Antibiotics in Dentistry: A Narrative Review of the Evidence beyond the Myth.

Antibiotics have undoubtedly revolutionized medicine and the health and survival of patients with life-threatening infections, being nonetheless free from potential adverse effects, and the risk of intestinal dysbiosis, antimicrobial resistance, and the resulting consequences for the patient's health and the public purse. The present study narratively reviewed the epidemiological data on worldwide antibiotic consumption and administration in dental practice, patients' adherence to prescriptions, the antimicrobial resistance phenomenon in dentistry, and the evidence supporting and recommending appropriate antibiotic use in dental care. Eligible systematic reviews and original studies in humans published in the English language from January 2000 to 26 January 2023 were considered. A total of 78 studies, 47 on the epidemiology of antibiotic use and prescription in dentistry, 6 on antibiotic therapy in dentistry, 12 on antibiotic prophylaxis in dentistry, 0 on adherence of dental patients to antibiotic prescription, and 13 on antimicrobial resistance in dentistry, were presently considered. Retrieved evidence revealed that antibiotics are frequently overused and misused in dental practice, dental patients frequently do not adhere to prescriptions, and antimicrobial resistance in dentistry is a still rising phenomenon also secondary to improper oral antiseptics use. The present findings highlighted the need to establish more evidence-based and accurate antibiotic prescriptions to sensitize dentists and dental patients to minimize and rationalize the use of antibiotics only when it is indicated and necessary, improve patients' adherence, and enhance knowledge and awareness of the antimicrobial resistance in dentistry.

Histological Evaluation of Root Canals by Performing a New Cleaning Protocol "RUA" in Endodontic Surgery.

AIM: To enhance cleaning during retro-preparation in endodontic microsurgery. MATERIALS AND METHODS: Forty mandibular premolars were instrumented, filled with a single cone technique, and then retro-preparation was performed and assigned to experiment A. In group A1, the cavity created by the retro preparation was cleansed with 2 mL of normal sterile saline. In group A2, the retro cavity was cleaned with 2 mL of sterile saline after the retro preparation. All the irrigation solutions mentioned above were delivered using an endodontic needle with a lateral vent and a gauge of 30. Subsequently, in group A2, 17% EDTA gel and 5.25% gel were inserted into the cavity and activated using ultrasonic tips. After the irrigation protocols, the specimens were decalcified for histological evaluation. RESULTS: In the experiment, the amount of hard tissue debris was significantly greater in group A1 compared to group A2 (p < 0.05). CONCLUSIONS: The samples in group A2, where the new protocol was performed, showed statistically significant results.

Mental Health Interest and Its Prediction during the COVID-19 Pandemic Using Google Trends.

This study aimed to analyze and predict interest in mental health-related queries created in Google Trends (GT) during the COVID-19 pandemic. The Google Trends tool collected data on the Google search engine interest and provided real-time surveillance. Five key phrases: "depression", "insomnia", "loneliness", "psychologist", and "psychiatrist", were studied for the period from 25 September 2016 to 19 September 2021. The predictions for the upcoming trend were carried out for the period from September 2021 to September 2023 and were estimated by a hybrid five-component model. The results show a decrease of interest in the search queries "depression" and "loneliness" by 15.3% and 7.2%, respectively. Compared to the period under review, an increase of 5.2% in "insomnia" expression and 8.4% in the "psychiatrist" phrase were predicted. The expression "psychologist" is expected to show an almost unchanged interest. The upcoming changes in the expressions connected with mental health might be explained by vaccination and the gradual removal of social distancing rules. Finally, the analysis of GT can provide a timely insight into the mental health interest of a population and give a forecast for a short period trend.

L-Carnitine in Drosophila: A Review.

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial ß-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of ß-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.

