TF Scores Research Articles

Abstract 2282: Predictive association of tumor cells hijacked NFATC2 activities with resistance to immune checkpoint inhibition in melanoma patients

Abstract Background: Immune checkpoint blockade (ICB) has emerged as an effective cancer therapy. However, only a small fraction of patients receives benefits whereas a significant subset of patients experienced severe or even lethal autoimmune diseases. Stratifying patients that would benefit from immunotherapy remain a highly unmet clinical need. Dysregulations of transcriptional programs have been implicated in cancer initiation and progression. To date, there is a paucity of studies on the predictive values of transcriptional factors on ICB response based on the most recently emerged ICB clinical trial datasets. We reasoned that cancer cells may hijack key transcriptional programs in hematological cells to evade the attack from immune cells and acquired tolerance to immunotherapy. Method: Herein, we used an R package singscore/1.14.0 to compute the TFs activity scores based on their validated gene targets (TGs). Leveraging melanoma clinical trial datasets, we analyzed the predictive association of the TF scores with resistance to anti-PD1 ICB. The R package, iGenSig was used to evaluate the potential confounding variables. Results: Our landscape correlation analysis revealed NFATC2 (Nuclear Factor Of Activated T Cells 2)-TGs as the most significant predictor of anti-PD-1 ICB resistance in melanoma. NFATCT-TGS as a predictor of anti-PD1 resistance is confounded by liver metastasis and achieved AUC range between 0.71 to 0.74 in three datasets (PRJEB23709, GSE160638, and Phs000452). In addition, prior anti-CTLA4 exposure (AUC=0.87 and 0.89) is associated with higher predictive efficacy of NFATC2-TGS than anti-CTLA4 naïve tumor (AUC=0.61 and 0.69) in phs000452 and GSE91061 datasets. Survival analysis revealed that NFATC2 is a better predictor of progressive-free survival (PFS; HR=5.95), and overall survival (OS; HR= 3.28-3.38) in anti-CTLA4 exposed tumor than anti-CTLA4 naïve tumor (PFS: HR=1.92, and OS; HR=1.64-2.17). Finally, NFATC2-TGS show strong inhibitory correlation with B cells and T cells infiltration, but strongly correlated with tumor purity. Conclusion: We demonstrate that NFATC2 TGS predicts ICB benefits in melanoma patients, and thus may guide the recruitment of melanoma patients for anti-PD1 ICB. Our data provide support to the hypothesis that melanoma acquired NFATC2 transcriptional program to avoid immune cells evasion and acquired tolerance to ICB immunotherapy Citation Format: Bashir Lawal, Yue Wang, Parisa Lotfinejad, Xiaosong Wang. Predictive association of tumor cells hijacked NFATC2 activities with resistance to immune checkpoint inhibition in melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2282.

Management of Acute High-Grade Acromioclavicular Joint Dislocations: Comparable Clinical and Radiological Outcomes After Bidirectional Arthroscopic-Assisted Stabilization With the Single Low-Profile Suture Button Technique Versus Double-Suture Button Technique

This study was to compare the two-year clinical and radiological outcomes of an arthroscopic-assisted bidirectional stabilization procedure using single low-profile (LPSB) or double suture button (DSB) techniques with additional percutaneous acromioclavicular (AC) cerclage fixation for patients with acute high-grade AC joint dislocation. This retrospective cohort study compared male patients aged between 18-56 years with acute high-grade AC joint dislocation fixed with either a LPSB or DSB technique. Patients were examined at least 24 months post-surgery. Subjective Shoulder Value (SSV), Taft (TF) and Acromioclavicular Joint Instability scores (ACJI) were evaluated. Coracoclavicular difference, ossification, AC joint osteoarthritis and dynamic posterior translation (DPT) were assessed on bilateral anteroposterior stress radiographs and modified Alexander views. The revision rate due to implant conflict and duration of surgery were reported. Group outcome differences were analyzed using standardized hypothesis tests. 28 patients aged 39.2 (LPSB) and 36.4 years (DSB) (p=0.319; CI -2.77 - 8.34) were eligible per cohort. The follow-up was 30.5 (LPSB) and 37.4 months (DSB) (p=0.02; CI -12.73 - -1.08). LPSB patients rated a significantly higher SSV (93.2% vs. 81.9% (DSB); p=0.004). TF and ACJI scores were similar between groups. Coracoclavicular difference markedly decreased from 12 mm to 3 mm for both cohorts (p<0.001). Ossification was identified in over 85% in both cohorts (p=0.160; CI -0.77 - 0.13) and osteoarthritis in 21.4% (LPSB) and 39.3% (DSB) (p=0.150). Persistent DPT was found in around 30% for both cohorts (p=0.561; CI -0.26 - 0.48). The revision rates were 0% (LPSB) and 7% (DSB) (p=0.491). LPSB surgery was shorter (59.7 vs. 71.5 mins [DSB]) (p=0.011). The results of the LPSB and DSB techniques with additional percutaneous AC cerclage fixation showed comparable outcomes with excellent clinical and satisfactory radiological results. The assessment of the subjective patients satisfaction was in favor of the LPSB technique and no postoperative revision event was observed following this procedure.

Treatment fidelity in a pragmatic clinical trial of music therapy for premature infants and their parents: the LongSTEP study

BackgroundTreatment fidelity (TF) refers to methodological strategies used to monitor and enhance the reliability and validity of interventions. We evaluated TF in a pragmatic RCT of music therapy (MT) for premature infants and their parents.MethodsTwo hundred thirteen families from seven neonatal intensive care units (NICUs) were randomized to receive standard care, or standard care plus MT during hospitalization, and/or during a 6-month period post-discharge. Eleven music therapists delivered the intervention. Audio and video recordings from sessions representing approximately 10% of each therapists’ participants were evaluated by two external raters and the corresponding therapist using TF questionnaires designed for the study (treatment delivery (TD)). Parents evaluated their experience with MT at the 6-month assessment with a corresponding questionnaire (treatment receipt (TR)). All items as well as composite scores (mean scores across items) were Likert scales from 0 (completely disagree) to 6 (completely agree). A threshold for satisfactory TF scores (≥4) was used in the additional analysis of dichotomized items.ResultsInternal consistency evaluated with Cronbach’s alpha was good for all TF questionnaires (α ≥ 0.70), except the external rater NICU questionnaire where it was slightly lower (α 0.66). Interrater reliability measured by intraclass correlation coefficient (ICC) was moderate (NICU 0.43 (CI 0.27, 0.58), post-discharge 0.57 (CI 0.39, 0.73)). Gwet’s AC for the dichotomized items varied between 0.32 (CI 0.10, 0.54) and 0.72 (CI 0.55, 0.89). Seventy-two NICU and 40 follow-up sessions with 39 participants were evaluated. Therapists’ mean (SD) TD composite score was 4.88 (0.92) in the NICU phase and 4.95 (1.05) in the post-discharge phase. TR was evaluated by 138 parents. The mean (SD) score across intervention conditions was 5.66 (0.50).ConclusionsTF questionnaires developed to assess MT in neonatal care showed good internal consistency and moderate interrater reliability. TF scores indicated that therapists across countries successfully implemented MT in accordance with the protocol. The high treatment receipt scores indicate that parents received the intervention as intended. Future research in this area should aim to improve the interrater reliability of TF measures by additional training of raters and improved operational definitions of items.Trial registrationLongitudinal Study of music Therapy’s Effectiveness for Premature infants and their caregivers – “LongSTEP”. ClinicalTrials.gov Identifier: NCT03564184. Registered on June 20, 2018

GRAND: a database of gene regulatory network models across human conditions.

Gene regulation plays a fundamental role in shaping tissue identity, function, and response to perturbation. Regulatory processes are controlled by complex networks of interacting elements, including transcription factors, miRNAs and their target genes. The structure of these networks helps to determine phenotypes and can ultimately influence the development of disease or response to therapy. We developed GRAND (https://grand.networkmedicine.org) as a database for computationally-inferred, context-specific gene regulatory network models that can be compared between biological states, or used to predict which drugs produce changes in regulatory network structure. The database includes 12 468 genome-scale networks covering 36 human tissues, 28 cancers, 1378 unperturbed cell lines, as well as 173 013 TF and gene targeting scores for 2858 small molecule-induced cell line perturbation paired with phenotypic information. GRAND allows the networks to be queried using phenotypic information and visualized using a variety of interactive tools. In addition, it includes a web application that matches disease states to potentially therapeutic small molecule drugs using regulatory network properties.

Comparative evaluation of 2% turmeric extract with nanocarrier and 1% chlorhexidine gel as an adjunct to scaling and root planing in patients with chronic periodontitis: A pilot randomized controlled clinical trial.

Context:Nanoparticles, owing to their smaller size, penetrate regions inaccessible to other delivery systems, such as periodontal pockets. Thus, the present study aimed to comparatively evaluate efficacy of 2% curcumin with nanocarrier and 1% chlorhexidine gel as a local drug delivery (LDD) in the treatment of periodontal pockets.Materials and Methods:Forty-five chronic periodontitis patients with pocket depth 5–7 mm in two or more teeth were selected. Full-mouth scaling and root planing (SRP) was done for all patients followed by random allocation to the three treatment groups, namely SRP group (Group 1), 2% curcumin with nanogel (Group 2), and 1% chlorhexidine gel (Group 3). Clinical parameter assessment and microbiological analysis of subgingival plaque samples for Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythia (Tf) was done at baseline, 21st day, and 45th day.Results:The results showed that when the two LDD agents were used as an adjunct to SRP in chronic periodontitis, there was an improvement in all clinical parameters. Evaluation of microbiological parameters also showed a significant reduction in Aa, Pg, and Tf levels. Comparison of 2% turmeric extract with a nanocarrier system with 1% chlorhexidine gel showed that both the agents had a comparable antibacterial effect on the three selected periodontopathic bacteria.Conclusion:The present study showed that both the LDD agents showed an effective improvement of clinical and microbiologic parameters. 2% curcumin delivered with a nanocarrier system showed results comparable to chlorhexidine gel and hence shows promising future as an LDD agent in the treatment of periodontal pockets.

Automatic detection and classification of dental fluorosis in vivo using white light and fluorescence imaging

ObjectivesTo assess a novel method of automatic fluorosis detection and classification from white light and fluorescent images. MethodsDental images from 1,729 children living in two fluoridated and two non-fluoridated UK cities were utilised. A novel detection and classification algorithm was applied to each image and TF scores were obtained using thresholding criteria. These were compared to clinical reference standard images. Comparisons between reference and automated assessments were undertaken to record correct and incorrect classifications and the ability of the system to separate the fluoridated and non-fluoridated populations. ResultsThe automated system performed well and was able to differentiate the two populations (P < 0.0001) to the same degree as the reference standard. When using the highest score from the clinical assessment the agreement between automated and clinical assessments was 0.56 (Kappa SE = 0.0160, p < 0.0001). ConclusionsAssessment of dental fluorosis is typically undertaken by clinical examiners in epidemiological studies. The training and calibration of such examiners is complex and time consuming and the assessments are subject to bias – frequently because of the examiner’s awareness of the water fluoridation status of subjects. The use of remote scoring using photographs has been advocated but still requires trained examiners. This study has shown that image-processing methodologies applied to white light and fluorescent images could automatically score fluorosis and statistically separate fluoridated and non-fluoridated areas. The system requires further refinement to manage confounding factors such as the presence of non-fluoride opacities and tooth stain.

Quantitative study of the proportion of the pore volume of human fluorotic enamel filled by resin infiltrant

