Importance Dental caries is a highly prevalent yet preventable disease affecting more than 40% of US children, with severe early childhood caries (S-ECC) leading to serious health and economic consequences. This randomized clinical trial addresses critical evidence gaps by evaluating 38% silver diamine fluoride (SDF) effectiveness for caries arrest in young US children with S-ECC to inform US Food and Drug Administration (FDA) regulatory approval. Objective To assess the efficacy of 38% SDF vs placebo for arresting active cavitated dentin caries lesions in the primary dentition of US children with S-ECC. Design, Setting, and Participants This phase III, multisite, randomized, blind, placebo-controlled clinical trial with 2 parallel arms had a data collection period from October 2018 through April 2023. Analyses were completed in 2024. Three sites recruited from and treated children in a variety of settings: medical and dental clinics, and Head Start and city/state-subsidized preschool programs. Enrolled participants included 830 generally healthy children aged 12 to 71 months with S-ECC and active cavitated lesions. Intervention Children were randomized to receive either 38% SDF or placebo, applied at baseline and at 6 months. Clinical examinations were conducted at baseline, 3 months, 6 months, and 8 months. OUTCOMES AND MEASURES The primary outcome was the proportion of arrested lesions at 6 months after 1 application. Secondary outcomes included arrest efficacy at 3 months and after 2 applications (8 months), and pain at or before 6 months and 8 months Results Of 830 enrolled children, 584 (70%) completed the study. Of those lost to follow-up (approximately 30%), 81 (9.8%) were lost due to COVID-19. Participants included 428 females (52%) and 402 males (48%) and were aged 1 to 6 years with high caries experience (mean [SD] decayed, missing, and filled teeth [dmft] (International Caries Detection and Assessment System ≥1), 11.36 [4.56]; range, 1-23). In intent-to-treat analyses, SDF arrested 57.5%, 54.0%, and 50.2% of lesions at 3 months, 6 months, and 8 months, respectively, vs placebo (18.8%, 22.5%, 17.4%, respectively). Differences (99.9% CI) in arrest rates were 38.7% (28.7%-48.6%), 31.5% (21.5%-41.6%), and 32.8% (22.3%-43.2%). There were no differences in pain. Averse events (AEs) were reported by 196 (47.3%) participants in the SDF group and 180 (43.3%) in the placebo group. Most AEs were mild to moderate in severity; 4 AEs (0.6%) were severe. Treatment-related AEs were similar between the 2 groups (SDF = 22.9%; placebo = 22.2%), as were discontinuation rates due to AEs (7.5% for both groups). Conclusion and Relevance In this randomized clinical trial, 38% SDF was significantly more effective than placebo for arresting dentin caries lesions in primary teeth in young children with S-ECC, providing a noninvasive treatment for young high-risk children and supporting its consideration for FDA drug approval. Trial Registration ClinicalTrials.gov Identifier: NCT03649659

OBJECTIVES:This study provides a descriptive, multi-institutional comparison of dental students' recognition accuracy and management decisions of oral soft tissue pathological entities across four US dental schools. While prior single-institution studies have evaluated diagnostic ability, this work provides a multi-institutional comparison to identify recognition and decision-making variability as well as potential educational implications. MATERIALS AND METHODS:A voluntary, anonymous online survey with twenty image-based multiple-choice questions was administered to 160 students. Each question included an image, patient demographics, and key case details. Management questions were provided with reference diagnoses to prevent conflation of diagnostic and management errors. Descriptive statistics, t-tests, logistic regression, chi-square tests, and multi-rater kappa statistics were used to analyze performance, with effect sizes, reference groups, and 95% confidence intervals reported. Model fit for logistic models was assessed using likelihood ratio tests. RESULTS:Students demonstrated a high level of recognition for conditions like candida (84%) and tobacco keratosis (95%). Subtle or clinically variable lesions were more challenging, such as erosive lichen planus (50%) and idiopathic leukoplakia (58%). Management accuracy frequently lagged behind recognition accuracy. Significant inter-school differences were observed for both recognition (χ2 = 27.66, p < 0.0001) and management (χ2 = 30.80, p < 0.0001), with students from School #4 outperforming peers. Kappa values remained low (< 0.2 for most items), indicating wide variability and limited internal agreement. CONCLUSION:Students demonstrated strong theoretical knowledge of common oral pathological entities but variability in identifying and managing rare or diagnostically nuanced conditions. Because this survey evaluates recognition rather than competence, findings highlight the need for case-based, competency-aligned teaching approaches to strengthen diagnostic reasoning and management decision-making.

