A novel closed-loop electromechanical stimulator to enhance osseointegration with immediate loading of dental implant restorations

Abstract: The degree of osseomechanical integration of dental implants is acutely sensitive to their mechanical environment. Bone, both as a tissue and structure, adapts its mass and architecture in response to loading conditions. Therefore, application of predefined controlled loads may be considered as a treatment option to promote early maturation of bone/implant interface prior to or in conjunction with crown/prosthesis attachment. Although many studies have established that the magnitude, rate of the applied strain, and frequency have significant effects on the osteogenic response, the actual specific relationships between strain parameters and frequency have not yet been fully defined. The purpose of this study was to develop a stimulator to apply defined mechanical stimuli to individual dental implants in vivo immediately after implantation, exploring the hypothesis that immediate controlled loading could enhance implant integration. An electromechanical device was developed, based on load values obtained using a two-dimensional finite element analysis of the bone/implant interface generating 1000 to 4000 me and operated at 30 and 3 Hz respectively. The device was then tested in a cadaveric pig mandible, and periosteal bone surface strains were recorded for potential future comparison with a three-dimensional finite element model to determine loading regimens to optimize interface strains and iterate the device for clinical use

General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial

BACKGROUND: Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs. METHODS: A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs. RESULTS: Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p < 0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4-13] to 5 [0-11] vs 8 [3-13] to 7 [3-12], respectively; p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0-3] to 1 [0-2] vs 1 [0-2] to 1 [0-3], p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of - £229.0 (95% CI - 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI - 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017). CONCLUSION: The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03241498

Profiling cytotoxic microRNAs in pediatric and adult glioblastoma cells by high-content screening, identification, and validation of miR-1300

MicroRNAs play an important role in the regulation of mRNA translation and have therapeutic potential in cancer and other diseases. To profile the landscape of microRNAs with significant cytotoxicity in the context of glioblastoma (GBM), we performed a high-throughput screen in adult and pediatric GBM cells using a synthetic oligonucleotide library representing all known human microRNAs. Bioinformatics analysis was used to refine this list and the top seven microRNAs were validated in a larger panel of GBM cells using state-of-the-art in vitro assays. The cytotoxic effect of our most relevant candidate was assessed in a preclinical model. Our screen identified ~100 significantly cytotoxic microRNAs with 70% concordance between cell lines. MicroRNA-1300 (miR-1300) was the most potent and robust candidate. We observed a striking binucleated phenotype in miR-1300 transfected cells due to cytokinesis failure followed by apoptosis. This was also observed in two stem-like patient-derived cultures. We identified the physiological role of miR-1300 as a regulator of endomitosis in megakaryocyte differentiation where blockade of cytokinesis is an essential step. In GBM cells, where miR-1300 is normally not expressed, the oncogene Epithelial Cell Transforming 2 (ECT2) was validated as a direct key target. ECT2 siRNA phenocopied the effects of miR-1300, and ECT2 overexpression led to rescue of miR-1300 induced binucleation. We showed that ectopic expression of miR-1300 led to decreased tumor growth in an orthotopic GBM model. Our screen provides a resource for the neuro-oncology community and identified miR-1300 as a novel regulator of endomitosis with translatable potential for therapeutic application

Microbial diversity and community composition of caecal microbiota in commercial and indigenous Indian chickens determined using 16s rDNA amplicon sequencing

Different alpha diversity indices for each sample of university farm data estimated using QIIME for primer pair P2 data. OTUs were clustered at > 97% similarity. (XLSX 12 kb

Marketing as a means to transformative social conflict resolution: lessons from transitioning war economies and the Colombian coffee marketing system

Social conflicts are ubiquitous to the human condition and occur throughout markets, marketing processes, and marketing systems.When unchecked or unmitigated, social conflict can have devastating consequences for consumers, marketers, and societies, especially when conflict escalates to war. In this article, the authors offer a systemic analysis of the Colombian war economy, with its conflicted shadow and coping markets, to show how a growing network of fair-trade coffee actors has played a key role in transitioning the country’s war economy into a peace economy. They particularly draw attention to the sources of conflict in this market and highlight four transition mechanisms — i.e., empowerment, communication, community building and regulation — through which marketers can contribute to peacemaking and thus produce mutually beneficial outcomes for consumers and society. The article concludes with a discussion of implications for marketing theory, practice, and public policy

Dynamic stability of a nonlinear multiple-nanobeam system

We use the incremental harmonic balance (IHB) method to analyse the dynamic stability problem of a nonlinear multiple-nanobeam system (MNBS) within the framework of Eringen’s nonlocal elasticity theory. The nonlinear dynamic system under consideration includes MNBS embedded in a viscoelastic medium as clamped chain system, where every nanobeam in the system is subjected to time-dependent axial loads. By assuming the von Karman type of geometric nonlinearity, a system of m nonlinear partial differential equations of motion is derived based on the Euler–Bernoulli beam theory and D’ Alembert’s principle. All nanobeams in MNBS are considered with simply supported boundary conditions. Semi-analytical solutions for time response functions of the nonlinear MNBS are obtained by using the single-mode Galerkin discretization and IHB method, which are then validated by using the numerical integration method. Moreover, Floquet theory is employed to determine the stability of obtained periodic solutions for different configurations of the nonlinear MNBS. Using the IHB method, we obtain an incremental relationship with the frequency and amplitude of time-varying axial load, which defines stability boundaries. Numerical examples show the effects of different physical and material parameters such as the nonlocal parameter, stiffness of viscoelastic medium and number of nanobeams on Floquet multipliers, instability regions and nonlinear amplitude–frequency response curves of MNBS. The presented results can be useful as a first step in the study and design of complex micro/nanoelectromechanical systems

The stigma turbine:A theoretical framework for conceptualizing and contextualizing marketplace stigma

Stigmas, or discredited personal attributes, emanate from social perceptions of physical characteristics, aspects of character, and “tribal” associations (e.g., race; Goffman 1963). Extant research emphasizes the perspective of the stigma target, with some scholars exploring how social institutions shape stigma. Yet the ways stakeholders within the socio-commercial sphere create, perpetuate, or resist stigma remain overlooked. We introduce and define marketplace stigma as the labeling, stereotyping, and devaluation by and of commercial stakeholders (consumers, companies and their employees, stockholders, institutions) and their offerings (products, services, experiences). We offer the Stigma Turbine (ST) as a unifying conceptual framework that locates marketplace stigma within the broader sociocultural context, and illuminates its relationship to forces that exacerbate or blunt stigma. In unpacking the ST, we reveal the critical role market stakeholders can play in (de)stigmatization, explore implications for marketing practice and public policy, and offer a research agenda to further our understanding of marketplace stigma and stakeholder welfare