Can patients detect peri­implant mucosal inflammation? Results from a multicentre randomized trial.

PURPOSE: The objective of this study was to compare patient-reported outcomes (PROs) of peri­implant soft tissue inflammation and aesthetics around single-tooth implants in the anterior maxillary region with three different implant-abutment interface designs. METHODS: Participants were randomized to one of three different types of implant-abutment interface designs [Conical (CI), flat-to-flat (FI), and Platform Switched (PS)]. Implants and provisional crowns with prefabricated titanium abutments were placed 5 months following extraction and/or ridge augmentation. Permanent ceramic crowns with zirconia abutments were placed after 12 weeks. To assess PROs, appearance and inflammation questionnaires were completed from provisional crown placement to the 3-year follow-up. RESULTS: Tooth appearance at the 3-year follow-up revealed a difference amongst CI, FI and PS implants (p=0.049; Kruskal-Wallis test). PS was rated better than FI (p=0.047) at 1 year for appearance of soft-tissue and satisfaction with colour. There were no differences for self-consciousness, smile and pain/discomfort while eating/hard food items. CONCLUSIONS: Although participants tended to rate the health of mucosa around PS implants as slighty better than the other two implant systems, the differences were minimal and inconsistent. Thus, patient satisfaction in terms self-perceived gingival health and esthetics was high for all 3 systems tested, suggesting that patients are unable to detect mucosal inflammation. CLINICAL SIGNIFICANCE: Patients find it difficult to perceive mucosal inflammation; hence, it is recommended that patients attend implant follow-up visits, even if they do not perceive inflammation. The study suggests that there is a relationship between the PROs and the clinical outcomes of tested implants.

Perceived Didactic Curricular Effectiveness of In-Person vs. Virtual Formats amongst Fourth-Year Dental Students.

PURPOSE: The COVID-19 pandemic altered the methodologies of dental education delivery, resulting in both immediate and more enduring changes. To assess student perceptions of learning effectiveness, graduating dental students from the class of 2020 were surveyed to identify student comfort with technology and content retention, individual motivation and mental focus, and access to resources pertaining to an abrupt transition to a virtual learning didactic seminar approach in March 2020. METHODS: a voluntary, 18-question electronic survey was distributed to fourth-year dental students prior to graduation to assess perceptions of learning outcomes and preferences of a virtual seminar format relative to previous in-person didactic seminars experienced. RESULTS: 34 of 80 dental students (42.5%) completed the electronic survey. Comfort and retention of concepts through virtual learning were reported ≥ by 91% and 85% of the respondents, respectively. Increased distractions and multitasking were reported with virtual learning in 56% and 71%, respectively. Desires to have all teaching conducted through virtual learning platforms was reported at 21%. CONCLUSIONS: the positive student responses obtained when comparing virtual to in-person seminars in the survey assessment demonstrates the long-term potential for such delivery modalities to be intentionally incorporated into an evolving predoctoral curriculum in a hybrid nature.

A Retrospective, Multicenter, Cross-Sectional Case Series Study Evaluating Outcomes of CAD/CAM Abutments on Implants from Four Manufacturers: 4-Year Mean Follow-up.

