archilla A, Amhaouache R. Influence of Helicobacter pylori infection on periodontitis: A meta-analysis. J Dent Res Rev 2022;9:211-6

How to cite this URL:
Rodriguez-Archilla A, Amhaouache R. Influence of Helicobacter pylori infection on periodontitis: A meta-analysis. J Dent Res Rev [serial online] 2022 [cited 2023 Jan 30];9:211-6. Available from: https://www.jdrr.org/text.asp?2022/9/3/211/361132




  Introduction Top


Periodontal disease comprises a group of very frequent inflammatory disorders that involve the supporting tissues of the teeth and are the most important cause of tooth loss in the adult population. The disease arises from oral microbial biofilms that lead to periodontal infection and ultimately destruction of the supporting periodontal tissues.[1] The main periodontal pathogens are Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, or Prevotella intermedia. The imbalance of the oral microbiota (dysbiosis) contributes to the development of both oral and periodontal diseases and other systemic diseases.[2]

Helicobacter pylori is a Gram-negative, helical rod-shaped bacterium commonly resident in the gastric mucosa. This bacterium has been recognized as the main risk factor for chronic gastritis that can evolve into a gastroduodenal ulcer or premalignant and malignant gastric lesions. For this reason, H. pylori has been classified as a Group I carcinogen by the International Agency for Research on Cancer.[3] H. pylori infection has previously been related to various oral diseases such as oral lichen planus or recurrent aphthous stomatitis.[4] H. pylori detection in dental plaque, saliva, oral mucosa, and other parts of the oral cavity raises the question of whether this bacterium can be included as a member of the normal oral microbiota, whether it can cause periodontitis or play a role in its progression.[5]

This study aimed to assess the possible relationship of H. pylori bacteria with periodontitis.


  Methods Top


Search strategy

A search for studies on H. pylori and periodontitis up to March 2022 was conducted in three databases: PubMed (MEDLINE, Cochrane Library), Web of Science (WoS), and Scopus. Search strategies included a combination of the Medical Subject Headings (MeSH) and free-text terms. The search terms were as follows: “Helicobacter pylori” [MeSH Terms] AND (“periodontitis” [MeSH Terms] OR “periodontal diseases” [MeSH Terms]); “Helicobacter pylori” AND “periodontitis”; TITLE-ABS-KEY (“Helicobacter pylori” [”periodontal” OR “periodontitis”]).

The inclusion criteria were as follows: (a) retrospective studies, (b) studies with well-defined H. pylori detection diagnostic methods, and (c) articles written in any language and with no restrictions on publication date. The exclusion criteria were: (a) articles with no full-text availability, (b) articles with a relevant risk of bias (score <7 stars on the Newcastle–Ottawa methodological quality assessment scale),[6] (c) articles without clinical data, and (d) studies with unusable data.

Statistic analysis

Data were processed with the statistical programs RevMan version 5.4 (The Cochrane Collaboration, Oxford, UK) and MedCalc statistical software version 20.027 (MedCalc Software Ltd. Ostend, Belgium). The pooled prevalence was calculated according to the DerSimonian and Laird method. For dichotomous outcomes, the odds ratio (OR) with the Mantel–Haenszel Chi-square formula, and for continuous outcomes, the inverse variance for the mean difference (MD) was used, all with 95% confidence intervals (95% CI). Heterogeneity was determined according to the Higgins statistic (I2) values. In cases of high heterogeneity (I2 >50%), the random effects model was applied. A P value below 0.05 was considered the minimum level of significance.


  Results Top


Study selection

In the initial search, 369 articles (89 in PubMed, 130 in WoS, and 150 in Scopus) were found between the years 1994 and 2021, 135 of them duplicates, remaining 234 articles for eligibility. Two hundred and eight articles were excluded for: (a) articles with no full-text availability (n = 42), (b) articles with a relevant risk of bias (<7 stars) according to the Newcastle–Ottawa scale (n = 60), (c) articles without clinical data (n = 51), and (d) studies with unusable data (n = 55). Finally, 26 studies were considered in this meta-analysis [Figure 1].
Figure 1: Flow diagram of study selection

Click here to view


Prevalence of Helicobacter pylori in periodontitis patients

[Table 1] shows the 26 studies[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32] that analyze H. pylori detection in periodontitis patients. The pooled prevalence of H. pylori in periodontitis patients was 47.93% (95% CI: 39.65%–56.26%). The variability by studies ranged from the minimum of 8% (95% CI: 2.22%–19.23%)[31] to the maximum prevalence of 87.5% (95% CI: 71.01%–96.48%).[24]
Table 1: Pooled prevalence (and 95% confidence interval) of Helicobacter pylori detection in periodontitis patients

Click here to view


Detection of Helicobacter pylori in periodontitis patients and controls

The evaluation of H. pylori detection in patients with and without periodontitis is shown in [Figure 2]. Sixteen studies[8],[9],[13],[15],[17],[19],[20],[21],[23],[24],[25],[26],[28],[29],[30],[32] assessed the H. pylori detection in the two groups [Figure 2a]. Periodontitis patients were 1.89 times more likely to be infected by H. pylori than controls, with a highly statistically significant relationship (OR = 1.89; 95% CI: 1.47–2.44; P < 0.001).
Figure 2: Study data and forest plot graphs for the Helicobacter pylori detection (a) and detection in dental plaque (b) in periodontitis patients and controls without the disease

Click here to view


Seven studies[10],[16],[18],[24],[26],[28],[31] examined the detection of H. pylori in dental plaque of periodontitis patients and controls [Figure 2b]. Periodontitis patients had a 2.78 times more probability of H. pylori detection in dental plaque compared to controls, found a highly statistically significant association (OR = 2.78; 95% CI: 2.06–3.76: P < 0.001).

Detection of Helicobacter pylori and periodontal status

[Table 2] presents the evaluation of other parameters related to H. pylori detection and the periodontal status. Four studies[12],[16],[18],[24] focused on H. pylori detection in the oral cavity and the stomach in periodontitis patients. These patients increased 2.32-fold the probability of H. pylori detection in the oral cavity concerning the stomach and observed highly statistically significant differences (OR = 2.32; 95% CI: 1.69–3.20; P < 0.001).
Table 2: Evaluation of different parameters related to Helicobacter pylori detection and periodontal status

Click here to view


Three studies[14],[27],[33] determined the plaque index (PI) in subjects with and without H. pylori infection. H. pylori-infected patients had a PI, 0.27 units higher than that of the subjects not infected by the bacteria, showing a highly statistically significant relationship (MD = 0.27; CI%: 0.21–0.32; P < 0.001).

Four studies[14],[27],[33],[34] analyzed probing depth (PD), finding a PD of 0.67 mm higher in H. pylori-positive patients against H. pylori-negative patients. A statistically significant association between PD and H. pylori detection was found (MD = 0.67; 95% CI: 0.22–1.33; P < 0.01).

Three studies[14],[27],[33] assessed clinical attachment loss (CAL) according to H. pylori detection. H. pylori-positive patients had a CAL of 0.83 mm. Greater than H. pylori-negative patients, with highly statistically significant differences (MD = 0.83; 95% CI: 0.38–1.28; P < 0.001).


  Discussion Top


Data from 26 studies on the possible relationship between H. pylori and periodontitis have been included in the present meta-analysis.

In this study, the pooled prevalence of periodontitis patients infected by H. pylori was 47.93%. This high prevalence of H. pylori in these patients would be justified by its ability to cooperate with some periodontal pathogens such as F. nucleatum and Fusobacterium periodonticum. These periodontal bacteria are early and late oral colonizers among periodontitis patients, justifying that dental plaque could serve as a reservoir for H. pylori. Nevertheless, the presence of H. pylori in dental plaque may be intermittent, perhaps as a result of gastroesophageal reflux. The main extragastric reservoir for H. pylori is the oral cavity, both dental plaque and saliva could perform as reservoirs of this bacterium who is implicated in the processes of infection and reinfection.[24]

In the present study, periodontitis patients were more likely to be infected by H. pylori than controls, with a highly statistically significant relationship (P < 0.001). Of the 16 studies that analyzed this variable, 14 of them[8],[9],[13],[15],[17],[19],[20],[23],[24],[25],[26],[28],[30],[32] confirmed this higher H. pylori detection in periodontitis patients, whereas the remaining two[21],[29] observed greater H. pylori detection in subjects without periodontitis. Several findings could explain the association between H. pylori infection and periodontitis risk. H. pylori has been detected in the gingival tissue and may play an important role in the development of periodontal disease. The gastrointestinal mucosa is the primary site of H. pylori colonization, although the oral mucosa is also, especially the gingival sulcus, due to the oral–oral or fecal–oral infection routes, with the oral cavity constituting another reservoir of H. pylori.[30]

In addition, the H. pylori infection rate correlates with the incidence of periodontal disease, increasing the depth of periodontal pockets and the severity of periodontitis. When H. pylori is located in the oral cavity, it acts as an additional risk factor for gastroduodenal ulcers and favors gastrointestinal infection through swallowing. Maintaining good oral hygiene with the removal of dental plaque potentially carrying H. pylori is an important measure to control infection by this bacterium and, therefore, gastric disease and periodontitis.[26]

In this study, periodontitis patients had higher detection of H. pylori in dental plaque compared to controls, with a highly statistically significant association (P < 0.001). All the studies[10],[16],[18],[24],[26],[28],[31] about the detection of H. pylori in dental plaque coincided in pointing out this greater detection in periodontitis patients. The presence of H. pylori in dental plaque could be associated not only with the oral infection by this bacterium but also with reinfection from the gastric mucosa. A positive association between oral and gastric detection of H. pylori has been suggested. Moreover, this higher prevalence of H. pylori in dental plaque was more frequently observed in patients with dyspepsia.[20]

The detection of H. pylori in dental plaque is very common and is usually associated with greater severity of periodontitis. Furthermore, H. pylori in dental plaque is rarely eradicated by antibiotic therapy and may be a source of future reinfection. Because periodontitis is associated with increased H. pylori colonization, early diagnosis and management of the periodontal disease are necessary. Therapeutic measures should be implemented for better control of dental plaque in the setting of treating both periodontal disease and H. pylori gastric disease.[28]

In the present study, the H. pylori detection in the oral cavity of periodontitis patients doubled the probability of detecting H. pylori also in the stomach, observing highly statistically significant differences (P < 0.001). All the studies[12],[16],[18],[24] that quantified the presence of H. pylori in the mouth and stomach corroborated this finding. H. pylori infection is considered a primary etiological factor for chronic gastritis, peptic ulcer, and stomach cancer. The eradication therapy is one of the main therapeutic measures for infectious gastric diseases. The H. pylori eradication from its oral reservoir could be useful in the prevention of periodontal disease and the treatment of all diseases linked to H. pylori infection.[18]

The coexistence of oral and gastric H. pylori infection is observed in more than 50% of periodontitis patients. Oral H. pylori detection could be a risk factor for recurrent gastric infection. If this is so, the oral cavity and dental plaque, as natural reservoirs of H. pylori, could act as a potential source of reinfection even after eradication treatment. This would justify the need for a combination of comprehensive medical and dental treatment modalities for patients with H. pylori infections.[16]

In this meta-analysis, H. pylori-infected patients had a significantly worse periodontal status by presenting a worse PI, more PD, and greater CAL than subjects not infected by H. pylori. All studies[14],[27],[33],[34] that assessed these parameters agreed in pointing out this worse periodontal status of H. pylori-positive individuals. The H. pylori detection in periodontitis patients leads to an increase in the detection of other periodontal bacteria such as P. gingivalis, P. intermedia, Fusobacterium nuclearum, or T. denticola and a decrease in the A. actinomycetemcomitans detection. Patients with more severe periodontitis show a higher H. pylori detection rate, evidencing the relationship between periodontal disease and infection by this bacterium.[33] Higher PD and CAL have been observed in periodontitis patients infected with H. pylori, leading to the assumption that H. pylori infection could aggravate periodontal destruction in these patients.[27]

This study has some limitations. The different diagnostic criteria for periodontitis and the different methods for evaluating H. pylori infection may have influenced the results and caused heterogeneity. Neither other potentially confounding factors such as smoking or diabetes mellitus closely related to periodontitis could not be considered.

Further studies in larger samples and with longer follow-ups are required to more precisely establish the relationship between H. pylori infection and periodontitis.


  Conclusions Top


In this meta-analysis, the pooled prevalence of H. pylori in periodontitis patients was 47.93%. Periodontitis patients were significantly more likely to be infected with H. pylori and also had an increase in the probability of H. pylori detection in dental plaque. Similarly, H. pylori detection was relevantly more likely in the oral microbiota than in the gastric microbiota of periodontitis patients. Finally, periodontal parameters (PI, PD, and CAL) were significantly worse in H. pylori-infected patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Al-Nasser L, Lamster IB. Prevention and management of periodontal diseases and dental caries in the older adults. Periodontol 2000 2020;84:69-83.  Back to cited text no. 1
    
2.
Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol 2000 2020;83:14-25.  Back to cited text no. 2
    
3.
Byun SH, Min C, Hong SJ, Choi HG, Koh DH. Analysis of the relation between periodontitis and chronic gastritis/peptic ulcer: A cross-sectional study using KoGES HEXA data. Int J Environ Res Public Health 2020;17:4387.  Back to cited text no. 3
    
4.
Rodriguez-Archilla A, Abouzahr Y. Relationship between Helicobacter pylori infection and recurrent aphthous stomatitis. J Dent Res Rev 2020;7:154-8.  Back to cited text no. 4
  [Full text]  
5.
Liu Y, Li R, Xue X, Xu T, Luo Y, Dong Q, et al. Periodontal disease and Helicobacter pylori infection in oral cavity: A meta-analysis of 2727 participants mainly based on Asian studies. Clin Oral Investig 2020;24:2175-88.  Back to cited text no. 5
    
6.
Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta Analyses. Ottawa (Canada): The Ottawa Hospital. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. [Last accessed on 2022 May 18].  Back to cited text no. 6
    
7.
Riggio MP, Lennon A. Identification by PCR of Helicobacter pylori in subgingival plaque of adult periodontitis patients. J Med Microbiol 1999;48:317-22.  Back to cited text no. 7
    
8.
Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol 2000;71:1528-34.  Back to cited text no. 8
    
9.
Dye BA, Kruszon-Moran D, McQuillan G. The relationship between periodontal disease attributes and Helicobacter pylori infection among adults in the United States. Am J Public Health 2002;92:1809-15.  Back to cited text no. 9
    
10.
Umeda M, Kobayashi H, Takeuchi Y, Hayashi J, Morotome-Hayashi Y, Yano K, et al. High prevalence of Helicobacter pylori detected by PCR in the oral cavities of periodontitis patients. J Periodontol 2003;74:129-34.  Back to cited text no. 10
    
11.
Gebara EC, Faria CM, Pannuti C, Chehter L, Mayer MP, Lima LA. Persistence of Helicobacter pylori in the oral cavity after systemic eradication therapy. J Clin Periodontol 2006;33:329-33.  Back to cited text no. 11
    
12.
Czesnikiewicz-Guzik M, Bielanski W, Guzik TJ, Loster B, Konturek SJ. Helicobacter pylori in the oral cavity and its implications for gastric infection, periodontal health, immunology and dyspepsia. J Physiol Pharmacol 2005;56 Suppl 6:77-89.  Back to cited text no. 12
    
13.
Anand PS, Nandakumar K, Shenoy KT. Are dental plaque, poor oral hygiene, and periodontal disease associated with Helicobacter pylori infection? J Periodontol 2006;77:692-8.  Back to cited text no. 13
    
14.
Teoman I, Ozmeriç N, Ozcan G, Alaaddinoğlu E, Dumlu S, Akyön Y, et al. Comparison of different methods to detect Helicobacter pylori in the dental plaque of dyspeptic patients. Clin Oral Investig 2007;11:201-5.  Back to cited text no. 14
    
15.
Souto R, Colombo AP. Detection of Helicobacter pylori by polymerase chain reaction in the subgingival biofilm and saliva of non-dyspeptic periodontal patients. J Periodontol 2008;79:97-103.  Back to cited text no. 15
    
16.
Al Asqah M, Al Hamoudi N, Anil S, Al Jebreen A, Al-Hamoudi WK. Is the presence of Helicobacter pylori in dental plaque of patients with chronic periodontitis a risk factor for gastric infection? Can J Gastroenterol 2009;23:177-9.  Back to cited text no. 16
    
17.
Medina ML, Medina MG, Martín GT, Picón SO, Bancalari A, Merino LA. Molecular detection of Helicobacter pylori in oral samples from patients suffering digestive pathologies. Med Oral Patol Oral Cir Bucal 2010;15:e38-42.  Back to cited text no. 17
    
18.
Silva DG, Stevens RH, Macedo JM, Albano RM, Falabella ME, Fischer RG, et al. Presence of Helicobacter pylori in supragingival dental plaque of individuals with periodontal disease and upper gastric diseases. Arch Oral Biol 2010;55:896-901.  Back to cited text no. 18
    
