Comparative Evaluation of Taper Preparation Variability of Three Different Niti Files- An In Vitro CBCT Study

The ultimate goal of an endodontic treatment is to achieve the fluid tight seal particularly at the apex as well as in coronal aspect of the root canal system. This is mainly influenced by the cleaning and shaping of root canal system and it has been recognized as an important phase of endodontic therapy. Cleaning and shaping as well as obturation are best accomplished when the file taper claimed by the manufacturer is accurate and the taper of the canal following instrumentation corresponds to the taper of the file. Despite the most advanced technology in manufacturing of dental instruments, variations in endodontic file tapers still exist. Therefore the purpose of this study is to compare the taper variation in root canal preparations among the three different NiTi files using CBCT. Methods: 24 upper 1st molar tooth with mesiobuccal root curvature 15-30 degree were selected and divided into three groups. Mesiobuccal roots (MB1) of three groups were prepared by three different NiTi file system respectively up to size25 taper.06 and CBCT were done separately for each group. The diameter was measured at 1, 3, and orifice in mm and canal taper preparation was calculated using CBCT. Result: Of the 3 file systems, fell within the ±.05 taper variability. All preparations demonstrated variability when compared to the nominal taper .06. Conclusion: Taper preparations of the investigated size 25 taper .06 were favorable but different from the nominal taper

Cost-effectiveness of interventions to control cardiovascular diseases and type 2 diabetes mellitus in South Asia: protocol for a systematic review.

INTRODUCTION: While a number of strategies are being implemented to control cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM), the cost-effectiveness of these in the South Asian context has not been systematically evaluated. We aim to systematically review the economic (cost-effectiveness) evidence available on the individual-, group- and population-level interventions for control of CVD and T2DM in South Asia. METHODS AND ANALYSIS: This review will consider all relevant economic evaluations, either conducted alongside randomised controlled trials or based on decision modelling estimates. These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries (India, Bangladesh, Pakistan, Sri Lanka, Nepal, Maldives, Bhutan and Afghanistan). We will identify relevant papers by systematically searching all major databases and registries. Selected articles will be screened by two independent researchers. Methodological quality of the studies will be assessed using a modified Drummond and a Phillips checklist. Cochrane guidelines will be followed for bias assessment in the effectiveness studies. RESULTS: Results will be presented in line with the PRISMA (Preferred Reporting Items for Systematic review and Meta-analysis) checklist, and overall quality of evidence will be presented as per the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION: The study has received ethics approval from the All India Institute of Medical Sciences, New Delhi, India. The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia. STUDY REGISTRATION NUMBER: PROSPERO CRD42013006479

Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization

The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds - PGLb1 and PGLb2 - have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman-Hodgkin-Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance

Cost-effectiveness of interventions to control cardiovascular diseases and diabetes mellitus in South Asia: a systematic review

OBJECTIVES: More than 80% of cardiovascular diseases (CVD) and diabetes mellitus (DM) burden now lies in low and middle-income countries. Hence, there is an urgent need to identify and implement the most cost-effective interventions, particularly in the resource-constraint South Asian settings. Thus, we aimed to systematically review the cost-effectiveness of individual-level, group-level and population-level interventions to control CVD and DM in South Asia. METHODS: We searched 14 electronic databases up to August 2016. The search strategy consisted of terms related to 'economic evaluation', 'CVD', 'DM' and 'South Asia'. Per protocol two reviewers assessed the eligibility and methodological quality of studies using standard checklists, and extracted incremental cost-effectiveness ratios of interventions. RESULTS: Of the 2949 identified studies, 42 met full inclusion criteria. Critical appraisal of studies revealed 15 excellent, 18 good and 9 poor quality studies. Most studies were from India (n=37), followed by Bangladesh (n=3), Pakistan (n=2) and Bhutan (n=1). The economic evaluations were based on observational studies (n=9), randomised trials (n=12) and decision models (n=21). Together, these studies evaluated 301 policy or clinical interventions or combination of both. We found a large number of interventions were cost-effective aimed at primordial prevention (tobacco taxation, salt reduction legislation, food labelling and food advertising regulation), and primary and secondary prevention (multidrug therapy for CVD in high-risk group, lifestyle modification and metformin treatment for diabetes prevention, and screening for diabetes complications every 2-5 years). Significant heterogeneity in analytical framework and outcome measures used in these studies restricted meta-analysis and direct ranking of the interventions by their degree of cost-effectiveness. CONCLUSIONS: The cost-effectiveness evidence for CVD and DM interventions in South Asia is growing, but most evidence is from India and limited to decision modelled outcomes. There is an urgent need for formal health technology assessment and policy evaluations in South Asia using local research data. PROSPERO REGISTRATION NUMBER: CRD42013006479

α/β-Peptides as Nanomolar Triggers of Lipid Raft-Mediated Endocytosis through GM1 Ganglioside Recognition

Cell delivery of therapeutic macromolecules and nanoparticles is a critical drug development challenge. Translocation through lipid raft-mediated endocytic mechanisms is being sought, as it can avoid rapid lysosomal degradation. Here, we present a set of short α/β-peptide tags with high affinity to the lipid raft-associated ganglioside GM1. These sequences induce effective internalization of the attached immunoglobulin cargo. The structural requirements of the GM1-peptide interaction are presented, and the importance of the membrane components are shown. The results contribute to the development of a receptor-based cell delivery platform

Rationally Designed Foldameric Adjuvants Enhance Antibiotic Efficacy via Promoting Membrane Hyperpolarization

The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds – PGLb1 and PGLb2 – have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman–Hodgkin–Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance