Effectiveness of thaumaturgic distraction in alleviation of anxiety in 4-6-year-old children during inferior alveolar nerve block administration: a randomized controlled trial.

Background: Dental anxiety is a matter of serious concern to pediatric dentists as it may impede the efficient delivery of dental care. If not adequately resolved, a persistent negative response pattern may emerge. Thaumaturgy, commonly known as magic trick, has become popular recently. It is a tool that distracts and relaxes the child by using magic trick while the dentist performs necessary treatment. Hence, the aim of this study was to evaluate the effectiveness of Thaumaturgic aid in alleviation of anxiety in 4-6 - year-old children during administration of local anesthesia using the inferior alveolar nerve block (IANB) technique. Methods: Thirty children aged between 4-6 years with dental anxiety requiring IANB were included in this study. Patients were divided equally into two groups: Group I, thaumaturgic aid group and Group II, conventional non-pharmacological group using randomization. Anxiety was measured before and after using the intervention with Raghavendra Madhuri Sujata-Pictorial scale (RMS-PS), Venham's anxiety rating scale, and pulse rate. All the data were tabulated and compared using statistical analysis. Results: Children in thaumaturgy group (Group- I) exhibited significantly lower anxiety during IANB in comparison with children in the conventional group (Group- II) and the difference was statistically significant. Conclusion: Magic tricks are effective in reducing anxiety among young children during IANB; Moreover, it expands the arsenal of behavior guidance techniques for treatment of children with anxiety and plays an important role in shaping the behavior of a child in pediatric dentistry.

Influence of Birth Characteristics and Feeding Practices on Eruption of Primary Teeth in Children: A Preliminary Cross-sectional Observational Study.

Background: The eruption process is under strong genetic control, external environmental factors also significantly contribute to this process. Therefore the present study was undertaken to identify the influence of birth characteristics and feeding practices on the eruption of the first primary tooth among healthy children in Pune, Maharashtra, India. Materials and methods: The study was undertaken among 200 children aged 3-24 months. Children with any underlying conditions, those not accompanied by their mother and with neonatal teeth/natal teeth were excluded. The birth weight, gestational age, and type of delivery were obtained from medical records of the child. Data on feeding practices and the age of eruption of the first primary tooth was recorded after a structured interview of the mother followed by oral examination of the child. Gestational age was categorized into >37 weeks and <37 weeks, birth weight was divided into three groups-<1500, 1500-2500, and >2500 gm and four groups according to feeding practice during the first 6 months of life (exclusively breastfed, exclusively bottle fed, combination of breastfeeding and bottle feeding, and spoon-feeding). Results: The mean age of eruption in the study population was 9.17 months. A9.05 months in males and 9.44 in females. A statistically significant correlation was noted with gestational age, birth weight, and feeding practices. Infants with a gestational age of >37 weeks, higher birth weight and those who were exclusively breastfed for the first 6 months had an earlier eruption of first primary teeth. Conclusion: External factors seem to influence the eruption of the primary tooth. More longitudinal studies with larger sample sizes and matching confounders are needed to clearly understand the factors affecting the primary tooth eruption. How to cite this article: Shetty SS, Mathur A, Gopalakrishnan D, et al. Influence of Birth Characteristics and Feeding Practices on Eruption of Primary Teeth in Children: A Preliminary Cross-sectional Observational Study. Int J Clin Pediatr Dent 2023;16(5):724-727.

Increased expression level of ANGPTL8 in white adipose tissue under acute and chronic cold treatment.

