Evaluation of the Efficacy of LASER, Desensitizing Agents, and their Combined Effect on Dentinal Hypersensitivity in Bicuspids: In Vitro Study.

Aim: This study aimed to know the potential of diode light amplification by stimulated emission of radiation (LASER) and desensitizing agents on blocking the dentinal tubules, which may further help in reducing the most common dental problem named dentinal hypersensitivity (DH). Materials and Methods: Sixty human permanent bicuspids were selected, and preparation was performed in the cervical region measuring 2.5 mm × 2.5 mm × 2.5 mm, followed by acid etching for 15 seconds. These are then divided according to the groups mentioned: group 1-nano-hydroxyapatite (HA) was applied for 15 minutes; group 2-biosilicate was applied for 15 minutes; group 3-diode LASER application was performed twice for 60 seconds in noncontact mode; group 4-nano-HA plus diode LASER application; and group 5-biosilicate plus diode LASER application. The same procedure was followed on the 1st, 7th, and 14th days and then rinsed and stored in artificial saliva, and the saliva was changed every 24 hours. The dentinal tubular occlusion was observed under a scanning electron microscope (SEM) after the 14th day. Result: The maximum dentinal tubular occlusion was observed in group 4, where nano-HA and diode LASER application was performed. Conclusion: All the investigated treatment groups have promising occluding potential, but the maximum was found in group 4 >group 5 >group 3 >group 1 >group 2. LASER plus desensitizing together prove to be potent and effective in reducing dentinal tubular diameter.

In Vitro Analysis of Outcome Differences Between Repairing and Replacing Broken Dental Restorations.

Objective In light of several advancements and considerations in endodontic dentistry, there still remains a need to comprehensively evaluate the outcome disparities between repairing and replacing broken dental restorations. This study aims to compare the effectiveness of repairing dental restorations versus replacing them, focusing on how each method affects the structural strength and longevity of the restorations. Methods The study included 60 freshly removed human maxillary premolars. Initial processing involved rigorous washing, descaling, and polishing of the teeth. To ensure preservation, the specimens were stored in sterile, distilled water. To occlude the root canals, a self-hardening composite resin was used, and the roots were coated with two coats of clear nail polish to prevent moisture penetration. A 245 carbide bur attached to a high-speed dental handpiece with air and water spray cooling produced standardized Class II cavities on the occluso-proximal surfaces. Each cavity had a buccolingual breadth of 2 mm, an occluso-cervical length of 4 mm, and a gingival boundary that was 1 mm coronal to the cement-enamel junction. Following this preparation, the teeth were randomly separated into three groups (Group A, Group B, and Group C), each containing 20 teeth. Results Our analysis showed that teeth with entirely replaced restorations had a higher average fracture resistance than those with repaired restorations. However, the difference in fracture resistance between the repair and replacement groups for each type of material was not statistically significant. Conclusion Based on the findings, repairing a dental restoration can be a conservative and less invasive alternative to a full replacement without a significant compromise in the restoration's ability to withstand fracture. Therefore, dental professionals might consider full restoration as a viable option, taking into account the need to preserve dental tissue as well as the restoration's durability and structural integrity.

A Comparative Evaluation of Efficacy of Various Obturating Techniques for the Presence of Voids.

Aim: Evaluation of the efficacy of different obturating techniques and assessment of the presence of voids in different regions of the canal. Materials and Methods: Sixty permanent single-rooted teeth with complete, mature root apices without any anatomic variation having straight patent root canals were included in the present study. Access cavity preparation followed by biomechanical preparation was done. Samples were divided into three groups-Group A: Single cone obturation, Group B: GuttaFlow 2, and Group C: GuttaCore, and obturation was carried out. The samples after obturation were stored at 370°C and 100% humidity in an incubator for 7 days to give adequate time for obturating materials to set. Cone beam computed tomography was performed with i-cat Cb 500 machine. The voids were checked on the root canal wall. The statistical analysis was done and the data after the statistical analysis was presented. Result: GuttaCore obturators presented a lesser volume of voids followed by GuttaFlow 2 than the single cone techniques. Conclusion: All the obturation techniques presented an inadequacy of obturation when the pre- and post-obturated volume of the root canal space was calculated. However, no statistically significant obturated volume differences were found between single cone and GuttaFlow 2 or between GuttaFlow 2 and GuttaCore system.

Comparative Evaluation of Effectiveness of Nisin, Amoxicillin/Clavulanic Acid (Augmentin) and Chlorhexidine on E. Faecalis as an Intracanal Irrigant: An In-vitro Study.

