Porphyromonas gingivalis virulence factors induce toxic effects in SH-SY5Y neuroblastoma cells: GRK5 modulation as a protective strategy.

Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer's disease (AD), remain unclear. This study assessed the effects of Pg's virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels. In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders.

Unlocking the Potential of Dental-Derived Mesenchymal Stem Cells in Regenerative Medicine.

Over the past few decades, life expectancy has been increasing in several countries [...].

Evaluating the effect of using anti-stress balls as a distraction technique in reducing pain during inferior alveolar nerve block injection: a randomized clinical trial.

OBJECTIVE: The aim of this study is to evaluate the effect of using anti-stress balls in reducing patients' pain during injection of the inferior alveolar nerve block (IANB). MATERIALS AND METHODS: In this randomized clinical trial, 32 individuals were divided into two groups. The conventional method of anesthesia injection was performed using IANB conventional injection technique. During the injection, individuals in the anti-stress ball group were asked to use the anti-stress ball as a distraction technique. For the control group, no supersede methods were used for pain control. Finally, both groups were asked to record their pain utilizing the numerical rating scale (NRS). The participants' vital signs were monitored before and after injection. Kolmogorov-Smirnov test, independent T-test, and Fisher's exact chi-square test were performed for statistical analysis (α = 0.05). RESULTS: Sixteen females and 16 males in the age range of 40 to 20 years old participated in this study. The mean pain score in the anti-stress ball group was significantly lower (p < 0.001). In both sexes, the pain score in the anti-stress ball group was significantly lower (males p < 0.001 and females p = 0.001). In addition, in all age ranges, the pain score in the control group was higher except for the above 35 years old participants (p = 0.078). Moreover, there were no significant differences in individuals' vital signs (p > 0.05). CONCLUSION AND CLINICAL RELEVANCE: Utilizing an anti-stress ball reduces patients' pain significantly during IANB in both sexes and individuals who are below 35 years without changing vital signs. CLINICAL REGISTRATION NUMBER: IRCT20220815055704N1.

Chemical, structural and cytotoxicity characterisation of experimental fluoride-doped calcium phosphates as promising remineralising materials for dental applications.

OBJECTIVES: This study aimed at evaluating the cytotoxicity, chemical and structural properties of experimental fluoride-doped calcium-phosphates as potential remineralising materials for dental applications. METHODS: Experimental calcium phosphates were formulated using ß-tricalcium phosphate, monocalcium phosphate monohydrate, calcium hydroxide, and different concentrations of calcium/sodium fluoride salts [(5 wt%: VSG5F), (10 wt%: VSG10F), (20 wt%: VSG20F)]. A fluoride-free calcium phosphate (VSG) was used as control. Each tested material was immersed in simulated body fluid (SBF), (24 h, 15 and 30 days) to assess their ability to crystallise into apatite-like. Cumulative fluoride release was assayed up to 45 days. Moreover, each powder was placed into a medium containing human dental pulp stem cells (200 mg/mL) and their cytotoxicity was analysed using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay (24 h, 48 h and 72 h incubation). These latter results were statistically analysed by ANOVA and Tukey's test (α = 0.05). RESULTS: All the experimental VSG-F materials produced fluoride-containing apatite-like crystals after SBF immersion. VSG20F presented prolonged release of fluoride ions into the storage media (45d). VSG, VSG10F and VSG20F showed a significant cytotoxicity at dilution of 1:1, while at 1:5, only VSG and VSG20F demonstrated a reduction in cell viability. At lower dilutions (1:10, 1:50 and 1:100) all specimens showed no significant toxicity to hDPSCs, but an increase in cell proliferation. SIGNIFICANCE: The experimental fluoride-doped calcium-phosphates are biocompatible and possess a clear ability to evoke fluoride-containing apatite-like crystallisation. Hence, they may be promising remineralising materials for dental applications.

Vital Pulp Therapy of Permanent Teeth with Reversible or Irreversible Pulpitis: An Overview of the Literature.

