Effect of nodule size and stiffness on phonation threshold and collision pressures in a synthetic hemilaryngeal vocal fold model.

Synthetic vocal fold (VF) replicas were used to explore the role of nodule size and stiffness on kinematic, aerodynamic, and acoustic measures of voiced speech production. Emphasis was placed on determining how changes in collision pressure may contribute to the development of phonotrauma. This was performed by adding spherical beads with different sizes and moduli of elasticity at the middle of the medial surface of synthetic silicone VF models, representing nodules of varying size and stiffness. The VF models were incorporated into a hemilaryngeal flow facility. For each case, self-sustained oscillations were investigated at the phonation threshold pressure. It was found that increasing the nodule diameter increased the open quotient, phonation threshold pressure, and phonation threshold flow rate. However, these values did not change considerably as a function of the modulus of elasticity of the nodule. Nevertheless, the ratio of collision pressure to subglottal pressure increased significantly for both increasing nodule size and stiffness. This suggests that over time, both growth in size and fibrosis of nodules will lead to an increasing cycle of compensatory vocal hyperfunction that accelerates phonotrauma.

A population-based survey on interarch malocclusion and background determinants.

Background: Genetics, environment, and ethnic factors are major contributors to the prevalence and variations of malocclusion. Aim: The aim of study was to determine the prevalence of interarch problems in school-aged children, 9 - 11 years, living in Tehran; and to describe the role of ethnicity, education, and economic status on them. Methods: The present data were part of the Comprehensive Evaluation of Skeleto-Dental Anomalies (CESDA) study conducted in 2015 among children living in Tehran, Iran. Cluster random sampling was applied among 19 districts of Tehran. A total of 38 schools were selected, and out of 1585 participants, the data of 1429 children were collected (response rate = 90%). The Chi-square test and binary logistic regression analysis were used for statistical analyses. Results: Of all participants, 758 were boys and 671 were girls. The mean age was 121 ± 8 months. The most significant background determinants associated with molar relationship were ethnicity and place of residence. Class I right molar relationship was seen in 57.9% of the children and was generally more frequent in boys. Normal overjet was observed in 47.1%; 41.5% had an increased overjet, 16.2% had an anteroposterior cross-bite, and 11.8% had a lateral cross-bite. Midline discrepancy was seen among 61.1% of the children. Ideal anteroposterior, vertical, and horizontal relationship were observed in 31%, 53%, and 34% of the children, respectively. Only 10% of the children aged 9 - 11 years old had an ideal interarch relationship. Gender and place of residence had persistently significant association with having an ideal anteroposterior, vertical, horizontal, and interarch relationships (P < 0.002) in all four binary logistic regression models. Conclusions: The majority of the children aged 9 - 11 years old have at least one interarch problem, although it is commonly preventable. Relevance for Patients: Early detection of children's orthodontic problems may help with effective prevention of further advanced anomalies.

Combining Circumvestibular Corticotomy with Maxillary Protraction as a Conservative Approach to Treatment in an Adolescent with Maxillary Deficiency: A Case Report with Long Term Follow-up.

Maxillary protraction with a face mask is an effective treatment for class III children with maxillary hypoplasia. However, in late adolescence, orthopedic approaches are not very effective for treatment of maxillary deficiency. The aim of this study was to report a minimally invasive technique to orthopedically treat a 16-year-old female adolescent with mild to moderate maxillary deficiency, before the cessation of growth. A circumvestibular corticotomy technique was performed followed by a regimen of rapid maxillary expansion and application of heavy extra-oral forces. After termination of the orthopedic and orthodontic phases, the patient was monitored for ten years. The dental and skeletal results immediately after treatment were compared with the results ten years after termination of treatment. A noticeable anterior displacement of "A" point was observed after the orthopedic phase and this remained unchanged for ten years.

Collision Pressure and Dissipated Power Dose in a Self-Oscillating Silicone Vocal Fold Model With a Posterior Glottal Opening.

PURPOSE: The goal of this study was to experimentally evaluate how compensating for the adverse acoustic effects of a posterior glottal opening (PGO) by increasing subglottal pressure and changing supraglottal compression, as have been associated with vocal hyperfunction, influences the risk of vocal fold (VF) trauma. METHOD: A self-oscillating synthetic silicone model of the VFs with an airflow bypass that modeled a PGO was investigated in a hemilaryngeal flow facility. The influence of compensatory mechanisms on collision pressure and dissipated collision power was investigated for different PGO areas and supraglottal compression. Compensatory behaviors were mimicked by increasing the subglottal pressure to achieve a target sound pressure level (SPL). RESULTS: Increasing the subglottal pressure to compensate for decreased SPL due to a PGO produced higher values for both collision pressure and dissipated collision power. Whereas a 10-mm2 PGO area produced a 12% increase in the peak collision pressure, the dissipated collision power increased by 122%, mainly due to an increase in the magnitude of the collision velocity. This suggests that the value of peak collision pressure may not fully capture the mechanisms by which phonotrauma occurs. It was also found that an optimal value of supraglottal compression exists that maximizes the radiated SPL, indicating the potential utility of supraglottal compression as a compensatory mechanism. CONCLUSIONS: Larger PGO areas are expected to increase the risk of phonotrauma due to the concomitant increase in dissipated collision power associated with maintaining SPL. Furthermore, the risk of VF damage may not be fully characterized by only the peak collision pressure.

Vocal fold dynamics in a synthetic self-oscillating model: Intraglottal aerodynamic pressure and energy.

Self-sustained oscillations of the vocal folds (VFs) during phonation are the result of the energy exchange between the airflow and VF tissue. Understanding this mechanism requires accurate investigation of the aerodynamic pressures acting on the VF surface during oscillation. A self-oscillating silicone VF model was used in a hemilaryngeal flow facility to measure the time-varying pressure distribution along the inferior-superior thickness of the VF and at four discrete locations in the anterior-posterior direction. It was found that the intraglottal pressures during the opening and closing phases of the glottis are highly dependent on three-dimensional and unsteady flow behaviors. The measured aerodynamic pressures and estimates of the medial surface velocity were used to compute the intraglottal energy transfer from the airflow to the VFs. The energy was greatest at the anterior-posterior midline and decreased significantly toward the anterior/posterior endpoints. The findings provide insight into the dynamics of the VF oscillation and potential causes of some VF disorders.

Vocal fold dynamics in a synthetic self-oscillating model: Contact pressure and dissipated-energy dose.

The energy dissipated during vocal fold (VF) contact is a predictor of phonotrauma. Difficulty measuring contact pressure has forced prior energy dissipation estimates to rely upon generalized approximations of the contact dynamics. To address this shortcoming, contact pressure was measured in a self-oscillating synthetic VF model with high spatiotemporal resolution using a hemilaryngeal configuration. The approach yields a temporal resolution of less than 0.26 ms and a spatial resolution of 0.254 mm in the inferior-superior direction. The average contact pressure was found to be 32% of the peak contact pressure, 60% higher than the ratio estimated in prior studies. It was found that 52% of the total power was dissipated due to collision. The power dissipated during contact was an order of magnitude higher than the power dissipated due to internal friction during the non-contact phase of oscillation. Both the contact pressure magnitude and dissipated power were found to be maximums at the mid anterior-posterior position, supporting the idea that collision is responsible for the formation of benign lesions, which normally appear at the middle third of the VF.

Intercalation of curcumin into liposomal chemotherapeutic agent augments apoptosis in breast cancer cells.

