To evaluate the treatment effects of AdvancSync 2 in patients of skeletal Class II malocclusion in selected skeletal, dental, soft tissue and airway parameters. Pretreatment and post-functional lateral cephalograms of 12 patients (06 males and 06 females with mean age of 14.25+0.75) with skeletal Class II malocclusion treated using AdvanSync 2 were evaluated. Paired t-test and Wilcoxon rank-sum intraclass correlation (ICC) test results were calculated.Statistically significant changes were found in skeletal parameters ofSNB, Wits, maxillo-mandibular differential, Björk’s sum, basal plane angle, Sn-GoGn, lower anterior facial height (LAFH), Na-perp-Pog. Changes in dental parameters U1-NA (angular and linear), L1 to NB (angular and linear), U1-SN angle, IMPA, Inter-incisal angle, L1 to A-Pog and U1 to A-Pog were also observed to be statistically significant at T1. Soft tissue skeletal convexity and nasolabial angle improved significantly post treatment, while, statistically significant change was observed only in posterior pharyngeal airway space among the chosen cephalometric airway parameters.Treatment with AdvanSync 2 corrected the Class II malocclusion by producing skeletal and dentoalveolar changes. Soft tissue facial convexity and nasolabial angle improved with treatment. Further, linear dimension of the posterior pharyngeal airway space showed significant improvement with AdvanSync 2 therapy.

Spinel (magnesium aluminate MgAl2 O4 ) ceramic-based polyphasic composite scaffold has been recently reported for craniofacial bone tissue engineering. Improving the osteogenic effects of such composite scaffolds with bone morphogenetic proteins (BMP2) is an intensely researched area. This study investigated the gene interactions of this scaffold with BMP2 and mesenchymal stem cells (MSCs). Human bone marrow MSCs were cultured in 3 groups: Group 1-Control (BMSCs), Group 2-BMSC with BMP2, and Group 3-BMSC with scaffold and BMP2. After RNA isolation, gene expression analysis was done by microarray. Differentially expressed genes (DEGs) (-1.0 > fold changes>1 and p value <.05) were studied for their function and gene ontologies using Database for Annotation, Visualization and Integrated Discovery (DAVID). They were further studied by protein-protein interaction network analysis using STRING and MCODE Cytoscape plugin database. Group 3 showed up regulation of 3222 genes against 2158 of Group 2. Group 3 had five annotation clusters with enrichment scores from 2.08 to 3.93. Group 2 had only one cluster. Group 3 showed activation of all major osteogenic pathways: TGF, BMP2, WNT, SMAD, and Notch gene signaling with effects of calcium and magnesium released from the scaffold. Downstream effect of all these caused significant activation of RUNX2, the key transcriptional regulator of osteogenesis in Group 3. STRING and MCODE Cytoscape plugin demonstrated the interactions. The enhanced MSC differentiation for osteogenesis with the addition of BMP2 to the polyphasic composite scaffold proposed promising clinical applications for bone tissue engineering.

Background:Biologic compounds have recently generated interest in cancer chemoprevention. Sulforaphane (SFN), an isothiocyanate from cruciferous vegetables, has profound epigenetic actions. Since epigenetic aetiology is crucial for oral cancer, this study evaluated the role of SFN in oral cancer prevention. Methods:Oral squamous cell carcinoma cells (UPCI-SCC-172) were treated with SFN in three concentrations: 10 μM, 20 μM and 30 μM for two time periods: 24 h and 48 h. MTT assay assessed cell proliferation. Histone deacetylase (HDAC) enzyme activity was colorimetrically estimated in the nuclear extracts. Flow cytometry determined cell cycle stages, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) changes. Extrinsic and intrinsic apoptotic pathways were evaluated from caspase enzyme assays. Results:Cell proliferation and HDAC activity (44% in 24 h and 40% in 48 h) were significantly inhibited (p < 0.01). For 10 μM concentration, G2/M cell cycle arrest was found with a reduction in G1 phase cell population at 24 h and 48 h. Concentrations of 20 μM and 30 μM SFN presented cells in apoptosis marked by increased sub G1 cells at 48 h. Concentrations of 10 μM and 20 μM SFN showed a 1.3 to 2.8-fold increase in ROS generation at 24 h and 48 h. The concentration of 30 μM SFN showed a drop in ROS production, denoting cells already in apoptosis. Fall in MMP was also dose- and time-dependent. Caspase enzyme assays (p < 0.001) demonstrated activation of both extrinsic and intrinsic apoptotic pathways. Conclusion:Inhibitory action of SFN on oral cancer cell proliferation and HDAC activity led to cell cycle arrest and apoptosis. These effects marked by increase in ROS, a decrease in MMP and activation of apoptotic pathways offer exciting therapeutic options.

