Development and validation of an LC-MS/MS method for the determination of ARN14988, an acid ceramidase inhibitor, and its application to a pharmacokinetic study in a mouse model.

Despite aggressive treatment approaches, the overall survival of glioblastoma (GBM) patients remained poor with a strong need for more effective chemotherapeutic agents. A previous study has shown that ARN14988 is more cytotoxic to GBM cells compared to US Food and Drug Administration-approved temozolomide. This finding makes ARN14988 a desirable candidate for further pharmacological assessment. Therefore, an efficient analytical method is needed to quantify ARN14988. Herein, we have developed and validated sample preparation and LC-MS/MS triple quadrupole (QQQ) method for quantification of ARN14988 in mouse plasma. In this method, the liquid-liquid extraction of ARN14988 from mouse plasma was performed using 5% ethyl acetate in hexane. The chromatographic separation was achieved using a C18 -column with mobile phases of 10 mm ammonium acetate (pH 5) and 0.1% formic acid in methanol, within a runtime of 10 min. The monitored transitions were m/z 391.20 → m/z 147.00 for ARN14988, and m/z 455.30 → m/z 165.00 for verapamil (internal standard) in positive electrospray ionization. The developed method for ARN14988 showed linearity over the range of 10-5,000 ng/ml (r2 > 0.99). The selectivity, sensitivity, matrix effect, recovery, stability, inter-day and intraday accuracy and precision were determined using four quality control samples. This validated method was successfully applied to the pharmacokinetic study of ARN14988 in mice.

Fibular free flap with proximal perforator skin paddle due to aberrant anatomy - a case report.

BACKGROUND: The fibular free flap is considered one of the most valuable options for mandible reconstruction. A perforator flap has gained widespread acceptance in oral and maxillofacial reconstruction. Typically, the fibula flap is obtained primarily with the distal perforator due to its reliable blood supply, with less attention given to the proximal perforators during the harvesting process. Normally, the distal perforator of the fibula exhibits stability and shows limited anatomical variations. However, there have been reported cases in which the distal perforator is absent. At times, these vascular abnormalities remain undetectable through Doppler examination or preoperative angiography evaluation. Therefore, this case details the experience of encountering the rare event of vascular abnormality in oral cancer surgery. CASE PRESENTATION: This article reports the case of a patient who presented with a congenital absence of the distal perforator in the peroneal artery, attributed to a vascular abnormality. Additionally, we provide a review of the concept of utilizing the proximal perforator as an alternative approach in the flap harvesting process. CONCLUSIONS: While the distal perforator of the peroneal artery is typically utilized for fibula free flap procedures, surgeons must remain cognizant of the potential for its absence due to aberrant anatomy. Recognizing an alternative approach in such cases can be pivotal for precise surgical planning and favorable outcomes in oral and maxillofacial reconstruction.

Eyes are faster than hands: A soft wearable robot learns user intention from the egocentric view.

To perceive user intentions for wearable robots, we present a learning-based intention detection methodology using a first-person-view camera.