Aim: The present study evaluated the antimicrobial efficacy of chlorhexidine gluconate (CHX), Nisin, and Amoxicillin/Clavulanic Acid (Augmentin) as an intracanal irrigant against Enterococcus faecalis (EF). Materials and Methods: Minimum Inhibitory Concentration (MIC) for EF against Nisin and Augmentin was determined by microbroth dilution technique. Time kill cycle (TKC) analysis was done for 0 MIC, ½ MIC, 1 MIC, and 2 MIC at 0 hour, 15 minutes, 30 minutes, and 45 minutes. At the end of each time period, dilutions were pipetted and swabs of agar plates were done. Incubation of agar plates was done at 37C for 24 hours. Colonies formed were counted. Results: The time kill curve analysis of EF for CHX, Nisin, and Augmentin at different concentrations and time periods showed a gradual decline in mean bacterial count between 0 and 45 minutes for CHX; this decline increases with increase in concentrations and time. Whereas in group Nisin, not much decline in bacterial count is noted for ½ MIC concentrations but a signification reduction of P < 0.001 after exposure to Nisin at 1 MIC ant 2 MIC concentrations. Group Augmentin showed not much reduction in bacterial count with increase in concentration and time. Conclusion: From this study, Nisin is found to be a promising agent in eliminating EF in comparison to other irrigants tested. However, the systemic effect of this irrigant, its biocompatibility, allergic potential, and bacterial resistance needs further investigation.

Evaluation of Different Techniques of Working Length Determination in Comparison with CBCT.

AIM: To estimate the working length of teeth using conventional tactile technique, radiovisiography technique, Apex locator, and confirmation of working length by cone beam computed tomography technique. MATERIALS AND METHODS: Forty patients with the age group between 20 and 50 years with irreversible pulpitis were included in this study. After taking a preoperative radiograph, the procedure was started. The cavity wall buildup was done using composite in the cases needed and then rubber dam application was done. The working length of mesiobuccal and mesiolingual canal was taken using cone beam computed tomography and this was considered as the standard value. Then using tactile method, length of the canal was measured using radiovisiographic software followed by apexlocator. RESULT: The Apex locator has showed best result as compared to tactile and radiovisiography. CONCLUSION: Apex locator values were closest to cone beam computed tomography working length measurement values and electronic apexlocator can be used efficiently as an alternative method for working length determination. The quality of various techniques according to ranks of working length determination was found to be Cone beam computed tomography (CBCT) > Apexloc > Radiovisiography (RVG) > Tactile. Thus, Apex locator can be used as an alternative to cone beam computed tomography for working length determination.

Knowledge user survey and Delphi process to inform development of a new risk of bias tool to assess systematic reviews with network meta-analysis (RoB NMA tool).

BACKGROUND: Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted. OBJECTIVES: Conduct (a) a Delphi process to determine expert opinion on an item's inclusion and (b) a knowledge user survey to widen its impact. DESIGN: Cross-sectional survey and Delphi process. METHODS: Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users' views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks. RESULTS: 22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assess both bias in individual NMA results and authors' conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines. CONCLUSIONS: This Delphi process and knowledge user survey informs the development of the RoB NMA tool.

Comparative evaluation of the efficacy of light amplification by the stimulated emission of radiation, desensitizing agents, and their combined effect on dentinal hypersensitivity in cuspids and bicuspids - In Vivo Study.

Context: Dentinal Hypersensitivity is the most common dental problem, in order to find a suitable treatment plan this study was conducted incorporating LASER and desensitizing agents on the patients complaining of dentinal hypersensitivity in cuspids and bicuspids. Most of the desensitizing agents provided incomplete relief hence the combination of LASER and Desensitizing agents proved to be successful. Aim: The aim of this study is to evaluate and compare the efficacy of individual desensitizing agents and c (LASER) and also to know their potential in reducing dentinal hypersensitivity when both desensitizing agents and LASER are combined together and applied on cuspids and bicuspids. Setting and Design: Sixty patients with sensitivity only in cuspids and bicuspids and not having caries, restoration, or undergoing any desensitizing therapy were selected. Patients were divided into 5 groups with 12 patients in each group. Materials and Methods: Air blast stimulus was given for 10 s from 1 cm distance on the affected group. Verbal analog score was recorded. Treatment was carried on according to the groups mentioned: Group I - nanohydroxyapatite was applied for 15 min; Group II - biosilicate was applied for 15 min; Group III - LASER application was done twice for 60 s in noncontact mode; Group IV - Nanohydroxyapatite plus LASER application; and Group V - biosilicate plus LASER application. Desensitizing agent was applied with the applicator tip and was left for 15 min. It was then rinsed and again the stimulus was given, and the score was recorded. The same treatment procedure was repeated on 1st, 7th, and 14th day and the score was recorded and analyzed using ANOVA. Results: The maximum reduction in sensitivity score was observed in patients where nanohydroxyapatite and LASER application was done. Conclusion: All the investigated treatments have promising desensitizing potential, but maximum was found in Group IV > Group V > Group III > Group I > Group II.

DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha).

Withania somnifera, commonly known as Ashwagandha, is a medicinal plant used for thousands of years for various remedies. Extracts of Ashwagandha contain more than 200 metabolites, with withanone (win) being one of the major ones responsible for many of its medicinal properties. Recently, several cases of liver toxicity resulting from commercially available Ashwagandha products have been reported. The first report of Ashwagandha-related liver damage was from Japan, which was quickly resolved after drug-withdrawal. Later, similar cases of liver toxicity due to Ashwagandha consumption were reported from the USA and Iceland. Towards understanding the liver toxicity of Ashwagandha extracts, we studied win, a representative withanolide having toxicophores or structural alerts that are commonly associated with adverse drug reactions. We found that win can form non-labile adducts with the nucleosides dG, dA, and dC. Using various biochemical assays, we showed that win forms adducts in DNA and interfere with its biological property. Win also forms adducts with amines and this process is reversible. Based on the data presented here we concluded that win is detoxified by GSH but under limiting GSH levels it can cause DNA damage. The work presented here provides a potential mechanism for the reported Ashwagandha-mediated liver damage.

Evaluation of N-400 Evoked Response Potential in schizophrenia: An endophenotype or a disease marker?

N400 evoked response potentials (ERP) reliably map key semantic deficits in schizophrenia. Assessing them as endophenotypes might help in better understanding of schizophrenia risk and their use as biomarkers. We aimed to study N400 as an endophenotype marker by comparing schizophrenia (SCZ), unaffected first-degree relatives (FDR) and healthy controls (HC) and, by assessing its ability to discriminate these groups. Drug naïve or free SCZ probands (n=30), their unaffected FDRs (n=30) and HC (n=30), underwent a 40-channel ERP recording while performing a custom-made, Hindi- sentence context paradigm task, containing congruent and incongruent conditions. Fifteen centro-parietal (CP) leads, further classified into three regions-midline (CPM), right (CPR) and left (CPL) were selected as electrodes-of-interest for assessing N400. During the incongruent condition, compared to both FDRs and HC, SCZ showed significantly longer N400 latency, at CPM, CPR and CPL, and significantly lesser (more negative) amplitude, at CPM; no significant difference was noted between FDR and HC groups. On discriminant functional analysis, significant N400 predictors could accurately classify 73.3% SCZ from HC and 75% of SCZ from FDR. We conclude that N400 deficits, elicited by the incongruent condition of the sentence task, could be potential biomarkers to define disease state in schizophrenia; they may not be endophenotype markers.

Long-term Vihangam Yoga meditation and scores on tests of attention.

Although the literature indicates that meditation has beneficial effects on several aspects of human functioning, few studies have specifically investigated the effects of meditation on various domains of attention. This study was conducted to examine the differences in various domains of attention between long-term concentrative meditators versus matched controls. 15 practitioners of Vihangam Yoga (> 10 yr. experience) were enrolled in the study. Controls matched on age, sex, and years of education were recruited. Both groups were administered the Stroop, Trail-Making, and Digit Symbol Substitution tests as well as the Digit Forward and Digit Backward tests. The group of Vihangam Yogis had significantly better mean performance on all tests of attention. Long-term Vihangam Yoga meditation improves attention span, processing speed, attention alternation ability, and performance in interference tests.

Prevalence of Obsessive-Compulsive Spectrum Disorders in Obsessive-Compulsive Disorder.

INTRODUCTION: There is growing awareness of the heterogeneity of obsessive-compulsive disorder (OCD) and of the multiple systems involved in its pathogenesis. Identification of obsessive-compulsive spectrum disorders (OCSDs) may have important implications in the management and prognosis of OCD, but there is a paucity of research in the domain of identification of OCSD in probands with OCD. There are few studies that have examined OCSD in the first-degree relatives (FDR) of OCD patients, some of these were not controlled, and these studies have no final agreements over outcomes, and therefore, this area needs to be further explored. OBJECTIVES: The objective of this study was to assess the prevalence of OCSDs in OCD probands; and its relationship to sociodemographic and clinical variables, comparing each aspect by a control group of schizophrenia probands. MATERIALS AND METHODS: Sixty patients each of OCD and schizophrenia, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders IV Text Revision,[1] above 18 years of age and giving informed consent, were interviewed using the Structured Clinical Interview for OCSD, Yale-Brown Obsessive-Compulsive Rating Scale, Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety. RESULTS: In OCD group, 22 OCSDs were found in 11 subjects whereas in schizophrenia group, 2 OCSDs (self-injury) were found in two probands. When the two groups were compared in terms of individual OCSDs, there was no significant difference between them. However, when the comparison was made taking into account all OCSDs taken together, it was significantly higher (P = 0.016) in the OCD group compared to the schizophrenia group. CONCLUSION: OCSDs were significantly more in OCD probands as compared to schizophrenia probands. This suggests a familial aggregation of these disorders.

Development and characteristics of a human cell assay for screening agents for melanoma prevention.

This paper describes the development and initial evaluation of a human cell assay to identify potentially efficacious agents for preventing melanoma. Four human cell lines were used: normal melanocytes, a radial growth-phase-like melanoma cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and 83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR; E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. None of the agents inhibited human leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like melanoma cells, the only cells that strongly expressed human leukocyte antigen-DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells relative to melanocytes, and ultraviolet B exposure dramatically reduced this expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed in all melanoma cell lines relative to melanocytes. In this study, all candidate preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth-phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B-treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin to E-cadherin levels and specific endpoint responses for both the radial growth-phase-like melanoma and vertical growth-phase-like melanoma cells were used to rank the agents. Agents were evaluated at clinically relevant concentrations. The rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis-retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and nordihydroguaiaretic acid were inactive. The results of these initial studies suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are the most responsive to chemopreventive agents, and may be the cell line of choice for screening melanoma prevention agents.

Differential expression of Eph receptors and ephrins in the cochlear ganglion and eighth cranial nerve of the chick embryo.

The cochleovestibular ganglion of the chick differentiates at early embryonic stages as VIIIth nerve axons enter the brainstem. The tonotopic organization of the auditory portion of the VIIIth nerve can be discerned at the time axons initially reach their brainstem targets. The mechanisms underlying this early organization are not known. Eph receptor tyrosine kinases and their ligands, the ephrins, have a demonstrated role in guiding axons to topographically appropriate locations in other areas of the nervous system. In order to begin to test whether Eph proteins have a similar role in the auditory system, we investigated the tonotopic expression of several Eph receptors and ephrins in the VIIIth nerve during embryonic ages corresponding to the initial innervation of the auditory brainstem. Expression patterns of EphA4, EphB2, EphB5, ephrin-A2, and ephrin-B1 were evaluated immunohistochemically at embryonic days 4 through 10. Protein expression was observed in the cochlear ganglion and VIIIth nerve axons at these ages. EphB5, ephrin-A2, and ephrin-B1 were expressed throughout the nerve. EphA4 and EphB2 had complementary expression patterns within the nerve, with EphA4 expression higher in the dorsolateral part of the nerve and EphB2 expression higher in the ventromedial part of the nerve. These regions may correspond to auditory and vestibular components, respectively. Moreover, EphA4 expression was higher toward the low-frequency region of both the centrally and peripherally projecting branches of cochlear ganglion cells. Regional variation of Eph protein expression may influence the target selection and topography of developing VIIIth nerve projections.

The fly ash influenced the heavy metal status of the soil and the seeds of sunflower. A case study.

In this study, four cultivars of sunflower (Helianthus annuus) were grown in the sandy loam soil, supplemented with graded (v/v) quantity (0, 20, 40, 60, 80, 100%) of the fly ash, released by the combustion of the coal from the thermal power plant. The presence of fly ash in the soil increased its porosity, water holding capacity, pH, E.C., C.E.C., the content of sulphate, carbonate, bicarbonate, chloride, phosphorus, potassium, calcium and various trace elements. However, in the seeds, except Fe, Pb, Mn and Zn, and other heavy metals remained untraced up to 40% of the fly ash, above that their quantity slightly increased but the values are very much under the permissible limits.

Neuropsychology of prefrontal cortex.

The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different functional operations within the PFC. The specification of the component 'executive' processes and their localization to particular regions of PFC have been implicated in a wide variety of psychiatric disorders.

EphB2 regulates axonal growth at the midline in the developing auditory brainstem.

Eph receptors play important roles in axon guidance at the midline. In the auditory system, growth of axons across the midline is an important determinant of auditory function. The avian cochlear nucleus, n. magnocellularis (NM), makes bilateral projections to its target, n. laminaris (NL). We examined the time course of NM axon growth toward the midline, the expression of Eph proteins at the midline during this growth, and the effects of Eph receptor misexpression on axonal growth across the midline. We found that NM axons reach the midline at E4. At this age, EphB receptors are expressed at the ventral floor plate. Expression extends dorsally to the ventricular zone beginning at E5. NM axons thus grow across the midline at a time when EphB receptor expression levels are low. Overexpression of EphB2 at E2 resulted in misrouted axons that deflected away from transfected midline cells. This effect was observed when midline cells were transfected but not when NM cells alone were transfected, suggesting that EphB2 acts non-cell autonomously and through reverse signaling. These data suggest an inhibitory role for midline Eph receptors, in which low levels permit axon growth and subsequently high levels prohibit growth after axons have crossed the midline.

Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels.

The human epidermal cell (HEC) assay, which uses carcinogen exposed normal skin keratinocytes to screen for cancer prevention efficacy, was used to screen possible preventive agents. The endpoints measured were inhibition of carcinogen-induced growth and induction of involucrin, an early marker of differentiation. Sixteen of twenty agents (apigenin, apomine, budesonide, N-(2-carboxyphenyl)retinamide, ellagic acid, ibuprofen, indomethacin, melatonin, (-)-2-oxo-4-thiazolidine carboxylic acid, polyphenon E, resveratrol, beta-sitosterol, sulfasalazine, vitamin E acetate, and zileuton) were positive in at least one of the two assay endpoints. Four agents (4-methoxyphenol, naringenin, palmitoylcarnitine chloride, and silymarin) were negative in the assay. Nine of the sixteen agents were positive for both endpoints. Agents that showed the greatest response included: ellagic acid > budesonide, ibuprofen > apigenin, and quinicrine dihydrochloride. Fifty-eight of sixty-five agents that have been evaluated in the HEC assay have also been evaluated in one or more rodent bioassays for cancer prevention and several are in clinical trials for cancer prevention. The assay has an overall predictive accuracy of approximately 91.4% for efficacy in rodent cancer prevention irrespective of the species used, the tissue model, or the carcinogen used. Comparison of the efficacious concentrations in vitro to plasma levels in clinical trials show that concentrations that produced efficacy in the HEC assay were achieved in clinical studies for 31 of 33 agents for which plasma levels and/or C(max) levels were available. For two agents, 9-cis-retinoic acid (RA) and dehydroepiandrosterone (DHEA), the plasma levels greatly exceeded the highest concentration (HC) found to have efficacy in vitro. Thus, the HEC assay has an excellent predictive potential for animal efficacy and is responsive at clinically achievable concentrations.

The human epithelial cell cytotoxicity assay for determining tissue specific toxicity: method modifications.

The Human Epithelial Cell Cytotoxicity (HECC) Assay (Meth Cell Sci, 22: 17-24, 2000) has been modified to include three additional cell lines and to allow protocol adjustments for slow growing cell lines. This manuscript presents methods using human epithelial cells from ten different normal human tissues including: skin, mammary, prostate, renal, bronchial, lung, oral, ecto-cervix, colon, and liver. The HECC Assay can also be used to evaluate other types of drugs, personal care products, environmental chemicals, and potential toxicants. Human epithelial cells at an early passage are seeded into multi-well dishes. The cells are exposed to multiple concentrations of each test agent. A preliminary assay using an exposure of five days at 1 mM (if soluble) and four log dilutions is used to determine the highest concentration for the HECC Assay. In the HECC Assay, cultures are exposed for three to four days. Following the exposure period, endpoint measurements for inhibition of growth, mitochondrial function, and PCNA (proliferating cell nuclear antigen) expression or albumin synthesis (hepatocytes) are made. Data are analyzed to determine the concentration that inhibited an endpoint by 50 percent (TC(50)) for each agent in each target epithelial cell line or culture and the data are compared to determine the relative sensitivity of each epithelial cell line to the test agent.