Craniofacial bone regeneration is crucial for restoring the form and function of underlying vital structures. However, the unique physicochemical and biologic requirements of it make this task challenging. Two types of polyphasic composite scaffolds were therefore developed by polymeric template replication process from magnesium aluminate (MgAl2O4) spinel, β-tricalcium phosphate (β-TCP) and polymers; poly lactic-co-glycolic acid (PLGA) or poly caprolactone (PCL). The scaffolds: spinel/β-TCP/PLGA and spinel/β-TCP/PCL were physicochemically characterized at each stage of development followed by evaluation of compressive strength, porosity, in vitro degradation and ion release. Their morphology was then assessed for trabecular parameters: trabecular number, thickness, spacing, structural model index and degree of anisotropy. Their interactions with mesenchymal stem cells were also studied. Both the scaffolds showed compressive strength and porosity of craniofacial bones. However, trabecular parameters, degradation, ion release, cell viability / proliferation / deposition inside the scaffold were better for spinel/β- TCP/PLGA. Further, its internal morphology was similar to cancellous bone, optimum for cellular and vascular permeation. The scaffold also underwent significant degradation in four months releasing calcium, magnesium and phosphorus. Up regulation of genes pertaining to bone morphogenesis, development, differentiation, mineralization, ossification, remodeling were found along with transmembrane and notch receptor genes. All these led to the activation of major osteogenic pathways mediated by TGF/BMP/WNT/integrin families and notch signaling, with significant contributions from Mg ions. The genes with specific role in osteogenesis were also validated. Overall, magnesium aluminate based polyphasic composite scaffold: spinel/β-TCP/PLGA demonstrated physical and biologic characteristics essential for in vitro craniofacial bone tissue engineering.

Background:Dental radiology represents the best model for evaluating the effects of low-dose ionizing radiation. Therefore, this study evaluated the awareness on radiation hygiene among dental ancillary personnel through a questionnaire and their absorbed doses by physical and biologic dosimetry. Methods:The multicentric study included two groups. Group I (N = 30) consisted of dental staff involved in dental radiology. An equal number of personnel who were not related to radiology formed the control group. Knowledge (K), attitude (A), and practice (P) of participants were assessed using a KAP questionnaire. Radiation exposure was evaluated by physical dosimetry at 3 time periods: at the beginning of the study (T1), after 10 months (T2), and at the end after 20 months (T3). Similarly, biologic dosimetry was also carried out at 3 time points by dicentric chromosome aberration assay. The data were compared using percentage analysis, analysis of variance (one-way analysis of variance), and Student's t- test. Results:The KAP survey demonstrated enhanced understanding of radiation protection measures and its sound practice by the participants. Physical dosimetry showed a significant increase in absorbed dose at 3 time points: T1, T2, and T3. However, no chromosomal aberrations were observed in blood lymphocytes for any of the participants in the optimized 4-day biodosimetry protocol. Conclusion:Good radiation protection protocols-safe distance from the radiation source and wear of lead aprons and thyroid collars-ensured low absorbed doses. The 4-day protocol is an important step toward developing biodosimetry laboratories in the Armed Forces Medical Services for clinical and national radiation countermeasure strategies.

BACKGROUND:Considering the limitations in isolating Bone Marrow Mesenchymal Stem Cells (BMSCs), alternate sources of Mesenchymal Stem Cells (MSCs) are being intensely investigated. This study evaluated dental pulp MSCs (DP-MSCs) isolated from orthodontically extracted premolar teeth from a bone tissue engineering perspective.METHODS:MSCs isolated from premolar teeth pulp were cultured and studied using BMSCs as the control. Flow cytometry analysis was performed for the positive and negative MSC markers. Multilineage differentiation focusing on bone regeneration was evaluated by specific growth induction culturing media and by alkaline phosphatase (ALP) activity. Data were compared by repeated measurement analysis of variance and Student's t-test at a p value <0.05.RESULTS:Proliferation rate, population doubling time, and colony formation of DP-MSCs were significantly higher (p < 0.001) than BMSCs. More than 85% of DP-MSCs expressed CD44, CD73, CD90, CD105, and CD166. Negative reaction was found for CD11b CD33, CD34, and CD45. Positive reaction was displayed by 7.2% of cells for early MSC marker, Stro-1. Both the cell populations differentiated into adipogenic, osteogenic, and chondrogenic lineages, with adequate ALP expression.CONCLUSION:Because DP-MSCs from orthodontic premolars hold a neural crest/ectomesenchymal ancestry, its prudent growth characteristics and multilineage differentiation open up exciting options in craniofacial tissue engineering.

Radiation induced xerostomia is a persistent clinical presentation that affects the quality of life in head and neck cancer patients even with the best of the intensity modulated radiotherapy protocols. Comprehensive review of the anatomic, histologic, developmental and neuronal entities of salivary glands from a regenerative perspective, ensuing radiation is taken. It also evaluates the systemic and glandular radiation responses that form the early and late clinical changes. From these, the article submits probable strategies; based on the current knowledge and future challenges involved, in reversing radiation induced xerostomia. Further, it elaborates on the status of radioprotectors and mitigators including the recently reported biologic and chemical derivatives and proposes the rationale of using combination radioprotector therapy in radiation injuries. A brief of palliative regimes, alternate treatment modes and technologic advancements in radiotherapy are also explained. Salivary gland histologic components, which need to be protected in the emerging radiotherapy protocols and can be targeted in different salivary gland regeneration therapies is highlighted. The paper contributes to an improved understanding in radiation induced xerostomia and deliberates on novel mechanisms towards enhancing quality of life in head and neck cancer radiotherapy patients.

Background Radiation-induced xerostomia is a distressing clinical condition that starts appearing from the initial stages of radiotherapy in head and neck cancer patients. Though submandibular glands contribute to maximum of the “resting salivary” secretions, most of the acute xerostomia experiments so far reported have been on animal parotid glands. Therefore, we assessed and quantified the histologic changes in submandibular glands of Sprague-Dawley (SD) rats using histomorphometry, 24 hours after radiation. Methods Three SD rats were given single-dose radiation of 15 Gray from a gamma cobalt-60 irradiator. Same number of non-radiated animals was the controls. Animals were sacrificed at 24 hours followed by histopathology and histomorphometry of submandibular glands, where the mean values were analyzed by Student’s t-test. Results Irradiated submandibular glands showed highly significant reduction in acinar area (53%: 77.16±5.05% to 36.55±4.90%) and acinar size (87%: 3,447.53 ± 461.03 mm2 to 428.25 ± 75.22 mm2) with concomitant increase in inter-acinar space (3.46 ± 0.67 mm to 10.08 ± 0.60 mm). Acini nuclei displayed anisonucleosis, poikilonucleosis and pyknosis. “Serous acini” had marked morphologic changes, with fluid accumulation between cells, generalized cytoplasmic vacuolation and vascular congestion, while “mucous acini” largely retained cell architecture. Similarly, ductal cells and nuclei also did not show apparent differences. This demonstrated radiosensitivity variations among different submandibular gland cell types. Conclusion Evaluation of acute submandibular acinar cell dysfunctions has helped in quantifying the histologic elements, which mainly contribute to the resting salivary secretions. Findings would aid in future research of radioprotector drugs, salivary glandular regeneration modalities and in devising prudent radiotherapy protocols to address radiation-induced xerostomia.