AimCapillarity theory predicts that the pore volume infiltrated by a liquid in a body with tubular capillaries is directly proportional to the capillary radius. The expected volume available for infiltration is the loosely bound water volume, which can be related to the capillary radii. We tested the hypothesis that the proportion of the pore volume infiltrated by resin infiltrant (Vratioresin) is correlated and agrees with the proportion of the pore volume with loosely bound water (Vratioa2). DesignSeven human fluorotic third molars (4 unerupted and 3 erupted; TF scores 4 to 7; fluoride content of inner coronal dentin ranged from 143 to 934μg Fluoride/g) were prepared and resin infiltration was performed during 10min in fluorotic enamel ground sections. Penetration depths were measured (polarizing microscopy and CLSM) and mineral volume and non-mineral volumes were measured at histological points (n=92) along transversal lines traced from the enamel surface to the enamel-dentin junction. ResultsNo well-mineralized surface layer was found. Infiltration depths ranged from 250μm to 900μm. Vratioresin ranged from 1.8 to 17.7% (mean of 10.13%±4.1%), was lower than Vratioa2 (p<0.00001 Hedge’s g=1.51, 95% CI: 1.18/1.83), and correlated positively with Vratioa2 (R=0.684; 95% CI: 0.557/0.780) and negatively with the air volume remained after infiltration (R=−0.79; 95% CI: −0.698/−0.780). Vratioa2 exceeded Vratioresin in 5% (1/4 of Vratioa2) on average. ConclusionVratioa2 and Vratioresin correlated well, but lacked good agreement. Organic matter, firmly bound water and air remained in enamel pores after resin infiltration.

Relative fluoride response of caries lesions created in fluorotic and sound teeth studied under remineralizing conditions

ObjectivesThe present in vitro pH cycling study investigated potential differences between caries lesions created in fluorosed and sound enamel with regards to their responsiveness to fluoride under remineralizing conditions. Methods360 human first molars (sound and fluorosed) were divided into four groups based on their Thylstrup–Fejerskov score (TF0-3). Each group was further divided into two treatment groups (n=45): deionized water or 383ppm fluoride. Artificial enamel caries lesions were created and pH cycled for 20d using an established net remineralization model. Quantitative light-induced fluorescence was used throughout the study to investigate lesion severity and changes thereof. Data were analyzed using two-way ANOVA. ResultsThere were no differences in lesion severity between all groups after lesion creation (plesion=0.1934). The TF score vs. treatment interaction was significant at all other time points (p10d=0.0280; p20d≤0.0001; psecdemin=0.0411). Relative differences in responsiveness to fluoride vs. deionized water increased with increasing TF scores. In comparison to lesions created in sound enamel, lesions created in enamel with moderate fluorosis (TF 2/3) were more prone to remineralization in the presence than in the absence of fluoride. Furthermore, lesions created in enamel with moderate fluorosis exhibited more remineralization in the presence of fluoride than lesions created in sound teeth, whereas the opposite was true for deionized water. ConclusionBearing in mind the limitations of laboratory research, the extent of enamel fluorosis severity may directly impact subsequent lesion re- and progression as well as the lesion's responsiveness to fluoride. Clinical relevanceCaries lesions in fluorotic teeth are more vulnerable to progression but respond more strongly to fluoride than those in non-impacted teeth.

Dental fluorosis in populations from Chiang Mai, Thailand with different fluoride exposures - Paper 2: The ability of fluorescence imaging to detect differences in fluorosis prevalence and severity for different fluoride intakes from water

BackgroundTo assess the ability of fluorescence imaging to detect a dose response relationship between fluorosis severity and different levels of fluoride in water supplies compared to remote photographic scoring in selected populations participating in an observational, epidemiological survey in Chiang Mai, Thailand.MethodsSubjects were male and female lifetime residents aged 8-13 years. For each child the fluoride content of cooking water samples (CWS) was assessed to create categorical intervals of water fluoride concentration. Fluorescence images were taken of the maxillary central incisors and analyzed for dental fluorosis using two different software techniques. Output metrics for the fluorescence imaging techniques were compared to TF scores from blinded photographic scores obtained from the survey.ResultsData from 553 subjects were available. Both software analysis techniques demonstrated significant correlations with the photographic scores. The metrics for area effected by fluorosis and the overall fluorescence loss had the strongest association with the photographic TF score (Spearman’s rho 0.664 and 0.652 respectively). Both software techniques performed well for comparison of repeat fluorescence images with ICC values of 0.95 and 0.85 respectively.ConclusionsThis study supports the potential use of fluorescence imaging for the objective quantification of dental fluorosis. Fluorescence imaging was able to discriminate between populations with different fluoride exposures on a comparable level to remote photographic scoring with acceptable levels of repeatability.

