Ingenane diterpenes from Euphorbia petiolata

From the whole plants of Euphorbia petiolata, four new ingenane-type diterpenoids, 3,20-O-diacetylingenol 5-O-(2' E,4' Z)-tetradecadienoate (1), 5,20-O-diacetylingenol 3- O-(2' E,4' Z)-tetradecadienoate (2), ingenol 3-O-(2' E,4' Z)-tetradecadienoate (3), and 5,20-O-isopropylidenylingenol 3-O-(2' E,4' Z)-tetradecadienoate (4) were isolated. Their structures were elucidated by spectroscopic methods and chemical transformations.     

Problems, obstacles and complications of femoral lengthening with the use of the Italian modification of the Ilizarov device]

The results of femoral lengthening using the Italian modification of the Ilizarov are presented. Mean age of the patients was 14 years (ranging from 7 to 29). The most frequent etiology of limb shortening was femoral hypoplasia (7 patients) and sequelae of septic arthritis of the hip and/or the knee (6 patients). Indications for surgical treatment were limb shortening from 3 to 12 cm (mean 6.5 cm), along with axial deviation ranging from 10 degrees to 40 degrees in 6 patients. Mean follow-up time was 15 months (ranging from 6 to 35 months). The Ilizarov apparatus was based on two distal rings, stabilized by "K" wires, and proximally by a ring connected with an Italian femoral arch, stabilized by a Schanz screw. Planned lengthening (ranging from 3.5 cm to 12 cm) was achieved in all treated patients. The healing index ranged from 0.8 to 2.1 month/cm (mean 1.4). Problems, obstacles and complications were analyzed according to the Paley classification. In all 16 patients without primary knee stabilization, limited knee flexion ranging from 5 degrees to 90 degrees (mean 40 degrees) was noted during the distraction phase, which didn't improve significantly during the consolidation phase. Knee flexion improved to a mean 90 degrees after a 6 month follow-up. Bone regenerate defects (cysts, narrowing) were noted in 4 patients. Secondary knee stabilization was performed in 2 cases. In the first case because of knee pain and a severe limitation of knee motion. In the second, during a revision procedure because of distal femur angulation. Premature consolidation was noted in one patient and was treated by osteotomy. In one case axial deviation during the consolidation phase required osteotomy. In another case a fracture of the femur was treated by a plaster cast. In one case 1.5 years after the lengthening procedure subluxation of the hip was noted. Permanent knee flexion limitation to less than 90 degrees was noted in 6 patients. Femoral lengthening with the use of the Italian modification of the Ilizarov device give a high incidence of knee range of motion limitation, which can be decreased by preserving more than 30 degrees knee flexion during the distraction phase.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

Osteomyelitis due to multiple carbapenemase-producing Gram-negative bacteria: The first case report of a GES-13-producing Pseudomonas aeruginosa isolate in Canada

A case of osteomyelitis in an infant following a burn injury sustained in Pakistan caused by a GES-13-producing Pseudomonas aeruginosa (the first reported in Canada) and an OXA-48 producing Klebsiella pneumoniae is described. The present case serves to highlight the importance of international travel as a risk factor for infection with carbapenemase-producing bacteria and the challenges in the laboratory detection of these organisms.     

Utility of common bile duct measurement in ED point of care ultrasound: A prospective study

Background

Measurement of the common bile duct (CBD) is considered a fundamental component of biliary point-of-care ultrasound (POCUS), but can be technically challenging.

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage

ObjectivesSystemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear.Materials and methodsWe performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis.ResultsOf 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 – 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02).ConclusionSIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.     

Three-dimensional directional nerve guide conduits fabricated by dopamine-functionalized conductive carbon nanofibre-based nanocomposite ink printing

A potential issue in current nerve guides is that they do not transmit electrical nerve impulses between the distal and proximal end of an injured nerve, i.e. a synapse. Conductivity is a desirable property of an ideal nerve guide that is being considered for peripheral nerve regeneration. Most conductive polymers reported for the fabrication of tissue engineering scaffolds, such as polypyrrole and polyaniline, are non-biodegradable and possess weak mechanical properties, and thus cannot be fabricated into 3D structures. Herein, we have designed a new nanocomposite material composed of dopamine, carbon nanofibers (CNF) and polycaprolactone (PCL) for the fabrication of nerve conduits, which facilitates the growth and migration of neurons toward the targeted end of an injured nerve. This support and navigation of the scaffold leads to better sensory and motor function. The results showed that the mechanical properties of the printed PCL increased by 30% in comparison with the pure PCL film, which is comparable with human nerves. The in vitro cell study of human glioma cells showed that the printed lines provided support for neural cell attachment, migration and differentiation toward the targeted end. In contrast, in the absence of printed lines in the scaffold, the cells attach and grow in random directions, forming a flower shape (cell cluster) on the surface of PCL. Thus, the proposed scaffold is a promising candidate for nerve guide application based on its signal transmission and navigating neurons in a correct pathway towards the targeted end.

Directional growth induced by dopamine-functionalized CNF-based nanocomposite ink printing.     

Validation of the Social Appearance Anxiety Scale in Patients With Systemic Sclerosis: A Scleroderma Patient‐Centered Intervention Network Cohort Study

Objective

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes.

Methods

Patients enrolled in the Scleroderma Patient‐centered Intervention Network Cohort completed the SAAS and measures of appearance‐related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple‐group CFA was used to determine whether SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size.

Results

A total of 938 patients with SSc were included. CFA supported a 1‐factor structure (Comparative Fit Index 0.92, Standardized Root Mean Residual 0.04, and Root Mean Square Error of Approximation 0.08), and multiple‐group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = 0.96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression.

Conclusion

The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes.