Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

IntroductionPrevious studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.MethodsNon-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.ResultsμCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points.ConclusionsHigh-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted

Excitonic Emission of Monolayer Semiconductors Near-Field Coupled to High-Q Microresonators.

We present quantum yield measurements of single layer WSe2 (1L-WSe2) integrated with high-Q ( Q > 106) optical microdisk cavities, using an efficient (η > 90%) near-field coupling scheme based on a tapered optical fiber. Coupling of the excitonic emission is achieved by placing 1L-WSe2 in the evanescent cavity field. This preserves the microresonator high intrinsic quality factor ( Q > 106) below the bandgap of 1L-WSe2. The cavity quantum yield is QYc ≈ 10-3, consistent with operation in the broad emitter regime (i.e., the emission lifetime of 1L-WSe2 is significantly shorter than the bare cavity decay time). This scheme can serve as a precise measurement tool for the excitonic emission of layered materials into cavity modes, for both in plane and out of plane excitation

A composite electrodynamic mechanism to reconcile spatiotemporally resolved exciton transport in quantum dot superlattices

Quantum dot (QD) solids are promising optoelectronic materials; further advancing their device functionality depends on understanding their energy transport mechanisms. The commonly invoked near-field F\"orster resonance energy transfer (FRET) theory often underestimates the exciton hopping rate in QD solids, yet no consensus exists on the underlying cause. In response, we use time-resolved ultrafast stimulated emission depletion (TRUSTED) microscopy, an ultrafast transformation of stimulated emission depletion (STED) microscopy to spatiotemporally resolve exciton diffusion in tellurium-doped CdSe-core/CdS-shell QD superlattices. We measure the concomitant time-resolved exciton energy decay due to excitons sampling a heterogeneous energetic landscape within the superlattice. The heterogeneity is quantified by single-particle emission spectroscopy. This powerful multimodal set of observables provides sufficient constraints on a kinetic Monte Carlo simulation of exciton transport to elucidate a composite transport mechanism that includes both near-field FRET and previously-neglected far-field emission/reabsorption contributions. Uncovering this mechanism offers a much-needed unified framework in which to characterize transport in QD solids and additional principles for device design.Comment: 47 pages, including supplemen

TWIST1 promotes invasion through mesenchymal change in human glioblastoma

Background: Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT) is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro. Results: To further define TWIST1 functions in GBM we tested the impact of TWIST1 over-expression on invasion in vivo and its impact on gene expression. We found that TWIST1 significantly increased SNB19 and T98G cell line invasion in orthotopic xenotransplants and increased expression of genes in functional categories associated with adhesion, extracellular matrix proteins, cell motility and locomotion, cell migration and actin cytoskeleton organization. Consistent with this TWIST1 reduced cell aggregation, promoted actin cytoskeletal re-organization and enhanced migration and adhesion to fibronectin substrates. Individual genes upregulated by TWIST1 known to promote EMT and/or GBM invasion included SNAI2, MMP2, HGF, FAP and FN1. Distinct from carcinoma EMT, TWIST1 did not generate an E- to N-cadherin "switch" in GBM cell lines. The clinical relevance of putative TWIST target genes SNAI2 and fibroblast activation protein alpha (FAP) identified in vitro was confirmed by their highly correlated expression with TWIST1 in 39 human tumors. The potential therapeutic importance of inhibiting TWIST1 was also shown through a decrease in cell invasion in vitro and growth of GBM stem cells. Conclusions: Together these studies demonstrated that TWIST1 enhances GBM invasion in concert with mesenchymal change not involving the canonical cadherin switch of carcinoma EMT. Given the recent recognition that mesenchymal change in GBMs is associated with increased malignancy, these findings support the potential therapeutic importance of strategies to subvert TWIST1-mediated mesenchymal change

The requirements and challenges in preventing of road traffic injury in Iran. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Road traffic injuries (RTIs) are a major public health problem, especially in low- and middle-income countries. Among middle-income countries, Iran has one of the highest mortality rates from RTIs. Action is critical to combat this major public health problem. Stakeholders involved in RTI control are of key importance and their perceptions of barriers and facilitators are a vital source of knowledge. The aim of this study was to explore barriers to the prevention of RTIs and provide appropriate suggestions for prevention, based on the perceptions of stakeholders, victims and road-users as regards RTIs.</p> <p>Methods</p> <p>Thirty-eight semi-structured interviews were conducted with informants in the field of RTI prevention including: police officers; public health professionals; experts from the road administrators; representatives from the General Governor, the car industry, firefighters; experts from Emergency Medical Service and the Red Crescent; and some motorcyclists and car drivers as well as victims of RTIs. A qualitative approach using grounded theory method was employed to analyze the material gathered.</p> <p>Results</p> <p>The core variable was identified as "The lack of a system approach to road-user safety". The following barriers in relation to RTI prevention were identified as: human factors; transportation system; and organizational coordination. Suggestions for improvement included education (for the general public and targeted group training), more effective legislation, more rigorous law enforcement, improved engineering in road infrastructure, and an integrated organization to supervise and coordinate preventive activities.</p> <p>Conclusion</p> <p>The major barriers identified in this study were human factors and efforts to change human behaviour were suggested by means of public education campaigns and stricter law enforcement. However, the lack of a system approach to RTI prevention was also an important concern. There is an urgent need for both an integrated system to coordinate RTI activities and prevention and a major change in stakeholders' attitudes towards RTI prevention. The focus of all activities should take place on road users' safety.</p