PURPOSE:To evaluate the effect of faucet-mounted water filters (FMWF) on the fluoride and calcium concentrations in tap water during their use. METHODS:A convenience sample of 15 different brands of FMWF was investigated (PUR, Brita, Waterdrop, Culligan, Engdenton, DuPont, Instapure, iSpring, OEMIRY, IVO, SJ WAVE, WINGSOL, ZeroWater, AIBERLE, MIST). Water samples were collected before the installation and after removal of the filters to determine baseline fluoride and calcium values. After mounting the filters, samples were collected after 1, 5, 10, 30, 50, 75, and 100 liters of water passed through each filter. Fluoride analysis was performed using a fluoride ion-specific electrode (Orion #96-909-00), while calcium analysis was performed using atomic absorption spectrometry. The data were analyzed using one-sample t-tests and one-way ANOVA. RESULTS:The study found significantly lower fluoride and calcium levels (P< 0.05) in water filtered through PUR, Brita, and AIBERLE filters than in unfiltered water, whereas water filtered through Waterdrop, WINGSOL, and MIST filters had higher levels of fluoride and calcium. Overall, the differences between filtered and unfiltered water were minor for fluoride (up to 4% reduction) but more substantial for calcium (up to 25% reduction). CLINICAL SIGNIFICANCE:The evaluated faucet-mounted water filters do not affect fluoride concentrations in tap water and thus the effectiveness of community water fluoridation in a clinically significant manner; however, some filters may reduce calcium concentrations significantly.

Objectives Dental caries remains a major public health concern, affecting over 2 billion people. It can lead to tooth destruction, pain, and reduced quality of life, making accurate diagnosis essential. The International Caries Detection and Assessment System (ICDAS) standardizes caries detection. Erosive tooth wear (ETW), mainly caused by dental erosion, is assessed using the Basic Erosive Wear Examination (BEWE) index. Advancements in digital imaging, including 3D intraoral scanners, have expanded diagnostic possibilities. This study investigated agreement between 3D intraoral scans and 2D photographs for caries and ETW assessment in orthodontic patients. Methods This retrospective study assessed caries and ETW on 394 occlusal surfaces using ICDAS and BEWE in orthodontic patients aged 13 years and older. Two calibrated examiners visually evaluated 2D photographs and 3D intraoral scans to determine agreement. Eligible cases were identified from axiUm and Dolphin Imaging software, requiring fully erupted first molars and second premolars with 2D and 3D records. Both image types were evaluated using a laptop computer under standardized conditions, with 2D images assessed via Dolphin Imaging and 3D scans reviewed using iTero. Results Agreement between 2D photographs and 3D scans was moderate for BEWE (69.5%) and ICDAS (70.8%). BEWE scores were underestimated in 5.8% and overestimated in 4.6% of cases. Agreement improved to 75.1% when scores were grouped. The weighted Kappa for BEWE was 0.57 (p < 0.0001), indicating moderate agreement. For ICDAS, 3D scans underestimated scores in 12.2% and overestimated in 17.0% of cases. The weighted Kappa was 0.54 (p < 0.0001), indicating moderate agreement. Spearman correlation coefficients were 0.607 for BEWE and 0.592 for ICDAS, reflecting a moderate positive correlation. Conclusions Moderate agreement was found between 2D photographs and 3D IOS for caries and erosive tooth wear assessment, supporting 3D IOS as an adjunctive diagnostic tool. Clinical significance 3D intraoral scans support the monitoring of caries and erosive tooth wear over time in clinical settings where routine digital records are available.

