• Users Online: 383
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Partners Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 2  |  Page : 106-112

Three-dimensional assessment of alveolar bone thickness in individuals with nonsyndromic unilateral complete cleft lip and palate


1 Department of Orthodontics and Dentofacial Orthopaedics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
2 Department of Biostatistics, Yenepoya Research Centre, Yenepoya University, Mangalore, Karnataka, India

Date of Web Publication26-Jul-2018

Correspondence Address:
Dr. Shahista Parveen
Department of Orthodontics and Dentofacial Orthopaedics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jclpca.jclpca_11_18

Rights and Permissions
  Abstract 


Background: Patients with cleft lip and palate (CLP) present with thin alveolar bone around the defect. Thin alveolar bone compromises orthodontic treatment. The aim of this study was to carry out three-dimensional (3D) assessment of the thickness of alveolar bone around the teeth adjacent to cleft and to compare the thickness of alveolar bone between cleft and noncleft side. Materials and Methods: Retrospective database of 16 cone-beam computed tomography (CBCT) scans of individuals with nonsyndromic unilateral complete CLP reported to two cleft centers in the year 2015 and 2016. Alveolar bone thickness of the teeth anterior and posterior to the cleft side in the buccal, lingual, mesial, and distal at three levels (3 mm, 6 mm, and 1 mm below the apex) from the cementoenamel junction (CEJ) using Dolphin 3D imaging software were measured. CBCT images of each cleft patient are divided into two groups, cleft and noncleft site. Each cleft side is subdivided into 1. Tooth anterior to the cleft 2. Tooth posterior to the cleft. Alveolar bone thickness of teeth at labial/buccal, palatal, and mesial/distal surfaces was measured. These subdivided groups were compared to contralateral teeth on the noncleft sites for individual surface. Statistical Analysis Used: Wilcoxon signed-ranks test and descriptive statistics were used. Results: The average alveolar bone thickness on the labial surface for teeth anterior to the cleft at 3 mm from CEJ is 0.15 (0, 0.80) mm and noncleft site is 0.85 (0.58, 1.28) mm (P < 0.05). The average alveolar bone thickness on the distal surface for teeth anterior to the cleft at 3 mm from CEJ is 0.90 (0.00, 1.65) mm and noncleft site is 1.11 (1.23, 3.60) mm (P < 0.05). The average alveolar bone thickness on the mesial surface for teeth posterior to the cleft at 3 mm from CEJ is 1.10 (0108, 1.38) mm and noncleft site is 1.45 (1.23, 1.98) mm (P < 0.05). Conclusions: The alveolar bone around the cleft sites is thin when compared with noncleft sites.

Keywords: Alveolar bone thickness, cone-beam computed tomography, nonsyndromic unilateral cleft lip and palate


How to cite this article:
Parveen S, Shetty R, Husain A, Mascarenhas R, D'Souza N, Shetty NK. Three-dimensional assessment of alveolar bone thickness in individuals with nonsyndromic unilateral complete cleft lip and palate. J Cleft Lip Palate Craniofac Anomal 2018;5:106-12

How to cite this URL:
Parveen S, Shetty R, Husain A, Mascarenhas R, D'Souza N, Shetty NK. Three-dimensional assessment of alveolar bone thickness in individuals with nonsyndromic unilateral complete cleft lip and palate. J Cleft Lip Palate Craniofac Anomal [serial online] 2018 [cited 2019 May 24];5:106-12. Available from: http://www.jclpca.org/text.asp?2018/5/2/106/237631




  Introduction Top


Cleft lip and palate (CLP) is caused by nonfusion of the maxillary process with the median nasal process and palatal processes of maxilla during 5th–12th week of intrauterine life. The incidence and distribution of CLP are varied with Afghans showing the highest incidence as 4.9 and Negroid population showing the lowest as 0.4/1000 live births.[1],[2],[3]

The esthetic defect caused by this anomaly is perceived as a major stigma and leads to many psychosocial problems. The repair of these defects is a multidisciplinary approach with the orthodontist playing a significant role.