Clinical Effects of Mercury in Conservative Dentistry: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

METHODS: A systematic literature search was conducted in four electronic databases (Ovid via PubMed, Web of Science, Scopus, and CENTRAL) including all available randomised controlled trials published in the last 15 years comparing the use of dental amalgam with composite resins in humans with a follow-up period of at least one year. The primary outcome was the Hg concentration in biological fluids (urine, hair, blood, and saliva) with the aim of assessing their reliability as biomarkers of Hg exposure. The risk of bias was assessed through the Cochrane Collaboration tool and the overall quality of evidence through the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. The results of the meta-analysis were expressed using a random-effects model, and their power was assessed through the trial sequential analysis (TSA). RESULTS: From the initial 2555 results, only 6 publications were included in the review: five were considered as having high risk of bias, whereas one as having moderate risk. Only two articles were eligible for quantitative analysis. The meta-analysis gathered data from 859 patients but was nevertheless not significant (p = 0.12). The TSA confirmed this evidence revealing that it was due to a lack of statistical power since the required information size (RIS) threshold is not reached. CONCLUSIONS: The existing evidence revealed that there are not enough data to support the hypothesis that restorations with dental amalgam can cause nephrotoxicity when compared with composite resins restorations.

Pain Catastrophizing in Childhood Migraine: An Observational Study in a Tertiary Headache Center.

Background: Migraine is the most common cause of primary headache in children leading to a decrease in the quality of life. During the last decade, pain catastrophizing construct became a major focus of interest in the study and treatment of pain. Aim of the study: To evaluate pain catastrophizing in episodic and chronic migraine children and adolescents selected in a tertiary headache Center.To test whether the children's pain catastrophizing might be associated (a) with the frequency of attacks and disability (b) with psychopathological aspects (c) with allodynia and total tenderness score as symptom of central sensitization.To test the best discriminating clinical variables and scores between episodic and chronic migraine, including pain catastrophizing. Methods: We conducted a cross sectional observational study on consecutive pediatric patients affected by migraine. We selected 190 headache patients who met the diagnostic criteria for Migraine without aura, Migraine with aura and Chronic migraine. We submitted all children to the Child version of the Pain Catastrophizing Scale (PCS-C), and to the disability scale for migraine (PedMIDAS), general quality of life estimated by children (PedsQL) and parents (PedsQL-P), anxiety and depression (SAFA-A; SAFA-D) scales. We also evaluated headache frequency and the presence and severity of allodynia and pericranial tenderness. Results: No difference was detected in Total Pain Catastrophizing score (PCS-C) between chronic and episodic migraine groups (ANOVA F = 0.59, p = 0.70); the PedMIDAS, the PedsQL-P for physical functioning and the Total Tenderness Score were discriminant variables between episodic and chronic migraine. The PCS-C was not correlated with migraine related disability as expressed by Ped MIDAS, but it was significantly correlated with general low quality of life, allodynia, pericranial tenderness, anxiety, and depression. Conclusion: Pain catastrophizing seems a mental characteristic of a clinical phenotype with psychopathological traits and enhanced expression of central sensitization symptoms. This clinical profile causes general decline in quality of life in the child judgment, with a probable parents' underestimation. In childhood age, it would not be a feature of chronic migraine, but the possibility that it could predict this evolution is consistent and worthy of further prospective evaluation.

The IG- file use to Gauge the Apical Diameter in Endodontics: An In Vitro Study.

AIM: The aim of this study was to evaluate the efficacy of the IG-file, a new instrument designed for apical diameter gauging. MATERIALS AND METHODS: After shaping with F1 Universal Protaper, 60 roots were randomly divided into two groups and assigned to two operators, One Expert in Endodontics (EO) and One Unexpert (UO).In each sample, after canal curvatures have been detected, the apical diameters were measured with the IG-file and the K-NiTi. The results were compared with the reference value obtained by retrograde apical gauging. The data were statistically analyzed. RESULTS: Among 60 samples, 10% of errors were recorded when the IG-files were used; in the K-NiTi group the incorrect measurements were 70%.In both groups (expert and unexpert) the IG-file measurements were more accurate than the K-NiTi (90 vs 33 and 90 vs 26,7). The differences were statistically significant.In curved canals, the difference between measurement rates performed with both instruments was statistically significant (85,7% IG-file vs 28,6% K-NiTi) as well as for the samples without curvatures (92,3% IG file vs 30,8% NiTi file).In root canals without curvatures overestimation errors in K-NiTi file group are more frequent than underestimation errors. This difference was statistically significant. CONCLUSION: A proper gauging of the apical diameter has a key role in endodontic therapy; an incorrect measurement can lead to clinical failures. This "in vitro" study highlights that IG-file improves measurement accuracy independently from clinician experience. Furthermore, in curved canals, the IG-file is more accurate than K-NiTi.