Groundwater quality and its health impact: An assessment of dental fluorosis in rural inhabitants of the Main Ethiopian Rift

This study aims to assess the link between fluoride content in groundwater and its impact on dental health in rural communities of the Ethiopian Rift. A total of 148 water samples were collected from two drainage basins within the Main Ethiopian Rift (MER). In the Ziway–Shala basin in particular, wells had high fluoride levels (mean: 9.4±10.5mg/L; range: 1.1 to 68mg/L), with 48 of 50 exceeding the WHO drinking water guideline limit of 1.5mg/L. Total average daily intake of fluoride from drinking groundwater (calculated per weight unit) was also found to be six times higher than the No-Observed-Adverse-Effects-Level (NOAEL) value of 0.06mg/kg/day. The highest fluoride levels were found in highly-alkaline (pH of 7 to 8.9) groundwater characterized by high salinity; high concentrations of sodium (Na+), bicarbonate (HCO3−), and silica (SiO2); and low concentrations of calcium (Ca2+). A progressive Ca2+ decrease along the groundwater flow path is associated with an increase of fluoride in the groundwater. The groundwater quality problem is also coupled with the presence of other toxic elements, such as arsenic (As) and uranium (U). The health impact of fluoride was evaluated based on clinical examination of dental fluorosis (DF) among local residents using the Thylstrup and Fejerskov index (TFI). In total, 200 rural inhabitants between the ages of 7 and 40years old using water from 12 wells of fluoride range of 7.8–18mg/L were examined. Signs of DF (TF score of ≥1) were observed in all individuals. Most of the teeth (52%) recorded TF scores of 5 and 6, followed by TF scores of 3 and 4 (30%), and 8.4% had TF scores of 7 or higher. Sixty percent of the teeth exhibited loss of the outermost enamel. Within the range of fluoride contents, we did not find any correlation between fluoride content and DF. Finally, preliminary data suggest that milk intake has contributed to reducing the severity of DF. The study highlights the apparent positive role of milk on DF, and emphasizes the importance of nutrition in management efforts to mitigate DF in the MER and other parts of the world.

Dental fluorosis, caries experience and snack intake of 13-15 year olds in Kenya

To determine the dental caries experience in relation to the severity of dental fluorosis and; to evaluate the dietary snacking habits of adolescents. A descriptive cross-sectional study. A peri-urban primary school in Nairobi, Kenya. Two hundred and seventy five adolescents aged 13-15 years among whom 128 were males and 149 were females. Two hundred and seventy five adolescents were examined for varying degrees of dental fluorosis according to the Thylystrup Fejerskov Index (TFI) scores and the dental caries was determined in the four first permanent molars. One hundred and five individuals were found to have had a TFI score of zero with a corresponding decayed missing and filled teeth (DMFT) for dental caries of 1.30-1.03 and 88 (52%) individuals had mild to moderate severity of dental fluorosis (TF scores 1-4) and had a corresponding mean DMFT of 1.53 +/- 1.005 for dental caries. Furthermore, 82 (48.2%) adolescents had severe degrees of dental fluorosis of TFI scores 5-9 and had a corresponding DMTF value of 1.85 +/- 1.24 for dental caries. When the prevalence of dental caries was compared among individuals with TFI scores zero (non-fluorosed teeth) with those who had fluorosed first permanent molars the Chi square test showed that there was a high statistical significance with a p-value of 0.001 (P = 0.005). Amongst the 175 adolescents with varying degrees of severity of dental fluorosis it was noted that 44 (26%) did not like taking snacks and had a DMFT of 1.54 +/- 1:1.17 while 126 (74%) adolescents who enjoyed taking snacks had a DMFT of 1.64 +/- 1.08. However, there was no statistical significance. While there was a statistically significant association between the severity of dental fluorosis and caries experience among the participants in the present study, there was no co-relation between the caries experience and snacking habits among those who had varying degrees of dental fluorosis.