BACKGROUND: Angiopoietin-like proteins (ANGPTL), primarily 3, 4, and 8, play a major role in maintaining energy homeostasis by regulating triglyceride metabolism. This study evaluated the level of ANGPTL3, 4, and 8 in the liver, brown adipose tissue (BAT), and subcutaneous white adipose tissue (SAT) of mice maintained under acute and chronic cold conditions. METHODS: C57BL/6J mice were exposed to cold temperature (4 °C) for 10 days with food provided ad libitum. Animal tissues were harvested at Day 0 (Control group, n = 5) and Days 1, 3, 5, and 10 (cold treatment groups, n = 10 per group). The expression levels of various genes were measured in the liver, SAT, and BAT. ANGPTL3, 4, and 8 expressions were measured in the liver. ANGPTL4, 8, and genes involved in browning and lipid metabolism [uncoupling protein 1 (UCP1), lipoprotein lipase (LPL), and adipose triglyceride lipase (ATGL)] were measured in SAT and BAT. Western blotting (WB) analysis and immunohistochemistry (IHC) were performed to confirm ANGPTL8 expression in these tissues. RESULTS: The expressions of ANGPTL3 and 8 mRNA were significantly reduced in mouse liver tissues after cold treatment (P < 0.05); however, the expression of ANGPTL4 was not significantly altered. In BAT, ANGPTL8 expression was unchanged after cold treatment, whereas ANGPTL4 expression was significantly reduced (P < 0.05). ANGPTL4 levels were also significantly reduced in SAT, whereas ANGPTL8 gene expression exhibited over a 5-fold increase. Similarly, UCP1 gene expression was also significantly increased in SAT. The mRNA levels of LPL and ATGL showed an initial increase followed by a gradual decrease with an increase in the days of cold exposure. ANGPTL8 protein overexpression was further confirmed by WB and IHC. CONCLUSIONS: This study shows that exposure to acute and chronic cold treatment results in the differential expression of ANGPTL proteins in the liver and adipose tissues (SAT and BAT). The results show a significant reduction in ANGPTL4 in BAT, which is linked to improved thermogenesis in response to acute cold exposure. ANGPTL8 was activated under acute and chronic cold conditions in SAT, suggesting that it is involved in regulating lipolysis and enhancing SAT browning.

Comparative Evaluation of Instrumentation Time, Obturation Time, and Radiographic Quality of Obturation Using Two Rotary Systems and Manual Technique for Primary Molar Pulpectomies - In vivo Study.

BACKGROUND: Ideal pulpectomy for primary dentition demands fast, simple procedures, with short treatment times and minimal appointments. Recently, exclusive pediatric rotary files are available for use in primary teeth. There is a paucity of literature on the clinical efficacy of pediatric rotary files. Hence, this study was planned to evaluate and compare pediatric rotary files and K-files. AIM: The aim of this study was to evaluate and compare instrumentation time, obturation time, and radiographic quality of obturation using rotary systems (Kedo-S; Pro-AF Baby GOLD files) and manual (K-files) technique in primary molar pulpectomies. MATERIALS AND METHODS: Forty-five primary mandibular molars from 42 children aged 5-9 were selected. Single-visit pulpectomy was performed after dividing selected teeth into three equal groups: (i) K-files, (ii) Kedo-S files, (iii) Pro-AF Baby GOLD files. Instrumentation and obturation times were recorded during the procedure. Immediate postoperative radiographs were taken and evaluated later for obturation quality by two independent evaluators blinded to the instrumentation technique. The results were then statistically analyzed. RESULTS: Kedo-S (Group II) files required the least instrumentation time followed by Pro-AF (Group III) and K-files (Group I). The superior quality of obturation in lesser time was achieved using Pro-AF files (Group III) followed by Kedo-S (Group II) and K-files (Group I). CONCLUSION: Pediatric rotary files are efficient alternatives to hand instrumentation and can be considered as the standard of care in pulpectomies of primary teeth.

Efficacy of casein phosphopeptide varnish reducing dental hypersensitivity: a randomized clinical trial

Introduction: Dentin hypersensitivity (DH) is the most common concern faced by most dentists in their day-to-day clinical practice. It is characterized by short-term, acute pain of variable intensity, which occurs in response to thermal, tactile, osmotic or chemical stimuli that cannot be attributed to any other type of defect or dental decay. Casein phosphopeptide varnish is a newer material used to treat dentinal hypersensitivity as it reduces demineralization and promotes remineralization. The aim of this study is to evaluate the efficacy of casein phosphopeptide based varnish (MI Varnish®) vs sodium fluoride-based varnish (Fluoritop SR® varnish) in treating dentinal hypersensitivity. Materials and methods: 40 subjects with a chief complaint of DH were divided into two equal groups, Group A (MI varnish®) and Group B (Fluoritop SR® varnish). Scaling and root planing was done and sensitivity was assessed using Visual analog scale (VAS) at baseline. On the 14th day, sensitivity was reassessed using VAS. The data obtained were subjected to statistical analysis using students‘t’ test.Results: On intragroup comparison, VAS scale showed a statistically significant difference for both the groups. On intergroup comparison, no statistical difference was found between both groups (p = 0.139). Conclusions: From the above results, it can be concluded that MI varnish® and Fluoritop SR® varnish are equally efficacious in reducing dentinal hypersensitivity (AU)

Qualitative and quantitative analysis of bacterial aerosols in dental clinical settings: Risk exposure towards dentist, auxiliary staff, and patients.