PURPOSE: To evaluate the clinical, radiographic, and prosthetic outcomes of a single custom CAD/CAM abutment system on implants from four manufacturers, with a mean clinical service of 4 years in a retrospective, multicenter case series study. MATERIALS AND METHODS: Adult subjects (n = 142) previously restored with titanium or gold-shaded titanium nitride custom CAD/CAM abutments (Atlantis, Dentsply Sirona; n = 259) connected to implants from four different manufacturers (Dentsply Sirona Implants [AT], Biomet 3i [BM], Nobel Biocare [NB], Straumann [ST]), irrespective of implant-abutment interface, and replacing one or more teeth in any position were recalled for a single-visit examination by calibrated investigators at six university clinics. The primary outcomes evaluated included abutment success and survival; secondary outcomes included assessment of papillae fill, probing pocket depth (PD), bleeding on probing (BOP), marginal bone levels (MBLs), and patient-reported outcome measures (PROMs). RESULTS: Two-hundred fifty-five (98.5%) abutments supported cement-retained restorations, and four (1.5%) abutments supported screw-retained restorations. Forty-two patients had 64 AT implants (25%), 31 patients had 61 BM implants (24%), 26 patients had 50 NB implants (19%), and 43 patients had 84 ST implants (32%). The overall implant-CAD/CAM abutment success rate was 92.66% (95% CI: 88.78%, 95.53%) for all implants examined, and the survival rate was 98.84% (95% CI: 96.65%, 99.76%) for all implants evaluated. The Jemt papillae index demonstrated a minimum of at least 50% to complete fill of the interproximal papillae in 65.0% of sites. PDs had a median value of 3.0 mm, and BOP was present on 19% of abutment surfaces. Mean MBL changes from the time of placement to exam were -0.24 ± 0.99 mm (-4.9 to 2.3; P = .058) for mesial sites and -0.32 ± 0.96 mm (-4.9 to 2.1; P = .000) for distal sites. PROMs expressed 93% of patients reporting good to very good masticatory function, 97% of patients reporting being satisfied or very satisfied with their esthetic outcomes, and 94% of patients indicating that they were satisfied or very satisfied with their overall implant-restorative outcomes. CONCLUSION: This retrospective, multicenter clinical study of FDA 510k-approved titanium CAD/CAM abutments of a single manufacturer on multiple implant systems demonstrated high levels of success and survival as well as stable peri-implant tissue outcomes, reflected by overwhelmingly positive PROMs.

Leveraging digital workflows for immediate single-tooth replacement therapy: A case report.

PURPOSE: Simplified and predictable immediate single-tooth replacement therapy can be optimised by leveraging recent advances in digital workflows that combine static surgical guidance and customised prosthesis design and fabrication. The present case report illustrates a novel approach to successfully executing immediate single-tooth replacement therapy via static computer-aided immediate implant placement and digital provisionalisation utilising angulated screw access, with a 1-year follow-up after delivery of the definitive restoration. MATERIALS AND METHODS: A healthy 27-year-old woman with congenital agenesis of the mandibular second premolars and who required replacement of the mandibular left second premolar underwent immediate single-tooth replacement therapy via computer-aided, restrictive implant placement and provisionalisation using custom prosthetic components designed prior to the surgical intervention being performed. RESULTS: After a 6-month healing period, the provisional crown was replaced with the definitive restoration. After 1 year, the peri-implant keratinised mucosa demonstrated vertical gain in the mid-buccal portion and stability in the interproximal aspects, and no changes in marginal bone level were observed. CONCLUSIONS: The present case report demonstrates the successful application of novel digital tools to facilitate both surgical and prosthetic aspects of immediate single-tooth replacement therapy. Digital workflows can optimise the clinical efficiency and predictability of tooth replacement therapy with dental implants by reducing surgical and restorative chair time and increasing patient satisfaction.

Comparison of 6-mm and 11-mm dental implants in the posterior region supporting fixed dental prostheses: 5-year results of an open multicenter randomized controlled trial.

OBJECTIVE: The aim of this multicenter, randomized controlled trial was to compare the clinical and radiographic outcomes of 6-mm or 11-mm implants, placed in the posterior maxilla and mandible, during a 5-year follow-up period. MATERIALS AND METHODS: Ninety-five patients with adequate bone height for 11-mm implants, were randomly allocated to a 6-mm group (test group with short implants) or an 11-mm group (control group with standard-length implants). Two or three implants of the same length were placed in each patient and after 6 weeks loaded with a splinted provisional restoration. This was followed by definitive splinted restoration 6 months after implant placement. Clinical and radiographic parameters, including the occurrence of complications were recorded. RESULTS: A total of 49 patients were enrolled to receive 6-mm implants (n = 108) and 46 patients to receive 11-mm implants (n = 101). Three implants (two of 6 mm and one of 11 mm in length) were lost before loading and one 6-mm implant after 15 months of function, and one 11-mm implant was lost during the first year of function. The 5-year survival rates were 96.0% and 98.9% in the 6-mm and 11-mm group, respectively. The mean marginal bone level changes 5 years post-loading were 0.01 ± 0.45 mm (bone gain) in the 6-mm group and -0.12 ± 0.93 mm (bone loss) in the 11-mm group (p = .7670). Clinical parameters, including plaque, bleeding on probing and pocket probing depth were not significantly different between the groups, and also technical complications were low. CONCLUSION: The clinical and radiographic outcomes of 6-mm short and 11-mm standard-length implants were not different during a 5-year evaluation period.

Pink Esthetic Score Outcomes Around Three Implant-Abutment Configurations: 3-Year Results.

PURPOSE: To evaluate the influence that three different implant-abutment interface designs had on peri-implant mucosal outcomes as assessed by the pink esthetic score (PES) 3 years after delayed implant placement and immediate provisionalization. MATERIALS AND METHODS: Adult subjects (n = 141) requiring replacement of a bounded single tooth in the anterior maxilla as well as first premolar sites were randomized to receive one of three unique implant-abutment interface designs (conical interface [CI]; flat-to-flat interface [FI]; or platform-switch interface [PS]). Treatment included immediate provisionalization with prefabricated titanium abutments, followed by custom computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia abutments and cement-retained, all-ceramic crowns delivered after 12 weeks. Bilateral (anterior sites) or unilateral (premolar sites) digital clinical photographs were made at 1, 3, 6, 12, 24, and 36 months post-implant placement. Five calibrated faculty evaluators who previously scored the 1-year PES image dataset scored the 24- and 36-month photographs using a digital, cloud-based tablet interface. RESULTS: Six hundred ten clinical photographs were evaluated, resulting in a total of 3,050 sum PES values and 21,350 individual PES values. Faculty evaluator intrarater and interrater reliability were found to be "substantial," with intraclass correlation coefficient (ICC) values of 0.76 and 0.77, respectively. All three implant-abutment interface groups demonstrated acceptable esthetics at 3 years (mean sum PES = 10.1 ± 1.9, 4.0 to 13.2), with no single group demonstrating significantly greater mean sum PES values than another at the 3-year follow-up or at any recall interval in between. CONCLUSION: No significant differences were observed in mean sum PES scores for subjects randomized to one of three different implant-abutment interface geometries. Within the limitations of this study thus far, the first 6 months following definitive prosthesis delivery appear to still be the most significant with regard to improvement in PES outcomes for all three treatment groups.

Comparison of two different surgical approaches to increase peri-implant mucosal thickness: A randomized controlled clinical trial.

BACKGROUND: Current evidence supports the positive effect of adequate peri-implant mucosal thickness (PMT) on both marginal bone level stability and esthetic outcomes. While the subepithelial connective tissue graft (sCTG) has been traditionally considered as the gold standard for peri-implant mucosal augmentation, acellular dermal matrix (ADM) may be a valid alternative. The primary aim of this randomized clinical trial was to determine the clinical efficacy of ADM in the augmentation of PMT as compared to an autologous sCTG. METHODS: Patients who could benefit from peri-implant mucosal augmentation at the time of implant placement were recruited. Participants were randomized to the control (simultaneous sCTG) or test (simultaneous ADM) group. The primary outcome in this study was changes in PMT between baseline and 16 weeks later. Keratinized mucosal width (KMW) changes, modified wound healing index (MWHI) variations and patient-reported outcome measures (PROMs) were recorded, as well. RESULTS: A total of 20 participants were recruited per an a priori power analysis. There were no statistically significant differences between groups at baseline for any of the parameters analyzed. The gain in PMT at 1 mm, 3 mm, and 5 mm from the expected mucosal margin was 0.44 ± 2.04 mm, 1.20 ± 1.48 mm, and 1.20 ± 0.89 mm in the sCTG group, and 0.05 ± 1.57 mm, 0.85 ± 1.29 mm, and 1.45 ± 1.17 mm in the ADM group. No statistically significant differences in terms of PMT, KMW, and MWHI changes were observed between groups. The perceived discomfort was higher at 2 and 4 weeks for patients in the sCTG group. CONCLUSION: ADM produces similar outcomes to sCTG in terms of mucosal augmentation at the time of implant placement.

Retention and recruitment of general dentists in an adjunct teaching model-A pilot study.