Resistance to common chemotherapeutic agents is a frequent phenomenon in late-stage breast cancers. An ideal system capable of the co-delivery of hydrophobic and hydrophilic chemotherapeutic agents can regulate the dosage and co-localization of pharmaceutical compounds and thereby improve the anticancer efficacy. Here, for the first time, we have intercalated curcumin (Cur) into a double-layered membrane of cisplatin (Cis) liposomes to obtain a dosage controlled co-delivery formulation, capable of inducing apoptosis in breast cancer cells. The concentrations of Cur and Cis in nanoliposome (Cur-Cis@NLP) were optimized by response surface methodology (RSM); RSM optimization showed 99.81 and 23.86% entrapment efficiency for Cur and Cis, respectively. TEM analysis demonstrated the fabrication of nanoparticles with average diameter of 100 nm. The anticancer and apoptotic effects of Cur-Cis@NLPs were also evaluated using MTT assay, fluorescent staining and flow cytometry assays. Cytotoxicity assessments of various Cur-Cis@NLPs concentrations demonstrated a concentration-dependent manner. In comparison to free and liposomal Cis, Cur-Cis@NLP reduced breast cancer cells' viability (82.5%) in a significant manner at a final concentration of 32 µg.mL-1 and 20 µg.mL-1 of Cur and Cis, respectively. Combination index values calculation of Cur-Cis@NLP showed an overall CI value <1, indicating synergetic effect of the designed co-delivery system. Additionally, flow cytometry assay demonstrated Cur-Cis@NLPs triggered apoptosis about 10-folds higher than liposomal Cis. This co-drug delivery system has a potential for the encapsulation and release of both hydrophobic and hydrophilic drugs, while taking the advantages of the reduced cytotoxic effect along with achieving high potency.

Sustainable feedstocks selection and renewable products allocation: A new hybrid adaptive utility-based consensus model.

Nowadays, preferred compromise response of renewable energies' demands regarding the candidate sustainable feedstocks is a crucial issue for market change management. Thus, selecting the most suitable sustainable feedstock is a key factor for optimum renewable products allocation problem. To address the issue, this study proposes a hybrid adaptive framework based on consensus evaluation approach, weighting and ranking procedure, and preferred demand assignment under dynamic hesitant fuzzy sets. In this respect, the consensus evaluation approach is tailored regarding the direct and indirect feedback mechanisms to enhance the quality evaluation of candidate sustainable feedstocks under assessment criteria. Thereby, the weight of each criterion is determined based on the developed dynamic hesitant fuzzy entropy method and the candidate sustainable feedstocks are ranked with respect to developed dynamic hesitant fuzzy positive and negative ideal solutions. Then, a revised multi-choice goal programming model is extended regarding the dynamic hesitant fuzzy closeness indexes to attend to preferred compromise response of demand centers by optimum renewable products allocation. Meanwhile, the presented hybrid adaptive framework is implemented to a real case study to represent the applicability and efficiency of the proposed approach. Furthermore, a comparative analysis is provided by defining eight comparison indexes to compare the obtained results with two recent studies in relevant literature for representing the validation and verification of the proposed approach. The comparative analysis shows that the proposed approach versus the two other approaches has merits such as modeling of uncertainty, experts' weights, adaptive structure, unanimous agreement-based approach, and last aggregation framework. Finally, a sensitivity analysis is represented to show the sensitiveness and robustness of the obtained results from changing the criteria weights, goals values, and consensus elimination. Thereby, the sensitivity analysis indicates that the obtained ranking results are sensitive to sustainability criteria unlike the technical criterion.

Microbiome Dysbiosis and Predominant Bacterial Species as Human Cancer Biomarkers.

PURPOSE: To evaluate bacterial agents as cancer biomarkers. METHODS AND RESULTS: Various bacterial species have been demonstrated to involve in human cancers. However, the data is not enough for better understanding of predominant specific species. Application of a rapid and early-diagnostic, cost-effective, non-invasive, and inclusive method is a crucial approach for obtaining valid results. The role of Helicobacter pylori (H. pylori) in gastric and duodenal cancer has been confirmed. From investigation among previous publications, we attempted to make it clear which bacterial species significantly and specifically increase in various cancer types. It was unraveled that there is significant change in Granulicatella adiacens (G. adiacens) in lung cancer (LC), Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC), H. pylori and Porphyromonas gingivalis (P. gingivalis) in pancreatic cancer, and Streptococcus spp. in oral cancer. CONCLUSION: Alteration in the cell cycle by means of different mechanisms such as inflammation, alteration in cell signaling, invasion and immune evasion, specific niche colonization, induction of DNA damage and mutation, expression of some microRNAs, and enhancing epigenetic effects are the most common mechanisms employed by bacterial species.

Bayesian Inference of Vocal Fold Material Properties from Glottal Area Waveforms Using a 2D Finite Element Model.