Quantification of Dental Fluorosis Using Fluorescence Imaging

Fluorescence imaging hardware and software have been recently employed to assess demineralization due to early dental caries. Dental fluorosis also presents as diffuse surface hypomineralization of enamel and in principle similar measurement methods might be applicable to both. The caries analysis system requires the user to select an area of sound enamel around the lesion so that the affected surface can be reconstructed and the lesion subtracted. Whereas early caries presents as discrete isolated lesions fluorosis is characterized by diffuse opacities covering most of the tooth. Consequently it is difficult to use commercial QLF software for the assessment of fluorosis, as there is typically no sound area of enamel to use for reconstruction. This study describes a fluorescent imaging device capable of recording digital images of the anterior teeth and also software that is able to objectively measure fluorosis area and severity. A convenience sample of 26 subjects with a range of fluorosis from TF scores 0–3 took part in the study. The upper left central incisor of these subjects was scored for fluorosis using the TF index, photographed using a conventional digital camera and imaged using the fluorescence imaging device. The TF index was then used to visually score the digital photographs and the fluorescence images. The data from the fluorescence method demonstrated a strong correlation with TF scores from fluorescence images (Kendall’s tau = 0.862). The fluorescence imaging method shows promise as an objective, potentially blinded system for the longitudinal assessment of enamel fluorosis in vivo.

Dental fluorosis and dental caries in permanent teeth: rural schoolchildren in high-fluoride areas in the Shaanxi province, China

Objectives. To study the dental fluorosis and caries in the permanent teeth of 12 to 13-year-old children in fluorosis-endemic areas; to assess the relationship between fluorosis and the fluoride content of the drinking water and the relationship between caries and the fluoride content of the water; finally, to analyze the effect of fluoride intake and water stored in clay pots on dental fluorosis. Material and methods. 477 children were divided into 5 groups (A to E) according to the fluoride concentration of the waters, i.e. by 0.4, 1.0, 1.8, 3.5, and 5.6 mg F/l, respectively. Dental fluorosis was assessed by TF score and caries by the DMF-T index. A questionnaire was used to obtain information about water storage and other information relevant to children's fluoride intake. Results. A positive relationship was found between the mean TF scores and the water fluoride concentration. In groups B and D, the TF score was higher in 13-year-olds than in 12-year-olds. Caries prevalence and mean DMF-T ranged from 2.6% and 0.03 (group E) to 22.1% and 0.38 (group A). Storage of water in clay pots seemed to increase the severity of fluorosis slightly, and to decrease the caries prevalence. Conclusions. Defluoridation of drinking water, or—alternatively—the provision of low-fluoride water sources, should be given high priority in the examined Shaanxi rural areas. Fluoride concentration of drinking water should be maximum 0.6 mg/l. Storage of water in the local clay pots may increase the severity of dental fluorosis.

Perception of dental fluorosis amongst Ethiopian children and their mothers

This study was conducted in three Ethiopian Rift Valley villages known for endemic fluorosis. Three-hundred-and-six adolescents (12-15 years) and 233 mothers participated. The aim was to study dental fluorosis in the youngsters and to assess the extent of agreement between clinical and self-rated discoloration and pitting of teeth, and also the level at which dental fluorosis is perceived as a problem both by children and their mothers. The children (154 M and 152 F) gave a simple self-assessment of tooth-color and quality of their teeth, and were subsequently examined for dental fluorosis. Finally, four color photographs of teeth with dental fluorosis (TF-scores 2, 3, 5, and 7) were used as references during a structured oral interview of the children, as well as their mothers. At TF score S 2, the prevalence of dental fluorosis on maxillary central incisors was 72% and 37% at TF score S 4. The mean TF score was significantly higher among boys than among girls of unemployed fathers compared to children of employed fathers. The likelihood of reporting problems with dental appearance increased with increasing individual TF scores. The child/mother pairs found teeth with TF scores 2 and 3 esthetically acceptable, while teeth with TF scores 5 and 7 were considered unacceptable. Mothers were more critical of severe fluorosis than were their children.

Drinking water fluoride levels, dental fluorosis, and caries experience in Brazil.