According to Profitt's classification of esthetic evaluation,[4] these patients have not only a major macroesthetic problem but also an equally dominant micro- and mini-esthetic problem. Previous studies of the teeth adjacent to the cleft site have indicated decreased alveolar bone height, a long supracrestal connective tissue attachment and a higher frequency of gingival recession.[5] de Almeida et al. have reported a 10-fold increase in gingival recession in cleft sites compared to noncleft individuals.[6] To successfully address these esthetic issues, it becomes imperative to evaluate the preexisting situation three-dimensionally (3D) before commencing any orthodontic tooth movements.

Orthodontic intervention in CLP patients commences during late mixed dentition period. Complex orthodontic tooth movements and biomechanics are involved for the correction of rotated teeth adjacent to cleft sites and creation of space for prosthetic replacement of the missing teeth. The complexity of the hard- and soft-tissue regeneration in these sites has necessitated the need for defining the preoperative morphology of the cleft areas.

Cone-beam computed tomography (CBCT) has opened up a plethora of applications in the dental field.[7] Multislice computed tomography is considered the preferred diagnostic tool for assessing cleft defects. However, according to SEDENTEXCT protocols, CBCT can be preferred over CT due to lower cost and less radiation dose.[8]

The cleft sites have both a horizontal and a probable vertical bone defect that needs to be addressed for the prosthetic rehabilitation using dental implants. Preservation of this interdental bone becomes crucial for excellent microesthetic rehabilitation. Furthermore, vertical augmentation of bone is possible only to the level of the peaks of alveolar bone on the teeth adjacent to defect sites. Preservation of the peaks of interdental bone on the teeth following orthodontic treatment is mandatory for an ideal esthetic outcome.

The knowledge regarding the timing of intervention by the orthodontist in the treatment becomes very crucial to prevent further damage to the preexisting bone defects in these patients. The present study is done to evaluate the preexisting alveolar bone on the teeth adjacent to the cleft sites which are usually the central incisor mesially and the canine tooth on the distal aspect using the Dolphin 3D imaging software. These measurements have been compared with the teeth on the noncleft sites.


  Materials and Methods Top


This retrospective study was carried out in our university hospital after obtaining approval from the Ethical Committee of our University (YUEC2017/008). CBCT scans from database of individuals with nonsyndromic unilateral complete CLP (NSUCCLP) reported to two cleft centers in the year 2015 and 2016 were screened. Permission was obtained from directors of those cleft centers to use the CBCT images which were made for the purposes of management of these patients. Out of selected cases, it was reconfirmed if informed consent was obtained for using the CBCT for research. Data were collected by two investigators who were blinded to the identity of the coded images.

The records of 52 individuals with NSUCCLP had been screened out of which 10 patients had undergone orthodontic treatment, the DICOM data of 12 patients were not clear due to movement of the head during scan capture. A total of 14 patients had undergone secondary alveolar bone grafting (SABG), hence data of these patients were not included in the study. CBCT images of NSUCCLP who have not undergone secondary bone grafting or orthodontic intervention have been selected for the study.

The final sample consisted of CBCT images of 16 NSUCCLP (10 males, 6 females; 11 left sided, 5 right sided; Mean age 12.93 ± 1.74 years). The sites that have been analyzed in this study were teeth anterior to the cleft, teeth posterior to the cleft, and contralateral teeth on noncleft side.

Data acquisition

The CBCT had been performed with a Promax 3D ® scanner Mid with Proface (Planmeca, Helsinki, Finland). The imaging conditions were voxel size 0.2–0.4, 90 kVp tube voltage, 14 mA tube current; 12 s exposure time; and 0.16 mm voxel size. The DICOM files have been imported into Dolphin 3D software, version 11.9, Build 24 (Dolphin Imaging, Chatsworth, CA, USA) whose accuracy, reliability, and reproducibility in making linear measurements has been previously studied.[9]

Standardization of landmarks

The site to be analyzed is segmented on the multiple planar views and layouts. The field of view (FOV) is rotated so that the coronal and sagittal slices pass through the center of the tooth and the long axis of the tooth is kept perpendicular to sagittal and coronal plane [Figure 1]. Now on the sagittal slice mark, the line that passes through the cementoenamel junction (CEJ).
Figure 1: Standardization of planes for alveolar bone thickness measurement