PURPOSE/OBJECTIVES: Retention and recruitment of part time clinical adjunct faculty members in dental education is becoming increasingly difficult as dental schools come to rely on this workforce for their increased involvement in clinical education. Contributing factors include full time faculty shortage, aging workforce, practice and student debt, practice and family commitments, and financial compensation. This study attempts to ascertain barriers to teaching so appropriate strategies can be formulated to address this issue. METHODS: In the spring of 2016 an email survey was sent to current and former adjunct faculty members to ascertain demographics and retention and recruitment strategies. Descriptive analyses were completed for all variables in the sample. RESULTS: Twenty nine of forty six subjects responded to the survey with a response rate of 63%. Subjects over the age of sixty comprised 55% with only 17% being under the age of forty five. Overall family and practice commitments along with compensation were the primary barriers to teaching part time. For new dentists, student loan debt was the primary barrier to teaching. Travel to teach was also a barrier as 70% of respondents drove 200 miles or less to the dental school. CONCLUSION: The study demonstrated that the aging part time work force is a great concern and new part time clinical adjunct faculty members must be recruited. Barriers to recruitment and retention of faculty must be considered and addressed to sustain this teaching model.

Graduate Periodontics Programs' Integration of Implant Provisionalization in Core Curricula: Implementation of CODA Standard 4-10.2.d.

The aim of this descriptive study was to provide an overview of the status of implementation of Commission on Dental Accreditation (CODA) Standard 4-10.2.d (Provisionalization of Dental Implants) by U.S. graduate periodontics programs since its introduction in 2013. Surveys were sent in May 2015 to 56 accredited postdoctoral periodontics program directors to ascertain program director characteristics; status of planning, implementation, and curriculum resulting from adoption of Standard 4-10.2.d; preferred clinical protocols for implant provisionalization; interdisciplinary educational collaborators; and competency assessment mechanisms. The survey response rate was 52% (N=29); the majority were male, aged 55 or older, and had held their position for less than ten years. Among the responding programs, 93% had formal educational curricula established in implant provisionalization. Graduate periodontics (96%) and prosthodontics (63%) faculty members were predominantly involved with curriculum planning. Of these programs, 96% used immediate implant provisionalization, with direct (chairside) provisionalization protocols (86%) being preferred over indirect protocols (14%) and polyethylethylketone provisional abutments (75%) being preferred to titanium (25%) provisional abutments. Straight and concave transmucosal emergence profile designs (46% each) were preferred in teaching, with only 8% of programs favoring convex transmucosal profiles. A majority of responding programs (67%) lacked protocols for communicating to the restorative referral a mechanism to duplicate the mature peri-implant mucosal architecture. Regional location did not play a significant role in any educational component related to implant provisionalization for these graduate periodontal programs. Overall, this study found that a clear majority of graduate periodontics programs had established formal curricula related to implant provisionalization, with substantial clinical and philosophical consensus within the specialty.

Goggatomy: A Method for Opening Small Cuticular Compartments in Arthropods for Physiological Experiments.

Most sense organs of arthropods are ensconced in small exoskeletal compartments that hinder direct access to plasma membranes. We have developed a method for exposing live sensory and supporting cells in such structures. The technique uses a viscous light cured resin to embed and support the structure, which is then sliced with a sharp blade. We term the procedure a "goggatomy," from the Khoisan word for a bug, gogga. To demonstrate the utility of the method we show that it can be used to expose the auditory chordotonal organs in the second antennal segment and the olfactory receptor neurons in the third antennal segment of Drosophila melanogaster, preserving the transduction machinery. The procedure can also be used on other small arthropods, like mosquitoes and mites to expose a variety of cells.

COMPARISON OF CANADIAN AND UNITED STATES PREDOCTORAL DENTAL IMPLANT EDUCATION.

OBJECTIVE: The objective of this study was to assess the current status of Canadian predoctoral implant programs in terms of director demographics, curriculum characteristics and preferences in the techniques that are used to teach and carry out implant therapy. We compared the findings to analogous data recently acquired from dental schools in the United States. METHODS: A survey instrument was sent electronically to directors of predoctoral implant programs at all 10 accredited dental schools in Canada. RESULTS: All 10 dental schools responded to the survey. Program directors were affiliated with prosthodontics (90%) or oral surgery (10%) departments. Most Canadian institutions (90%) formally integrate their implant program into the third year of the curriculum. Clinical implant curricula include simulated exercises and direct patient care under supervision in 90% of predoctoral programs. Frequently taught restorative modalities include the posterior single-tooth implant crown (100%), mandibular implant-retained overdenture (90%), anterior implant-supported single crown (60%) and posterior 3-unit implant-supported bridge (50%). All programs reported the routine use of guided surgery planning software and surgical guides to aid in implant treatment planning. Preferred clinical protocols include implant-level impressioning (90%), use of open-tray impression copings (70%), custom abutment fabrication (60%), coronal fixation by screw-retention (60%) and use of titanium (100%) or zirconia (60%) abutments. Half of the program directors reported feeling that graduating students were adequately prepared to provide implant therapy on graduation. The demographics of Canadian directors of predoctoral implant programs were very similar to those of their counterparts in the United States. The largest divergences existed in clinical curriculum preferences and subjective perception of student preparedness in oral implantology on graduation. CONCLUSION: Greater homogeneity exists among Canadian dental schools with regard to predoctoral implant program curricula, compared with those in the United States. Further investigation is warranted to examine the reasons for Canadian program directors' current perceptions of lack of preparedness of graduating predoctoral students.

Electronic assessment of peri-implant mucosal esthetics around three implant-abutment configurations: a randomized clinical trial.

OBJECTIVES: To objectively assess the influence that three different implant-abutment interface designs had on peri-implant mucosal esthetics at 1 year post-implant placement via the pink esthetic score (PES). Additionally, to demonstrate the novel employment of a tablet-based digital imaging format to reliably assess and score clinical images as part of a multicenter clinical trial according to PES criteria. MATERIALS AND METHODS: Adult subjects (n = 141) with healed tooth-bound edentulous sites in the anterior maxilla as well as first premolar region were randomized to receive one of three different implant-abutment interface designs (conical interface = CI; flat-to-flat interface = FI; or platform switch interface = PS). Immediate provisionalization was performed with prefabricated titanium abutments, with definitive custom CAD/CAM zirconia abutments and all-ceramic cement-based crowns being delivered 12-week post-implant placement. Bilateral (anterior sites) or unilateral (premolar sites) digital clinical photographs were made at 1, 3, 6, and 12 months post-implant placement. Five calibrated faculty evaluators of different clinical backgrounds scored images during a 4-week timeframe on a standardized, tablet-based, digital imaging format. RESULTS: Six hundred and forty-nine clinical photographs were evaluated resulting in a total of 3245 sum PES values and 22,715 individual PES values. Faculty evaluator intra- and inter-rater reliability was found to be "strong" (ICC = 0.84) and "substantial" (ICC = 0.64), respectively, demonstrating repeatability of both the PES, evaluator calibration, and standardization of tablet-based scoring. All implant-abutment interface groups demonstrated significant improvements in mean sum PESs up to 1 year, with the largest improvement between restoration delivery and 6 months. No significant differences were found between groups in mean sum PESs both for individual study visits as well as for changes between study visits. CONCLUSIONS: No significant differences in mean sum PESs were found between subjects randomized to three different implant-abutment interfaces. However, significant differences were found as a function of time for all three groups, with the largest improvement in mean sum PESs occurring between definitive abutment and restoration delivery and 6 months. Use of electronic, tablet-based digital imaging scoring formats represents a novel and repeatable methodology for scoring PES images in large, multicenter clinical trials.

An overview of U.S. predoctoral dental implant programs and their directors.

The aim of this study was to provide an overview of current predoctoral implant programs in the United States, including curricular characteristics and clinical practices regarding implant therapy education and program directors' characteristics. An electronic survey was sent to predoctoral implant program directors of all 64 accredited U.S. dental schools; 52 of the 60 eligible programs responded, for a response rate of 87%. The responding program directors were primarily affiliated with either prosthodontics departments (44%) or restorative dentistry departments (40%). Structurally, 80.8% of the responding schools integrate their implant programs into the third year of the curriculum. Clinical implant therapy exercises reported were simulation exercises without direct patient care (90.4% of responding schools) and direct patient care under supervision (94.2%). The most frequently taught restorative modalities are posterior single-tooth implant crown (96.2%), mandibular implant-retained overdenture (88.5%), and anterior implant-supported single crown (61.5%). A majority (74.5%) of responding programs utilize analog surgical guide planning, while 25.5% reported use of digital guided surgery planning software. All schools in the Northwest and 66.7% in the South Central regions utilize custom abutments as the primary abutment design, while a majority of schools in the North Central (62.5%), Northeast (53.8%), Southwest (66.7%), and Southeast (80%) regions use stock abutments (p=0.02). Regional differences were significant with regard to fixation modality, with all the Northwest programs using screw retention and 90% of Southeast and 87.5% of North Central programs using cement retention (p=0.002). This study demonstrated that while institutions share program director and curricular similarities, clinical practices and modalities vary significantly by region.