Numb chin syndrome: A reflection of malignancy or a harbinger of MRONJ? A multicenter experience.

INTRODUCTION: Numb chin syndrome (NCS) or mental neuropathy (MN) is a disorder characterized by sensory neuropathy on the distribution of the inferior alveolar nerve or mental nerve. The most frequent causes are of odontogenic origin (infections, wrong therapies). Other etiologies are related to primary tumor, metastasis, osteoradionecrosis and medication-related osteonecrosis of the jaw (MRONJ). The aim of this study is to highlight the clinical importance of NCS as one of the first symptoms of cancer or as consequence of drug therapy. MATERIALS AND METHODS: The present study was conducted from 2010 to 2016 by recruiting patients who present NCS as one of the symptoms, having excluded those in which it depends on a clear odontogenic cause, on systemic degenerative diseases or metabolic disorders. Data collection included suspected diagnosis at the time of presentation of the symptom, final diagnosis, mandibular localization, treatment performed and diagnostic delay between the first medical examination and the definitive diagnosis. RESULTS: This study included 29 patients in which NCS had not a clear odontogenic cause. NCS was the first symptom of malignancy in 11 cases and the clinical sign of metastasis in 4 cases. In a single patient, it was the first symptom of an immune-mediated disease. In the remaining 13 patients, NCS represented the symptom of MRONJ. CONCLUSION: NCS can be the first symptom of malignancy, especially in patients with a previous history of cancer, but also a prodromal sign of MRONJ. It should be recognized in order to require deeper examinations for early diagnosis of the disease.

Symptoms of central sensitization and comorbidity for juvenile fibromyalgia in childhood migraine: an observational study in a tertiary headache center.

BACKGROUND: Central sensitization is an important epiphenomenon of the adult migraine, clinically expressed by allodynia, pericranial tenderness and comorbidity for fibromyalgia in a relevant number of patients. This study aimed to evaluate the frequency and the clinical characteristics of allodynia, pericranial tenderness, and comorbidity for Juvenile Fibromialgia (JFM) in a cohort of migraine children selected in a tertiary headache center. METHODS: This was an observational cross-sectional study on 8-15 years old migraine patients. Allodynia was assessed by a questionnaire. Pericranial tenderness and comorbidity for JFM as well as their possible association with poor quality of life and migraine related disability, and with other clinical symptoms as anxiety, depression, sleep disorders and pain catastrophizing, were also evaluated. RESULTS: One hundred and fifty one patients were selected, including chronic migraine (n°47), migraine without aura (n° 92) and migraine with aura (n° 12) sufferers. Allodynia was reported in the 96,6% and pericranial tenderness was observed in the 68.8% of patients. Pericranial tenderness was more severe in patients with more frequent migraine and shorter sleep duration. Allodynia seemed associated with anxiety, pain catastrophizing and high disability scores. Comorbidity for JFM was present in the 0.03% ofpatients. These children presented with a severe depression and a significant reduction of quality of life as compared to the other patients. CONCLUSIONS: This study outlined a relevant presence of symptoms of central sensitization among children with migraine. Severe allodynia and comorbidity for JFM seemed to cause a general decline of quality of life, which would suggest the opportunity of a routine assessment of these clinical features.

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.

Positively charged polymers modulate the fate of human mesenchymal stromal cells via ephrinB2/EphB4 signaling.