Click here to view


Measurement on sagittal/coronal slice

To check the reliability of data, measurements were repeated on two different planes (coronal/sagittal and axial). The alveolar bone at labial/buccal, palatal, mesial, and distal surface was measured on the coronal/sagittal at 3 mm, 6 mm above the CEJ, and 1 mm below the apex [Figure 2] and [Figure 3].
Figure 2: Alveolar bone thickness of a tooth anterior to the cleft

Click here to view
Figure 3: Alveolar bone thickness of tooth posterior to the defect

Click here to view


Axial slice

For testing the reliability, measurements were repeated at 3 mm, 6 mm above the CEJ, and 1 mm prior to the apex on the axial slice and compared with sagittal/coronal slice.

The measurements have been repeated for the contralateral teeth on noncleft side and compared with the cleft side [Figure 4].
Figure 4: Alveolar bone thickness of contralateral noncleft site

Click here to view


Statistical analysis

All statistical analyses were performed using SPSS software package (IBM SPSS Statistics for Windows, Version 22.0., IBM Corp, Armonk, NY, USA). As the data was not following normal distribution, nonparametric tests were used. The descriptive statistics, median, and interquartile range were calculated. Wilcoxon signed-rank test was used to compare the alveolar bone thickness of teeth on cleft and noncleft side (split-mouth technique). The measurements for alveolar bone thickness on axial and coronal/sagittal slices were also analyzed and compared using Wilcoxon signed-rank test. P < 0.05 is considered to be statistically significant.


  Results Top


The alveolar bone thickness in the tooth anterior to the cleft and contralateral tooth on non cleft site was compared in sagittal/coronal slices in [Table 1]. The buccal alveolar bone for the teeth anterior to the cleft at 3 mm thinner when compared to the noncleft site. The distal alveolar bone for the teeth anterior to the cleft at 3 mm is thinner when compare to the noncleft side (P < 0.05).
Table 1: Comparison of alveolar bone thickness of the teeth anterior to the cleft and the corresponding contralateral teeth on noncleft side- sagittal/coronal view

Click here to view


Comparison of alveolar bone thickness of the tooth posterior to the cleft and contralateral noncleft site in sagittal/coronal view.[Table 2] The alveolar bone at buccal, palatal, and mesial surfaces of the teeth anterior to the cleft at 3 mm thinner when compared to the noncleft site.
Table 2: Comparison of alveolar bone thickness of the teeth posterior to the cleft and the corresponding contralateral teeth on noncleft side- sagittal/coronal view

Click here to view


Buccal bone at 3 mm from CEJ for the cleft side was thin. The buccal bone thickness progressively increases at 6 mm and 1 mm below the apex [Table 1] and [Table 2]. Palatal bone plate is the thickest of all at 1 mm below the apex. The mesial/distal alveolar bone on the cleft was also very thin. As we go toward the apex, the thickness of the alveolar bone plates increases and is highest at the area 1 mm prior to the apex. Wilcoxon signed-ranks test showed no significant difference (P > 0.05) between the measurements carried out on axial and coronal/sagittal slices [Table 3].
Table 3: Comparison of measurements between sagittal/coronal and axial slices (cleft site)

Click here to view



  Discussion Top


Measurement of the buccal bone is critical as it is extremely thin. The spatial resolution of the CBCT machines would therefore be critical. Spatial resolution is the minimum distance needed to distinguish between two objects and is often incorrectly assumed to be equal to a scan's reported resolution or voxel size.[10] Due to the multifactorial nature of spatial resolution, each machine and scan must be evaluated individually. The comparison of the alveolar bone on the cleft and noncleft side partly nullifies the issue of spatial resolution.[10] Ballrick et al. found that the 0.2-mm voxel size has an average spatial resolution of 0.4 mm, which means that it can distinguish two objects with a minimum distance of 0.4 mm.[11] Movement of the individual during image capture which may reduce the clarity of the scans, may also contribute to the spatial resolution, and may be a limiting factor in this study. The accuracy of linear measurements using Dolphin 3D imaging software was determined by Fernandes et al.[9] It was found linear measurements on multiplanar images of 0.2 and 0.4 voxel were reliable and accurate when compared with direct caliper measurements. The reconstruction Dolphin software uses the increased bit depth to improve its primary and secondary reconstructions, resulting in a cleaner and more defined volume. This software also allows the clinician to change the values of gray scale displayed on the screen using a process called windowing.

