ORIGINAL RESEARCH

https://doi.org/10.5005/jp-journals-10005-2657
International Journal of Clinical Pediatric Dentistry
Volume 16 | Issue S-2 | Year 2023

Clinical and Radiographic Evaluation of Nigella sativa and Aloe vera as Pulpotomy Medicaments in Primary Teeth: A Randomized Controlled Trial

Rana M Sharaf¹ https://orcid.org/0000-0001-8695-4689, Noha S Kabil² https://orcid.org/0000-0002-2897-1840, Fadia S Youssef³ https://orcid.org/0000-0002-5871-2639, Basma G Awad⁴ https://orcid.org/0000-0002-2315-6396

^1,2,4Department of Pediatric Dentistry and Dental Public Health, Ain Shams University, Cairo, Egypt

³Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

Corresponding Author: Rana M Sharaf, Department of Pediatric Dentistry and Dental Public Health, Ain Shams University, Cairo, Egypt, e-mail: ranasharaf@hotmail.com

ABSTRACT

Aim: To evaluate the clinical and radiographic efficacy of Nigella sativa and Aloe vera as pulp medicaments in primary molars in comparison to formocresol.

Materials and methods: This randomized controlled trial is a three-arm, parallel-group study. This research included 66 vital, carious primary molars that required pulpotomy treatment in 4–7-year-old children. Teeth were randomly assigned to one of the three groups: groups (1–3) Nigella sativa, Aloe vera, and formocresol, respectively. All teeth were covered with stainless steel crowns (SSC) after the pulpotomy procedure was done and were assessed clinically and radiographically at 3, 6, and 12 months following Zurn and Seale criteria.

Results: After 12 months, the clinical success rate was found to be 40, 90, and 72.7% for Nigella sativa, Aloe vera, and formocresol groups, respectively. While the radiographic assessment showed a success rate of 20, 72.7, and 81.8%, respectively.

Conclusion: Aloe vera can be considered as an alternative pulpotomy medicament to formocresol. On the other hand, Nigella sativa is not recommended to be used in pulpotomy procedures. Further long-term follow-up clinical studies and histological studies are recommended.

Clinical significance: Although formocresol is the most popular used material in pulp therapy, concerns were raised regarding its toxicity and carcinogenicity by the International Agency for Research on Cancer (IARC). Consequently, herbal medicine is expanding rapidly worldwide nowadays and herbal extracts are suggested as an alternative to formocresol for their proposed antibacterial and anti-inflammatory properties.

How to cite this article: Sharaf RM, Kabil NS, Youssef FS, et al. Clinical and Radiographic Evaluation of Nigella sativa and Aloe vera as Pulpotomy Medicaments in Primary Teeth: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2023;16(S-2):S195–S201.

Source of support: Nil

Conflict of interest: None

Keywords: Aloe vera, Formocresol, Nigella sativa, Primary molars, Pulpotomy, Randomized controlled trial

INTRODUCTION

One of the main objectives of pediatric dentistry is to preserve primary teeth in the oral cavity till their natural exfoliation time.¹ Premature extraction of deciduous teeth was found to cause various features of malocclusion and space loss in the mixed and permanent dentitions, which might lead to the need for orthodontic treatment later on. Hence, primary tooth preservation is always preferred over extraction whenever it is clinically possible to maintain arch integrity by acting as a natural space maintainer.²

Dental caries is an infectious, chronic condition that represents the most prevalent chronic disease in children worldwide therefore, it has received significant attention to identify its causes and management.³ Pulpal exposures are common in teeth with extensive decay owing to the anatomy of primary teeth. The first line of treatment for such cases is pulp therapy to maintain the vitality and function of the radicular pulp and sustain the tooth to preserve function, space, esthetics, and speech.³

Depending on the extension of the caries lesion, different pulp treatment techniques are available, where vital complete pulpotomy is the most common. Pulpotomy is recommended in a tooth with a normal pulp, or with reversible pulpitis, or after a traumatic pulp exposure and when there are no radiographic signs of infection or pathologic resorption. It is described as the removal of the coronal pulp tissue, followed by achieving hemostasis of the remaining pulp with slight mechanical pressure with moist cotton under proper isolation.⁴

For decades, formocresol, which is composed of formaldehyde and cresol, has been successfully used as a pulp dressing material with good clinical and radiographic outcomes. Formocresol is the most commonly used material in pulp therapy for its well-known bacteriostatic and fixative properties.³^,⁵ In 2004, concerns were raised regarding its toxicity and carcinogenicity by the International Agency for Research on Cancer (IARC). Formaldehyde has been declared a human carcinogen, leading professionals to search for a safer, less toxic pulp medicament with a better success rate.⁶

A large number of pulp medicaments have been proposed in the literature for the pulpotomy procedure to substitute formocresol, such as mineral trioxide aggregate (MTA), ferric sulfate, sodium hypochlorite, calcium hydroxide, laser, electrosurgery, freeze-dried bone, collagen, and bone morphogenic protein.³^,⁷ Currently, the use of biocompatible materials has become more attractive in modern dentistry. In this regard, the field of phytotherapy, which is the utilization of plants or plant extracts for medicinal reasons, has emerged once again in the past few years.⁸

Evidence shows that herbal remedies have been utilized in disease management for >5,000 years,⁸ there is a worldwide growing interest nowadays due to their promising results, safety, economic benefits, and fewer side effects. In the dental practice, herbal extracts can be considered a great alternative to the formocresol for their proposed anti-inflammatory, antioxidant, antifungal, antibacterial, antiviral, and analgesic properties. According to the World Health Organization, 80% of people around the world use herbal medicine for their healthcare needs. Moreover, around 25% of the medicines used in developed countries are derived from plants.⁹

A wide range of plants have been used for their remarkable medicinal benefits, such as Allium sativum, propolis, turmeric, Nigella sativa, Aloe vera, Thymus vulgaris, castor oil, and Ankaferd blood stopper.¹⁰ Plant extracts have been used in the dental field for several years in mouthwashes, and toothpastes to treat or prevent dental caries and gingival diseases. Moreover, herbal extracts have been used as root canal irrigants, hemostatic agents, pulp medicaments and in the treatment of chronic oral diseases.⁹

Hence, the purpose of this study was to evaluate and compare the pulp response clinically and radiographically after complete vital pulpotomy in primary molars using formocresol as the control group and Nigella sativa, and Aloe vera ethanolic extracts as the tested groups.

MATERIALS AND METHODS

Study Design

This study was designed as a three-parallel arms randomized controlled trial, with a 1:1:1 allocation ratio. Each participant was randomly allocated to one of the following study groups to avoid selection bias.

Ethical approval number (041906) was obtained from the Research Ethical Committee of the Faculty of Dentistry, Ain Shams University. The current study was registered at ClinicalTrial.gov with the registration number (NCT04719247). The design followed the Consolidated Standards of Reporting Trials checklist (CONSORT 2010).

A verbal and written consent were signed by the caregivers of the participants prior to the conduction of the study after explaining the objectives and assuring them of the complete confidentiality of the data. Moreover, an assent form was signed by the patients themselves who were above 6 years old, after explaining the procedures to be done and their objectives.

Primary Outcome

The success of the natural material extracts as pulp medicaments after vital pulpotomy procedure in primary molars, in comparison to the standard formocresol pulpotomy by assessing different clinical and radiographic signs and symptoms at 3, 6, and 12 months of follow-up is the primary outcome.

Sample Size Calculation

A power analysis was designed to have adequate power to apply a statistical test of the null hypothesis that no difference would be found in the clinical and radiographic success between the tested materials and formocresol when used as pulpotomy medicaments in primary molars. According to the results of Alolofi et al.,¹¹ adopting an α level of (0.05) a β of (0.2) (i.e., power of 80%) and effect size (W) of (0.517) calculated based on the results of the previous studies; the predicted sample size (n) was found to be (54) teeth (i.e., 18 teeth per group). The sample size was increased by (20%) to compensate for possible dropouts during different follow-up intervals to be a total of (66) teeth (i.e., 22 teeth per group). Sample size calculation was performed using G*Power version 3.1.9.7.

Participants Details

A total of 66 molars were randomly selected from the outpatient clinic of the Department of Pediatric Dentistry and Dental Public Health. Only patients who met the inclusion criteria were included in this study till the predetermined number of teeth was reached. Participation of subjects through the trial is illustrated in the CONSORT flow diagram (Flowchart 1).