Understanding the mechanisms by which mesenchymal stromal cells (MSCs) interact with the physical properties (e.g. topography, charge, ζ-potential, and contact angle) of polymeric surfaces is essential to design new biomaterials capable of regulating stem cell behavior. The present study investigated the ability of two polymers (pHM1 and pHM3) with different positive surface charge densities to modulate the differentiation of MSCs into osteoblast-like phenotype via cell-cell ephrinB2/EphB4 signaling. Although pHM1 promoted the phosphorylation of EphB4, leading to cell differentiation, pHM3, characterized by a high positive surface charge density, had no significant effect on EphB4 activation or MSCs differentiation. When the MSCs were cultured on pHM1 in the presence of a forward signaling blocking peptide, the osteoblast differentiation was compromised. Our results demonstrated that the ephrinB2/EphB4 interaction was required for MSCs differentiation into an osteoblast-like phenotype and that the presence of a high positive surface charge density altered this interaction.

Temperature Profiles Along the Root with Gutta-percha Warmed through Different Heat Sources.

OBJECTIVES: To evaluate temperature profiles developing in the root during warm compaction of gutta-percha with the heat sources System B and System MB Obtura (Analityc Technology, Redmond, WA, USA). Thirty extracted human incisor teeth were used. Root canals were cleaned and shaped by means of Protaper rotary files (Dentsply-Maillefer, Belgium), and imaging was performed by micro-CT (Skyscan 1072, Aartselaar, Belgium). METHODS: Teeth were instrumented with K-type thermocouples, and the roots were filled with thermoplastic gutta-percha. Vertical compaction was achieved through the heat sources System B and System MB, and temperature profiles were detect-ed by means of NI Dac Interface controlled by the LabView System. With both heat sources, higher temperature levels were recorded in the region of the root far from the apex. When the warm plugger tip was positioned at a distance of 3 mm from the root apex, temperature levels of about 180°C were used to soften gutta-percha, and no statistically significant differences were observed between peak temperatures developed by the two heating sources at the root apex. However, a temperature level higher than 40°C was maintained for a longer time with System MB. RESULTS: Statistically significant differences were observed in peak temperature levels recorded far from the root apex. Thus, with a temperature of about 180°C and the warm plugger positioned at 3 mm from the root apex, both heating sources led to a temperature slightly higher than 40°C at the apex of the root, suggesting that the gutta-percha was properly softened. SIGNIFICANCE: A temperature level higher than 40°C was maintained for a longer time with System MB, thus providing an ad-equate time for warm compaction of the gutta-percha.

[Deciduous dentition: anatomical study by µ-CT]. / Dentizione decidua: studio della complessità anatomica mediante µTC.

Endodontics is the branch of deciduous teeth pediatric dentistry that deals with the treatment of the root canal system. The goal of therapy is to maintain as long as possible the element in the dental arch to prevent alterations of orthognathodontic, infectious, and functional history and eruptive sequence. Although manual instrumentation has been widely used and still preferred by some practitioners, has limitations that affect the actual ability to clean the channel, the ability to create steps, perforations, dentinal plugs and fractures of the instrument. On the other hand, the disadvantages are the high cost of the instruments in nickel-titanium, which must be frequently replaced, and the risk of compromising the stability of the tooth due to an excessive consumption of dentinal tissue. The use of computed microtomography (µCT) of extracted elements has a considerable advantage in the study of dental hard tissues. The purpose of this study was to analyze the anatomy of the endodontic system of the elements deciduous.

[µCT analysis of mandibular molars before and after instrumentation by Reciproc files]. / Analisi anatomiche di molari mandibolari pre- e post-strumentazione con Reciproc mediante µTC.