INTRODUCTION: Cross-infection or contamination are the major threats related to any medical profession. Microorganisms present in the dental clinic can cause cross-infection to the dentist, auxiliary staff and even towards the patients. AIMS: The study was conducted to assess the level of atmospheric microbial contamination and composition of aerosols before, during and after dental treatment procedures in four clinical settings. METHODS AND MATERIALS: The present study was conducted over a two-week period in a private dental college setting. An equal number of culture medium plates (blood agar) were placed 30 min prior to the initiation of work sessions in the selected area and 1 h after the working session began and after 2 h of cessation of the working period. After the collection of samples, the culture medium plates were incubated aerobically at 37°C in an incubator for 48 h. The number of colonies was expressed as colonies per media plate. After counting the colonies bacterial cell morphology was determined by a microscopic examination using a Reichert-Jung Series 150 light microscope. STATISTICAL ANALYSIS: Statistical analysis such as ANOVA test for mean values and post hock was done using statistical package for social sciences (SPSS). RESULTS: It shows that colony count increased after the working session and which reduced by itself once the working session was concluded which was significant (P < 0.001). The highest increase in the mean colony count was found in the department of periodontology during the treatment sessions. In the blood agar plates, the S. epidermidis was found maximum 62%, micrococcus was 22%, diphtheroid was 10%, fungi 4% and the least S. aureus 2%. CONCLUSION: This study demonstrates that aerosols increase during and after work sessions and, therefore, increases the chance for infectious agent transmission in clinical settings.

Perception of undergraduates enrolled in health science courses from Asmara Eritrea towards Hepatitis B.

INTRODUCTION: Hepatitis B (HB) is one of the highly infectious and the most common cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It is transmitted through blood and body fluids. Most healthcare related personnel are at very high susceptibility towards this infection from the infected patients. AIMS: To evaluate the knowledge and practice towards the hepatitis disease and its cross-infection among dental and medical undergraduate students for the first time ever from Eritrea. SETTINGS AND DESIGN: It is a cross-sectional survey conducted in the only institute offering undergraduate courses in the field of health sciences. MATERIALS AND METHODS: A total of 115 medical and 50 dental undergraduate students from a health science institute situated in Asmara Eritrea filled the form and submitted for evaluation. The questionnaire consisted of the demographic variables such as college of study, year of course, age, gender, apart from questions regarding the knowledge, attitude, and practice towards hepatitis and its transfusion. All the data was transferred to excel and applied statistical test using SPSS software. STATISTICAL ANALYSIS USED: Chi-square test was to test the association between the knowledge and practice variable within the stream of study. RESULTS: The overall knowledge of the undergraduate students was found to be very high when assessed through this survey although practice scores were not satisfactory. When asked, "Do you think you can be affected by Hepatitis?", in regular practice 33 individual gave incorrect answers. CONCLUSION: There is no doubt that the overall knowledge of the undergraduate students is found to be very high but practice scores and awareness towards chances of cross-infection is poor which requires further sessions of education and practice-based courses to be planned for the students.

ANGPTL4: A Predictive Marker for Diabetic Nephropathy.