Vital pulp therapy (VPT) has been recently proposed as an alternative approach even in symptomatic mature permanent teeth with deep caries' lesions, aiming to maintain the pulp vitality over time and/or to avoid non-surgical root canal therapy (NSRCT). However, to date, the diagnosis of reversible or irreversible pulpitis is only based on clinical pain quantity and quality, without precisely reflecting the pulp inflammation status. Therefore, the aim of the present study was to provide an overview based on the current scientific literature to demonstrate the clinical effectiveness of VPT on mature permanent teeth, validating the use of hydraulic calcium silicate-based cements and their role in pain management. VPT may be successfully applied not only in mature permanent teeth diagnosed with reversible pulpitis, but also in permanent dental elements with signs and symptoms of irreversible pulpitis. Hydraulic cements showed favorable outcomes in terms of decrease of pro-inflammatory mediators and of post-operative pain. Pain plays a central role in the chance to perform VPT in mature permanent teeth, since it may be considered as a pre-operative diagnostic criterion as well as a treatment success parameter. In addition, proper assessment of pulp inflammation and choice of appropriate materials are key factors in enhancing VPT success.

Fracture Strength and Failure Modes of Endodontically Treated Premolars Restored with Compact and Hollow Composite Posts Subjected to Cyclic Fatigue.

Physical and mechanical properties of continuous carbon or glass fiber reinforced endodontic posts are relevant to increase the retention and resistance of the tooth-restoration system. Hollow posts have been recently designed for delivering the luting cement through the post hole, thus enhancing the post-dentin interface by reducing the risk of air bubbles formation. Methods: Three type of endodontic posts, a carbon fiber hollow post, a glass fiber hollow post and a compact glass fiber post were investigated. Mechanical properties of these posts were assessed through bending tests. Teeth were subjected to fatigue cycling and the strength of restored teeth was detected through static tests. Failure modes were investigated through optical and scanning electron microscopy. Results show that composite posts increase the mechanical stability by more than 100% compared to premolars restored with particulate composite. Carbon fiber posts retain the highest strength (1467 N ± 304 N) among the investigated post and core restoration, but an unfavorable type of fracture has been observed, preventing the tooth re-treatment. Instead, more compliant posts (i.e., glass fiber reinforced composite, providing a strength of 1336 N ± 221 N), show a favorable mode of fracture that allows the re-treatment of teeth in the case that failure occurs. Glass fiber hollow posts show a good trade-off between strength and a favorable type of fracture.

An in-vitro study investigating the effect of air-abrasion bioactive glasses on dental adhesion, cytotoxicity and odontogenic gene expression.

OBJECTIVE: To assess the microtensile bond strength (MTBS) and interfacial characteristics of universal adhesives applied on dentine air-abraded using different powders. The analysis includes the cytotoxicity of the powders and their effect on odontogenic gene expression. METHODS: Sound human dentine specimens were air-abraded using bioglass 45S5 (BAG), polycarboxylated zinc-doped bioglass (SEL), alumina (AL) and submitted to SEM analysis. Resin composite was bonded to air-abraded or smear layer-covered dentine (SML) using an experimental (EXP) or a commercial adhesive (ABU) in etch&rinse (ER) or self-etch (SE) modes. Specimens were stored in artificial saliva (AS) and subjected to MTBS testing after 24 h and 10 months. Interfacial nanoleakage assessment was accomplished using confocal microscopy. The cytotoxicity of the powders was assessed, also the total RNA was extracted and the expression of odontogenic genes was evaluated through RT-PCR. RESULTS: After prolonged AS storage, specimens in the control (SML) and AL groups showed a significant drop in MTBS (p > 0.05), with degradation evident within the bonding interface. Specimens in BAG or SEL air-abraded dentine groups showed no significant difference, with resin-dentine interfaces devoid of important degradation. The metabolic activity of pulp stem cells was not affected by the tested powders. SEL and BAG had no effect on the expression of odontoblast differentiation markers. However, AL particles interfered with the expression of the odontogenic markers. SIGNIFICANCE: The use of bioactive glass air-abrasion may prevent severe degradation at the resin-dentine interface. Unlike alumina, bioactive glasses do not interfere with the normal metabolic activity of pulp stem cells and their differentiation to odontoblasts.

Fracture resistance of endodontically-treated maxillary premolars restored with different type of posts and direct composite reconstructions: A systematic review and meta-analysis of in vitro studies.

OBJECTIVE: To conduct a systematic review and meta-analysis to assess if the presence of an endodontic post may increase the fracture resistance of endodontically-treated maxillary premolars directly restored with composite. METHODS: A comprehensive systematic literature search according to the PRISMA statement was conducted to assess in vitro studies including endodontically-treated maxillary premolars, restored with different type of posts supporting direct composite reconstructions. Two groups of meta-analyses were performed using fixed effects model and additional Trial Sequential Analysis (TSA) was carried out. Moreover, risk of bias was conducted and quality of evidence for any performed meta-analysis was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twenty-four articles met the inclusion criteria and 13 studies also underwent quantitative evaluation. Fracture resistance of endodontically-treated premolars restored with fiber posts was significantly less than sound teeth (p value: < 0.00001), however endodontically-treated premolars with a fiber post provided an increase in fracture resistance when compared to equivalent teeth restored without post (p value: 0.003). TSA revealed high power of both meta-analyses. Moderate risk of bias was reported in 23/24 studies; only 1 study showed high risk of bias. GRADE system showed moderate strength of evidence due to the presence of a study with high risk of bias and to wide confidence intervals. SIGNIFICANCE: Within the limitation of the present systematic review and meta-analysis, it can be concluded that endodontically-treated maxillary premolars restored with a fiber post and direct composite restoration demonstrated increased fracture resistance when compared to equivalent teeth without post.

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.

The implementation of hydraulic calcium silicate-based endodontic cements (HCSCs) in biologically based endodontic procedures for the primary dentition has been recently investigated, focusing on the biological response of stem cells from human exfoliated deciduous teeth (SHEDs) towards them. The present systematic review aimed to present a qualitative synthesis of the available literature consisting of in vitro assays, which assessed the cytocompatibility and bioactive properties of HCSCs in direct contact with SHEDs. Following the PRISMA statement, an electronic database search was carried out in Medline, Scopus, Embase, Web of Science, and SciELO on March 31st and updated on November 16th, 2020. In vitro studies evaluating the biological response of SHEDs to the treatment with HCSCs were eligible. Within the term biological response, assays assessing the cytocompatibility (i.e., cell viability, migration, proliferation), cell plasticity or differentiation (i.e., osteo/odontogenic marker expression), and bioactivity or biomineralization (i.e., mineralized nodule formation) were included. A total of seven studies were included after the selection process. The study sample comprised an extensive range of cell viability, migration, proliferation, adhesion, and bioactivity assays regarding the biological response of SHEDs towards five different commercially available HCSCs (MTA, ProRoot MTA, Biodentine, iRoot BP Plus, and Theracal LC). Biodentine, MTA, and iRoot BP Plus showed significant positive results in cytocompatibility and bioactivity assays when cultured with SHEDs. The results from in vitro assays assessing the cytocompatibility and bioactivity of the HCSCs MTA, Biodentine, and iRoot BP Plus towards SHEDs support their use in vital pulp treatment for the primary dentition.

Cuspal Deflection and Temperature Rise of MOD Cavities Restored through the Bulk-Fill and Incremental Layering Techniques Using Flowable and Packable Bulk-Fill Composites.

Background: The aim of this study was to investigate cuspal deflection caused by material shrinkage and temperature rise occurring in the pulp chamber during photopolymerization. The aim of this study was also to investigate the effect of flowable and packable bulk-fill composites on cuspal deflection occurring in mesio-occlusal-distal (MOD) cavities restored through the bulk-fill or through the incremental layering technique. Additionally, mechanical and thermal properties of bulk-fill composites were considered. Methods: Two bulk-fill composites (high-viscosity and low-viscosity), largely differing in material composition, were used. These composites were characterized through linear shrinkage and compressive test. Cuspal deformation during restoration of mesio-occlusal-distal cavities of human premolars was evaluated using both the bulk-fill and the incremental layering techniques. Temperature rise was measured through thermocouples placed 1 mm below the cavity floor. Results: Shrinkage of the flowable composite was significantly higher (p < 0.05) than that of packable composite, while mechanical properties were significantly lower (p < 0.05). For cusp distance variation, no significant difference was observed in cavities restored through both restorative techniques, while temperature rise values spanned from 8.2 °C to 11.9 °C. Conclusions: No significant difference in cusp deflection between the two composites was observed according to both the restorative techniques. This result can be ascribed to the Young's modulus suggesting that the packable composite is stiffer, while the flowable composite is more compliant, thus balancing the cusp distance variation. The light curing modality of 1000 mW/cm2 for 20 s can be considered thermally safe for the pulp chamber.