Exciton-photon interaction in a quantum dot embedded in a photonic microcavity

We present a detailed analysis of exciton-photon interaction in a microcavity made out of a photonic crystal slab. Here we have analyzed a disk-like quantum dot where an exciton is formed. Excitonic eigen-functions in addition to their eigen-energies are found through direct matrix diagonalization, while wave functions corresponding to unbound electron and hole are chosen as the basis set for this procedure. In order to evaluate these wave functions precisely, we have used Luttinger Hamiltonian in the case of hole while ignoring bands adjacent to conduction band for electron states. After analyzing Excitonic states, a photonic crystal based microcavity with a relatively high quality factor mode has been proposed and its lattice constant has been adjusted to obtain the prescribed resonant frequency. We use finite-difference time-domain method in order to simulate our cavity with sufficient precision. Finally, we formulate the coupling constants for exciton-photon interaction both where intra-band and inter-band transitions occur. By evaluating a sample coupling constant, it has been shown that the system can be in strong coupling regime and Rabi oscillations can occur for Excitonic state population.Comment: Journal of Physics B: Atomic and Molecular Physics (to appear

Barriers and facilitators to provide effective pre-hospital trauma care for road traffic injury victims in Iran: a grounded theory approach

BACKGROUND: Road traffic injuries are a major global public health problem. Improvements in pre-hospital trauma care can help minimize mortality and morbidity from road traffic injuries (RTIs) worldwide, particularly in low- and middle-income countries (LMICs) with a high rate of RTIs such as Iran. The current study aimed to explore pre-hospital trauma care process for RTI victims in Iran and to identify potential areas for improvements based on the experience and perception of pre-hospital trauma care professionals. METHODS: A qualitative study design using a grounded theory approach was selected. The data, collected via in-depth interviews with 15 pre-hospital trauma care professionals, were analyzed using the constant comparative method. RESULTS: Seven categories emerged to describe the factors that hinder or facilitate an effective pre-hospital trauma care process: (1) administration and organization, (2) staff qualifications and competences, (3) availability and distribution of resources, (4) communication and transportation, (5) involved organizations, (6) laypeople and (7) infrastructure. The core category that emerged from the other categories was defined as "interaction and common understanding". Moreover, a conceptual model was developed based on the categories. CONCLUSIONS: Improving the interaction within the current pre-hospital trauma care system and building a common understanding of the role of the Emergency Medical Services (EMS) emerged as key issues in the development of an effective pre-hospital trauma care process

Exploring corrections to the optomechanical Hamiltonian

We compare two approaches for deriving corrections to the “linear model” of cavity optomechanics, in order to describe effects that are beyond first order in the radiation pressure coupling. In the regime where the mechanical frequency is much lower than the cavity one, we compare: (I) a widely used phenomenological Hamiltonian conserving the photon number; (II) a two-mode truncation of C. K. Law’s microscopic model, which we take as the “true” system Hamiltonian. While these approaches agree at first order, the latter model does not conserve the photon number, resulting in challenging computations. We find that approach (I) allows for several analytical predictions, and significantly outperforms the linear model in our numerical examples. Yet, we also find that the phenomenological Hamiltonian cannot fully capture all high-order corrections arising from the C. K. Law model

Parenteral provision of micronutrients to pediatric patients: an international expert consensus paper

© 2020 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1002/jpen.1990INTRODUCTION:Micronutrients (vitamins and trace elements) are essential to all nutrition. For children and neonates who are dependent upon nutrition support therapies for growth and development, the prescribed regimen must supply all essential components. This paper aims to facilitate interpretation of existing clinical guidelines into practical approaches for the provision of micronutrients in pediatric parenteral nutrition. METHODS:An international, interdisciplinary expert panel was convened to review recent evidence-based guidelines and published literature to develop consensus- based recommendation on practical micronutrient provision in pediatric parenteral nutrition. RESULTS:The guidelines and evidence have been interpreted as answers to 10 commonly asked questions around the practical principles for provision and monitoring of micronutrients in pediatric patients CONCLUSION: Micronutrients are an essential part of all parenteral nutrition and should be included in the pediatric nutrition therapy care plan.Published versio