|Year : 2022 | Volume
| Issue : 2 | Page : 111-117
Role of TheraCal LC in pediatric dentistry: A narrative review
Durairaj Bala Anusha, Gajula Shivashankarappa Prathima, Adimoulame Sanguida, Sundaramurthy Nandakumar, Muthukrishnan Kavitha
Department of Pediatric and Preventive Dentistry, Indira Gandhi Institute of Dental Sciences, Sri Balaji Vidyapeeth (SBV) Deemed to be University, Pillaiyarkuppam, Puducherry, India
|Date of Submission||26-May-2021|
|Date of Decision||10-Dec-2021|
|Date of Acceptance||13-Dec-2021|
|Date of Web Publication||26-Apr-2022|
Dr. Gajula Shivashankarappa Prathima
Department of Pediatric and Preventive Dentistry, Indira Gandhi Institute of Dental Sciences, Sri Balaji Vidyapeeth (SBV) Deemed to be University, Pillaiyarkuppam, Puducherry 607402
Source of Support: None, Conflict of Interest: None
Aim: This narrative review aims to provide an insight into a resin-modified newer calcium silicate-based material called TheraCal LC, its uses, and scope in Pediatric Dentistry. Materials and Methods: Literature search was conducted through various databases such as PubMed, Hinari, Cochrane, and Google Scholar by three independent reviewers using both MeSH terms and free terms. The articles published in English relevant to Pediatric Dentistry were selected, whereas unpublished articles in other languages and studies done in permanent teeth in children above 15 years were excluded. From the search results obtained, n = 258 articles were relevant. The reference list of all the articles included were hand-searched; full text evaluation was done and duplicates were removed. Results: A total of 26 published articles encompassing animal in-vitro and clinical studies using TheraCal LC in primary and young permanent teeth were included. TheraCal LC exhibits shorter setting time, superior mechanical properties, esthetic, weakly radiopaque, and lower biocompatibility. This makes it suitable for its use as a good pulp capping material in deep dentinal carious lesions in primary and young permanent teeth as a protective liner/base. However, few animal studies showed that TheraCal LC is not suitable for pulpotomy and furcation perforation repair, and limited human studies were available. Conclusion: TheraCal LC is found to be a promising alternative as a pulp-capping material to other calcium silicate-based materials in the management of deep carious lesions for pediatric dental practice. However, more clinical studies with long-term follow-up are necessary for its use as a pulpotomy material.
Keywords: Direct Pulp Capping, Furcation Perforation Repair, Indirect Pulp Capping, Pulpotomy, TheraCal LC
|How to cite this article:|
Bala Anusha D, Prathima GS, Sanguida A, Nandakumar S, Kavitha M. Role of TheraCal LC in pediatric dentistry: A narrative review. J Int Oral Health 2022;14:111-7
|How to cite this URL:|
Bala Anusha D, Prathima GS, Sanguida A, Nandakumar S, Kavitha M. Role of TheraCal LC in pediatric dentistry: A narrative review. J Int Oral Health [serial online] 2022 [cited 2022 Aug 18];14:111-7. Available from: https://www.jioh.org/text.asp?2022/14/2/111/344055
| Introduction|| |
A continuous search for the pursuit of newer materials in managing deep carious lesions, its knowledge, and practice in the field of Pediatric Dentistry has assumed a crucial part in promoting the nature of treatment as well as its performance. The evolution of newer materials is aimed at improving the setting time, bond strength, biocompatibility, bioactivity, ease of handling, and patient comfort. Furthermore, it should retain the primary teeth in integrity with dental arch until physiological exfoliation. Conventional materials used for pulp capping are calcium hydroxide, glass ionomer cement, and mineral trioxide aggregate (MTA), but they exhibit longer setting time, staining potential, poor bonding, and long-term solubility. Moreover, the pulpotomy material used in cases of large carious lesions exposing pulp or procedural accidental pulpal exposure should be biocompatible and bioactive and should preserve radicular pulp.
