The Effect of an Enamel Matrix Derivative (Emdogain) Combined with Bone Ceramic on Bone Formation in Mandibular Defects: A Histomorphometric and Immunohistochemical Study in the Canine

Background. The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD) and an osteoconductive bone ceramic (BC) in improving bone regeneration. Materials and Methods. Four cylindrical cavities (6 × 6 mm) were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments—filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated)—and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Results. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. Conclusion. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation

The Effect of Fragaria vesca Extract on Smear Layer Removal: A Scanning Electron Microscopic Evaluation

Introduction: Successful endodontic treatment depends on elimination of the microorganisms through chemomechanical debridement. The aim of this in vitro study was to evaluate the effectiveness of Fragaria vesca (wild strawberry) extract (FVE) on the removal of smear layer (SL). Methods and Materials: In this analytical-observational study, 40 extracted mandibular and maxillary human teeth were selected. After canal preparation with standard step-back technique, the teeth were randomly divided into 4 groups according to the irrigation solution: saline (negative control), 5.25% NaOCl+EDTA (positive control), FVE and FVE+EDTA. The teeth were split longitudinally so that scanning electron microscopy (SEM) photomicrographs could be taken to evaluate the amount of remnant SL in coronal, middle and apical thirds. The data were analyzed statistically by the Kruskal-Wallis and Mann Whitney U tests and the level of significance was set at 0.05. Results: Significant differences were found among the groups (P<0.001). The use of NaOCl+EDTA was the most effective regimen for removing the SL followed by FVE+EDTA. FVE alone was significantly more effective than saline (P<0.001). Conclusion: FVE with and without EDTA could effectively remove the smear layer; however, compared to NaOCl group it was less effective.Keywords: Fragaria vesca; Irrigation; Scanning Electron Microscopy; Smear Laye

Orofacial Pathological Lesions in Children and Adolescents: A 25-year survey in Iran

Statement of the Problem: Oral pathological conditions presented in children are various and often different from those of adults. There is considerable variation in the prevalence of these lesions among different regions of the world. Purpose: The aim of this study was to assess the frequency and clinical-pathological features of oral lesions diagnosed in children and adolescents throughout 25 years in an oral pathology department. Materials and Method: This cross-sectional study was conducted in the Department of Oral and Maxillofacial Pathology at Dental School of Isfahan University of Medical Sciences. All the medical reports and biopsy files of the patients aged <18 years that were diagnosed during January 1990 and December 2015 were retrieved. The data regarding histopathologic diagnosis, site of lesions, and date of diagnosis and demographic characteristics of patients were elicited. The lesions were categorized based on their origin and age group of the patients. Descriptive statistics were used as appropriate. The critical level of significance was set at p< 0.05. Results: 1267 lesions were recorded. The mean age of the samples was 12.5±3.9. Of lesions, (408, 49.3%) were in posterior area. The most common lesions were odontogenic cysts (416, 32.9%) and reactive lesions (317, 25.1%) and the least common lesions were allergic and immunologic disorders (2, 0.2%). In age groups of 7-12 and 13-18 years, odontogenic cysts [(208, 38.1%), (198, 31.4%)] and reactive lesions [(143, 26.3%), (147, 23.3%)] were the most common lesions, respectively. During the 25 years of survey, the prevalence of pulp and periapical disease increased (p <0.001), that of bone pathology decreased (p< 0.05) and trend of other lesions did not significantly change over this time. Conclusion: The most frequent lesions were odontogenic cysts and reactive lesions. The prevalence of lesions was not changed dramatically during the 25 year. The frequency of oral lesions in Isfahan province (in Iran) is different from other regions in the world and even, to some extent, different from other regions in Iran, which is in agreement with the hypothesis of geographical distribution of these lesions

Pulp Response following Direct Pulp Capping with Dentin Adhesives and Mineral Trioxide Aggregate; An Animal Study

