The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs

Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy‐ and fluorine‐substituted analogs of SDB‐006 (N‐benzyl‐1‐pentyl‐1H‐indole‐3‐carboxamide) were synthesized and could not be differentiated by gas chromatography–mass spectrometry (GC–MS), but were distinguishable by liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). In a fluorescence‐based plate reader membrane potential assay, SDB‐006 acted as a potent agonist at human cannabinoid receptors (CB₁ EC₅₀ = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC₅₀ = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC₅₀ = 146 nM). Using biotelemetry in rats, SDB‐006 and RCS‐4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB‐CHMINACA (>2°C, 3 mg/kg).     

Differential diagnosis and treatment of enchondromas and atypical cartilaginous tumours of the pelvis: analysis of 21 patients

Introduction

Studies focusing on enchondroma and atypical cartilaginous tumour (ACT) of the pelvis are lacking. The purpose of this study was to verify possible clinical and radiological findings with regard to distinguishing enchondromas from ACT of the pelvis. In addition, this study analysed functional and oncological outcomes in patients with enchondromas or ACT of the pelvis treated with curettage or resection.

Materials and methods

We retrospectively reviewed the medical records of 21 patients with confirmed enchondroma or ACT of the pelvis treated by curettage or resection from 1985 to 2018. The minimum follow-up was 18 months. The relationship between clinical and radiological factors and tumour type or local recurrence was assessed using Fisher exact test and Mann–Whitney U test.

Results

Endosteal scalloping (p = 0.039), tumour size (0.005) and age (0.006) were shown to statistically favour ACT over enchondroma; by contrast, enchondroma and ACT patients had no difference in pain frequency (p = 0.5528). All patients with enchondroma had no local recurrence; in contrast, local recurrence occurred in one patient with ACT, initially treated with resection. The patient with local recurrence had a disease progression with a higher histological grade than the original tumour. Patients treated with curettage had better functional outcomes than patients treated with resection (p = 0.001).

Discussion

Endosteal scalloping, tumour size and age could be helpful in the differential diagnosis between enchondroma and ACT of the pelvis. In addition, our study showed that ACT of the pelvis can be safely treated with curettage due to a low risk of local recurrence and better functional results compared with resection. In case of recurrence, we suggest to treat these patients with resection for the risk of disease progression.

     

Which is Better for Patients with Breast Cancer: Totally Implanted Vascular Access Devices (TIVAD) or Peripherally Inserted Central Catheter (PICC)?

World Journal of Surgery -     

Connectivity as an alternative to boundary integral equations: Construction of bases

In previous papers Herrera developed a theory of connectivity that is applicable to the problem of connecting solutions defined in different regions, which occurs when solving partial differential equations and many problems of mechanics. In this paper we explain how complete connectivity conditions can be used to replace boundary integral equations in many situations. We show that completeness is satisfied not only in steady-state problems such as potential, reduced wave equation and static and quasi-static elasticity, but also in time-dependent problems such as heat and wave equations and dynamical elasticity. A method to obtain bases of connectivity conditions, which are independent of the regions considered, is also presented.     

Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States

Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 × 10⁶ copies ml^–1. The median HCV RNA concentration was 3.5 × 10⁶ copies ml^–1 and the cut-off for the upper 25th percentile (high titre) was 5 × 10⁶ copies ml^–1. Male patients had a median HCV RNA concentration of 3.9 × 10⁶ copies ml^–1, which was significantly higher than the median HCV RNA level for females (2.75 × 10⁶ copies ml^–1; P  < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly ( P  < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African–American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders ( P  < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 ( P  < 0.001 for all comparisons).     

Short-term Wear Evaluation of Thin Acetabular Liners on 36-mm Femoral Heads

Background

Dislocation remains the leading cause of revision THA. One approach to decreasing prosthetic dislocation risk has been the use of larger femoral head component sizes. The upper limit of head size in metal-on-polyethylene hip arthroplasty has historically been limited because of concerns about increased wear on thin polyethylene components. It is not known to what degree this concern should apply to more wear-resistant polyethylene components.

Questions/purposes

We therefore determined (1) in vitro wear rates of polyethylene liners of varying thicknesses, (2) whether there were differences in the microscopic wear characteristics as a function of polyethylene thickness, and (3) whether thin polyethylene components resulted in early catastrophic failures.

Methods

We used a hip wear simulator to compare the wear performance of 12 highly crosslinked polyethylene acetabular inserts. The internal diameter of all components was 36 mm, and there were three samples tested of each thickness (1.9, 3.9, 5.9, or 7.9 mm). Testing was conducted for 2.4 million cycles. Gravimetric mass loss was converted to volumetric loss, which was subsequently converted to theoretical linear penetration rates.

Results

Wear rates decreased with increasing polyethylene thickness. Mean ± SD wear rates for the 1.9-, 3.9-, 5.9-, and 7.9-mm groups were 5.0 ± 0.5, 3.2 ± 0.3, 2.5 ± 1.1, and 2.2 ± 1.3 mm³/million cycles, respectively (p < 0.016). Calculated penetration rates were 0.015, 0.012, 0.011, and 0.010 mm/million cycles, respectively (p < 0.016). There were no catastrophic failures in any group.

Conclusions

Thinner polyethylene components demonstrated higher wear rates, although even the highest wear rate observed in the thinnest polyethylene specimen was lower than that commonly reported for noncrosslinked polyethylene components. While encouraging, these findings should be validated in vivo before clinical recommendations can be made.