Cleaning and shaping are important section for the root canal treatment. A number of different methodologies have been developed to overcome these problems, including the introduction of rotary instruments nickel-titanium (NiTi). In endodontics NiTi have been shown to significantly reduce procedural errors compared to manual techniques of instrumentation. The efficiency of files is related to many factor. Although previous investigations that have used µCT analysis were hampered by insufficient resolution or projection incorrect. The new generation of µCT performance best offer, as micron resolution and accurate measurement software for evaluating the accurate anatomy of the root canal. The aim the paper was to evaluate the efficiency of Reciproc files in root canal treatment, evaluated before and after instrumentation by using µ-CT analysis.

Effect of nickel chloride on cell proliferation.

OBJECTIVE: Metal alloys used in dentistry and in other biomedical fields may release nickel ions in the oral environment. The release of nickel might influence the normal biological and physiological processes, including tissue wound healing, cell growth and proliferation. The aim of this study was to evaluate in vitro the effects of nickel ions on cell cycle, viability and proliferation. MATERIALS AND METHODS: Human osteosarcoma cells (U2OS) and human keratinocytes (HaCat) were exposed to different nickel chloride (NiCl(2)) concentrations (0 - 5mM) for various periods exposure. The viability of cultured cells was estimated by flow cytometry using Annexin V-FITC and Propidium Iodide (PI). Cell proliferation was evaluated by using carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and flow cytometry. Finally, the effects of NiCl(2) on cell cycle were assessed and quantified by flow cytometry. Statistical analysis was performed by means of ANOVA followed by Tukey's test. RESULTS: NiCl(2) induced a dose and time dependent decrease in cell viability. After 24h, 1mM NiCl(2) caused a similar and significant reduction of viability in U2OS and HaCat cells, while higher NiCl(2) concentrations and longer exposure times showed a reduced cytotoxic effect in HaCat as compared to U2OS cells. Exposure to NiCl(2) caused a dose- and time-dependent inhibition of cell proliferation in both cell lines tested, with a prominent effect on U2OS cells. Furthermore, both cell lines exposed to NiCl(2) exhibited significant changes in cell cycle distribution after 24h exposure 2mM NiCl2, as compared to untreated cells (p<0.05). CONCLUSION: Our results indicate that release of nickel ions may affect cell proliferation. The inhibition of cell growth by NiCl2 is mediated by both cell cycle arrest and by induction of cell death.

Microcomputed tomography analysis of mesiobuccal orifices and major apical foramen in first maxillary molars.

OBJECTIVE: Aim of the study was to determined by microcomputed tomography (µCT) the horizontal distance between the main (MB1) and the second mesiobuccal canal (MB2) orifices, the vertical distance between the MB1 and MB2 orifices planes, and the distance between the anatomic apex and major apical foramen (AF). Furthermore, we characterized the entire internal and external anatomy of the MB, distalbuccal (DB) and palatal (P) maxillary first molars roots. MATERIALS AND METHODS: Twenty-two intact extracted first maxillary molars were scanned by X-ray computed transaxial µCT and then 2D and 3D images were processed and analyzed. RESULTS: The results showed that 77.27% of the mesiobuccal (MB) roots presented a second MB canal, and 29.41% of the MB2 were independent from the MB1 canals. In 15 teeth, there were three root canal orifices on the chamber floor, and 10 of these teeth presented MB2 canals. The mean vertical distance between the MB1 and MB2 planes was 1.68 ± 0.83 mm. Seven teeth had four orifices. The mean horizontal interorificial distance between the MB1 and MB2 orifices was 1.21 ± 0.5 mm. Accessory canals were observed in 33.33% of the roots, loops in 6.06%, while isthmuses were found in 15 of the 22 MB roots. Of the total roots, 74.24% presented one foramen, while all of the roots showed a major apical foramen that was not coincident with the anatomic apex. CONCLUSIONS: Our µCT analysis provided interesting features on the horizontal and vertical distance between the MB1 and MB2 orifices and on the distance of AF and anatomic apex. CLINICAL RELEVANCE: These results have an important clinical value because might support the endodontist in the recruitment, negotiation and obturation of maxillary first molar canal system.

Effect of mineral trioxide aggregate on mesenchymal stem cells.

INTRODUCTION: Mineral trioxide aggregate (MTA) is known to stimulate the hard tissue repair process. The purpose of this study was to evaluate the ability of MTA to support the adhesion, proliferation, and migration of human bone marrow-derived mesenchymal stem cells (hMSCs). METHODS: White ProRoot MTA and white Portland cement were mixed and left to set 24 hours. MSCs were cultured on the samples and observed after 24 hours by confocal laser scanning microscopy (CLSM) by using the cytoskeleton marker CellTracker. Cell proliferation was evaluated by means of alamar blue assay in the presence and absence of differentiation medium during a period of 28 days, and cells seeded on polystyrene culture wells were the control. To assess the effect on migratory ability of hMSCs, a transwell migration assay was performed for 18 hours, positioning MTA and Portland cement in 6-well plates and the cells in 8-µm pore inserts. RESULTS: hMSCs observed under CLSM showed attachment and spread activity on the upper surface of the MTA. Cell proliferation was significantly higher on MTA than on Portland cement. A rate proliferation increase of the MTA group compared with the control was observed after 14 days in presence of basic medium, whereas the same effect was reached after 21 days in presence of differentiation medium. Moreover, MTA was able to enhance cell migration significantly more than Portland cement. CONCLUSIONS: Our findings suggest that MTA was able to assist hMSC adhesion, growth, and migration.

Light shielding effect of overlaying resin composite on the photopolymerization cure kinetics of a resin composite and a dentin adhesive.

OBJECTIVES: The purpose of this study was to simultaneously determine the impact of exposure times and incremental resin composite overlaying thickness on the cure kinetics of a light activated composite and a dentin adhesive at selected depths of a simulated restoration. METHODS: Levels and kinetics of polymerization of a light activated resin composite (Z250, 3M-ESPE) and dentin adhesive (Excite, Ivoclar) cured with a halogen light unit (Demetron, Kerr, USA) operating at low/medium intensity (500 mW/cm2) for different exposure durations (20 and 60 s) were measured at selected depths (0.3, 0.6 and 1mm) using a modified calorimetric analyzer (DSC 25, METLLER-TOLEDO). RESULTS: Final polymerization levels of materials up to 1mm through the composite are not significantly different while the light shielding effect of incremental resin composite overlaying progressively reduces their reaction rates. SIGNIFICANCE: Prolonged irradiation time at low/medium energies is effective for proper conversion of a resin composite and dentin adhesive; 60 s irradiation time provides the maximum obtainable conversion through the dental resin composite for thicknesses up to 1mm.

Inlay shading effect on the photopolymerization kinetic of a dental composite material used as bonding system in an indirect restoration technique.

OBJECTIVES: To define the inlay shading effect on the polymerization levels and kinetics of a light activated bonding system for an indirect restoration technique. MATERIALS AND METHODS: For the bonding system, an adhesive: Excite (Ivoclar-vivadent) and a composite: Z250 (3M-ESPE, St Paul Minnesota, USA) were investigated. A Demetron (Kerr USA) light curing unit was used. The composite inlay blocks of 2 mm thick were used for the experiment (Artglass A2 Heraeus, Kulzer, Dormagen, Germany). The bonding composite was photocured using a 2 mm composite inlay block as a shielding system while the adhesive was shielded by a 2.3 mm thick wafer, composed of the inlay material and the previously cured bonding composite. The kinetics and levels of polymerization were measured by a differential scanning calorimeter technique (DSC 25, Mettler, Orange, CA, Toledoh, küsnacht, switzerland). RESULTS: The inlay shielded dental composite reaches a significantly lower level of polymerization compared to the unshielded composite. Inlay shielded composite, has a slower polymerization kinetic compared to unshielded composite. The resin adhesive shielded by the inlay-composite wafer reaches polymerization values not significantly different from those of the unshielded adhesive. SIGNIFICANCES: The degree of cure of the light-cured composite resins for use as a base for indirect composite restorations, may be severely reduced as a result of inlay shielding.