Flowchart 1: Flowchart of recruitment

Inclusion criteria followed the guidelines of the American Academy of Pediatric Dentistry.⁴ It involved patients aged 4–7 years old, who were medically free. The teeth selected were vital primary lower second molars with deep carious lesions which were indicated for pulpotomy. The included molars had no clinical or radiographic signs and symptoms of irreversible pulpitis such as pain on percussion, tooth mobility, presence of sinus or fistula, history of swelling, periapical pathosis or signs of internal or external root resorption. On the other hand, children with known allergies to any of the tested materials, and children whose parents refused to sign the consent for the treatment were totally excluded. As well as molars that were badly broken down and in case of uncontrolled bleeding after amputation of the coronal pulp.

Randomization and Allocation Concealment

The 66 molars were randomly divided using a computer-generated tool (https://www.sealedenvelope.com) into three groups: group I to group III in which 22 molars were allocated in each group.

Group I → Nigella sativa, group II → Aloe vera, group III → formocresol.

Numbered opaque sealed envelopes were used, each containing the predetermined treatment according to the allocation sequence. The main investigator was blinded for the allocation sequence throughout the whole trial period.

Blinding

This study was triple-blinded, the participants, coinvestigators, and statistician were blinded throughout the study, whereas the main investigator could not be blinded because the materials are obvious due to the significant difference in color and smell.

Material Preparation

Nigella sativa and Aloe vera plants were authenticated by their morphological characteristics by a consultant of plant taxonomy at the Ministry of Agriculture. Nigella sativa plants were crushed into fine powder and then exposed to exhaustive maceration using absolute distilled ethanol.¹²Aloe vera leave was cut, and the thick epidermis was removed. The solid mucilaginous, thick straw-colored gel was collected in a sterile container,¹³ and an ethanolic extract was prepared by exhaustive maceration using absolute distilled ethanol.¹²

Clinical Procedure

Preoperative radiographs were taken as a baseline by the parallel technique using a film holder (TCP X-ray holder, USA) and phosphor plate (AC TEON®) 2, and FONA scanner (FONA ScaNeo, FONA, Italy/OrisWin DG Suite imaging software). In all groups, local anesthesia (ARTINIBSA™ 40 mg/0.01 mg/mL, Spain) was given to teeth, and a rubber dam was applied for isolation. All caries were removed, and the pulp chamber was deroofed using a number 5 round bur with a high-speed handpiece and water spray. After access to the pulp chamber was achieved, coronal pulp tissue was removed using a sterile small sharp excavator (Maillefer Dentsply size 51/52), followed by applying gentle pressure with a moist cotton pellet on the amputated pulp stumps for hemostasis. When hemostasis could not be achieved the tooth was excluded from the study.

After hemostasis, a drop of the preprepared ethanolic plant extract or formocresol (Sultan®, USA) was applied on a cotton pellet depending on the assigned group. The damped cotton pellet was then put on the amputated pulp stumps for 5 minutes followed by a mix of reinforced zinc oxide eugenol (Zinconol, Prevest DenPro®, India). Finally, the tooth was restored with SSC (KidsCrown, Shinhung, Korea) which was cemented with glass ionomer cement (MEDICEM, Promedica, Germany) (Fig. 1). Postoperative radiographs were also taken by the parallel technique.

Figs 1A to D: (A) Carious lower second primary molar; (B) Pulpotomy was done and hemostasis was achieved; (C) After applying the ethanolic plant extract on the pulp tissue; (D) The tooth is covered with a SSC

Follow-up

During the follow-up phase, patients were recalled for clinical and radiographic evaluation by two blinded and calibrated coinvestigators after 3, 6, and 12 months with interexaminer and intraexaminer reliability of 0.74 and 0.82.

Teeth were evaluated clinically for the presence of pain, soft tissue swelling, or mobility and clinical signs were scored according to the modified Zurn and Seale criteria.¹⁴ Using the same scoring system, radiographic evaluation was done,¹⁴ the presence of pathological internal or external root resorption, interradicular or periapical bone loss, widening in the periodontal ligament space, canal obliteration, and interradicular or periapical radiolucency were assessed. Furthermore, Any clinical or radiographic changes were considered as failure (scores 2, 3, and 4)¹⁵ (Fig. 2).

Figs 2A to G: Follow-up Nigella sativa group; (A) Preoperative radiograph; (B) 3 months follow-up; (C) 6 months follow-up; (D) 12 months follow-up. Follow-up Aloe vera group; (E) Preoperative radiograph; (F) 6 months follow-up; (G) 12 months follow-up

Statistical Methods

Categorical and ordinal data were presented as frequency and percentage values. Categorical data were analyzed using Fisher’s exact test. Ordinal data were analyzed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Bonferroni correction for intergroup comparisons. The significance level was set at p ≤ 0.05 within all tests. Statistical analysis was performed with R statistical analysis software version 4.1.3 for Windows.¹⁸

RESULTS

A total of 66 teeth were included in the study according to the precalculated sample size, but two teeth were lost during the follow-up period. No statistically significant difference was found between the number of boys and girls in the different groups where 32 boys (48.48%) and 34 girls (51.51%) participated in this study. The age of the participants ranged from 4 to 7 years with a mean age of 5.58 years with no significant difference between the mean age values in the three groups.

All groups showed 100% clinical success after 3 months of follow-up. On the other hand, after 6 months, 20% of the cases in the Nigella sativa group scored (2) and (3), while 18.2% of the cases in the Aloe vera group scored (2) the rest of the cases scored (1) with no statistically significant difference between tested groups (p = 0.092). After 12 months follow-up, clinical success rate was highest for the Aloe vera group at 90.9%, followed by the formocresol group at 72.7%, and finally Nigella sativa group at 40%. There was a statistically significant difference between the Aloe vera group and the Nigella sativa group (Table 1).

**Table 1:** Frequency and percentage values for clinical outcome in different groups
Time	Score		Groups			p–value
Time	Score		Nigella sativa	Aloe vera	Formocresol	p–value
3 months	Success	n	20	22	22	NA
	Success	%	100.0%	100.0%	100.0%
	Failure	n	0	0	0
	Failure	%	0.0%	0.0%	0.0%
6 months	Success	n	16	18	22	0.090 ns
	Success	%	80.0%	81.0%	100%
	Failure	n	4	4	0
	Failure	%	20.0%	18.2%	0.0%
12 months	Success	n	8^B	20^A	16^AB	0.002*
	Success	%	40.0%	90.9%	72.7%
	Failure	n	12	2	6
	Failure	%	60.0%	9.1%	27.3%

Values with different superscript letters within the same horizontal row are significantly different. *, significant (p ≤ 0.05); ns, nonsignificant (p > 0.05); NA, not applicable

Regarding the radiographic success rate, all groups were successful after 3 months of follow-up. After 6 months, 40% of the cases in the Nigella sativa group and 18.2% of the cases in the formocresol group failed with scores (2) and (3) and the difference between tested groups was statistically significant (p = 0.005). After 12 months of follow-up, the success rate was highest for the formocresol group at 81.8%, followed by Aloe vera with a success rate of 72.7%, while the lowest radiographic success rate was found in the Nigella sativa group at 20%. The success of the Nigella sativa group was significantly lower than the other two groups (Table 2).

**Table 2:** Frequency and percentage values for radiographic outcome in different groups
Time	Score		Groups			p-value
Time	Score		Nigella sativa	Aloe vera	Formocresol	p-value
3 months	Success	n	20	22	22	NA
	Success	%	100.0%	100.0%	100.0%
	Failure	n	0	0	0
	Failure	%	0.0%	0.0%	0.0%
6 months	Success	n	12^B	22^A	18^AB	0.005*
	Success	%	60.0%	100.0%	81.8%
	Failure	n	8	0	4
	Failure	%	40.0%	0.0%	18.2%
12 months	Success	n	4^B	16^A	18^A	<0.001*
	Success	%	20.0%	72.7%	81.8%
	Failure	n	16	6	4
	Failure	%	80.0%	27.3%	18.2%

Values with different superscript letters within the same horizontal row are significant;*, significant (p ≤ 0.05); ns, nonsignificant (p > 0.05); NA, not analyzed

DISCUSSION

Pulp therapy is the appropriate alternative to extraction in most clinical situations, in an attempt to preserve primary teeth in the oral cavity till natural exfoliation time. Pulpotomy is the most common technique for vital teeth with exposed pulp where the inflamed coronal pulp is removed, and the vital radicular pulp is preserved. The success of this procedure depends on the mechanism of action of the pulp medicament used and its capability to either devitalize (as formocresol) or regenerate (as MTA) the radicular pulp.³^,⁵

Despite that formocresol pulpotomy is the most widely used technique with a high reported success rate but it had been suggested to cause nasopharyngeal cancer and leukemia. This controversy about its carcinogenicity and mutagenicity shifted the population’s interest towards finding an alternative pulp dressing.⁶ Hence, recent regenerative materials were proposed as MTA and Biodentin with a good success rate, but they are not cost-effective.¹⁶ Accordingly, the demand towards the use of natural products has emerged due to its known efficiency and safety in disease management as well as its affordable price.