The main aim of this study was to consider the association between water fluoride levels and caries prevalence in three Brazilian populations. A total of 457 6-12-year-old lifetime residents from three economically deprived groups with 2-3, 0.7, and less than 0.01 ppm F in their water supplies were examined. Dental caries was recorded on permanent upper central incisors and first molars and all primary teeth (dmft). There was a significant trend (P < 01) for the mean dmft to decrease with increasing levels of fluoride in the drinking water. Caries experience in the six permanent teeth was significantly lower (P < 01) in the area with 0.7 ppm F than in the other two groups For the 2-3 ppm F group significantly more caries was found in subjects with higher TF scores (P < 05). Optimization of fluoride levels in the drinking water remains a valuable dental public health measure in Brazil.

Perceptions of Dental Fluorosis

Mild dental fluorosis has long been accepted as a side-effect of water fluoridation and, more recently, has been recognized as a consequence of the use of other fluoride-based caries-preventive strategies. Traditionally, dental health professionals have not seen this as being of public health importance, but members of the public have not been asked their opinion. The purpose of the present study was to gather the opinions of lay groups concerning the appearance of the teeth of children with various degrees of fluorosis. Twenty-eight children, born in 1978, who had earlier participated in a study of fluorosis in Perth (Western Australia), allowed 110 observers to look at their upper central incisors under good viewing conditions. Fluorosis in these teeth ranged from TF score 0 (no fluorosis) to TF score 3. The observers were university students, parents, public servants, or dentists. They responded to statement items about the appearance of the teeth. The results, based on just over 3000 responses, showed that lay and dental observers could distinguish between different fluorosis levels. In response to a statement that the teeth appeared pleasing, a large majority agreed when the TF score was 0, but agreement declined as the TF score increased; when the TF score was 3, most people disagreed. Similarly, observers felt that the appearance would increasingly embarrass the child as the TF score increased. Observers, except the dentists, tended to feel that higher TF scores indicated neglect on the part of the child.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental Fluorosis and Fluoride Exposure in Western Australia

Dental fluorosis in children is reported from many locations, and its prevalence may be increasing. This study aimed to measure fluorosis in 12-year-olds in fluoridated and non-fluoridated areas of Western Australia and to relate this to exposure. School dental clinics in Perth (F- 0.8 mg/L) and the Bunbury area (F- less than 0.2 mg/L) were the sampling units. Parents provided data on residence in fluoridated areas and on use of supplements and toothpaste. Exposure to water and supplemental fluoride between birth and four years was calculated. Clinical examinations (upper left central incisor) based on the TF classifications of fluorosis (which requires teeth to be dried) were conducted for 338 children in Perth and 321 in the Bunbury region. Re-examinations (n = 50) gave a weighted kappa of 0.78. Contingency analysis estimated bivariate relationships, and multiple logistic regression estimated odds ratios (OR) for risk factors. Fluorosis prevalence in the Perth region was 0.40, and in the Bunbury region 0.33 (chi 2 = 3.69, df = 1, p = 0.055). Prevalence was 0.44 in children with fluoride exposure equivalent to optimal water fluoridation and 0.20 among those with the lowest exposure (chi 2 = 35.99, df = 1, p = 0.0001). Increasing exposure was associated with higher fluorosis prevalence and higher TF scores, but overall, 27.3% of participants had TF score 1 (barely discernible), and only 9.4% had TF score greater than or equal to 2.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of adrenalectomy and dexamethasone on the antinociceptive effects of physostigmine.

The tail-flick procedure was used to study the antinociceptive effects of physostigmine in adrenalectomized and sham-operated rats. At 5 days after surgery, they were tested 30 min after either 0.32 or 0.45 mg/kg IP physostigmine. Adrenalectomized animals showed significantly greater elevation of TF scores from predrug latencies than the sham controls at both doses of physostigmine. Following 3 days of dexamethasone replacement therapy on days 18, 19, and 20 post-surgery the antinociceptive effects of physostigmine were uniformly attenuated across doses or surgical groups. On the other hand, animals receiving saline injection instead of dexamethasone did not manifest any reduction of the physostigmine antinociceptive effect. The potentiation by adrenalectomy and the reduction following dexamethasone of the antinociceptive effects of physostigmine suggest that these effects may be mediated through hypothalamic-pituitary-adrenal mechanisms and are consistent with beta-endorphin-induced sensitization of opiate or cholinergic receptors.