Introduction: Pulp vitality and its continuous dentin prodution are essential for long-term success of direct pulp capping (DPC). The aim of present study was to evaluate the histopathological response of the canine pulp following DPC using either different dentin adhesive resins (DAR), calcium hydroxide (CH) or mineral trioxide aggregate (MTA). Methods and Materials: DPC was done on 72 dog’s teeth using 6 types of dental materials (n=12) (4 types of DAR, white MTA and CH). Therefore, six healthy dogs were anesthetized and 2 teeth from each dog were allocated to either type of mentioned DPC agents. The dental pulps were exposed mechanically by drilling in the center of class V cavities. The different types of capping materials included DARS (Clearfil S3 Bond, Optibond FL, Single Bond and Clearfil SE Bond), white MTA and CH. After 7, 21 and 63 days, two dogs were euthanized in each interval. Microscopic evaluations were done according to following criteria: intensity of inflammation, presence of necrosis and formation of hard tissue. The recorded data were analyzed by the Kruskal-Wallis, Friedman, Cochran’s and Fisher’s exact tests using SPSS software version 12 at significant level of 0.05. Results: No significant differences were found regarding necrosis among DPC materials (P&gt;0.05). However, MTA caused higher amount of hard tissue formation after 63 days in comparison with 21 days. Conclusion: MTA provided the highest degree of hard tissue formation after 63 days. However, further studies should be performed for administering a definitive material.Keywords: Dentin Adhesive Systems; Direct Pulp Capping; Mineral Trioxide Aggregat

Retro MTA and tricalcium phosphate/retro MTA for guided tissue regeneration of periodontal dehiscence defects in a dog model: a pilot study

Objectives: Retro MTA is a fast setting Calcium silicate cement used in endodontic regeneration procedures in recent years. Beta-tricalcium phosphate (β-TCP) is another common biomaterial used for bone augmentation procedures. The present pilot study was undertaken to evaluate and compare the efficacy of Retro MTA and a mixture of Retro MTA / β-TCP for periodontal tissue regeneration. Materials and methods: In 4 beagle dogs, periodontal dehiscence type defects were created. In each side, one dehiscence defect was left empty as a control site and three treatment modalities were randomly applied for the others: Retro MTA covered with a collagen membrane, Retro MTA + β-TCP covered with a membrane and covering the defect with a membrane without any bone augmentation. After 8 weeks Animals were sacrificed and Histomorphometric and histologic analysis were conducted. Results: Histologic analysis showed more cementum formation for both Retro MTA+ β-TCP (3.74 ± 0.34 mm) and Retro MTA group (3.24 ± 0.56 mm) compared to control group 1 (1. 15 ± 0.45 mm) and control group 2 (0.78 ± 0.65 mm). Formation of newly formed bone and cementum in the experimental groups were significantly higher as compared to the control groups (P < 0.0001). Conclusions: Retro MTA or Retro MTA+ β-TCP covered with a collagen membrane resulted in regeneration of periodontal tissues. However, Retro MTA+ β-TCP showed tendency towards better results than the use of Retro MTA alone. KEYWORDS: Bone regeneration; Calcium silicate cement; Guided tissue regeneration; MT

The Association of Fat-Mass-and Obesity-Associated Gene Polymorphism (rs9939609) With Colorectal Cancer: A Case-Control Study

Background and Aim: The association between the rs9939609 polymorphism of fat mass and obesity-associated gene (FTO) and risk of colorectal cancer is controversial. This study aims to evaluate the relationship between FTO rs9939609 polymorphism and colorectal cancer (CRC) in Iranian people. Methods: A case-control study was conducted on 125 patients with CRC and 250 healthy subjects in Tehran, Iran. Demographic data and blood samples were collected from all participants. Genotyping of rs9939609 polymorphism was performed by the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. Results: The occurrence of AA genotype of FTO rs9939609 polymorphism in the colorectal cancer patients was significantly higher compared to that of healthy subjects (16.4 vs. 2.9%, respectively, P=0.02). The association between the frequency of risk allele of the FTO polymorphism and CRC (B=1.67, P=0.042) remained significant after adjustment for age. Further adjustment for gender (model 2) and marital status (model 3) did not change this result (B=1.67, P= 0.042 and B=1.67, P=0.043, respectively). The results remained significant after additional adjustment for ethnicity (B=1.57, P= 0.047). Conclusion: We found a positive association between the A allele of the rs9939609 polymorphism and CRC. Future studies are required to identify the underlying mechanisms

