Metformin as targeted treatment in fragile X syndrome.

BACKGROUND: Individuals with fragile X syndrome (FXS) have both behavioral and medical comorbidities and the latter include obesity in approximately 30% and the Prader-Willi Phenotype (PWP) characterized by severe hyperphagia and morbid obesity in less than 10%. Metformin is a drug used in individuals with type 2 diabetes, obesity or impaired glucose tolerance and it has a strong safety profile in children and adults. Recently published studies in the Drosophila model and the knock out mouse model of FXS treated with metformin demonstrate the rescue of multiple phenotypes of FXS. MATERIALS AND METHODS: We present 7 cases of individuals with FXS who have been treated with metformin clinically. One case with type 2 diabetes, 3 cases with the PWP, 2 adults with obesity and/or behavioral problems and, a young child with FXS. These individuals were clinically treated with metformin and monitored for behavioral changes with the Aberrant Behavior Checklist and metabolic changes with a fasting glucose and HgbA1c. RESULTS: We found consistent improvements in irritability, social responsiveness, hyperactivity, and social avoidance, in addition to comments from the family regarding improvements in language and conversational skills. No significant side-effects were noted and most patients with obesity lost weight. CONCLUSION: We recommend a controlled trial of metformin in those with FXS. Metformin appears to be an effective treatment of obesity including those with the PWP in FXS. Our study suggests that metformin may also be a targeted treatment for improving behavior and language in children and adults with FXS.

Magnetic properties and signatures of ordering in triangular lattice antiferromagnet KCeO2.

The magnetic ground state and the crystalline electric field level scheme of the triangular lattice antiferromagnet KCeO2 are investigated. Below TN=300 mK, KCeO2 develops signatures of magnetic order in specific heat measurements and low energy inelastic neutron scattering data. Trivalent Ce3+ ions in the D3d local environment of this compound exhibit large splittings among the lowest three 4f1 Kramers doublets defining for the free ion the J=5/2 sextet and a ground state doublet with dipole character, consistent with recent theoretical predictions in M. S. Eldeeb et al. Phys. Rev. Materials 4, 124001 (2020). An unexplained, additional local mode appears, and potential origins of this anomalous mode are discussed.

Root canal morphology of fused mandibular canine and lateral incisor.

This clinical report briefly describes the appearance, frequency, and treatment of fused teeth. Presented is a tooth showing the unusual canal morphology and root lengths of a unilateral mandibular canine and lateral incisor fusion.

Effect of sonic versus ultrasonic instrumentation on canal preparation.

The instrumentation time, and the resulting root canal angulation change and shape after using ultrasonic, sonic, and hand instrumentation techniques were studied in the mesial canals of 55 extracted human mandibular first and second molars. After instrumentation, the roots were sectioned horizontally in the apical, middle, and coronal thirds and evaluated for shape, mesial and distal canal widths, and canal diameter. MM3000 and hand were significantly faster than the other techniques (p less than 0.005). MM3000 resulted in less angulation change than the Enac (p less than 0.005). Hand instrumentation was judged to have given the best shape (p less than 0.01).

The sealing ability of the Thermafil obturation technique.

Forty straight canals of maxillary canines and 40 curved canals in 20 mesial roots of mandibular molars were instrumented and randomly assigned to two groups of 40 canals each. For the experimental group, the canals were obturated using the Thermafil obturation technique. Lateral condensation was used for the obturation of the control group. Kerr pulp canal sealer was used in both group. The specimens were stored in 100% humidity for 1 wk. All teeth were suspended in black India ink for 14 days and decalcified in 5% nitric acid over a 2-day period. The teeth were then dehydrated in a graded series of alcohol to 100%. Methyl salycilate was used to clear and store the teeth for 48 h. Linear dye leakage measurements showed that canines obturated with the lateral condensation technique leaked significantly less than those obturated using the Thermafil technique (p = 0.02). The difference was not statistically significant in the molar roots.

An evaluation of the Canal Master, balanced force, and step-back techniques.

The step-back (SB), balanced-force (BF) , and Canal Master (CM) instrumentation techniques were compared in 53 mesial canals of mandibular molars using two different instrument types: Flex-R and CM. Canal angulation changes from preoperative to postrotary and postinstrumentation were measured using the Schneider technique (ST) and the long-axis technique (LAT). Instrumentation times were recorded, and then the roots were sectioned at 1, 3, and 5 mm from the apex. Measurements were made of the minimal remaining root structures and canal diameter. Rotary instrumentation resulted in a average loss of curvature of 2.37 degrees, as measured by the ST. The ST showed significant changes in canal angulation between CM (-7.74 degrees) and SB (-5.28 degrees) groups, with p < 0.05. LAT showed significant changes for CM versus BF and SB (p<0.001), with a mean change in angulation of -7.69 degrees, -1.68 degrees, and _0.1 degrees respectively. The BF technique (5.5) was significantly faster than either SB (7.1 min) or CM (8.3 min), with p < 0.05. The remaining mesial-distal root structure at all levels was similar among groups.

Apical sealing ability of metal versus plastic carrier Thermafil obturators.