Bayesian estimation has been previously demonstrated as a viable method for developing subject-specific vocal fold models from observations of the glottal area waveform. These prior efforts, however, have been restricted to lumped-element fitting models and synthetic observation data. The indirect relationship between the lumped-element parameters and physical tissue properties renders extracting the latter from the former difficult. Herein we propose a finite element fitting model, which treats the vocal folds as a viscoelastic deformable body comprised of three layers. Using the glottal area waveforms generated by self-oscillating silicone vocal folds we directly estimate the elastic moduli, density, and other material properties of the silicone folds using a Bayesian importance sampling approach. Estimated material properties agree with the "ground truth" experimental values to within 3% for most parameters. By considering cases with varying subglottal pressure and medial compression we demonstrate that the finite element model coupled with Bayesian estimation is sufficiently sensitive to distinguish between experimental configurations. Additional information not available experimentally, namely, contact pressures, are extracted from the developed finite element models. The contact pressures are found to increase with medial compression and subglottal pressure, in agreement with expectation.

Toward Development of a Vocal Fold Contact Pressure Probe: Bench-Top Validation of a Dual-Sensor Probe Using Excised Human Larynx Models.

A critical element in understanding voice production mechanisms is the characterization of vocal fold collision, which is widely considered a primary etiological factor in the development of common phonotraumatic lesions such as nodules and polyps. This paper describes the development of a transoral, dual-sensor intraglottal/subglottal pressure probe for the simultaneous measurement of vocal fold collision and subglottal pressures during phonation using two miniature sensors positioned 7.6 mm apart at the distal end of a rigid cannula. Proof-of-concept testing was performed using excised whole-mount and hemilarynx human tissue aerodynamically driven into self-sustained oscillation, with systematic variation of the superior-inferior positioning of the vocal fold collision sensor. In the hemilarynx experiment, signals from the pressure sensors were synchronized with an acoustic microphone, a tracheal-surface accelerometer, and two high-speed video cameras recording at 4000 frames per second for top-down and en face imaging of the superior and medial vocal fold surfaces, respectively. As expected, the intraglottal pressure signal exhibited an impulse-like peak when vocal fold contact occurred, followed by a broader peak associated with intraglottal pressure build-up during the de-contacting phase. As subglottal pressure was increased, the peak amplitude of the collision pressure increased and typically reached a value below that of the average subglottal pressure. Results provide important baseline vocal fold collision pressure data with which computational models of voice production can be developed and in vivo measurements can be referenced.

Estimating Vocal Fold Contact Pressure from Raw Laryngeal High-Speed Videoendoscopy Using a Hertz Contact Model.

The development of trauma-induced lesions of the vocal folds (VFs) has been linked to a high collision pressure on the VF surface. However, there are no direct methods for the clinical assessment of VF collision, thus limiting the objective assessment of these disorders. In this study, we develop a video processing technique to directly quantify the mechanical impact of the VFs using solely laryngeal kinematic data. The technique is based on an edge tracking framework that estimates the kinematic sequence of each VF edge with a Kalman filter approach and a Hertzian impact model to predict the contact force during the collision. The proposed formulation overcomes several limitations of prior efforts since it uses a more relevant VF contact geometry, it does not require calibrated physical dimensions, it is normalized by the tissue properties, and it applies a correction factor for using a superior view only. The proposed approach is validated against numerical models, silicone vocal fold models, and prior studies. A case study with high-speed videoendoscopy recordings provides initial insights between the sound pressure level and contact pressure. Thus, the proposed method has a high potential in clinical practice and could also be adapted to operate with laryngeal stroboscopic systems.

Toward Development of a Vocal Fold Contact Pressure Probe: Sensor Characterization and Validation Using Synthetic Vocal Fold Models.

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

Autotransplantation and Orthodontic Treatment after Maxillary Central Incisor Region Trauma: A 13-Year Follow-Up Case Report Study.

The anterior maxilla is the most prone region to the trauma during childhood, and tooth loss sometimes happens due to trauma. Replacing the missing teeth has always been one of the dentists' challenges in children and adolescents, since their dentofacial growth is not complete. Autotransplantation of mandibular premolars with two-thirds or three-quarters of root formation provides the best prognosis for the tooth survival. This case report describes the management of a 10-year-old boy suffering a severe dental injury who received the autotransplantation of the premolars from mandible to restore the space caused by trauma in maxillary central incisor region and a 13-year follow-up of the autotransplantation.