BACKGROUND: ANGPTL4 is a glycoprotein that is involved in regulating triglyceride metabolism by inhibiting LPL activity under fasting conditions. Additionally, ANGPTL4 has been suggested as a link between hypertriglyceridemia and albuminuria in the nephrotic syndrome. In this study, we examined levels of circulating ANGPTL4 in people with diabetic nephropathy (DN) and its association with established DN-associated proteins such as IGFBP1 and IGFBP4. METHODS: We quantified circulating ANGPTL4, IGFBP1, IGFBP3, and IGFBP4 in fasting plasma samples of 122 Kuwaiti participants using a multiplexing assay. The study involved 36 controls, as well as 86 people with type 2 diabetes (T2D) including 37 people with normal kidney function and 49 people with DN. RESULTS: ANGPTL4 level was increased in people with DN (241.56 ± 14.1 µg/ml) compared to the control group (178.43 ± 24.09 µg/ml). The increase in ANGPTL4 correlated with clinical parameters of DN including albumin-to-creatinine ratio (r = 0.271, P = 0.002), serum creatinine (r = 0.381, P = 0.0001), and eGFR (r = -0.349, P < 0.0001). Furthermore, ANGPTL4 correlated positively with both IGFBP1 (r = 0.202, P = 0.026) and IGFBP4 (r = 0.364, P < 0.0001). Multiple regression analysis showed increased IGFBP1 and TG as predictors of higher ANGPTL4 in people with DN. In people with T2D, only IGFBP1 acted as a positive predictor of a rise in ANGPTL4. CONCLUSION: In this study, our data showed a significant increase in circulating ANGPTL4, IGFBP1, and IGFBP4 in patients with DN. The elevation in ANGPTL4 correlated significantly with clinical markers of DN such as ACR, serum creatinine, and eGFR, as well as IGFBP1 and IGFBP4. Altogether, this suggests a potential role for ANGPTL4 in DN perhaps through its role in inhibiting LPL activity and promotes ANGPTL4 as a biochemical marker for the detection of a diabetic kidney disease in patients with T2D.

Concomitant Interstitial Lung Disease with Psoriasis.

Background: We encounter interstitial lung disease (ILD) patients with psoriasis. The aim of this case series was to examine clinical and radiographic characteristics of patients with concomitant psoriasis and ILD. Methods: This is a retrospective review of our institutional experience of ILD concomitant with psoriasis, from the database in the Advanced Lung/Interstitial Lung Disease Program at the Mount Sinai Hospital. Out of 447 ILD patients, we identified 21 (4.7%) with antecedent or concomitant diagnosis of psoriasis. Clinical, radiographic, pathological, and outcome data were abstracted from our medical records. Results: Median age was 66 years (range, 46-86) and 14 (66.7%) were male. Thirteen (61.9%) had not previously or concomitantly been exposed to immunosuppressive therapy directed against psoriasis. Two (9.5%) ultimately died. Clinical diagnosis of ILD included idiopathic pulmonary fibrosis, 11 (52.4%); nonspecific interstitial pneumonia (NSIP), 2 (9.5%); cryptogenic organizing pneumonia, 2 (9.5%); chronic hypersensitivity pneumonitis, 2 (9.5%); and the others, while radiographic diagnosis included usual interstitial pneumonia pattern, 9 (42.9%); NSIP pattern, 6 (28.6%); organizing pneumonia pattern, 4 (19.0%); hypersensitivity pneumonitis pattern, 2 (9.5%); and the others. Conclusions: We report 21 ILD cases with antecedent or concomitant diagnosis of psoriasis. Further prospective studies are required to determine the association between ILD and psoriasis.

Antimicrobial efficacy of 980 nm diode laser on Enterococcus feacalis in conjunction with various irrigation regimes in infected root canals: An in vitro study.

AIM: The aim of the present study was to evaluate and compare the antimicrobial efficiency of different irrigating solutions against Enterococcus faecalis with or without the use of 980 nm diode laser in infected root canals. MATERIALS AND METHODS: A total of 100 freshly extracted human single-rooted teeth were divided into three experimental groups (n = 30) and one control group (n = 10). Experimental group was subdivided into two subgroups A and B (n = 15), whereas control group was subdivided into positive and negative controls (n = 5). After access cavity preparation, the root canals were prepared using ProTaper rotary instruments. A volume of 5 ml of 5.25% sodium hypochlorite and 17% Ethylenediaminetetraacetic acid, 1.2 ml of 2% chlorhexidine gluconate, and 2 ml of neem solution was used for irrigation in Group I, II, and III, respectively. E. faecalis (ATCC 29212) was inoculated into each canal of experimental groups and incubated for 2 weeks under aerobic conditions at 37°C. In all the subgroups B, laser irradiation was performed, whereas, in subgroup A, no laser irradiation was done. In negative control, E. faecalis was not inoculated in samples, but in positive control, E. faecalis inoculation and incubation procedure was followed. With circumferential filing using #40 reamer, dentinal chips were collected using sterile paper points, vortexed in sterile saline, was then applied to UTI Hicrome agar culture plates and incubated at 37°C for 48 h. The cfu/ml for each plate was calculated using a bacterial colony counter. The data obtained were subjected to statistical analysis using SPSS software version 20.0. RESULTS: The study showed that the least number of bacterial cfu/ml was observed in Group IB. The order of bacterial colony count (cfu/ml) was observed as Group IB

A 1-year appraisal of pit and fissure sealants following disinfection with and without chlorhexidine solution: An in vivo randomized trial.

OBJECTIVE: The objective of this study is to evaluate the effect of chlorhexidine on the outcome of pit and fissure sealant (PFS) in permanent molars. METHODS: A double-blind randomized controlled trial using split-mouth design was conducted for a period of 1 year. The clinical trial registry was done in the Indian Council of Medical Research, and the clinical trial number obtained was CTRI/2016/08/007222. The age group of participants involved in the trial was 7-14 years. Maxillary or mandibular permanent molar which satisfies the criteria for application of PFS was included in the trial. Based on the eligibility criteria and considering the unknown observer/instrumentation errors, the sample size is 33 for each group. Simple randomization of treatment allocation was carried out using computer-generated random number for treatment assignment of the right molar tooth. The left molar received the alternative treatment. The outcomes of PFS were evaluated by a lone proficient assessor by means of the mouth mirrors and probes following the US public health service criteria. RESULTS: A 6-month evaluation for the PFS with and without chlorhexidine showed 77.27% and 89.39% retention, respectively. PFS without chlorhexidine suffered a greater loss of surface texture and marginal discoloration in comparison to PFS with chlorhexidine at 3-, 6-, and 12-month intervals, but it was statistically insignificant. CONCLUSION: The present study showed improvement in outcome of PFS when an additional step of chlorhexidine is added although the results were statistically nonsignificant.

Calcifying epithelial odontogenic cyst.

OBJECTIVE: The Calcifying Odontogenic Cyst was first described as a distinct clinicopathologic entity by Gorlin and his colleagues in 1962. Gold (1963) chose a similar, but not identical term for the lesion, namely 'keratinizing and calcifying odontogenic cyst'. The calcifying cystic odontogenic tumor (CCOT) is a new designation of calcifying odontogenic cyst (COC) recommended by the 2005 classification of the World Health Organization (WHO). The calcifying odontogenic cyst is not a common lesion; the dentinogenic ghost cell tumor is even less common and should be considered rare. The lesions have in common the peculiar abnormal keratinization of odontogenic and metrical (hair) epithelial cells that is termed 'ghost cell' or 'shadow cell' keratinization. A rare, well-circumscribed, solid or cystic lesion derived from odontogenic epithelium that resembles follicular ameloblastoma but contains 'ghost cells' and spherical calcifications. The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinicopathologic and behavioural features. Because of this diversity, there has been confusion and disagreement on the terminology and classification of these lesions. Here we present a classic case of Calcifying Odontogenic Cyst (COC) or Calcifying Cystic Odontogenic Tumor in a 37 years old male patient. which is provisionally diagnosed by means of clinical & radiographical findings and later on confirmed by histological examination.

Interstitial Lung Disease in Women of Child-Bearing Age.

Interstitial lung disease (ILD) is an inflammatory and fibrotic infiltrative process of the lung that is often associated with collagen vascular disease in women. Untreated, it results in collagen deposition in the lung interstitium that can lead to a slow suffocating death. Pregnancy planning is often not discussed with women who have ILD due to concerns about potentially aggravating the disease process, or due to lack of knowledge about the safety of medications used to treat ILD. With improved understanding of the pathophysiology of both autoimmune disease and ILD, it has become clear that safe, planned pregnancies are possible in most women with ILD. In this article, our aim is to review diagnosis, treatment, and disease course of ILD in women who are planning a pregnancy or are pregnant. Better understanding of the disease process and knowledge of safe treatments will likely lead to improved pregnancy planning in women with ILD.

A Comparative Evaluation of Sealing Ability of New MTA Based Sealers with Conventional Resin Based Sealer: An In-vitro Study.

INTRODUCTION: Root canal obturation is the most important step in the root canal treatment that aims to obtain a complete hermetic seal and to prevent the re-growth of microorganisms in the root canal system. To accomplish this, many endodontic obturation materials and sealers are being used. AIM: To evaluate and compare the apical microleakage of a resin based sealer; Adseal with Mineral Trioxide Aggregate (MTA) based sealers; Pro root MTA and MTA Fillapex. MATERIALS AND METHODS: Total 75 extracted human single rooted teeth were taken and decoronated at cemento-enamel junction. The access cavities and biomechanical preparation were performed using endodontic rotary system. The teeth were randomly divided into five groups with n=15; Group I - Gutta-percha and Adseal sealer; Group II - Gutta-percha and MTA Fillapex; Group III- Gutta-percha and Pro root MTA; Group IV- Gutta-percha without sealer (positive control group); Group V- Root canal remained empty (negative control). All the specimens were stored at 37(0)C with 100% humidity for one week. All root surfaces except the apical 2mm were covered with two layers of nail varnish and then immersed in an aqueous solution of 2% methylene blue dye for 72 hours. Roots were longitudinally split using a diamond disk. Linear apical dye penetration was measured under Stereomicroscope at 40X magnification. STATISTICAL ANALYSIS: The data obtained was subjected to statistical analysis using paried t-test, ANOVA for interclass comparison, with SPSS statistical software (version 20.0). RESULTS: The intraobserver reliability was found to be insignificant in each of the triplicate study of all the three study samples. MTA Fillapex group showed maxmium apical microleakage followed by Pro root MTA and Adseal sealer. CONCLUSION: The results concluded that Adseal sealer showed minimal dye penetration followed by Pro root MTA and MTA Fillapex. Thus, concluding that Adseal sealer is better in apical sealing than Pro root MTA and MTA Fillapex.

Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.

Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations. Our findings reveal that relative to control participants, patients with idiopathic pulmonary fibrosis demonstrate excessive monocyte migration and underexpression of PLXNC1 in the lungs and circulation, a finding that is recapitulated in the setting of scleroderma-related interstitial lung disease. Relative to wild type, PLXNC1-/- mouse macrophages are excessively migratory, and PLXNC1-/- mice show exacerbated collagen accumulation in response to either inhaled bleomycin or inducible lung targeted TGF-ß1 overexpression. These findings are ameliorated by replacement of PLXNC1 on bone marrow-derived cells or by genetic deletion of Syt7. These data demonstrate the previously unrecognized observation that PLXNC1 deficiency permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.-Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D., Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali-Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog, E. L. Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.

A comparative evaluation of microleakage and compressive strength of Ketac Molar, Giomer, Zirconomer, and Ceram-x: An in vitro study.

BACKGROUND: Microleakage around dental restorative material and strength to withstand the masticatory forces is major problem in dentistry. Instead, many new materials available, very few actually bond to tooth surface and bear masticatory load. AIM: The aim of this study is to evaluate and compare the microleakage and compressive strength of Ketac Molar, Giomer, Zirconomer, and Ceram-x. MATERIALS AND METHODS: For the evaluation of microleakage, Class V cavities were prepared on sixty human premolar teeth and divided into four study groups (n = 15): Group I (Ketac Molar), Group II (Giomer), Group III (Zirconomer), and Group IV (Ceram-x). The samples were thermocycled and subjected to dye penetration test. The sections were made and evaluated under stereomicroscope at × 40 magnification. For the compressive strength evaluation, sixty cylindrical specimens were fabricated measuring 5 mm × 6 mm and grouped into four study groups (n = 15): Group I (Ketac Molar), Group II (Giomer), Group III (Zirconomer), and Group IV (Ceram-x). All were then subjected to the Universal Testing Machine at crosshead speed of 1 mm/s. STATISTICAL ANALYSIS USED: The data were analyzed using paired t-test and ANOVA. RESULTS: The microleakage was found insignificant (P > 0.05) for all study groups, with Giomer showing maximum followed by Zirconomer, Ceram-x, and Ketac Molar. The compressive strength was found to be highly significant (P < 0.01) with the maximum score for Giomer followed by Ceram-x, Zirconomer, and Ketac Molar. CONCLUSION: The sealing ability was maximum in Ketac Molar, Zirconomer, Ceram-x, and Giomer whereas the compressive strength was maximum for Giomer followed by Ceram-x, Zirconomer, and Ketac Molar.

Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer.

Metabolic diseases like obesity, atherosclerosis and diabetes are frequently associated with increased risk of aggressive cancers. Although metabolic dysfunctions in normal cells are manifested due to defective signaling networks that control cellular homeostasis, malignant cells utilize these signaling networks for their increased survival, growth and metastasis. Despite decades of research, a common mechanistic link between these chronic pathologies is still not well delineated. Evidences show that the unfolded protein response (UPR) and the endoplasmic reticulum stress (ERS) pathways are often dysregulated in both metabolic diseases and cancer. The UPR also triggers coordinated signaling with both PI3K/AKT/mTOR and Autophagy pathways in order to promote stress-adaptive mechanisms. Whereas, uncontrolled UPR and the resultant ERS escalates cells towards metabolic dysfunctions and ultimately cell death. In this review, we will discuss findings that implicate a crucial role for the multifunctional ERS-induced protein, TRIB3. The 'pseudokinase' function of TRIB3 facilitates the inactivation of multiple transcription factors and signaling proteins. The MEK1 binding domain of TRIB3 enables it to deactivate multiple MAP-kinases. In addition, the COP1 motif of TRIB3 assists ubiquitination and proteasomal degradation of numerous TRIB3 associated proteins. The most well studied action of TRIB3 has been on the PI3K/AKT/mTOR pathway, where TRIB3-mediated inhibition of AKT phosphorylation decreases insulin signaling and cell survival. Conversely, cancer cells can either upregulate the AKT survival pathway by suppressing TRIB3 expression or alter TRIB3 localization to degrade differentiation inducing nuclear transcription factors such as C/EBPα and PPARγ. The gain-of-function Q84R polymorphism in TRIB3 is associated with increased risk of diabetes and atherosclerosis. TRIB3 acts as a crucial 'stress adjusting switch' that links homeostasis, metabolic disease and cancer; and is being actively investigated as a disease biomarker and therapeutic target.

Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7/Dox breast cancer cells.

Development of multidrug resistance (MDR) remains a significant problem in cancer chemotherapy and underscores the importance of using chemosensitizers. Well known MDR mechanisms include: (i) upregulation of drug-efflux; (ii) increased signaling via AKT; and (iii) decreased apoptosis. Therefore, chemosensitizers should target multiple resistance mechanisms. We investigated the efficacy of nelfinavir (NFV), a clinically approved anti-HIV drug, in increasing doxorubicin (DOX) toxicity in a MDR breast cancer cell line, MCF-7/Dox. As compared to parental MCF-7 cells, the MCF-7/Dox were 15-20 fold more resistant to DOX-induced cytotoxicity at 48 h post-exposure (DOX IC50 = 1.8 µM vs. 32.4 µM). Coexposures to NFV could significantly (p < 0.05) decrease DOX-IC50 in MCF-7/Dox cells. Multiple exposures to physiologic concentrations of NFV (2.25 µM or 6.75 µM) decreased DOX-IC50 by 21-fold and 50-fold, respectively. Interestingly, although single exposure to NFV transiently induced P-glycoprotein (P-gp) levels, multiple treatments with NFV inhibited both P-gp expression and efflux function, which increased intracellular DOX concentrations. Single exposure to NFV augmented the markers of cell-survival (AKT) and autophagy (LC3-II), whereas multiple exposures enabled suppression of both total AKT (t-AKT) and insulin like growth factor-1 (IGF-1)-induced phosphorylated AKT (p-AKT) levels. Multiple exposures to NFV also resulted in increased unfolded protein response (UPR) transducers, e.g. Grp78, p-PERK, p-eIF2α, and ATF-4; and endoplasmic reticulum (ER) stress induced death sensors, e.g. CHOP & TRIB-3. Multiple exposures to NFV also abrogated the mitogenic effects of IGF-1. In mice carrying MCF-7/Dox tumor xenografts, intraperitoneal (i.p.) injection of NFV (20 mg/kg/day) and DOX (2 mg/kg/twice/wk) decreased tumor growth more significantly (p < 0.01) than either agent alone. Immunohistochemical (IHC) analysis revealed decreased p-AKT and Ki-67 levels. Thus, NFV overcomes MDR in breast cancer cells and should be tested as an adjunct to chemotherapy.