Conventional pulp-capping materials such as calcium hydroxide exhibit higher solubility and formation of tunnel defects and increase the local pH leading to necrotic layer formation at the material–pulp interface. Compared with calcium hydroxide (Dycal), MTA is more effective causing less caustic effect to pulp following application; however, it also has higher solubility due to longer time required for setting, tendency for discoloration, and low calcium ion release. These disadvantages are overcome by TheraCal LC due to its ability to release more calcium than either calcium hydroxide or MTA, better color stability, and lower solubility. Furthermore, TheraCal LC frequently forms better quality dentinal bridge of greater thickness compared with GIC and Dycal.,
TheraCal LC is a fourth generation calcium silicate-based single paste material indicated for use in vital pulp therapy and as a protective liner or base under restoration. It possesses shorter setting time, better sealing ability, higher pH, good antimicrobial activity, less solubility, remineralizing potential, easy handling, less film thickness, and is well tolerated by odontoblastic cells., Furthermore, it causes decreased incidence of hard tissue staining due to good bioactive capacity. Although it has been used in permanent dentition, its use in Pediatric Dentistry is limited. Therefore, this review narrates the role, advantages, and disadvantages of TheraCal LC and provides an insight to its robust use in Pediatric Dentistry.
To fulfill the above aim, a research question was formulated based on PICO
- i. Problem—Deciduous and young permanent teeth with deep caries requiring vital pulp therapy;
- ii. Interventions—TheraCal LC;
- iii. Comparisons—Calcium hydroxide, glass ionomer cement, Biodentine, and MTA;
- iv. Outcomes—Improved mechanical properties and thereby useful for routine clinical practice.
| Materials and Methods|| |
Databases such as PubMed, Hinari, Cochrane, and Google Scholar were used for comprehensive literature search and identification of studies. The study was conducted without any restriction on publication time, and it followed Reporting guidelines partially based on PRISMA. For the PubMed database, combination of both MeSH terms and free terms was used as follows: (((((((((TheraCal LC) OR (Primary teeth)) OR (deciduous teeth)) OR (children)) OR (young permanent)) AND (resin modified calcium silicate)) OR (TheraCal)) OR (bioactive liners)) AND ((((((restoration) OR (base)) OR (vital pulp therapy)) OR (pulp capping)) OR (pulpotomy)) OR (furcation repair)) OR (perforation repair). For the Hinari and Cochrane databases, the following search terms were used alternatively: (TheraCal LC) AND ((Primary teeth) OR (vital pulp therapy) OR (pulp therapy) OR (young permanent teeth)). In Google Scholar, the keywords used were “TheraCal LC in primary and young permanent teeth” OR “vital pulp therapy” OR “perforation repair.” The search results obtained through these databases were analyzed and cross-checked to identify any duplicates present and eliminate them.
Titles and abstracts were screened by three authors (GSP, SA, and DBA) independently during the initial phase. Only those articles published in the English language and relevant to Pediatric Dentistry were included. From the search results obtained, only n = 258 articles were relevant. Full-text evaluation was done for the studies selected during the initial phase. For definitive inclusion, three exclusion criteria were considered such as manuscripts not published, published articles in languages other than English, and studies done in mature permanent teeth in subjects above the age group of 15 years. The references of all the selected studies were also cross-checked for retrieving every potentially relevant article, and in total n = 26 articles met all the eligibility criteria. Among them, studies included were animal studies (n = 2) assessing the biocompatibility of TheraCal LC in pulp capping and perforation repair, in-vitro studies (n = 16) assessing the properties, bioactivity, and efficacies of TheraCal LC in vital pulp therapy in deciduous teeth, comparative studies, clinical and radiographic studies (n = 4) with follow-up period of more than 6 months, period that assessed the effectiveness of TheraCal LC in the treatment of human deciduous and young permanent teeth with deep dentinal caries approximating pulp and review articles (n = 4) comparing the efficacy of TheraCal LC with other similar materials. Flowchart of review process and the search strategy used as per PRISMA statement were shown in [Figure 1].
|Figure 1: Flowchart of review process and search strategy according to PRISMA statement|
Click here to view
Risk of bias and quality assessment
Assessment of any methodological bias in the in-vitro studies included in this article was done independently using the checklist “Modified CONSORT guidelines for reporting Pre-clinical In-vitro Studies on Dental Materials.” Each of the parameters and items included in the checklist was analyzed for each in-vitro study for their fulfillment, and using Yes (Y) or No (N) terms, the parameters were recorded. Furthermore, the compliance for each study was calculated in percentage. The characteristics of each in-vitro study relevant to Pediatric Dentistry included in this article and the quality assessment results obtained using the aforementioned guidelines were presented in [Table 1] and [Table 2]. The mean value of percentage (%) compliance obtained from the included in-vitro studies was 56%. The highest score obtained was 57% and the lowest score obtained was 50%. Criteria such as determination of sample size, methods used for randomization, mechanism used for concealment, implementation, and blinding (Items 5–9) were not satisfied by any of the included studies. Most of the included studies fulfilled certain criteria such as scientific background, objectives, intervention, outcomes, statistical analysis, and outcomes (items 2–4, 10, and 11).
|Table 1: Characteristics of included studies relevant to Pediatric Dentistry|
Click here to view
The characteristics of clinical trials included in this article were shown in [Table 3] based on their outcomes. Two authors (GSP and DBA) independently reviewed the included studies for assessing risk of bias using “OHAT risk of bias assessment tool for human studies.” Six domains concerned to randomization methods, blinding, outcomes, drop-outs during follow-up and baseline sample characteristics were assessed. Each of the studies was categorized into either definitely high risk, probably high risk, probably low risk, and definitely low risk based on the aforementioned domains. When there was any uncertainty about the potential for bias or difficulty in finding information, the study was rated “unclear.” In case of any discrepancies between the authors, solution was obtained through mutual agreement and discussion. Risk of bias results of the studies obtained was presented in [Table 4] and [Figure 2].
|Table 4: Assessment of risk of bias of the included studies evaluated with OHAT tool|
Click here to view
TheraCal LC (Bisco, Schaumburg, USA) was introduced in 2011, to overcome the reduced bonding capacity of calcium silicate materials to overlying resin restoration. It is a resin-modified, light cured, white colored, tricalcium silicate-based hybrid material.,, It does not require any mixing like other conventional pulp-capping materials as it is directly dispensed from a flowable syringe which is an advantage in Pediatric Dentistry. The advantages of TheraCal LC compared with other pulp therapy materials were described in [Table 5].
|Table 5: Advantages and disadvantages of TheraCal LC compared with other materials|
Click here to view
According to Gandolfi et al. and Cantekin, when TheraCal LC is placed at a thickness of 1–1.7 mm and cured with a light-emitting diode (LED) cure unit of 1200 mW/cm2 for 20 s, the depth of curing is higher which is suitable for immediate placement of final restoration, thus reducing the number of appointments in Pediatric Dentistry. As per Wassel et al., this ability to polymerize up to 1.7 mm depth might avoid untimely dissolution of the material, thereby preventing marginal leakage.
TheraCal LC is a hydraulic silicate material diffused with water from the environment and sets by hydration reaction when placed over moist dentine. This results in release of calcium (Ca) and hydroxyl ions (OH), leading to the production of calcium apatite on the surface and differentiation of odontoblasts to form new dentine. However, the hydroxyl ions provide alkaline pH between 8 and 11 and create a hostile environment for the survival of bacteria and its proliferation.,
Properties of TheraCal LC
TheraCal LC contains high molecular weight compounds with higher amounts of additives such as camphorquinone (4.11 µg/mm2) and ethyl-4-(dimethylamino)benzoate (19.95 µg/mm2) and it has less pore volume. These small-sized pores increase the sealing ability and decrease the internal and external surface of material, leading to reduced elution rate. However, it majorly contains calcium silicate, so transmission of light while curing is poor, thereby posing curing difficulties to dentists. Additionally, the mechanical, thermal, biocompatible properties and radiopacity of TheraCal LC have been explained below.
According to Cantekin, TheraCal LC with overlying methacrylate-based composite as final restoration exhibited higher shear bond strength of 19.3 MPa compared to resin-modified GIC (5.7 MPa) and MTA (8.8 MPa), thereby resisting contraction forces and renders gap-free restoration margins. Furthermore, Alzraikat et al. added that the strength of TheraCal LC to bond to dentin is unaffected by the type of adhesive system, thereby allowing it to be used with any type of adhesive system. TheraCal LC exhibited setting expansion similar to Dycal enabling better marginal seal when compared with MTA which exhibited shrinkage. It demonstrated higher compressive strength and superior push-out bond strength compared with other pulp-capping materials.
Following polymerization of TheraCal LC, the lowest temperature rise to about 7.53 ± 1.34°C was observed in permanent teeth. In an animal study conducted by Zach and Cohen, pulpal necrosis occurred when the temperature elevated to 5.6°C in about 15% of teeth. As the temperature increased further to about 11.1°C and 16.6°C, a greater number of teeth (about 60% and 100%) showed pulpal necrosis. According to Savas et al., TheraCal LC exerts lowest mean temperature rise and lower specific heat capacity contributing to high thermal insulating properties and preserving the health of underlying vital pulp in permanent teeth. Contrary to the aforementioned study, Ertuğrul and Ertuğrul observed an increase in the intrapulpal temperature of 5.97 ± 0.48°C using TheraCal LC in the primary tooth pulp chamber, which was below the values observed for Dycal and direct compomer restoration but above the critical value of 5.5°C. Thus, TheraCal LC could be a suitable indirect pulp-capping material for use in both primary and permanent teeth, but it should be used with caution due to induction of potentially adverse pulpal effects.
There is a controversy regarding radiopacity of Theracal LC wherein Gandolfi et al. in their study showed it to be weakly radiopaque material (1.07 ± 0.06), i.e., lesser than the ISO standard 6976:2002 requirement of radiopacity ≥3 mm Al. However, the material is sufficiently radiopaque to be distinguishable even when placed in thin layers.
Jeanneau et al. in their in-vitro study using TheraCal LC in pulp stem cells extracted from human immature permanent molar showed that the material exerted toxicity toward pulpal fibroblast and exhibits lower bioactivity and high inflammatory tendency. When placed in entire tooth culture model as a capping material, TheraCal LC caused partial or complete disorganization of underlying pulp tissue. Nam et al., Kim et al., and Luis Sanz et al. in their in-vitro study on biocompatibility of this material using human exfoliated deciduous teeth stem cells (SHEDs) concluded that the viability and migration rate of cells were lower and slower for TheraCal LC when compared with other self-cure calcium silicate-based materials such as Biodentine and MTA. Poggio et al. added that TheraCal LC exhibited superior cytocompatibility than Dycal, but antibacterial activity against Streptococcus mutans was lower for TheraCal LC when used in pulp capping.
Clinical applications of TheraCal LC
TheraCal LC is used as a protective liner/base with restorative material, in indirect and direct pulp capping. However, few clinical studies are available regarding its extended use in pulpotomy and furcation repair in Pediatric Dentistry.,
TheraCal LC when used as a base under a compomer restoration in primary teeth demonstrated the material to be stable, durable, caused lowest increase in intrapulpal temperature during polymerization process, and stimulated hydroxyapatite and secondary dentine bridge formation.
As per Arandi et al.,, TheraCal LC when used as an indirect pulp-capping liner provides firm, protective lining while contacting dentinal or pulpal fluids. Besides, it provides a strong mechanical barrier and acts as an insulator to protect the dental pulp complex against microbial damage and induces formation of a dentine-like bridge between restorative material and pulp. In harmony with the results obtained from the study done by Gandolfi et al. and Beegum et al., TheraCal LC discharged more calcium and hydroxyl ions than MTA, Calcimol LC, Dycal, and composite, making it a uniquely durable and highly stable material.
According to an in-vitro study conducted by Nam et al., Differentially Expressed Genes profiles of primary tooth pulp demonstrated overlapping results, indicating their bioactive effects on pulp, i.e., cells exposed to TheraCal LC for more than 24 h exhibited significantly enhanced calcium ion concentration, immune responses, inflammatory response, and neutrophilic chemotaxis when compared with MTA., A clinical study done by Menon et al. in primary and young permanent molars using TheraCal LC as an indirect pulp-capping agent showed a success rate of 87.8%, which was higher than Dycal (84.6%) both clinically and radiographically. It provided a hermetic seal to prevent bacterial contamination which was similar to the study done by Gurcan and Seymen.
In an in-vitro study done by Kamal et al. (2018) using TheraCal LC as direct pulp-capping material in extracted permanent teeth, severe inflammatory response following 1 week was observed which was contradicted by Chen and Suh who suggested comparable or better clinical outcomes with less cytotoxicity using TheraCal LC. Following 1 and 6 months, pulp tissue disorganization, numerous vacuolations, formation of new calcified matrix, and dentin bridge formation with mild chronic inflammatory responses were observed. In human exfoliated primary teeth, the resin monomers in this material exerted toxicity in dental pulp cells and lowered cell viability and migration, resulting in reduced hard tissue regeneration. To prevent this, Nam et al. suggested that the material should be kept in thin coatings and cured sufficiently in an increment of 1 mm.
A clinical study was done by Erfanparast et al. in primary molars using TheraCal LC as a direct pulp-capping agent. It showed 91.8% success rate clinically and radiographically without any evidence of internal root resorption. Although TheraCal LC has resin contents owing to the appropriate curing and superior handling characteristics, it could be used as an alternative material in pulp capping.
In an animal study conducted by Lee et al., partial pulpotomy done using TheraCal LC resulted in the formation of less favorable odontoblastic layer, mild dental pulp congestion, lower calcific barrier, and higher inflammatory reactions. Pulpotomy done by Collado-González et al. in primary teeth using TheraCal LC exhibited decreased cell proliferation, viability, and migration with limited cell attachment. No evidence of tooth discoloration was observed. Histologically, infiltration of chronic inflammatory cells, hard tissue, and osteodentin formation were observed. In one clinical study conducted by Wassel et al., internal root resorption was noticed despite the radiographic success rate of 96.7% and 100% success rate clinically with no signs of pain, abscess, fistula, mobility, and gingivitis.
Furcation perforation repair
TheraCal LC when used as a furcation perforation repair material, Alazrag et al. in their in-vitro study showed that the material exhibited lower sealing capacity, high distribution of gap, poor marginal adaptability, low solubility, less biocompatibility, and less microleakage. Thus, it may not be considered as a good perforation repair material, although more studies need to be conducted to arrive at a definitive conclusion.
| Conclusion|| |
The advantages of TheraCal LC exceed its disadvantages; it is definitely a promising alternative to other calcium silicate-based materials for managing deep carious lesions in Pediatric dental practice. However, further clinical studies with long-term follow-up are necessary for determining the clinical efficacy of this material in direct pulp capping. To understand the extended purpose of this material for pulpotomy and furcation perforation repair in Pediatric Dentistry, more clinical studies with larger sample size and long-term follow-up period are necessary.
Financial support and sponsorship
Conflicts of interest
The authors declare no conflict of interest.
GSP conceived the idea and study design. GSP, SA, and DBA performed the literature search and MK performed the extraction of data. DBA drafted the manuscript. GSP and NK reviewed the manuscript.
Ethical policy and Institutional Review Board statement
Patient declaration of consent
Data availability statement
Data are available itself in manuscript.
| References|| |
Gurcan AT, Seymen F. Clinical and radiographic evaluation of indirect pulp capping with three different materials: A 2-year follow-up study. Eur J Paediatr Dent 2019;20:105-10.
Erfanparast L, Iranparvar P, Vafaei A. Direct pulp capping in primary molars using a resin-modified Portland cement-based material (TheraCal) compared to MTA with 12-month follow-up: A randomised clinical trial. Eur Arch Paediatr Dent 2018;19:197-203.
Wassel M, Amin D, Badran A. Clinical, radiographic and histological evaluation of TheraCal pulpotomy in human primary teeth. Egypt Dent J 2017;63:2175-85.
Gandolfi MG, Siboni F, Prati C. Chemical-physical properties of TheraCal, a novel light-curable MTA-like material for pulp capping. Int Endod J 2012;45:571-9.
Arandi NZ, Rabi T. TheraCal LC: From biochemical and bioactive properties to clinical applications. Int J Dent 2018;2018:3484653.
Jain B, Tiku A. A comparative evaluation of shear bond strength of three different restorative materials to Biodentine and TheraCal LC: An in-vitro
study. Int J Appl Dent Sci 2019;5:426-9.
Nam O, Kim J, Choi S, Kim Y. Time-dependent response of human deciduous tooth-derived dental pulp cells treated with TheraCal LC: Functional analysis of gene interactions compared to MTA. J Clin Med 2020;9:531.
Faggion CM Jr. Guidelines for reporting pre-clinical in vitro
studies on dental materials. J Evid Based Dent Pract 2012;12:182-9.
Kunert M, Szymanska M. Bio-inductive materials in direct and indirect pulp capping—A review article. Materials 2020;13:1204.
Cantekin K. Bond strength of different restorative materials to light-curable mineral trioxide aggregate. J Clin Pediatr Dent 2015;39:143-8.
Alzraikat H, Taha NA, Qasrawi D, Burrow MF. Shear bond strength of a novel light cured calcium silicate based-cement to resin composite using different adhesive systems. Dent Mater J 2016;35:881-7.
Gasperi TL, Silveira JACD, Schmidt TF, Teixeira CDS, Garcia LDFR, Bortoluzzi EA. Physical-mechanical properties of a resin-modified calcium silicate material for pulp capping. Braz Dent J 2020;31:252-6.
Nilsen BW, Jensen E, Örtengren U, Michelsen VB. Analysis of organic components in resin-modified pulp capping materials: Critical considerations. Eur J Oral Sci 2017;125:183-94.
Savas S, Botsali MS, Kucukyilmaz E, Sari T. Evaluation of temperature changes in the pulp chamber during polymerization of light-cured pulp-capping materials by using a VALO LED light curing unit at different curing distances. Dent Mater J 2014;33:764-9.
Ertuğrul CÇ, Ertuğrul İF. The effect of current pulp capping materials against intrapulpal temperature increase in primary teeth. An in-vitro
study by pulpal microcirculation simulation model. J Dent Sci 2021;16:85-90.
Jeanneau C, Laurent P, Rombouts C, Giraud T, About I. Light-cured tricalcium silicate toxicity to the dental pulp. J Endod 2017;43:2074-80.
Kim Y, Lee D, Song D, Kim H, Kim S. Biocompatibility and bioactivity of set direct pulp capping materials on human dental pulp stem cells. Materials 2020;13:3925.
Luis Sanz J, Forner L, Llena C, Girones J, Melo M, Rengo S, et al
. Cytocompatibility and bioactive properties of hydraulic calcium silicate-based cements (HCSCs) on stem cells from human exfoliated deciduous teeth (SHEDs): A systematic review of in vitro
studies. J Clin Med 2020;9:3872.
Poggio C, Arciola C, Beltrami R, Monaco A, Dagna A, Lombardini M, et al
. Cytocompatibility and antibacterial properties of capping materials—Research article. Sci World J 2014;2014:1-10.
Beegum MS, George S, Anandaraj S, Sumi Issac J, Khan S, Ali Habibullah M. Comparative evaluation of diffused calcium and hydroxyl ion release from three different Indirect pulp capping agents in permanent teeth—An in vitro
study. Saudi Dent J2021;33:1149-53.
Nam O, Lee H, Kim J, Chae Y, Hong S, Kang S, et al
. Differential gene expression changes in human primary dental pulp cells treated with biodentine and TheraCal LC compared to MTA. Biomedicines 2020;8:445.
Menon NP, Varma BR, Janardhanan S, Kumaran P, Xavier AM, Govinda BS. Clinical and radiographic comparison of indirect pulp treatment using light-cured calcium silicate and mineral trioxide aggregate in primary molars: A randomized clinical trial. Contemp Clin Dent 2016;7:475-80.
] [Full text]
Chen L, Suh BI. Cytotoxicity and biocompatibility of resin-free and resin-modified direct pulp capping materials: A state-of-the-art review. Dent Mater J 2017;36:1-7.
Kamal EM, Nabih SM, Obeid RF, Abdelhameed MA. The reparative capacity of different bioactive dental materials for direct pulp capping. Dent Med Probl 2018;55:147-52.
Lee H, Shin Y, Kim SO, Lee HS, Choi HJ, Song JS. Comparative study of pulpal responses to pulpotomy with ProRoot MTA, RetroMTA, and TheraCal in dogs’ teeth. J Endod 2015;41:1317-24.
Collado-González M, García-Bernal D, Oñate-Sánchez RE, Ortolani-Seltenerich PS, Álvarez-Muro T, Lozano A, et al
. Cytotoxicity and bioactivity of various pulpotomy materials on stem cells from human exfoliated primary teeth. Int Endod J 2017;50(Suppl. 2):e19-30.
Alazrag MA, Abu-Seida AM, El-Batouty KM, El Ashry SH. Marginal adaptation, solubility and biocompatibility of TheraCal LC compared with MTA-Angelus and Biodentine as a furcation perforation repair material. BMC Oral Health 2020;20:298.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]