Numerical and analytical investigation of irrigant penetration into dentinal microtubules.

Irrigation is one of the most important steps in root canal therapy. Sodium hypochlorite is inserted into the root canal to eliminate bacteria and dissolve necrotic tissue. Dentinal tubules are micrometer sized channels along the dentin thickness. An irrigant should have the ability to penetrate into these tubules to remove bacteria residing in them. The difference between the concentrations of the inserted irrigant and the dentinal tubule fluid is the main factor of penetration. This study attempts to model dentinal tubules with precise dimensions and to study the time dependent irrigant penetration into them by using Computational Fluid Dynamics (CFD). The effects of needle type and position in the dentinal tubule were also considered. The results showed that concentration distribution would be different when the tubule was modeled as a frustum compared to the cylindrical shape tubule. Dentinal tubule curvature, however, did not have a noticeable effect in irrigant penetration. It was also concluded that when the needle working length is 3 mm, concentration can be considered constant at the tubule's entrance for tubules located at more than 1 mm from the apex. Moreover, by irrigating the root canal with a side-vented needle instead of an open-ended one, the concentration would be less for the tubules located in the apex region. Analytical solutions for different cases were also obtained, and their predictions were found to be in good agreement with the numerical results. Therefore, the presented analytical solutions can be directly used to obtain irrigant concentration in tubules with no need for additional computer simulations.

The effect of caffeine on orthodontic tooth movement in rats.

OBJECTIVES: to determine the effect of different doses of caffeine on orthodontic tooth movement (OTM) in rats. MATERIALS AND METHODS: Forty male 250-300 g Sprague-Dawley rats were randomly divided into four groups of ten animals each and received 0 (control), 1 g/l, 2 g/l and 3 g/l caffeine in tap water for 3 days. Orthodontic appliances were ligated between the maxillary first molars and incisors on the 4th day of the study period. All rats were sacrificed after 2 weeks of treatment after which OTM was measured. Hematoxylin/eosin-stained sections of the molars were prepared and the mesial roots were examined for resorption-lacunae depth and osteoclast number. ANOVA was used for statistical analysis (P<0.05). RESULTS: A significant decrease in OTM was observed only in the 2 g/l (P=0.043) and 3 g/l (P<0.01) caffeine-receiving rats compared to the control animals. Osteoclast counts and resorption-lacunae depths demonstrated significant differences between each of the caffeine groups and control rats (P<0.05). None of the variables showed significant differences between the caffeine groups (P>0.05). CONCLUSION: According to our findings, one of the effects of caffeine consumption during orthodontic treatment in rats was decreased root resorption. Additionally, concentrations of 2 g/l and 3 g/l inhibited OTM which seems to be due to its influence on osteoclast numbers.

Mathematical modeling in municipal solid waste management: case study of Tehran.

BACKGROUND: Solid Waste Management (SWM) in metropolises with systematic methods and following environmental issues, is one of the most important subjects in the area of urban management. In this regard, it is regarded as a legal entity so that its activities are not overshadowed by other urban activities. In this paper, a linear mathematical programming model has been designed for integrated SWM. Using Lingo software and required data from Tehran, the proposed model has been applied for Tehran SWM system as a case study. RESULTS: To determine the optimal status of the available system for Tehran's Solid Waste Management System (SWMS), a novel linear programming model is applied. Tehran has 22 municipal regions with 11 transfer stations and 10 processing units. By running of the model, the transfer stations and processing units are decreased to 10 and 6 units, respectively. CONCLUSIONS: The proposed model is an alternative method for improvement the SWMS by decreasing the transfer stations and processing units.

The effects of diode laser (660 nm) on the rate of tooth movements: an animal study.

