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Summary Emerging technologies in stem cell engineering have produced sophisticated organoid platforms by controlling stem cell fate via biomaterial instructive cues. By micropatterning and differentiating human induced pluripotent stem cells (hiPSCs), we have engineered spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter. We investigated how geometric confinement directed the structural morphology and contractile functions of the cardiac organoids and tailored the pattern geometry to optimize organoid production. Using modern data-mining techniques, we found that pattern sizes significantly affected contraction functions, particularly in the parameters related to contraction duration and diastolic functions. We applied cardiac organoids generated from 600 μm diameter circles as a developmental toxicity screening assay and quantified the embryotoxic potential of nine pharmaceutical compounds. These cardiac organoids have potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity., Graphical abstract, Highlights • Micropattern-based geometric confinement directs cardiac organoid development • Cardiac organoid structure-function relationships are guided by organoid size • Cardiac organoids can be used as an in vitro embryotoxicity assessment tool, Advances in organoid engineering have produced sophisticated organoid platforms by controlling stem cell fate via biomaterial instructive cues. Ma and colleagues show that micropatterning is a versatile tool to engineer cardiac organoids with different architectures and cardiac functions. Furthermore, the cardiac organoid development was sensitive to numerous drug compounds and demonstrated potential as an embryotoxicity screening platform.

Background and purpose Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. Methods The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS > 2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. Results An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS > 2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%–53%), and 10/34 patients allocated to coiling (29%; 17%–46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%–94%), and 18/27 patients allocated to coiling (67%; 47%–81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%–60%]) than EVT (9/48 [19%; 10%–31%]). Conclusion Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

A new, rapid and simple method is described and applied to resolve and quantify mixtures of prednisolone acetate, sulfacetamide and phenylefrine. The determination was accomplished by micellar electrokinetic capillary chromatography (MEKC) using a fused silica capillary (57 cm x 75 microm ID). The separation was carried out at 25 degrees C and 30 kV, using a 5 mM phosphate-5 mM borate buffer adjusted to pH 8.2, 40 mM sodium dodecylsulfate (SDS) as background electrolyte. Under these conditions, the run time was 6.5 min and the limits of quantification were about 0.5 mg l(-1) for every component. Repeatability and reproducibility studies achieved were showing no significant differences at 95% confidence level. Then, multivariate calibration regression spectrophotometric methods (PLS-1, PLS-2 and PCR) were applied providing, especially PLS-1, a clear example of the high resolving power of these techniques. The MEKC method has been applied for quantifying these compounds in different commercial pharmaceuticals products and the method gave good results when it is compared with the spectrophotometric method. The pharmaceutical preparations do not require any separation step by the two described procedures.

Two spectrophotometric methods are described and applied to resolve ternary mixtures of the corticosteroid hydrocortisone (HYD) and the antibiotics nystatin (NYS) and oxytetracycline (OXY). The simultaneous determination of these three compounds was firstly accomplished by a derivative method using the “ratio spectrum-zero crossing derivative” and then by multivariate methods partial least squares (PLS)-1, -2 and principal component regression (PCR). Multivariate calibration methods provide, specially PLS-2 in this case, a clear example of the high resolving powder of these techniques. The two described procedures do not require any separation step. Repeatability and reproducibility studies were achieved over two series of 10 standards for each compound showing no significant differences at 95% confidence level in the four spectrophotometric methods. A comparison of the derivative and multivariate calibration results obtained in pharmaceutical formulations was performed resulting in agreement of the values obtained and the results was confirm by a high-pressure liquid chromatography (HPLC) method.

Four spectrophotometric methods are described and applied to resolve ternary mixtures of the corticosteroid Dexamethasone (DEX), the antibiotic Polymyxin B (PLX) and its encouraging Trimethoprim (TMP). The simultaneous determination of these three compounds was firstly accomplished by a derivative method using the “ratio spectrum-zero crossing derivative” (satisfactory results in synthetic mixtures in different ratios and pharmaceutical formulations for DEX and TMP) and then by multivariate methods (satisfactory results in synthetic mixtures in different ratios and pharmaceutical formulations for DEX, PLX and TMP). Absorption spectra of compounds were used to optimise the spectral data set performs the calibration by partial least squares (PLS) 1 and 2 and principal component regression (PCR) algorithms. These calibration models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over synthetic and pharmaceutical mixtures. The four described procedures do not require any separation step. Repeatability and reproducibility studies were achieved over two series of 10 standards for each compound showing no significant differences at 95% confidence level in the four spectrophotometric methods. A comparison of the derivative and multivariate calibration results obtained in pharmaceutical formulations was performed resulting in agreement of the values obtained. © 2001 Elsevier Science B.V. All rights reserved.

Two-component mixtures of cefsulodin and clavulanic acid were analysed by a first-derivative spectrophotometric method using a zero-crossing technique of measurement. The relative ease offered by this derivative technique for the quantification of these drugs, with closely overlapping spectral bands, was clearly demonstrated. As the absorption band of clavulanic acid closely overlaps with that of cefsulodin, both direct and derivative spectrophotometric methods have been investigated and evaluated by an exhaustive statistical analysis of the experimental data. The first-derivative spectrophotometric method was found to be more rapid, accurate and reproducible. The procedure does not require any separation step. The calibration graphs were linear in the range 2.0-56.0 micrograms ml-1 for cefsulodin and 2.0-28.0 micrograms ml-1 for clavulanic acid. The lower detection limits of cefsulodin and clavulinic acid (P 0.05 level) were calculated to be 0.16 and 0.24 microgram ml-1, respectively. Mixtures of cefsulodin and clavulanic acid in ratios of 1:4-7:2 were satisfactorily resolved. Both components were also determined in physiological solutions used to prepare intravenous infusions of these antibiotics.