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.

Spin-2 twisted duality in (A)dS

Starting from the dual Lagrangians recently obtained for (partially) massless spin-2 fields in the Stueckelberg formulation, we write the equations of motion for (partially) massless gravitons in (A)dS in the form of twisted-duality relations. In both cases, the latter admit a smooth flat limit. In the massless case, this limit reproduces the gravitational twisted-duality relations previously known for Minkowski spacetime. In the partially-massless case, our twisted-duality relations preserve the number of degrees of freedom in the flat limit, in the sense that they split into a decoupled pair of dualities for spin-1 and spin-2 fields. Our results apply to spacetimes of any dimension greater than three. In four dimensions, the twisted-duality relations for partially massless fields that appeared in the literature are recovered by gauging away the Stueckelberg field.Comment: 15 pages. Introductory remarks, clarifications and references adde

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

Experimental realization of Counterfactual Quantum Cryptography

In counterfactual QKD information is transfered, in a secure way, between Alice and Bob even when no particle carrying the information is in fact transmitted between them. In this letter we fully implement the scheme for counterfactual QKD proposed in [T. Noh, \PRL \textbf{103}, 230501 (2009)], demonstrating for the first time that information can be transmitted between two parties without the transmission of a carrier

Premessa

n/

Once-Weekly Exenatide as Adjunct Treatment of Type 1 Diabetes Mellitus in Patients Receiving Continuous Subcutaneous Insulin Infusion Therapy

Objective The use of once-weekly exenatide in type 2 diabetes mellitus is well supported, but little is known about its effectiveness in type 1 diabetes. The objective of this study was to determine the clinical efficacy of once-weekly exenatide on glycemic control in patients with type 1 diabetes when added to basal-bolus insulin therapy. Methods For this retrospective study, patients with type 1 diabetes, aged 18 years and older, receiving continuous subcutaneous insulin infusion, using a continuous glucose monitoring device or regularly measuring blood glucose levels and receiving 2 mg of exenatide once weekly for at least 3 months were included. Demographic information, glycated hemoglobin (A1C), body weight, body mass index, systolic and diastolic blood pressures, total daily insulin dose, basal and bolus insulin doses, 28-day continuous subcutaneous insulin infusion glucose average and incidence of hypoglycemia were collected at baseline and 3 months after beginning therapy with once-weekly exenatide. Results An electronic medical record search identified 11 patients with type 1 diabetes who met the inclusion criteria. Comparing baseline and 3 months after initiation of once-weekly exenatide revealed reductions of 0.6% in A1C (p=0.013), 3.7% in body weight (p=0.008), 1.7 kg/m2 in body mass index (p=0.003), 13% in total daily insulin dose (p=0.011) and 9.3 units in bolus insulin dose (p=0.015). Conclusions This study revealed that the addition of once-weekly exenatide to insulin therapy for type 1 diabetes patients leads to significant improvements in A1C, body weight, body mass index and insulin doses

A case-driven hypothesis for multi-stage crack growth mechanism in fourth-generation ceramic head fracture

Background Ceramic bearings are used in total hip arthroplasty due to their excellent wear behaviour and biocompatibility. The major concern related to their use is material brittleness, which significantly impacts on the risk of fracture of ceramic components. Fracture toughness improvement has contributed to the decrease in fracture rate, at least of the prosthetic head. However, the root cause behind these rare events is not fully understood. This study evaluated head fracture occurrence in a sizeable cohort of patients with fourth-generation ceramic-on-ceramic implants and described the circumstances reported by patients in the rare cases of head fracture. Methods The clinical survivorship of 29,495 hip prostheses, with fourth-generation ceramic bearings, was determined using data from a joint replacement registry. The average follow-up period was 5.2 years (range 0.1-15.6). Retrieval analysis was performed in one case for which the ceramic components were available. Results Clinical outcomes confirmed the extremely low fracture rate of fourth-generation ceramic heads: only two out of 29,495 heads fractured. The two fractures, both involving 36 mm heads, occurred without a concurrent or previous remarkable trauma. Considering the feature of the fractured head, a multi-stage crack growth mechanism has been hypothesized to occur following damage at the head-neck taper interface. Conclusions Surgeons must continue to pay attention to the assembly of the femoral head: achieving a proper head seating on a clean taper is a prerequisite to decrease the risk of occurrence of any damage process within head-neck junction, which may cause high stress concentration at the contact surface, promoting crack nucleation and propagation even in toughened ceramics

Creation and characterization of He-related color centers in diamond

Diamond is a promising material for the development of emerging applications in quantum optics, quantum information and quantum sensing. The fabrication and characterization of novel luminescent defects with suitable opto-physical properties is therefore of primary importance for further advances in these research fields. In this work we report on the investigation in the formation of photoluminescent (PL) defects upon MeV He implantation in diamond. Such color centers, previously reported only in electroluminescence and cathodoluminescence regime, exhibited two sharp emission lines at 536.5 nm and 560.5 nm, without significant phonon sidebands. A strong correlation between the PL intensities of the above-mentioned emission lines and the He implantation fluence was found in the 10^15-10^17 cm^{-2} fluence range. The PL emission features were not detected in control samples, i.e. samples that were either unirradiated or irradiated with different ion species (H, C). Moreover, the PL emission lines disappeared in samples that were He-implanted above the graphitization threshold. Therefore, the PL features are attributed to optically active defects in the diamond matrix associated with He impurities. The intensity of the 536.5 nm and 560.5 nm emission lines was investigated as a function of the annealing temperature of the diamond substrate. The emission was observed upon annealing at temperatures higher than 500{\deg}C, at the expenses of the concurrently decreasing neutral-vacancy-related GR1 emission intensity. Therefore, our findings indicate that the luminescence originates from the formation of a stable lattice defect. Finally, the emission was investigated under different laser excitations wavelengths (i.e. 532 nm and 405 nm) with the purpose of gaining a preliminary insight about the position of the related levels in the energy gap of diamond

The eagle jugular syndrome

The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia, and the carotid variant characterized by pain and sometimes by cerebral ischemia. We observed a further variant characterized by a styloid elongation coursing adjacent to the transverse process of C1, causing significant compression of the internal jugular vein