Management of Endodontic and Periodontal Lesions: the Role of Regenerative Dentistry and Biomaterials.

Regenerative dentistry represents a novel interdisciplinary approach involving biomaterials, several molecules and mesenchymal stem cells (MSCs), preferably derived from oral tissues. The pivotal role of MSCs depends on the fact that they can differentiate into different cell lineages and have the strategic role to release bioactive substances that stimulate the renewal and regeneration of damaged tissues. The role of regenerative dentistry is promising in all the branches of dentistry: the most intriguing application is related to the management of endodontic and periodontal defects, overcoming the surgical approach and the implantology as a consequence of a poorly efficient therapeutic plan.

COVID-19 Outbreak: An Overview on Dentistry.

Coronavirus disease 2019, also called COVID-19, is the latest infectious disease to rapidly develop worldwide [...].

Phosphorene Is the New Graphene in Biomedical Applications.

Nowadays, the research of smart materials is focusing on the allotropics, which have specific characteristics that are useful in several areas, including biomedical applications. In recent years, graphene has revealed interesting antibacterial and physical peculiarities, but it has also shown limitations. Black phosphorus has structural and biochemical properties that make it ideal for biomedical applications: 2D sheets of black phosphorus are called Black Phosphorene (BP), and it could replace graphene in the coming years. BP, similar to other 2D materials, can be used for colorimetric and fluorescent detectors, as well as for biosensing devices. BP also shows high in vivo biodegradability, producing non-toxic agents in the body. This characteristic is promising for pharmacological applications, as well as for scaffold and prosthetic coatings. BP shows low cytotoxicity, thus avoiding the induction of local inflammation or toxicity. As such, BP is a good candidate for different applications in the biomedical sector. Properties such as biocompatibility, biodegradability, and biosafety are essential for use in medicine. In this review, we have exploited all such aspects, also comparing BP with other similar materials, such as the well-known graphene.

Small molecule GSK-3 antagonists play a pivotal role in reducing the local inflammatory response, in promoting resident stem cell activation and in improving tissue repairing in regenerative dentistry.

Regenerative dentistry is attracting growing interest in the scientific community, mainly because of its translational and promising therapeutic approach. The latest research carried out by the scientific community are aimed at triggering the local cellular response, in order to induce a physiological self-repairing of damaged oral tissues. Such physiological processes mainly involve the activation of local stem cell populations: mesenchymal stem cells, in fact, retain the ability to proliferate and to differentiate towards functional mature elements, thus leading towards healing of damaged tissues. Glycogen Synthase Kinase-3 (GSK-3) is a key-regulator of the Wnt/ß-catenin pathway; it phosphorylates ß-catenin, that then is degraded in the cytosol. The activation of such signalling, mediated by Wnt ligand/receptor association, inhibits GSK-3, leading to translocation of ß-catenin to the nucleus and to gene transcription. Selective inhibitors of GSK-3 have been linked to the activity of Wnt signalling and to the regeneration of injured tissues, including complex dental and oral structures. Small Molecule GSK-3 Antagonists are the most interesting class of molecules acting with a "Bystander effect": reducing local inflammation and local bone resorption and triggering the activity and differentiation of resident "sleeping" MSCs. The aim of this narrative topical review is to describe the current knowledge on the role of small molecule GSK-3 antagonists in regenerative dentistry, with strategic insights towards the translational applications in nanomaterials in dentistry and in dental repairing.

Commitment of Oral-Derived Stem Cells in Dental and Maxillofacial Applications.