Radiation threat perceptions have seen an increase in recent times.Since much of the current understanding of radiation biology has come from nuclear accidents, this short communication briefly takes stock of the major/minor radiation fallouts in last three decades in terms of the type/amount of radioactive nuclide dissemination, which causes the internal/external biologic contamination, causalities, environmental issues and level of public awareness and preparedness towards it.Also, it highlights the ill effects of increased use of diagnostic ionizing radiation.The paper recaps the evolution of radioprotectors and mitigators from initial sulfhydryl compounds to the present-natural antioxidants and biologic cell response modifiers.From these, the emerging strategies in radiation counter measures: training for rescuers, biodosimetry for absorbed doses, development of new radiation decontamination devices/products and the shift towards combination radiotherapy using bio resources/biomimetic/ stem cell approaches, with minimal toxicity are touched upon.Beneficial spin-offs like thyroid disease treatment, radiopharmaceutical mediated molecular imaging and innovative development of lead free radiation deterrent materials for diagnostic radiology are also mentioned.Overall, it presents a road map for better management of radiation insults.

Hydroxyapatite (HAp) is one of the most emerging biocompatible ceramic widely used as scaffolds in various biomedical applications such as orthopedics and dentistry. In spite of the superior properties for biomedical applications, they exhibit poor mechanical properties. This has lead to the concept of fabricating composite out of bioactive and bioinert material to derive bioactivity in combination with desirable mechanical properties. In this study, bioinert magnesium aluminate (MgAl2O4) spinel scaffolds are prepared through polymeric foam replication process followed by sintering. Sintered foams have exhibited good structural integrity and the stress–strain curves recorded during the uniaxial compression have shown a plateau indicating high‐energy absorption capability. Sonochemical process has been employed for the simultaneous synthesis and deposition of HAp formulation from the stoichiometric solution of precursors on the spinel scaffolds. Sonochemical process has resulted in the formation of phase pure HAp with unique morphology of nanorods coated throughout the three‐dimensional foam structures. Cytotoxicity evaluation of this new scaffold material has not shown any alteration in the viability, growth, and morphology of the cells. The new scaffold material thus developed is expected to have high potential for biomedical applications.

Abstract Objective: To quantify cell free fetal DNA (cffDNA) with fetal specific epigenetic marker, hypermethylated RASSF1A, in maternal plasma of normal pregnant women from 20 weeks of gestation and to assess its relationship with maternal age, height, pre-pregnancy weight and body mass index (BMI). Methods: Hundred normal pregnant women within the gestational age of 21–40 weeks were randomly selected and grouped into five (n = 20). Group 1: 21–24, Group 2: 25–28, Group 3: 29–32, Group 4: 33–36 and Group 5: 37–40 weeks. Maternal plasma DNA was extracted, digested with methylation-sensitive restriction enzyme, BstUI and the fetal specific DNA (cffDNA) was quantified by Real-time polymerase chain reaction (qRT-PCR). Results: The mean hypermethylated RASSF1A concentrations in different gestational groups were Group 1: 30.1 ± 14.9, Group 2: 52.6 ± 22.18, Group 3: 93.2 ± 19.08, Group 4: 172.8 ± 26.81 and Group 5: 337.8 ± 52.9 copies/ml. Pearson’s correlation analysis showed highly significant positive correlation between cffDNA and gestational age (r = 0.899, p < 0.001). BMI was also found to be positively related to cffDNA (r = 0.217, p < 0.05). However, it did not show any correlation with maternal age, height and pre-pregnancy weight. Conclusions: The gestational age-dependent increase of hypermethylated RASSF1A; the fetal specific epigenetic marker in maternal plasma was demonstrated, in an Indian study group of normal pregnant women. Findings would form the basis of future studies involving pregnancy complications that would aid in the early diagnosis of placental pathologies with hypermethylated RASSF1A.