Comparison of pro-inflammatory cytokines and bone metabolism mediators around titanium and zirconia dental implant abutments following a minimum of 6 months of clinical function.

OBJECTIVES: Dental implant abutments are fundamental prosthetic components within dentistry that require optimal biocompatibility. The primary aim of this cross-sectional study was to preliminarily assess differences in the pro-inflammatory cytokine and bone metabolism mediator protein expression in the peri-implant crevicular fluid (PICF) adjacent to transmucosal abutments. MATERIAL AND METHODS: Abutments were fabricated from either titanium or zirconia in patients previously receiving single-tooth implant therapy. All subjects sampled in this study had an identical implant system and implant-abutment connection. Participants (n = 46) had an average time of clinical function for 22 months (6.2-72.8 months, ±SD 17 months) and received a clinical and radiographic examination of the implant site at the time of PICF sampling using a paper strip-based sampling technique. Cytokine, chemokine, and bone metabolism mediator quantities (picograms/30 s) were determined using a commercial 22-multiplexed fluorescent bead-based immunoassay instrument. A total of 19 pro-inflammatory cytokines and seven bone metabolism mediators were evaluated. RESULTS: Multivariable analyses provided no evidence of a group (titanium or zirconia), gender, or age effect with regard to the expression of pro-inflammatory mediators evaluated. Significant (P = 0.022) differences were observed for the bone mediator leptin, with titanium abutments demonstrating significantly elevated levels in comparison with zirconia. Osteopontin demonstrated a significant (P = 0.0044) correlation with age of the subjects. CONCLUSIONS: No significant differences in pro-inflammatory cytokine or bone metabolism mediator profiles were observed biochemically, with the exception of leptin, for the abutment biomaterials of titanium or zirconia The molecular PICF findings support the observed clinical biocompatibility of both titanium and zirconia abutments.

Minimally invasive preparation and design of a cantilevered, all-ceramic, resin-bonded, fixed partial denture in the esthetic zone: a case report and descriptive review.

UNLABELLED: Resin-bonded, fixed partial dentures have the potential to offer a minimally invasive, fixed-prosthetic approach to tooth replacement in patients who may not be candidates for implant therapy. However, traditional preparation protocols often recommend extensive preparation designs on two abutment teeth, thereby potentially compromising the long-term health of the adjacent abutments and often resulting in unilateral debonding of one of the retainers in the long term. In light of advances in high-strength ceramic systems capable of being reliably bonded to tooth structure and offering improved esthetic outcomes, as well as clinical and case-series research demonstrating improved survivability of cantilevered resin-bonded fixed partial dentures, new preparation designs and methodologies can be advocated. The following case report demonstrates the clinical application of sonoabrasion, coupled with a dental operating microscope, to minimally prepare a single abutment for a cantilevered, all-ceramic resin-bonded fixed partial denture. Relevant historic and contemporary literature regarding double versus single-retainer resin-bonded fixed partial dentures are reviewed, as well as clinical conditions that are most favorable for such restorations to have an optimal long-term prognosis. CLINICAL SIGNIFICANCE: If appropriate clinical conditions exist, a cantilevered, all-ceramic, resin-bonded, fixed partial denture may be the most conservative means of tooth replacement in a patient who is not a candidate for an endosseous implant.

Presence of wax esters and squalene in human saliva.

OBJECTIVE: The purpose of this study was to determine the presence and relative composition of neutral lipids in human saliva. DESIGN: Whole unstimulated saliva was collected from 12 subjects ranging from 21 to 29 years old. Samples were lyophilized, and lipids were extracted using chloroform-methanol. Lipids were analysed by thin-layer chromatography. RESULTS: Human saliva contains cholesterol, fatty acids, triglycerides, wax esters, cholesterol esters and squalene. The mean total neutral lipid content was 12.1±6.3 µg/ml. CONCLUSIONS: These lipids in human saliva closely resemble the lipids found on the skin surface. These salivary lipids are most likely produced by the sebaceous follicles in the oral mucosa and sebaceous glands associated with major salivary glands.