ABSTRACT Peri-implantitis is an inflammatory condition of the tissues surrounding dental implants, characterized by progressive bone loss. Pathological mechanisms of peri-implantitis remain largely unknown, and effective therapeutic approaches have not been established. Recent studies on periodontitis, another inflammatory bone disease of the oral cavity, have indicated that cellular senescence is involved in its pathology and could be a therapeutic target. In contrast, the involvement of cellular senescence in the pathology of peri-implantitis remains largely unexplored. In this cross-sectional pilot study, we investigated senescence gene expression in convenience surgical samples to explore senescent burden in the tissues affected by peri-implantitis. Genes associated with senescence-associated secretory phenotype, anti-apoptosis, and cell cycle arrest were analyzed as senescence genes. In total, we analyzed 19 healthy control and 23 diseased samples. There were significant differences in age, sex, and BMI between the groups. We detected significant upregulation of SASP genes and anti-apoptotic genes, including IL6, MMP2, MMP13, MMP14 , and BCLXL , in peri-implantitis samples. PPARG was also elevated in peri-implantitis samples, suggesting alterations in metabolic states in the tissue. However, an elevation in the expression of genes for cell cycle inhibitors, such as p16, CDKN1A, CDKN2B , and TP53 , which are crucial markers of senescent cells, was not observed in the peri-implantitis group. Thus, although we detected several genes upregulated in mucosal tissue affected by peri-implantitis, which might indicate pathological changes, the accumulation of senescent cells in the diseased mucosal tissue was inconclusive. A future comprehensive study that includes analyses beyond gene expression would be needed.

OBJECTIVE:To evaluate the demineralization-inhibiting properties of 0.5% chitosan (CHI) and 2% sodium linear polyphosphate (LPP) alone or associated with fluoride (1350 ppm, NaF) and/or stannous (3500 ppm, SnCl2) plus fluoride ions in experimental toothpaste formulations. METHODS:Bovine enamel specimens were randomly allocated into 12 groups (n = 14) and subjected to a 5-day pH cycling period (3-h demineralization 2 × /d, 1-min 1:3 toothpaste slurry 2 × /d, remineralization all other times). Sections were analyzed using digital transverse microradiography (integrated mineral loss-ΔZ, lesion depth-L, and maximum mineral density of the lesion surface zone-SZmax). The fluoride availability in the toothpaste slurry was measured using an ion-selective electrode. ANOVA was used to test for a group effect, followed by pair-wise comparisons using Fisher's Protected Least Significant Differences (alpha=0.05). RESULTS:For the ΔZ data, CHI and LPP in isolation did not differ from placebo [geometric means (confidence intervals); vol%min x µm]: [4561(3852,5401)] and [4582 (3890,5396)] vs. [5168(4369,6114)], respectively, (p ≥ 0.268), and did not provide additional protection when associated with F [1843 (1531,2219)], Sn [5080(4354,5926)] and F+Sn [2298(1860,2838)]. Sn-containing toothpastes did not differ from placebo (p ≥ 0.05). All F-based toothpastes resulted in less demineralization than F-free toothpastes. The L data followed similar trends to the ΔZ data. The SZmax data showed that CHI and LPP did not differ from placebo: vol%min 1 (35,49) and 42 (34,51) vs. 46 (41,51), respectively (p > 0.243). When associated with F, only CHI [29(21,40)] presented less mineral content at the surface lesion, and the polymers did not provide additional mineral content at the surface layer when associated with Sn [38(34,44), p > 0.377], or F+Sn [15(36,57), p > 0.23]. For the mean mineral distribution for all lesions as a function of experimental toothpastes, some lesions showed surface softening without a clear lesion body (F), and some lesions showed a more pronounced (Placebo). The fluoride values ranged from 0 (Placebo) to 1490 (CHI+F). CONCLUSION:None of the polymers could enhance the protection provided by fluoride or fluoride plus stannous.

Background/Objectives: Superficial oral mucosal (SOM) lesions are prevalent among patients with Sjögren’s disease (SjD) due to mucosal dryness. Given the limited evidence on screening and referral for SOMs, and the presence of relevant information only in dental clinical notes, a natural language processing (NLP) pipeline was developed to screen for SOMs among SjD patients. This retrospective study analyzed dental clinical notes from 180 linked electronic dental and health records, including both with and without a diagnosis of SjD. Materials and Methods: An annotation schema with four classes (SOMs, signs and symptoms of dry mouth, treatment for xerostomia, referral to specialists) was inductively created using the Extensible Human Oracle Suite of Tools (eHOST) to manually annotate clinical notes. Relevant keyterms were retrieved using a rule-based approach with Python’s Natural Language Toolkit (NLTK). SjD and control groups were compared using Fisher’s Exact tests. Four annotators reviewed ninety-three records. Results: SjD patients (mean age 54.8 ± 11.7 years) had fewer total visits across 15 years but had more dental visits per year (10.2 ± 13.3) than controls. SjD patients were more likely to have oral candidiasis (p = 0.041), exhibit signs and symptoms of dry mouth (p = 0.004), receive treatments for xerostomia (p < 0.001), be treated with cholinergic agonists (p = 0.005), and be referred to a specialist (p = 0.046), but findings were not significant for all SOMs. Additionally, SjD patients had a higher proportion of sialadenitis (p = 0.045), rheumatoid arthritis (p = 0.001), systemic lupus erythematosus (p < 0.001), myalgia/myositis/fibromyalgia (p = 0.010), and anxiety/nervousness (p = 0.004). Conclusions: These findings encourage the feasibility of using text mining from dental clinical notes for screening and management of oral conditions.

Objectives:To assess the effectiveness of virtual reality relaxation (VRR) as an intervention for reducing anxiety in adolescents and adults during the orthodontic bonding procedure. Materials and Methods:This prospective clinical study included 53 patients undergoing fixed orthodontic treatment at the Indiana University School of Dentistry. Participants were randomly assigned to one of two groups: the experimental group using VRR during orthodontic direct bonding or the control group receiving no distraction. Physiological measures (blood pressure [BP], heart rate [HR], and oxygen saturation) and psychological assessments (5-item State-Trait Anxiety Inventory-Short Form, and the Visual Analog Scale for Anxiety [VAS-A]) were collected at baseline (T0) and 30 minutes into the bonding procedure after bonding of one arch (T1). Repeated measures of analysis of variance were used to compare groups and timepoints. Results:At T0, no statistically significant differences were found between the control and VRR groups across any psychological or physiological measures (P > .05). Although both groups showed significant reductions for physiological and psychological measures from T0 to T1 (P < .01), the VRR group reported significantly lower VAS-A scores, HR, and diastolic BP at T1 than the control group (P < .05). Conclusions:VRR effectively reduced psychological and physiological anxiety during orthodontic bonding procedures, supporting VRR as a promising adjunctive tool in managing dental anxiety during orthodontic care.

Importance:Dental caries is a highly prevalent yet preventable disease affecting more than 40% of US children, with severe early childhood caries (S-ECC) leading to serious health and economic consequences. This randomized clinical trial addresses critical evidence gaps by evaluating 38% silver diamine fluoride (SDF) effectiveness for caries arrest in young US children with S-ECC to inform US Food and Drug Administration (FDA) regulatory approval. Objective:To assess the efficacy of 38% SDF vs placebo for arresting active cavitated dentin caries lesions in the primary dentition of US children with S-ECC. Design, Setting, and Participants:This phase III, multisite, randomized, blind, placebo-controlled clinical trial with 2 parallel arms had a data collection period from October 2018 through April 2023. Analyses were completed in 2024. Three sites recruited from and treated children in a variety of settings: medical and dental clinics, and Head Start and city/state-subsidized preschool programs. Enrolled participants included 830 generally healthy children aged 12 to 71 months with S-ECC and active cavitated lesions. Intervention:Children were randomized to receive either 38% SDF or placebo, applied at baseline and at 6 months. Clinical examinations were conducted at baseline, 3 months, 6 months, and 8 months. OUTCOMES AND MEASURES:The primary outcome was the proportion of arrested lesions at 6 months after 1 application. Secondary outcomes included arrest efficacy at 3 months and after 2 applications (8 months), and pain at or before 6 months and 8 months. Results:Of 830 enrolled children, 584 (70%) completed the study. Of those lost to follow-up (approximately 30%), 81 (9.8%) were lost due to COVID-19. Participants included 428 females (52%) and 402 males (48%) and were aged 1 to 6 years with high caries experience (mean [SD] decayed, missing, and filled teeth [dmft] (International Caries Detection and Assessment System ≥1), 11.36 [4.56]; range, 1-23). In intent-to-treat analyses, SDF arrested 57.5%, 54.0%, and 50.2% of lesions at 3 months, 6 months, and 8 months, respectively, vs placebo (18.8%, 22.5%, 17.4%, respectively). Differences (99.9% CI) in arrest rates were 38.7% (28.7%-48.6%), 31.5% (21.5%-41.6%), and 32.8% (22.3%-43.2%). There were no differences in pain. Averse events (AEs) were reported by 196 (47.3%) participants in the SDF group and 180 (43.3%) in the placebo group. Most AEs were mild to moderate in severity; 4 AEs (0.6%) were severe. Treatment-related AEs were similar between the 2 groups (SDF = 22.9%; placebo = 22.2%), as were discontinuation rates due to AEs (7.5% for both groups). Conclusion and Relevance:In this randomized clinical trial, 38% SDF was significantly more effective than placebo for arresting dentin caries lesions in primary teeth in young children with S-ECC, providing a noninvasive treatment for young high-risk children and supporting its consideration for FDA drug approval. Trial Registration:ClinicalTrials.gov Identifier: NCT03649659.

Précis: The relationship between structural and hemodynamic parameters in patients with primary open angle glaucoma is strongest in the temporal region of the optic nerve. Purpose: To investigate the relationship between radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in quadrants and sectors of the optic nerve head (ONH) in patients with and without primary open angle glaucoma (POAG). Methods: In a cross-sectional prospective analysis, 191 subjects (80 early-stage POAG; 111 non-glaucomatous controls) were assessed for RNFL thickness and RPC VD in each quadrant [superior (S), inferior (I), nasal (N) and temporal (T)] and sector [inferior-temporal (IT), temporo-inferior (TI), temporo-superior (TS), superior-temporal (ST), inferior-nasal (IN), naso-inferior (NI), naso-superior (NS), and superior-nasal (SN) sectors] of the ONH via optical coherence tomography angiography (OCTA, Avanti, Optovue). Pearson correlations were used to test for associations between measurements, with P<0.05 considered statistically significant. Results: Significantly stronger positive correlations were found between RPC VD and RNFL thickness in the S, I, and T quadrants in POAG patients compared to non-glaucomatous controls (all P<0.05). The temporal quadrant in POAG patients displayed the largest difference in correlation compared to controls. A stronger positive correlation was also found between RPC VD and RNFL thickness in the temporal sectors of the ONH in POAG patients compared to controls, with the largest difference in the TS sector (all P<0.05). Conclusion: Early-stage POAG patients have a stronger relationship between RPC VD and RNFL in the temporal regions of the ONH compared to non-glaucomatous controls, with the TS sector demonstrating the largest difference between groups. Temporal sector VD loss may represent an early-stage biomarker for vascular-linked POAG disease.

Introduction > The aim of this study was to investigate the effects of direct attachment shape and location on the forces and moments generated by thermoplastic aligners during simulated maxillary central incisor torque. Materials and methods > A total of 7 typodonts were digitally printed with different attachment design and locations. Five clear aligners were fabricated for each typodont and placed on an orthodontic force tester (OFT) with the maxillary central incisor rotated palatally 1 degrees around the incisal edge. Forces and moments were measured 2 times by the load cells. Analysis of variance (Anova) was used to determine the effects of group, tooth, and the group-by-tooth interaction on the outcomes; A two-sided 5% significance level was used for all tests. Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Results > The two-way interactions between group and tooth were significant (P < 0.001) for all outcomes except facial/palatal moment around the X axis (M-x) (P > 0.05). The horizontal ellipsoid attachment at the middle third generated the highest M-x (-25.74 +/- 8.93 Nmm) with facial crown/palatal root, while the rectangular attachment at the middle third yielded the lowest M-x (3.31 +/- 12.92 Nmm). Conclusions > Changing attachment shape and location had a significant effect on the forces and moments generated during simulated maxillary incisor torque. The best design for the incisor torque movement was found to be the horizontal ellipsoid attachment at the middle third. Besides the desired torque moment, all attachment shape and location combinations produced a vertical extrusive force as a side effect.

This in vitro study aimed to compare the direct (visual exam) versus indirect (3D-colored digital images exam) assessments of ICDAS (dental caries), BEWE (erosive tooth wear), and TF (enamel fluorosis lesions) indices performed on the occlusal surfaces of extracted human teeth for the detection and severity differentiation of dental caries, erosive tooth wear, and enamel fluorosis lesions. A total of 453 occlusal surfaces from extracted human teeth were mounted on 28 typodont models. Surfaces were examined directly (visual) and indirectly using 3D-coloured intraoral scans (TRIOS 4, 3Shape). Three indices were assessed: International Caries Detection and Assessment System (ICDAS; caries), Basic Erosive Wear Examination (BEWE; erosive tooth wear), and Thylstrup-Fejerskov (TF; fluorosis). Agreement between methods was analysed using weighted kappa statistics and percentage agreement. Substantial agreement was observed between direct and indirect methods: ICDAS (κ = 0.72, 64

OBJECTIVES:This in vitro investigation assessed how frequency of erosive challenges and duration of toothbrushing abrasion influenced non-carious cervical lesions (NCCLs) development and morphology. DESIGN:Experimental units were prepared using extracted human premolars assigned to four erosive-abrasive frequency protocols (n=16): F0. No acid exposure (negative control), F2.5 K. Acid exposure (1 % citric acid at natural pH) every 2500, F5K. 5000 and F15K. 15000 brushing-strokes. All groups were brushed for 55000 total brushing-strokes. Three-dimension images of the teeth were captured at baseline, after 15000, 35000 and 55000 brushing-strokes, using an intraoral scanner (TRIOS4, 3Shape). WearCompare software (Leeds Digital Dentistry) was used to analyze volumetric tooth loss (mm3) by superimposition followed by subtraction analysis. Lesion angle was measured (ImageJ, NIH) and morphology visually classified. Data were analyzed using ANOVA and Fisher's Exact tests adopting two-sided 5 % significance level. RESULTS:Tooth loss increased with brushing-strokes overall (p<0.001) and for each erosive-abrasive protocol (p<0.001). Acid exposure significantly increased tooth loss (p<0.001), regardless of brushing interval (p<0.001), however by 35000 strokes no tooth loss difference was observed among acid-exposed groups (p>0.05). Control had significantly sharper mean lesion angle (59°) than all acid-exposed groups (∼145°) (p<0.001), and significantly different lesion shape with 94 % wedge-shaped lesions versus 0 %, respectively (p<0.001). In contrast to the control, acid exposure was associated to more striated lesions. CONCLUSIONS:Simulated NCCLs developed and progressed differently and more rapidly in the presence of acidic challenges, regardless of their frequency. Exposure to acid impacted the morphology of lesions.

Objective To determine whether decreased femoral head enhancement on MRI differentiates septic arthritis from transient synovitis. Materials and methods This retrospective study included children < 10 years old with hip effusion on post-contrast MRI for suspected musculoskeletal infection. Two pediatric radiologists independently assessed femoral head enhancement. Kocher and modified Kocher scores were calculated from clinical and lab data. Differences between septic arthritis and transient synovitis were analyzed using Student’s t -tests and Fisher’s exact tests. Sensitivity and specificity for diagnosing septic arthritis were calculated for Kocher scores, their individual components, decreased femoral head enhancement, and muscle edema. Interobserver agreement was assessed. Results Thirty-four children were included (20 transient synovitis, 14 septic arthritis). Kocher and modified Kocher scores were significantly higher in septic arthritis ( p = 0.003, 0.008). Interobserver agreement for femoral head enhancement was substantial (kappa = 0.70). On consensus read, decreased femoral head enhancement was seen in 71.4% of septic arthritis and 50.0% of transient synovitis cases ( p = 0.296). Bone marrow edema was present in two septic arthritis cases. Muscle edema had moderate to high sensitivity (71.4%, 92.9%) but moderate to low specificity (75.0%, 50.0%) for septic arthritis. Conclusion Decreased femoral head enhancement does not reliably distinguish septic arthritis from transient synovitis. Relying on this finding alone may lead to unnecessary interventions in children with transient synovitis. Muscle edema and bone marrow edema may support the diagnosis of septic arthritis. Clinical evaluation and inflammatory markers remain critical in guiding decisions for hip aspiration.

Background: Erenumab has proven efficacious in treating migraine headache. Temporomandibular disorder (TMD) is a painful disorder which has high co-occurrence rates with migraine. We hypothesized that erenumab-aooe may also be beneficial in reducing pain in TMD-related myalgia. Methods: This phase II randomized placebo-controlled clinical trial evaluated the safety and efficacy of the off-label use of erenumab in reducing TMD-related pain. The TMD diagnosis was established using the Diagnostic Criteria for Temporomandibular Disorders. The primary outcome was pain interference as assessed by the 0-to-10-point Brief Pain Inventory (BPI). Secondary outcomes were depression, anxiety and somatic symptoms; jaw function; and percent of days taking pain medication. Subjects were randomized at baseline to receive either erenumab 140 mg or placebo administered subcutaneously every 4 weeks for a total of five treatments. Outcome assessments were conducted at baseline, 4, 8, 12, 16, 20 and 24 weeks. Results: Thirty subjects were enrolled with 15 randomized to each treatment group. Baseline pain was mild (BPI interference of 2.19; BPI severity of 2.95). There were no significant treatment effects at any time points with the between-group BPI interference at 24 weeks being-0.19 (95% confidence interval-1.94 to 1.56; p = 0.82). The outcomes were similar between erenumab and placebo for all outcomes except the Patient Health Questionnaire 4-item scale (PHQ-4) which showed that depression/anxiety symptoms were modestly worse (p = 0.03) in the erenumab group. Five participants withdrew during the trial (4 in erenumab arm, 1 in placebo arm). Conclusions: Erenumab was not efficacious in reducing TMD myalgic pain in this phase II trial of 30 subjects with relatively mild pain. Clinical Trial Registration: The study was registered in clinicaltrials.gov (ID: NCT04884763).

Purpose: To compare oxygen saturation measurements when pulse oximeter sensors were simultaneously placed on the index finger and the second toe, and compare blood pressure recordings with non-invasive blood pressure (NIBP) cuffs simultaneously placed on the upper arm and the lower calf in children receiving general anesthesia. Methods: A total of 50 children, aged three to nine years, defined as ASA Class I or II receiving comprehensive dental treatment in the operating room with general anesthesia, were included. Pulse oximeter sensors were simultaneously placed on each subject's index finger and ipsilateral second toe. Non-invasive blood pressure cuffs were simultaneously placed on the upper arm and ipsilateral lower calf above the ankle. The same anesthesia regimen was used on all patients. Following induction of general anesthesia, measurements were simultaneously recorded every five minutes during the dental procedure. Results: Index finger oxygen saturation measurements were significantly lower than the second toe (P<0.001). Arm systolic blood pressure measurements were significantly lower than calf measurements (P<0.001). Arm diastolic blood pressure measurements were significantly lower than calf measurements (P<0.001). Conclusions: Discrepancy of vital sign measurements may be notable depending on the site from which measurements are obtained. If blood pressure is taken on the calf of a child in the Trendelenburg position, the reading will likely produce a higher systolic and diastolic measurement and should be interpreted with caution. A pulse oximeter placed on the first finger or second toe of healthy children can be regarded as interchangeable in a clinical setting.

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments.

BACKGROUND:Accumulation of senescent cells is increasingly recognized as a mechanism of aging and is considered an attractive therapeutic target for various age-associated diseases. The prevalence and severity of periodontitis increase with age, and preclinical studies have demonstrated that senescent cells could be a potential therapeutic target for age-associated periodontitis. However, clinical data linking cellular senescence and periodontitis are limited. METHODS:Gingival tissues affected with periodontitis and healthy controls were collected from patients with or without periodontitis in a cross-sectional study. RNA isolated from these samples was analyzed for senescence gene expression by quantitative polymerase chain reaction (qPCR) assays. The associations of the gene expression levels with periodontal diagnosis, presence or absence of attachment loss or bleeding on probing, and age were examined. Additionally, we analyzed the expression of senescence genes in the gingival tissues of mice with or without ligature-induced periodontitis. RESULTS:A total of 54 human gingival tissue samples were included in the study. Among the genes analyzed, p16, TP53, MMP2, and MMP14 exhibited significantly higher expression in the periodontitis group compared to the control group. Furthermore, these genes were associated with clinical signs of periodontitis, such as bleeding score and attachment loss at diagnosis. There were no statistically significant positive correlations between gene expression levels and age. The ligature-induced periodontitis significantly increased expression levels of p16 and other senescence genes in mouse gingival tissues. CONCLUSION:Gene expression analysis indicates the accumulation of senescent cells in gingival tissue affected with periodontitis, supporting the concept that senotherapeutics could be effective in treating periodontitis. PLAIN LANGUAGE SUMMARY:Biological stressors cause cells to age, known as cellular senescence. These senescent cells play a significant role in age-related diseases and are considered a key target for treatment. Periodontitis, a gum disease, damages the tissues that support teeth and is a leading cause of tooth loss worldwide. When people get older, they have a higher chance of being affected by periodontitis. Studies using animal models have shown that the accumulation of senescent cells may be driving periodontitis in older individuals. Therefore, targeting senescent cells may be a potential treatment approach for periodontitis. However, clinical evidence showing the accumulation of senescent cells in gum tissue affected with periodontitis is limited. This study aimed to investigate whether periodontitis is accompanied by senescent cell accumulation in the gum tissue by examining gene expression in tissues with and without periodontitis. A total of 54 human gum tissues (27 healthy and 27 diseased) were collected during gum surgeries. Our analysis found that four genes related to cellular senescence (p16, TP53, MMP2, and MMP14) were significantly higher in samples affected with periodontitis. This indicates that senescent cells accumulate in diseased gum tissue. Additionally, results from an animal experiment suggested that being affected with gum disease may be a mechanism accelerating cellular aging in the gum tissue. The findings support the concept that targeting senescent cells would be an effective approach to treat gum disease.