Objectives: Cell free fetal DNA (cffDNA) and its hypermethylated RASSF1A gene signify a recent advancement in non-invasive prenatal diagnosis of feto-placental anomalies like pre-eclampsia. The study uses hypermethylated RASSF1A gene to quantify cffDNA and to assess its relationship with placental and urine proteins in pre-eclampsia cases.Design and methods: DNA was isolated from plasma samples of clinically diagnosed cases of pre-eclampsia (n = 103) and normal pregnancy (n = 616) from 21 weeks of gestation. Through methylation sensitive enzyme (BstUI) digestion; followed by real time-polymerase chain reaction (RT-PCR), quantification of hypermethylated RASSF1A was done. Immunoassays determined: placental protein-13 (pp-13) and pregnancy associated plasma protein A (PAPP-A) and pyrogallol red molybdate assay for 24 h urine protein.Results: Highly significant differences between control and pre-eclampsia cases for hypermethylated RASSF1A concentrations were found; Group I: 33 +/- 7.35 vs 74.46 +/- 16.71, Group II: 53.75 +/- 16.65 vs 244.22 +/- 35.68, Group III: 93.25 +/- 19.08 vs 412.31 +/- 80.18, Group IV: 144.30 +/- 18.13 vs 1056.89 +/- 153.78, Group V: 307.55 +/- 40.76 vs 2763.76 +/- 259.76 copies/ml. Multivariate Pearsons correlation analysis of hypermethylated RASSF1A with pp-13, PAPP-A and urine proteins showed positive and very highly significant (P < 0.001) associations.Conclusions: Diagnostic potential of fetal specific, hypermethylated RASSF1A was evaluated. Its positive relationship with placental and urine proteins submit the case for considering it as a reliable marker for pre-eclampsia. (C) 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Pre-eclampsia is a hypertensive disorder in pregnancy, which accounts for 10-15% of the maternal and perinatal mortality worldwide. Abnormal placental development and tissue hypoxia are its main etiologic factors. The present diagnostic methods of blood pressure monitoring and renal function evaluation are insufficient in the early detection of pre-eclampsia. Since molecular events portent well ahead of the disease onset, biomarker research for the early diagnosis of pre-eclampsia has recently generated ambitious clinical targets. However, no clinically validated biomarker has so far been reported for the prediction of pre-eclampsia. Therefore, this review takes stock of the current understanding of pre-eclampsia from a molecular biology perspective and critically evaluates the following diagnostic potentials claimed for the biomarkers: placental proteins, angiogenic markers, and cell-free fetal DNA (cffDNA) in maternal circulation. Though the emerging evidences in favor of the fetal-specific epigenetic marker, hypermethylated RASSF1A of cffDNA, are highlighted, it pitches for a broader strategy of 'combination biomarker approach' for the reliable forecasting and triaging of pre-eclampsia.

The Army Dental (AD) Corps is an essential entity under the Indian Army, rendering comprehensive dental care to the combatants and dependents of the Army, Navy, and Air Force. It has a pan-Indian presence, with deployments in all terrains, deep seas, and air spaces in addition to overseas establishments. It delivers high-end clinical services through different levels: Primary dental units, secondary and tertiary dental centers. In addition, it runs some of the finest training schools for dental and paradental professionals. It maintains high standards in clinical practice in all disciplines of dentistry. All these has been made possible largely because of the consistent research pursuits; the corps accomplishes to addresses the clinical requirements and emerging challenges. Research in the AD Corps is done in three modes: (i) Armed Forces Medical Research Committee Projects (AFMRC) done every year by the Indian Army, (ii) Interdisciplinary research among medical and dental specialities, and (iii) Defence Research and Development Organization (DRDO). Through these, it has embarked on advanced, cutting-edge research for new technologies, protocols, and products in the dental sciences. This paper takes stock of current trends in the AD Corps in these domains and highlights its thrust areas toward quality dental treatment.