Sixty straight maxillary canines, 40 straight mandibular incisors, and 40 curved mesial canals of 27 mandibular molars were instrumented and randomly assigned to one of seven groups of 20 canals. Experimental groups were obturated with metal or plastic carrier Thermafil obturators. Control groups were obturated using the lateral condensation technique. An additional group of 20 unobturated curved molar canals served as positive controls. Kerr Pulp Canal Sealer was used in all obturation groups. The presence or absence of apical extrusion of gutta-percha was recorded. Teeth were suspended in black India ink for 2 wk, cleared, and then examined under a dissecting microscope at x20 magnification. No leakage was found in any of the obturated canals, whereas unobturated controls showed total dye penetration. Plastic carrier Thermafil and metal carrier Thermafil groups produced a significantly greater incidence of apical extrusion of gutta-percha compared with lateral condensation groups (p < 0.001). Extrusion for Thermafil groups occurred significantly more frequently in straight compared with curved canals (p = 0.002). The Thermafil groups showed a higher frequency of filled lateral and accessory canals than in the lateral condensation group; however, this was statistically insignificant (p = 0.48).

Comparison of concentric condensation technique with laterally condensed gutta-percha.

Sixty mandibular premolars with large, straight canals and 60 nonjoining narrow, curved canals from mesial mandibular molar roots were obturated with gutta-percha via 1 of 3 methods: lateral condensation with sealer, or concentric condensation without sealer. The sealer used was a zinc oxide-eugenol without radiopacifiers. The premolar teeth were radiographed next to a step wedge, both before and after obturation. All teeth were exposed to India ink as a test for linear dye leakage, then cleared, and the leakage recorded. The pre- and postobturation radiographs were scanned at 2 and 6 mm from the apex using a Joyce-Loebel microdensitometer to establish the radiographic density of the obturation material, and a density ratio for the obturation was calculated using the cross-sectional diameter of the obturating material. The incidence of gutta-percha extrusion and Micro-Flow Compactor breakage was recorded. Two-way analysis of variance for linear dye leakage revealed no significant differences between the lateral and concentric condensation groups when sealer was used (p > 0.05). The concentric condensation without sealer groups exhibited significantly greater leakage (p < 0.00001) than the other groups, showing the importance of using sealers. One-way analysis of variance found no significant differences in radiographic density ratios between groups at 2 mm (p > 0.05) or 6 mm from the apex (p > 0.05). The incidence of extrusion was not significant, but a high rate of #30 condensor breakage was found.

Adhesion of sealer cements to dentin with and without the smear layer.

The influence of a smear layer on the adhesion of sealer cements to dentin was assessed in recently extracted human anterior teeth. A total of 120 samples was tested, 40 per sealer; 20 each with and without the smear layer. The teeth were split longitudinally, and the internal surfaces were ground flat. One-half of each tooth was left with the smear layer intact, while the other half had the smear removed by washing for 3 min with 17% EDTA followed by 5.25% NaOCl. Evidence of the ability to remove the smear layer was verified by scanning electron microscopy. Using a specially designed jig, the sealer was placed into a 4-mm wide x 4-mm deep well which was then set onto the tooth at a 90-degree angle and allowed to set for 7 days in 100% humidity at 37 degrees C. This set-up was then placed into a mounting jig which was designed for the Instron Universal Testing Machine so that only a tensile load was applied without shearing or applying preloading forces. The set-up was subjected to a tensile load at a crosshead speed of 1 mm per min. The results show significant differences (p less than 0.001) among AH26, Sultan, and Sealapex, with AH26 being the strongest and Sealapex being the weakest. The only significant difference with regard to the presence or absence of the smear layer was found with AH26, which had a stronger bond when the smear layer was removed.

Effect of varying the ultrasonic power setting on canal preparation.

The purpose of this study was to evaluate the effect of instrumenting root canals using an ultrasonic device (Enac) at different power levels on the prepared canal shape and instrumentation time, and to compare these results with those obtained using a standardized hand instrumentation technique. The mesial canals (120) of 60 human mandibular first and second molars were randomly assigned to one of six groups. In groups A through D, the canals were instrumented using the Enac ultrasonic unit at different power settings (1, 2, 3, and 5, respectively). Group E was hand instrumented. Group F served as uninstrumented controls. The roots were then sectioned horizontally and the canal shapes examined, as was the mesiodistal canal diameter as it relates to the external root surface. Instrumentation time for each group was recorded. Ultrasonic instrumentation at the different power settings was significantly faster than hand instrumentation (p less than 0.001). However, the difference between the different power levels was not significant. There were no significant differences between the different groups as to the effect on the prepared canal shape. The only problem arising from using the Enac at a power level more than the recommended (5) was the greater tendency to break size #15 files during instrumentation. Using the Enac at power level 3 provided satisfactory instrumentation capability with minimal risk of file breakage.

Removal of canal obstructions with the Endo Extractor.

This report describes a series of clinical cases demonstrating the use of the Endo Extractor to remove canal obstructions. Each of the obstructions was removed with the new technique after conventional methods had failed. Preoperative, working, and postoperative radiographs are shown.

Chondromyxoid fibroma.

A brief review of the literature concerning chondromyxoid fibroma is presented. 7 previous cases and the present case of the tumor in the jaws are described. Parallels to the extra oral lesions are drawn and in the light of previously published data, distinctive diagnostic features are discussed. The importance of close cooperation between the surgeon, the radiologist and the pathologist is stressed to avoid a misdiagnosis and radical treatment of the malignant counterpart of a rare benign tumor.