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

MECHANICALLY MEDIATED GROWTH AND REMODELING OF COLLECTING LYMPHATIC VESSELS

Lymphatic dysfunction plays a key role in pathologies such as immune disorders, infection, cancer, obesity, and cardiovascular disease; regarding the latter, lymphatic dysfunction may exacerbate edema in myocardial infarction (MI) and chronic heart failure. Secondary lymphedema is a progressive and debilitating disease characterized by fluid retention and tissue swelling that can arise due to dysfunction in lymphatic pumping. Secondary lymphedema is a common complication in breast cancer treatment where the surgical removal of lymphatic vessels/lymph nodes can induce overloads that triggers lymphatic pathologies that can present months or even years after surgery. Although the local mechanical environment is known to regulate lymphatic function, the role of sustained mechanical overloads (e.g., high pressure and high flow) in lymphatic dysfunction has yet to be established. Towards this end, our long-term goal was to develop a mechanistic understanding of mechanically-mediated growth and remodeling (G&R) of collecting lymphatic vessels in health and disease and to ultimately identify novel therapeutic interventions to minimize the risk of occurrence, severity, or complications of lymphatic dysfunction. This PhD thesis focuses on developing a novel rat tail model to study lymphatic G&R and to employ a combined experimental-computational approach to quantify the modes by which sustained high pressure and high flow compromise the normal function of the lymphatic system via maladaptive remodeling. First, we introduced and used a novel rat tail model to study the effect of mechanical loads (specifically axial stretch) on the lymphatic contractility. Second, we developed a computational framework to study lymphatic pumping in the context of a lymphangion chain. Lastly, we developed and tested the feasibility of a novel lymphatic ligation model to study lymphatic remodeling post-surgery. Lastly, the methods and results from this study can pave the way for future studies of lymphatic remodeling in health and disease.Ph.D

Histopathologic Responses of Dog’s Dental Pulp to Mineral Trioxide Aggregate, Bio Active Glass, Formocresol, Hydroxyapatite

Introduction: Bio Active Glass (BAG) is often used as a filler material for regeneration of dental bone defects. Mineral trioxide aggregate (MTA) is used as retrofilling agent, repair of root resorption and pulpotomy agent in primary dentition. Formocresol (FC) is old and standard fixation agent in pulpotomy procedures. Hydroxyapatite (HA) is a biologic constitute. It is used in ridge augmentation, bony defect repair and pulpotomy agent in teeth. The purpose of this study was evaluation of histopathologicresponses of dog’s dental pulp to MTA, BAG, FC and HA after three months follow up.Materials and Methods: For this experimental prospective study forty-eight teeth were randomly selected in four dogs. Animals were anesthetized and pulpotomized. Three months later, animals were anesthetized and sacrificed. Then, teeth were extracted and histologic sections were prepared. Histologic sections were observed by an oral pathologist. The sections were observed from the viewof inflammation, hyperemia, necrosis, vitality, calcification and dentinal bridge. Relative frequency of histopathologic outcomes of dental pulp was analyzed and reported. Mean differences of fourgroups were analyzed by Kruskal-Wallis and Mann-Whitney tests.Results: Relative frequency of inflammation of FC, MTA, HA and BAG groups were 29.2, 25.9, 42.4 and 29.2 percent, respectively. Relative frequency of hyperemia of FC, MTA, HA and BAGgroups were 75.1, 63.6, 59.2, 81.6 and 62.5 percent, respectively. Relative frequency of necrosis of FC, MTA, HA and BAG groups were 29.2, 11.1, 12.1, 0 percent, respectively. Relative frequency ofcalcification of FC, MTA, HA and BAG groups were 75, 51.9, 69.7 and 54.8 percent, respectively. Relative frequency of dentinal bridge of FC, MTA, HA and BAG groups were 29.2, 70.4, 30.3 and 29.2 percent, respectively.Conclusion: Histopathologic reactions of dental pulp to four materials (MTA, HA, BAG, FC) were different. Histopathologic outcomes of MTA was more proper than those of BAG, HA and FC. Considering these findings, use of mineral trioxide aggregate and bioactive glass in pulpotomy is more favorable than using Formocresol and Hydroxyapatite