With the advent of new rotary instruments and equipments, single visit endodontics has spawned considerable interest in dental practice.However, little consensus exist regarding the right procedures: canal preparation, irrigation, debridement and obturation, to be followed for this modality.Here in, we report a simple protocol for single visit endodontics, adhering to basic principles of root canal treatment with routinely used instruments and materials.The case series involved all types of teeth: upper/lower and single/multi rooted.The high rate of success with respect to treatment outcome and post operative pain observed in this series validate our protocol on single visit endodontics as a reliable, economical and predictable option.

Adult orthodontics is recently gaining popularity due to its importance in esthetics, oral and general health. However, none of the currently available alumina or zirconia based ceramic orthodontic brackets meet the esthetic demands of adult patients. Inherent hexagonal lattice structure and associated birefringence limits the visible light transmission in polycrystalline alumina and make them appear white and non transparent. Hence focus of the present study was to assess the feasibility of using magnesium aluminate (MgAl2O4) spinel; a member of the transparent ceramic family for esthetic orthodontic brackets. Transparent spinel specimens were developed from commercially available white spinel powder through colloidal shaping followed by pressureless sintering and hot isostatic pressing at optimum conditions of temperature and pressure. Samples were characterized for chemical composition, phases, density, hardness, flexural strength, fracture toughness and optical transmission. Biocompatibility was evaluated with in-vitro cell line experiments for cytotoxicity, apoptosis and genotoxicity. Results showed that transparent spinel samples had requisite physico-chemical, mechanical, optical and excellent biocompatibility for fabricating orthodontic brackets. Transparent spinel developed through this method demonstrated its possibility as a prospective biomaterial for developing esthetic orthodontic brackets.

BACKGROUND:Surface roughness of nickel titanium orthodontic arch wires poses several clinical challenges. Surface modification with aesthetic/metallic/non metallic materials is therefore a recent innovation, with clinical efficacy yet to be comprehensively evaluated.METHODS:One conventional and five types of surface modified nickel titanium arch wires were surface characterized with scanning electron microscopy, energy dispersive analysis, Raman spectroscopy, Atomic force microscopy and 3D profilometry. Root mean square roughness values were analyzed by one way analysis of variance and post hoc Duncan's multiple range tests.RESULTS:Study groups demonstrated considerable reduction in roughness values from conventional in a material specific pattern: Group I; conventional (578.56 nm) > Group V; Teflon (365.33 nm) > Group III; nitride (301.51 nm) > Group VI (i); rhodium (290.64 nm) > Group VI (ii); silver (252.22 nm) > Group IV; titanium (229.51 nm) > Group II; resin (158.60 nm). It also showed the defects with aesthetic (resin/Teflon) and nitride surfaces and smooth topography achieved with metals; titanium/silver/rhodium.CONCLUSIONS:Resin, Teflon, titanium, silver, rhodium and nitrides were effective in decreasing surface roughness of nickel titanium arch wires albeit; certain flaws. Findings have clinical implications, considering their potential in lessening biofilm adhesion, reducing friction, improving corrosion resistance and preventing nickel leach and allergic reactions.

Edentulism is a major health concern of old age. Indigenous implant based over dentures offer a cost effective option for severely resorbed dental ridges. Here, we report rehabilitation of a resorbed mandibular arch with indigenous implant supported overdenture and maxillary arch with a conventional denture. Two ball and socket implants were placed bilaterally in the parasymphyseal area. Existing denture was relined to accommodate the ‘ball head’ of the implant in the interim period. Four months later, when patient was taken up for denture fabrication, the ‘socket part’ of the ball and socket implant was incorporated into the new denture base. The socket provided a fitting surface for the implant. Implant supported overdenture significantly increased the retention, support and stability of the lower denture. Further, it worked well with the upper conventional denture. The simple design and efficacy of indigenous implant based overdenture holds promising aspects in the treatment of edentulism.