Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids.

Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem. We propose a nanofibrillar hydrogel (EKGel) for the initiation and growth of breast cancer PDOs. PDOs grown in EKGel have histopathologic features, gene expression, and drug response that are similar to those of their parental tumors and PDOs in BME. In addition, EKGel offers reduced batch-to-batch variability, a range of mechanical properties, and suppressed contamination from murine cells. These results show that EKGel is an improved alternative to BME matrices for the initiation, growth, and maintenance of breast cancer PDOs.

Prevalence of beta-lactam allergy: a retrospective chart review of drug allergy assessment in a predominantly pediatric population.

BACKGROUND: Research suggests that 90% of patients labeled beta-lactam allergic are able to tolerate penicillins following further assessment. This study aims to define and describe the frequency of true beta-lactam allergy following allergy patient evaluation in a predominantly pediatric population. METHODS: 306 primary care patients referred between January 2010 and June 2015 were assessed for a suspected beta-lactam allergy. Patient demographics, history and test results were extracted from electronic medical records. Testing performed was based on specialist recommendation following review of patient history. RESULTS: 34% of the study participants had intradermal testing. Oral challenge was given to 96.7% of the sample. 96% of patients with a prior history of beta-lactam allergy were advised that they could re-introduce beta-lactam antibiotics following evaluation. CONCLUSIONS: Among patients with a documented beta-lactam allergy or a recent history of a reaction there is a low rate of 'true' beta-lactam allergy. Consistent evaluation of beta-lactam antibiotic allergies can reduce rates of broad spectrum antibiotic prescribing, among other harmful consequences.

Bioactive steroidal alkaloids from Buxus macowanii Oliv.

Chemical investigation of the crude methanolic extract of Buxus macowanii resulted in the isolation of five new steroidal alkaloids, 31-hydroxybuxatrienone (1), macowanioxazine (2), 16α-hydroxymacowanitriene (3), macowanitriene (4), macowamine (5), along with five known steroidal bases, Nb-demethylpapillotrienine (6), moenjodaramine (7), irehine (8), buxbodine B (9) and buxmicrophylline C (10). Structures of compounds 1-10 were elucidated with the aid of spectroscopic methods including 1D and 2D NMR techniques and mass spectrometry. Compounds 1, 3, and 4 belong to a rare class of Buxus alkaloids having Δ(1,2) 9(10→19) abeo triene system. All isolates were evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity and found to exhibit moderate to weak anti-AChE activity with IC50 values in the range of 10.8-98µM. Compounds 1 and 6 were also moderately active in BACE1 inhibitory assay.