Tissue engineering is based on the interaction between stem cells, biomaterials and factors delivered in biological niches. Oral tissues have been found to be rich in stem cells from different sources: Stem cells from oral cavity are easily harvestable and have shown a great plasticity towards the main lineages, specifically towards bone tissues. Dental pulp stem cells (DPSCs) are the most investigated mesenchymal stem cells (MSCs) from dental tissues, however, the oral cavity hosts several other stem cell lineages that have also been reported to be a good alternative in bone tissue engineering. In particular, the newly discovered population of mesenchymal stem cells derived from human periapical inflamed cysts (hPCy-MSCs) have showed very promising properties, including high plasticity toward bone, vascular and neural phenotypes. In this topical review, the authors described the main oral-derived stem cell populations, their most interesting characteristics and their ability towards osteogenic lineage. This review has also investigated the main clinical procedures, reported in the recent literature, involving oral derived-MSCs and biomaterials to get better bone regeneration in dental procedures. The numerous populations of mesenchymal stem cells isolated from oral tissues (DPSCs, SHEDs, PDLSCs, DFSCs, SCAPs, hPCy-MSCs) retain proliferation ability and multipotency; these features are exploited for clinical purposes, including regeneration of injured tissues and local immunomodulation; we reported on the last studies on the proper use of such MSCs within a biological niche and the proper way to storage them for future clinical use.

Mechanical and Thermal Properties of Dental Composites Cured with CAD/CAM Assisted Solid-State Laser.

Over the last three decades, it has been frequently reported that the properties of dental restorative composites cured with argon laser are similar or superior to those achieved with conventional halogen and light emitting diode (LED) curing units. Whereas laser curing is not dependent on the distance between the curing unit and the material, such distance represents a drawback for conventional curing units. However, a widespread clinical application of this kind of laser remains difficult due to cost, heavy weight, and bulky size. Recently, with regard to the radiation in the blue region of the spectrum, powerful solid-state lasers have been commercialized. In the current research, CAD (computer-aided design)/CAM (computer-aided manufacturing) assisted solid-state lasers were employed for curing of different dental restorative composites consisting of micro- and nanoparticle-reinforced materials based on acrylic resins. Commercial LED curing units were used as a control. Temperature rise during the photopolymerisation process and bending properties were measured. By providing similar light energy dose, no significant difference in temperature rise was observed when the two light sources provided similar intensity. In addition, after 7 days since curing, bending properties of composites cured with laser and LED were similar. The results suggested that this kind of laser would be suitable for curing dental composites, and the curing process does not suffer from the tip-to-tooth distance.

Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications.

Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts.

Chromographic Analysis and Cytotoxic Effects of Chlorhexidine and Sodium Hypochlorite Reaction Mixtures.

INTRODUCTION: The literature reveals controversies regarding the formation of para-chloroaniline (PCA) when chlorhexidine (CHX) is mixed with sodium hypochlorite (NaOCl). This study aimed to investigate the stability of PCA in the presence of NaOCl and to examine the in vitro cytotoxic effects of CHX/NaOCl reaction mixtures. METHODS: Different volumes of NaOCl were added to CHX (mix 1) or PCA (mix 2). Upon centrifugation, the supernatant and precipitate fractions collected from samples were analyzed using high-performance liquid chromatography. The cytotoxic effects of both fractions were examined on human periodontal ligament and 3T3 fibroblast cell lines. RESULTS: High-performance liquid chromatographic analysis showed no PCA signal when NaOCl was mixed with CHX (mix 1). In mix 2, the intensity of PCA was decreased when NaOCl was added to PCA, and chromatographic signals, similar to that of CHX/NaOCl, were also observed. The mortality of precipitates exerted on both cell lines was lower compared with that of supernatants. CONCLUSIONS: The discrepancy in the data from the literature could be caused by the instability of the PCA in the presence of NaOCl. The CHX/NaOCl reaction mixture exhibits a wide range of cytotoxic effects.

Polyacrylic resins regulate transcriptional control of interleukin-6, gp80, and gp130 genes in human gingival fibroblasts.

Studies have failed to identify the molecular mechanisms that regulate the genotoxic and cytotoxic effects of methacrylate resins, which are important in the biocompatibility of dental materials. Interleukin (IL)-6 has a crucial role in the control of acute-phase protein response during inflammation. In humans, the synthesis and release of two major acute-phase proteins, C-reactive protein and serum amyloid A, are regulated by IL-6. This study focused on IL-6 and activation of its receptors gp80 and gp130 in human gingival fibroblasts in order to assess the effects of the commercial acid resins Jet Kit, Unifast, and Duralay on control of inflammation.

Morphological, diagnostic and surgical features of ectopic thyroid gland: a review of literature.

Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition.