An Examination of the Effects of Atorvastatin and Parathyroid Hormone on Osteoblast Activity

HMG-CoA reductase inhibitors, also known as statins, are a ubiquitous class of medication used for lowering cholesterol. In-vitro and animal studies have suggested that statins can activate osteoblast differentiation and have anabolic effects on bones; however, observational and experimental studies in humans have shown conflicting results.1-5 The exact mechanism of statins on bone growth is unknown; however, there are several hypotheses. The “Lipid Hypothesis” (Figure 1) suggests that lipid oxidation leads to activation of PPARγ, and production of isoprostanes including isoPGF2α and isoPGEα. PPARγ is associated with inhibition of osteoblast differentiation, while isoprostanes markers are associated with the induction of osteoclast differentiation and inhibition of osteoblast differentiation. This led to the the hypothesis that statins can decrease lipid oxidation, which can inhibit the action of PPARγ and isoprostane-mediated bone loss.6 The “statins hypothesis” (Figure 2) suggests that the anabolic bone activity of statins is due to the induction of osteoblast differentiation, suppression of osteoblast apoptosis and inhibiting osteoclastogenesis. Statins inhibits HMG-CoA reductase, which decrease the productions of isoprenoids farnesyl pyrophosphate (FPP) and Geranylgeranyl pyrophosphate (GGPP). The decrease in FPP and GGPP leads to upregulation of bone morphogenetic protein-2 (BMP-2) downstream, stimulating bone formation by increasing mesenchymal condensation. Statins inhibit osteoblast apoptosis by upregulating TGFβ/Smad3 kinases signaling. It also decreases osteoclastogenesis by upregulating osteoprotegerin (OPG), a decoy receptor that binds to RANKL to inhibit osteoclast differentiation.

Towards joint reconstruction of noise and losses in quantum channels

The calibration of a quantum channel, i.e. the determination of the transmission losses affecting it, is definitely one of the principal objectives in both the quantum communication and quantum metrology frameworks. Another task of the utmost relevance is the identification, e.g. by extracting its photon number distribution, of the noise potentially present in the channel. Here we present a protocol, based on the response of a photon-number-resolving detector at different quantum efficiencies, able to accomplish both of these tasks at once, providing with a single measurement an estimate of the transmission losses as well as the photon statistics of the noise present in the exploited quantum channel. We show and discuss the experimental results obtained in the practical implementation of such protocol, with different kinds and levels of noise.Comment: 6 pages, 4 figure

Stability of U-500 regular insulin in prefilled syringes

Objective: To evaluate the stability of U-500 regular insulin in prefilled syringes stored under refrigeration for up to 28 days. Methods: U-500 regular insulin was drawn up in 1 mL insulin syringes in a clean, nonsterile environment to emulate conditions of a patient’s home. Samples were assayed using a stability-indicating reverse-phase high-performance liquid chromatography method immediately after preparation (day 0) and after 7, 14, 21, and 28 days under refrigeration. Before evaluation, all samples were diluted to a concentration of 40 units/mL in the starting mobile phase. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point. Results: At least 93.3% of the initial U-500 insulin concentration remained throughout the 28-day study period, with no statistically significant changes in the amount remaining. The percent of initial concentration remained above 97% for the first 21 days of the study. Conclusion: A prefilled syringe with U-500 regular insulin is stable for at least 28 days when stored under refrigeration. These data are similar to those reported for U-100 regular insulin, indicating that prefilling syringes with U-500 insulin is a safe and effective practice for patients who are unable to accurately draw up their own point-of-care doses

Self-directed learning through journal use in an elective pharmacy course

Introduction: The objective of this study was to implement and assess the use of electronic self-directed learning journals in a one-semester pharmacy elective course as a development tool to promote self-learning amongst students. Description of Course: In a toxicology doctor of pharmacy elective course, students completed self-directed assignments based on in-class material in an electronic journal. Students participated in group discussions based on the assignment. Journals were graded for completeness and pursuit of individual interests was encouraged. Evaluation: Students responded positively to journal assignments and their educational value. Faculty members also recognised a high level of learning by students based on their group discussions. Performance on course learning objectives and quality of in-class discussions also indicated that the use of journals in the elective course was successful. Future Plans: Based on these findings, journals will continue to be used in this course, will be further assessed, and may be expanded to additional courses in the pharmacy curriculum

Quantum state reconstruction using binary data from on/off photodetection

The knowledge of the density matrix of a quantum state plays a fundamental role in several fields ranging from quantum information processing to experiments on foundations of quantum mechanics and quantum optics. Recently, a method has been suggested and implemented in order to obtain the reconstruction of the diagonal elements of the density matrix exploiting the information achievable with realistic on/off detectors, e.g. silicon avalanche photo-diodes, only able to discriminate the presence or the absence of light. The purpose of this paper is to provide an overview of the theoretical and experimental developments of the on/off method, including its extension to the reconstruction of the whole density matrix.Comment: revised version, 11 pages, 6 figures, to appear as a review paper on Adv. Science Let

Direct experimental observation of nonclassicality in ensembles of single photon emitters

In this work we experimentally demonstrate for the first time a recently proposed criterion adressed to detect nonclassical behavior in the fluorescence emission of ensembles of single-photon emitters. In particular, we apply the method to study clusters of NV centres in diamond observed via single-photon-sensitive confocal microscopy. Theoretical considerations on the behavior of the parameter at any arbitrary order in presence of poissonian noise are presented and, finally, the opportunity of detecting manifold coincidences is discussed

Self consistent, absolute calibration technique for photon number resolving detectors

Well characterized photon number resolving detectors are a requirement for many applications ranging from quantum information and quantum metrology to the foundations of quantum mechanics. This prompts the necessity for reliable calibration techniques at the single photon level. In this paper we propose an innovative absolute calibration technique for photon number resolving detectors, using a pulsed heralded photon source based on parametric down conversion. The technique, being absolute, does not require reference standards and is independent upon the performances of the heralding detector. The method provides the results of quantum efficiency for the heralded detector as a function of detected photon numbers. Furthermore, we prove its validity by performing the calibration of a Transition Edge Sensor based detector, a real photon number resolving detector that has recently demonstrated its effectiveness in various quantum information protocols.Comment: 9 pages, 2 figure

Native NIR-emitting single colour centres in CVD diamond

Single-photon sources are a fundamental element for developing quantum technologies, and sources based on colour centres in diamonds are among the most promising candidates. The well-known NV centres are characterized by several limitations, thus few other defects have recently been considered. In the present work, we characterize in detail native efficient single colour centres emitting in the near infra-red in both standard IIa single-crystal and electronic-grade polycrystalline commercial CVD diamond samples. In the former case, a high-temperature annealing process in vacuum is necessary to induce the formation/activation of luminescent centres with good emission properties, while in the latter case the annealing process has marginal beneficial effects on the number and performances of native centres in commercially available samples. Although displaying significant variability in several photo physical properties (emission wavelength, emission rate instabilities, saturation behaviours), these centres generally display appealing photophysical properties for applications as single photon sources: short lifetimes, high emission rates and strongly polarized light. The native centres are tentatively attributed to impurities incorporated in the diamond crystal during the CVD growth of high-quality type IIa samples, and offer promising perspectives in diamond-based photonics.Comment: 27 pages, 10 figures. Submitted to "New Journal of Phsyics", NJP-100003.R

Nanodiamonds-induced effects on neuronal firing of mouse hippocampal microcircuits

Fluorescent nanodiamonds (FND) are carbon-based nanomaterials that can efficiently incorporate optically active photoluminescent centers such as the nitrogen-vacancy complex, thus making them promising candidates as optical biolabels and drug-delivery agents. FNDs exhibit bright fluorescence without photobleaching combined with high uptake rate and low cytotoxicity. Focusing on FNDs interference with neuronal function, here we examined their effect on cultured hippocampal neurons, monitoring the whole network development as well as the electrophysiological properties of single neurons. We observed that FNDs drastically decreased the frequency of inhibitory (from 1.81 Hz to 0.86 Hz) and excitatory (from 1.61 Hz to 0.68 Hz) miniature postsynaptic currents, and consistently reduced action potential (AP) firing frequency (by 36%), as measured by microelectrode arrays. On the contrary, bursts synchronization was preserved, as well as the amplitude of spontaneous inhibitory and excitatory events. Current-clamp recordings revealed that the ratio of neurons responding with AP trains of high-frequency (fast-spiking) versus neurons responding with trains of low-frequency (slow-spiking) was unaltered, suggesting that FNDs exerted a comparable action on neuronal subpopulations. At the single cell level, rapid onset of the somatic AP ("kink") was drastically reduced in FND-treated neurons, suggesting a reduced contribution of axonal and dendritic components while preserving neuronal excitability.Comment: 34 pages, 9 figure