Low-level laser has been indicated to have the capability to facilitate the differentiation of the osteoclastic and osteoblastic cells which are responsible for the bone remodeling process. The aim of this study was to evaluate the effects of InGaAlP laser with a wavelength of 660 nm on the rate of tooth movement and histological status. Thirty male Wistar rats of 7 weeks old were selected for this study. The rats were randomly divided into two groups of 15 each to form the experimental (laser-irradiated) and control (non-irradiated) groups. The control group received unilateral orthodontic appliance design (one quadrant), but the laser-irradiated group received split-mouth design, with orthodontic appliance on both sides and laser irradiation on one side only (group b) and on the contralateral side (group c). The orthodontic appliance consisted of a NiTi closed coil spring with a length of 5 mm which was ligated to maxillary molar and incisor. A total of 60 g of force was applied to the rat molar. The diode laser (660 nm) was irradiated with an output power of 25 mW in continuous mode for a total time of 5 min in the laser-irradiated group. After 14 days of orthodontic tooth movement, the amount of tooth movements was measured. In the laser-irradiated group, the amount of tooth movement was significantly greater than that of the non-irradiated group (2.3-fold), but there was no significant difference between the non-irradiated and indirectly irradiated groups. Histopathological studies revealed that the number of osteoclasts in the laser-irradiated group was significantly greater than that of the non-irradiated group (1.5-fold) while this number was almost the same in the non-irradiated and indirectly irradiated groups. The results suggested that low-level laser can accelerate the rate of bone remodeling. However, in order to utilize the low-level laser as an adjunct in orthodontic practice on patients, further research studies are needed for finding the appropriate dosage for the human tissues.

Frequency of bacterial agents isolated from patients with nosocomial infection in teaching hospitals of Mazandaran University of Medical Sciences in 2012.

BACKGROUND: The antibiotic resistance of nosocomial organisms is rapidly increasing. The purpose of this study was to determine the frequency of bacterial agents isolated from patients with nosocomial infection. METHODS: This study was performed in the different wards of teaching hospitals of Mazandaran University of Medical Sciences (northern Iran). The study population consists of the patients with the symptoms of nosocomial infection admitted in these hospitals in 2012. The patient data (including age, sex, type of infection, type of isolated organisms and their antibiotic susceptibility) were collected and analyzed. RESULTS: The total number of hospitalizations was 57122 and the number of nosocomial infection was 592. The overall prevalence of nosocomial infection was 1.03% that was mostly in Burn unit and intensive care unit. The most common nosocomial infection was wound infection (44.6%) and the most common organisms were Pseudomonas aeruginosa and Acinetobacter. CONCLUSION: Given the increasing numbers of nosocomial infection in this region, especially infection with Pseudomonas aeruginosa, it is necessary to make a precise reporting and improve the procedures of infection control in hospitals.

Pantoprazole, a proton pump inhibitor, increases orthodontic tooth movement in rats.

OBJECTIVES: Pantoprazole, is a proton pump inhibitor (PPI) prescribed for the treatment of upper gastrointestinal disorders, which in high doses has been suggested to decrease calcium absorption leading to hypocalcaemia and therefore osteoporosis. The aim of this study was to assess whether pantoprazol, could alter the rate of orthodontic tooth movement (OTM) in rats. MATERIALS AND METHODS: A time course study was established using 72 rats which were divided into six groups of 12 samples each (four: vehicle; eight: pantoprazole + vehicle). Pantoprazole at a dose of 200 mg/kg suspended in carboxymethyl cellulose (0.25 percent) was administered by a gastric tube. The upper incisors and first molars were ligated by a 5 mm nickel-titanium closed-coil spring to deliver an initial force of 60 g. Animals were euthanized two weeks after orthodontic treatment followed by assessment of tooth movement and histomorphometric evaluation of the detached maxillae. Lateral skull radiographs were obtained once a week, starting from the first day to the 6(th) week of the study. OTM and bone density data were analyzed using independent sample t-test and repeated measures ANOVA. RESULTS: No significant changes in OTM measurements and optical density were observed in vehicle-receiving animals during the study (P=0.994). OTM was significantly increased after six weeks pantoprazole therapy which continued until the 7(th) week of the experiment (P=0.007). Optical density significantly increased in the pantoprazole-treated rats after six weeks. CONCLUSION: Long term PPI therapy at high doses could lead to osteoporosis and enhanced OTM.