There had been a paradigm shift toward the use of natural materials replacing the currently available chemical agents. Herbs and herbal extracts have been used in the dental field owing to their anti-inflammatory, antibacterial, and antioxidant characteristics.⁹ The most proposed bacteriostatic and bactericidal mechanisms of natural antibacterial agents are related to the integrity of the cell wall and cytoplasmic membrane. Leakage of the cell wall and damage of the peptidoglycan layer caused by the active compounds of some medicinal plants on gram-positive pathogenic bacteria were mentioned in multiple studies.¹⁷

Therefore, this study was designed to assess the pulp reaction clinically and radiographically when herbal extracts (Nigella sativa and Aloe vera) are used as pulp medicaments in primary molars in comparison to the formocresol at 3, 6, and 12 months follow-up.

Nigella sativa is an herbal plant with a prosperous historical and religious background. It is usually called black seed or black cumin. Nigella sativa is cultivated in many areas including the Middle East, South Europe, India, Turkey, Syria, and Saudi Arabia. It is well known for its many therapeutic potentials as antidiabetic, antihypertensive, gastro, pulmonary and renal protective effects.¹⁸

Due to the beneficial medical properties of the Nigella sativa, it is proposed to be used in multiple applications in dentistry as in the management of oral ulcers, gingival and periodontal diseases, and in dental caries prevention. The proven antibacterial, analgesic and anti-inflammatory actions of the black seed extract made it a good candidate for pulpotomy procedures.¹⁹ Various in vitro studies have found an inhibitory action of Nigella sativa on the growth of Streptococcus mutans.¹⁷^,²⁰

Nigella sativa revealed an anti-inflammatory effect by its significant inhibition action of the nitric oxide release by macrophages.²¹^,²² Accordingly, the Nigella sativa has been considered as a test group in the current study.

Aloe vera which is also known as Aloe barbadensis Miller from Liliaceae family, is a perennial xerophyte that looks like a cactus plant. It can survive in hot and dry climates as it stores water in its leaves, so it is cultivated in Asia, Africa, and other tropical areas. It is known as the “medicinal plant” as it was used in history by Egyptian queens and kings as part of their regular beauty regimens as well as to treat injured soldiers.²³

The Aloe vera plant is made of two different parts that have completely different substances, compositions, and therapeutic properties. The pericyclic tubules which are found just beneath the outer green rind of the leaf, are specialized cells that produce a bitter yellow exudate called latex and have laxative properties. The inner part of the leaf has the parenchymal tissue which contains the aloe gel that was used in this study.²⁴

It has many beneficial medical uses owing to its antiviral, antifungal, antioxidative, anti-inflammatory, and analgesic properties. The antibacterial effect of Aloe vera gel has been assessed on cariogenic bacteria where an antibacterial effect was reported on Streptococcus mutans bacteria in multiple in vitro studies.²⁵^-²⁹

In dentistry, Aloe vera has been used in the treatment of aphthous ulcers³⁰ and lichen planus as well as in healing extraction sockets.³¹ In literature, Aloe vera was found as a promising pulp dressing material yet, there is not enough evidence hence, it was chosen as a test group in this study.

In spite of all the concerns towards formocresol, it is still the most commonly used pulp medicament in the pulpotomy procedure in primary teeth and is considered “the gold standard” with a high clinical and radiographical success rate, hence, it was important to include it in the current study as a control group.

As per the results, the formocresol group showed a clinical success rate after 12 months of follow-up of 72.7% which came in accordance with a previous study that reported a success rate of 76%.³² Moreover, other studies reported success rates ranging from 46.2 to 100%.¹¹^,¹⁵^,³³^-³⁶ Regarding the radiographic success of the formocresol group, 81.8% success was recorded in the present study after 12 months of follow-up while other studies described a success rate ranging from 58.3 to 100%.¹¹^,¹⁵^,³²^-³⁵^,³⁷ The high success rate of formocresol as a pulp medicament might be attributed to its good bacteriostatic and fixative properties.