The biological width around a tooth is ideally 3 mm.[12] The maintenance of this biological width is extremely important to maintain the pink and white esthetics. One of the reasons for the decrease in the biological width is the orthodontic tooth movement into the sites of very thin alveolar bone, thereby causing its resorption.[13],[14] Clinically, this is evident by the gingival recession in the associated areas. Determining the morphology of the lingual and the buccal plates of bone before orthodontic tooth movement using 3D imaging would prevent or at least reduce the occurrence of dehiscence in the alveolar bone.[15],[16]

Bone level was measured at 3, 6 from CEJ, and 1 mm below the apex as advocated by Garib et al.[17] It was observed even at 3 mm from CEJ, the average thickness of bone at the cleft site even at 3 mm was only 150 (0, 0.80) mm [Table 1]. Therefore, the bone thickness was analyzed from 3 mm from CEJ.

The alveolar bone thickness had been evaluated previously by Ercan et al.[18] where only the buccal alveolar bone in NSULP had been measured at four levels (0, 1, 2, and 4 mm from alveolar crest) on the teeth adjacent to the cleft side and compared to the buccal bone on the noncleftside. The bone thickness was found to be 1.02 ± 0.28 mm at 2 mm from the crestal level on the cleft side at the central incisor region which is more compared to the measurements of the present study where the buccal bone thickness on the cleft side at 3 mm is 0.15 (0, 0.80). In the study by Ercan et al., no mention has been made regarding standardization for method of measurements in rotated or tilted teeth on cleft side. Their comparison between cleft and noncleft side indicated a significant difference, with the noncleft side having a thicker buccal alveolar bone. This is same as the results obtained in the present study where it was found that the buccal bone thickness at 3 mm on noncleft side was significantly thicker than cleft side [Table 1] and [Table 2]. Garib et al. have measured the alveolar bone thickness in bilateral CLP patients and their results are comparable to the present study.[17] However, in his study, the thickness of bone in the teeth distal to the cleft side is 1.46 ± 0.87 which is more when compared to the present study 0.90 (0.00, 1.65) [Table 1].

Ghoneima et al.[19] have reported overall buccal bone thickness at 3 mm to be 1.12 (0.97 ± 1.27), whereas the present study showed the overall buccal bone thickness at 3 mm to be 0.150 (0, 0.80). In his study, overall distal bone thickness at 3 mm was found to be 0.78 (0.46–1.10), whereas the present study showed the overall distal bone thickness at 3 mm to be 0.90 (0.00, 1.65). The difference in alveolar bone thickness in the two studies could be due to the differences in races, type of primary alveolar bone grafting.

Several authors have researched bone loss in the cleft region of unilateral cleft patients using various radiographic methods.[20],[21],[22] Bragger et al. reported that radiographic alveolar bone loss was greater at the cleft site as compared with controls, due to the presence of a long supracrestal connective tissue attachment.[20] Teja et al. evaluated the periodontal conditions and bone levels in patients with unilateral alveolar cleft using parallel periapical standardized radiographs and showed reduced bone levels on both the mesial and distal surfaces of central incisors adjacent to the cleft as compared to contralateral control teeth.[21] However, no difference in the bone level for canines was noted between cleft and noncleft sites. Quirynen et al. evaluated 75 patients with UCLP with regard to periodontal health status and showed that bone loss was significantly higher for teeth on the cleft side as compared with the contralateral noncleft control teeth.[22] de Almeida et al.[6] found that teeth adjacent to a cleft display a 10-fold higher prevalence of gingival recession compared to the same teeth in noncleft patients. In the cleft area, predisposing factors for the development of mucogingival problems include malpositioned tooth, lower crestal bone level, shallow vestibule secondary to cheiloplasty scar, and decreased amount of keratinized mucosa. Orthodontic tooth movement toward the cortical bone plate involves osteoclastic activity leading to bone dehiscences, contributing to the development of gingival recession in the long term. This will compromise the amount of vertical grafting required to correct the bone defect in the cleft patients before prosthetic correction using endosseous implants.

The study by Trindade and Silva Filho indicates that the cleft patients usually present with either anterior and posterior crossbites that need to be corrected before bone grafting.[23] However, this study contraindicates the commencement of orthodontic treatment of individuals with NSUCCLP before secondary bone grafting owing to the extremely thin alveolar bone.

Limitations

There was significant difference in the measurement of the alveolar bone at the level of apex of the teeth when measured on the coronal and axial slices [Table 3]. This difference is due to variation in the root morphology which can be visualized on one of the slices and is masked in the other. Single slice could not capture the apex in a multirooted teeth where plane had to be shifted to measure buccal or palatal bone. Differentiation of thickness of bones at 6 mm above the CEJ and 1 mm below apex of the root was challenging in the presence of deciduous teeth. It may be better to have CBCT data with smaller FOV which gives the better resolution of image. As we had used retrospective data from the centers, the accuracy of the measurements in some of the patients had been affected due to the availability of larger FOV with lower resolution.

Future scope

Newer CBCT machines with improved spatial resolutions to measure thin alveolar bone around the teeth may be used to get precise measurements. To validate the importance of SABG, it is necessary to compare postorthodontic alveolar bone thickness with and without ABG.


  Conclusions Top


  1. The alveolar bone around the teeth adjacent to the cleft site is thinner than noncleft site
  2. The reduced alveolar bone thickness makes these teeth more susceptible to periodontal breakdown
  3. Secondary bone grafting may be an essential treatment protocol before orthodontic intervention to preserve the labial/buccal bone as well as interdental bone to optimize the prosthetic rehabilitation of CLP patients
  4. Dehiscences were more on cleft site as compared to noncleft sites.


Financial support and sponsorship

This study is self-supported.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Aljohar A, Ravichandran K, Subhani S. Pattern of cleft lip and palate in hospital-based population in Saudi Arabia: Retrospective study. Cleft Palate Craniofac J 2008;45:592-6.  Back to cited text no. 1
    
2.
Singh M, Jawadi MH, Arya LS, Fatima. Congenital malformations at birth among live-born infants in Afghanistan, a prospective study. Indian J Pediatr 1982;49:331-5.  Back to cited text no. 2
    
3.
Iregbulem LM. The incidence of cleft lip and palate in Nigeria. Cleft Palate J 1982;19:201-5.  Back to cited text no. 3
    
4.
Proffit WR, Fields HW, Sarver DM. Contemporary Orthodontics. 5th ed. St. Louis, Missouri: Mosby Publication; 2013.  Back to cited text no. 4
    
5.
Brägger U, Schürch E Jr., Salvi G, von Wyttenbach T, Lang NP. Periodontal conditions in adult patients with cleft lip, alveolus, and palate. Cleft Palate Craniofac J 1992;29:179-85.  Back to cited text no. 5
    
6.
de Almeida AL, Gonzalez MK, Greghi SL, Conti PC, Pegoraro LF. Are teeth close to the cleft more susceptible to periodontal disease? Cleft Palate Craniofac J 2009;46:161-5.  Back to cited text no. 6
    
7.
Baumrind S, Carlson S, Beers A, Curry S, Norris K, Boyd RL, et al. Using three-dimensional imaging to assess treatment outcomes in orthodontics: A progress report from the University of the Pacific. Orthod Craniofac Res 2003;6 Suppl 1:132-42.  Back to cited text no. 7
    
8.
European Commisssion. Cone Beam CT for Dental and Maxillofacial Radiology: Evidence-Based Guidelines (radiation protection no. 172). Luxembourg: SEDENTEXCT; 2012.  Back to cited text no. 8
    
9.
Fernandes TM, Adamczyk J, Poleti ML, Henriques JF, Friedland B, Garib DG, et al. Comparison between 3D volumetric rendering and multiplanar slices on the reliability of linear measurements on CBCT images: An in vitro study. J Appl Oral Sci 2015;23:56-63.  Back to cited text no. 9
    
10.
Molen AD. Considerations in the use of cone-beam computed tomography for buccal bone measurements. Am J Orthod Dentofacial Orthop 2010;137:S130-5.  Back to cited text no. 10
    
11.
Ballrick JW, Palomo JM, Ruch E, Amberman BD, Hans MG. Image distortion and spatial resolution of a commercially available cone-beam computed tomography machine. Am J Orthod Dentofacial Orthop 2008;134:573-82.  Back to cited text no. 11
    
12.
Lindhe J, Karring T, Araujo M. The anatomy of periodontal tissues. In: Lindhe J, Karring T, Lang NP, editors. Clinical Periodontology and Implant Dentistry. 4th ed. Copenhagen, Denmark: Blackwell Munksgaard; 2003. p. 3-48.  Back to cited text no. 12
    
13.
Boloor V, Thomas B. Comparison of periodontal status among patients with cleft lip, cleft palate, and cleft lip along with a cleft in palate and alveolus. J Indian Soc Periodontol 2010;14:168-72.  Back to cited text no. 13
  [Full text]  
14.
Mulie RM, Hoeve AT. The limitations of tooth movement within the symphysis, studied with laminagraphy and standardized occlusal films. J Clin Orthod 1976;10:882-93, 886-9.  Back to cited text no. 14
    
15.
Wehrbein H, Bauer W, Diedrich P. Mandibular incisors, alveolar bone, and symphysis after orthodontic treatment. A retrospective study. Am J Orthod Dentofacial Orthop 1996;110:239-46.  Back to cited text no. 15
    
16.
Garib DG, Henriques JF, Janson G, Freitas MR, Coelho RA. Rapid maxillary expansion tooth tissue-borne versus toothborne expanders: A computed tomography evaluation of dentoskeletal effects. Angle Orthod 1973;64:278-302.  Back to cited text no. 16
    
17.
Garib DG, Yatabe MS, Ozawa TO, Filho OG. Alveolar bone morphology in patients with bilateral complete cleft lip and palate in the mixed dentition: Cone beam computed tomography evaluation. Cleft Palate Craniofac J 2012;49:208-14.  Back to cited text no. 17
    
18.
Ercan E, Celikoglu M, Buyuk SK, Sekerci AE. Assessment of the alveolar bone support of patients with unilateral cleft lip and palate: A cone-beam computed tomography study. Angle Orthod 2015;85:1003-8.  Back to cited text no. 18
    
19.
Ghoneima A, Allam E, Kula K. Effects of primary alveolar grafting on alveolar bone thickness in patients with cleft lip and palate. J Craniofac Surg 2017;28:1337-41.  Back to cited text no. 19
    
20.
Brägger U, Nyman S, Lang NP, von Wyttenbach T, Salvi G, Schürch E Jr., et al. The significance of alveolar bone in periodontal disease. A long-term observation in patients with cleft lip, alveolus and palate. J Clin Periodontol 1990;17:379-84.  Back to cited text no. 20
    
21.
Teja Z, Persson R, Omnell ML. Periodontal status of teeth adjacent to nongrafted unilateral alveolar clefts. Cleft Palate Craniofac J 1992;29:357-62.  Back to cited text no. 21
    
22.
Quirynen M, Dewinter G, Avontroodt P, Heidbüchel K, Verdonck A, Carels C, et al. A split-mouth study on periodontal and microbial parameters in children with complete unilateral cleft lip and palate. J Clin Periodontol 2003;30:49-56.  Back to cited text no. 22
    
23.
Silva Filho OG, Freitas JAS. Morphological characterization and embryological origin. In: Trinity IEK, Silva Filho OG, coordinators. Labiopalatine clefts: an interdisciplinary approach.São Paulo: Livraria Santos, 2007.p.17-49.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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
Materials and Me...
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed582    
    Printed14    
    Emailed0    
    PDF Downloaded47    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]