19.
Sambashivaiah S, Bilichodmath S, Nanjaiah N, Kulal R. Helicobacter pylori in periodontal pockets of chronic periodontitis patients with and without type II diabetes mellitus: A randomized controlled trial. Microbiol Res 2011;3:e12.  Back to cited text no. 19
    
20.
Agarwal S, Jithendra KD. Presence of Helicobacter pylori in subgingival plaque of periodontitis patients with and without dyspepsia, detected by polymerase chain reaction and culture. J Indian Soc Periodontol 2012;16:398-403.  Back to cited text no. 20
[PUBMED]  [Full text]  
21.
Salehi MR, Shah Aboei M, Naghsh N, Hajisadeghi S, Ajami E. A comparison in prevalence of Helicobacter pylori in the gingival crevicular fluid from subjects with periodontitis and healthy individuals using polymerase chain reaction. J Dent Res Dent Clin Dent Prospects 2013;7:238-43.  Back to cited text no. 21
    
22.
Zheng Y, Liu M, Shu H, Chen Z, Liu G, Zhang Y. Relationship between oral problems and Helicobacter pylori infection. Arch Oral Biol 2014;59:938-43.  Back to cited text no. 22
    
23.
Ding YJ, Yan TL, Hu XL, Liu JH, Yu CH, Li YM, et al. Association of salivary Helicobacter pylori infection with oral diseases: A cross-sectional study in a Chinese population. Int J Med Sci 2015;12:742-7.  Back to cited text no. 23
    
24.
Sujatha S, Jalihal UM, Sharma S. Association between periodontal disease and oral and gastric Helicobacter pylori infection. Indian J Gastroenterol 2015;34:343-4.  Back to cited text no. 24
    
25.
Wang M, Zhang J, Zhou L, Chen G. The clinical study on the effects of chronic periodontitis and periodontal initial therapy for the infection and eradication of Helicobacter pylori. Chin J Gerontol 2015;35:5886-7.  Back to cited text no. 25
    
26.
Zheng P, Zhou W. Relation between periodontitis and Helicobacter pylori infection. Int J Clin Exp Med 2015;8:16741-4.  Back to cited text no. 26
    
27.
Hu Z, Zhang Y, Li Z, Yu Y, Kang W, Han Y, et al. Effect of Helicobacter pylori infection on chronic periodontitis by the change of microecology and inflammation. Oncotarget 2016;7:66700-12.  Back to cited text no. 27
    
28.
Nisha KJ, Nandakumar K, Shenoy KT, Janam P. Periodontal disease and Helicobacter pylori infection: A community-based study using serology and rapid urease test. J Investig Clin Dent 2016;7:37-45.  Back to cited text no. 28
    
29.
Pataro AL, Cortelli SC, Abreu MH, Cortelli JR, Franco GC, Aquino DR, et al. Frequency of periodontal pathogens and Helicobacter pylori in the mouths and stomachs of obese individuals submitted to bariatric surgery: A cross-sectional study. J Appl Oral Sci 2016;24:229-38.  Back to cited text no. 29
    
30.
Yang J, Zhang Q, Chen M, Wu WZ, Wang R, Liu CJ, et al. Association between Helicobacter pylori infection and risk of periodontal diseases in Han Chinese: A case-control study. Med Sci Monit 2016;22:121-6.  Back to cited text no. 30
    
31.
Valadan Tahbaz S, Yadegar A, Amirmozafari N, Yaghoobee S, Ehsani Ardakani MJ, Zojaji H. Occurrence of Helicobacter pylori and its major virulence genotypes in dental plaque samples of patients with chronic periodontitis in Iran. Gastroenterol Hepatol Bed Bench 2017;10:S70-8.  Back to cited text no. 31
    
32.
Adachi K, Notsu T, Mishiro T, Yoshikawa H, Kinoshita Y. Influence of Helicobacter pylori infection on periodontitis. J Gastroenterol Hepatol 2019;34:120-3.  Back to cited text no. 32
    
33.
Gülseren D, Karaduman A, Kutsal D, Nohutcu RM. The relationship between recurrent aphthous stomatitis, and periodontal disease and Helicobacter Pylori infection. Clin Oral Investig 2016;20:2055-60.  Back to cited text no. 33
    
34.
Bali D, Rosamma J, Bali A. The association of dental plaque and Helicobacter pylori infection in dyspeptic patients undergoing endoscopy. J Clin Diagn Res 2010;4:3614-21.  Back to cited text no. 34
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed434    
    Printed10    
    Emailed0    
    PDF Downloaded47    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]