As per the Nigella sativa group, the clinical and radiographic success at 12 months were reported to be 40 and 20%, respectively. Results were not consistent with previously reported studies where clinical success at 6 months follow-up was found to be 90³⁸ and 78.9%³⁹ in two different studies. Whereas the radiographic success in these studies was 90% and 82.2%.

In this study, failures in the Nigella sativa group were in the form of internal root resorption, external root resorption, and widening in the periodontal ligament. The high failure rate in this group might be due to the longer follow-up period compared to other published studies. Moreover, it might also be explained by the unsatisfactory histologic results that were reported in a study where signs of pulp necrosis were seen as no odontoblastic layer was found, and the pulp space had some empty areas and other areas with dystrophic calcification.³⁸

The Aloe vera group showed the highest clinical success in the current study at 12 months follow-up which was 90.9%, while the radiographic success was found to be 72.7%. Failures in the Aloe vera group were presented as widening in periodontal ligament, and internal root resorption.

Multiple studies were found in literature agreeing with these results considering Aloe vera as a promising pulp dressing agent. A study reported a 96.5% clinical success rate when acemennan was used as a pulp dressing after the pulpotomy procedure, while the radiographic success was found to be 93.1%.³⁴ Dumne et al. found 97.1–97.3% clinical and radiographic success rates, respectively after 6 months of follow-up of using Aloe vera as pulpotomy medicament.³⁷ Furthermore, 96.6–54.8% were the clinical and radiographic success rates mentioned by Subramanyam and Somasundaram¹⁵ On the other hand, Kalra et al. disagreed with the previous results as the overall success rate of Aloe vera as a pulp medicament after 12 months follow-up was found to be only 6.9%.⁴⁰

This high clinical success of Aloe vera in the current study might be explained by the antioxidative, analgesic, anti-inflammatory, and antibacterial properties that are attributed to the Aloe vera components such as acemannan and anthraquinones. The antiedematous effect of the Aloe vera extract was reported by inhibiting cyclooxygenase in the arachidonic acid pathway and also the reduction of the number of migrating neutrophils was seen.⁴¹ The Aloe vera’s success can also be related to its acceptable biocompatibility as it showed wound healing abilities by promoting the proliferation of fibroblasts, tertiary bridge formation as well as the production of hydroxyproline and hyaluronic acid in the fibroblasts.⁴²

The antibacterial property of Aloe vera against Streptococcus pyogenes, Streptococcus mutans and Enterococcus faecalis, has been confirmed by Kumar and Saikiran et al.⁹^,¹⁹

The presence of acemannan a constituent of the Aloe vera gel is believed to have further enhanced this study’s success results through its ability to activate macrophages, accelerate tissue regeneration, and provide additional antibacterial and antiviral effects to the Aloe vera gel. The anthraquinones being another component of the Aloe vera gel act like tetracycline and stop the bacterial protein synthesis, hence inhibiting the bacterial growth and might have affected the results of the present study positively.⁴³

CONCLUSION

Finally, the results of this study showed a statistically significant difference in the clinical and radiographic success between the tested groups. Where Nigella sativa group was significantly less successful than the other tested materials. Aloe vera ethanolic extract is a promising alternative to formocresol as a pulp medicament in vital pulpotomy procedures in primary teeth as it showed higher clinical success than formocresol although not significant. Therefore, the null hypothesis was not accepted. The promising results of the herbal medicine in this study could be considered a beginning for further investigations on natural materials in pulpotomy procedures in primary molars, as well as an initial step to a series of studies exploring the effectiveness of these extracts as pulp dressing materials.

¹R Core Team (2022). R: A language and environment for statistical computing. R foundation for statistical computing, Vienna, Austria. URL https://www.R-project.org/

ORCID

Rana M Sharaf https://orcid.org/0000-0001-8695-4689

Noha S Kabil https://orcid.org/0000-0002-2897-1840

Fadia S Youssef https://orcid.org/0000-0002-5871-2639

Basma G Awad https://orcid.org/0000-0002-2315-6396

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