Orbital cellulitis and cavernous sinus thrombosis with contralateral sinus disease in a COVID-19 positive adolescent patient.

Patients with COVID-19 have been reported to have elevated coagulation factors, which is a well-documented cause of venous thromboembolism events such as deep vein thrombosis and pulmonary embolism. Other venous thrombotic events, however, such as cavernous sinus thrombosis (CST) have been less commonly observed, specifically in combination with primary orbital cellulitis. Due to its unique anatomic location, the cavernous sinus is susceptible to thrombophlebitis processes including septic thrombosis and thrombosis most commonly from sinusitis.

Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers.

Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple studies of PAM pathway-driven tumors.

Identification of Trypanosoma brucei AdoMetDC Inhibitors Using a High-Throughput Mass Spectrometry-Based Assay.

Human African trypanosomiasis (HAT) is a fatal infectious disease caused by the eukaryotic pathogen Trypanosoma brucei (Tb). Available treatments are difficult to administer and have significant safety issues. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the parasite polyamine biosynthetic pathway.

Discovery of substituted benzamides as follicle stimulating hormone receptor allosteric modulators.

Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of protein formulations are used during clinical protocols for ovulation induction and for in vitro fertilization that are followed by a selection of assisted reproductive technologies. In order to increase patient convenience and compliance several research groups have searched for orally bioavailable FSH mimetics for innovative fertility medicines.

EFFECTS OF PARENTAGE AND SIZE OF THE POLLEN LOAD ON PROGENY PERFORMANCE IN CAMPANULA AMERICANA.

To examine the effects of maternal and paternal parentage and the size of the pollen load on seed size and weight and on progeny performance we conducted a controlled crossing experiment using a natural population of Campanula americana. We found that seed size was positively correlated with early seedling performance for all but one of traits we measured (days to emergence), but was not significantly correlated with any of the later vegetative measures or reproductive output. We detected significant effects due to the maternal parent for the vegetative traits days to emergence, days to first leaf, and final plant height, as well as total seed weight, and mean seed weight per fruit.

Effects of parentage, prior fruit set and pollen load on fruit and seed production in Campanula americana L.

We conducted a controlled crossing experiment to examine the effects of maternal and paternal parentage, the size of the pollen load, and prior fruit production on the proportion of flowers that set fruit, seed number per fruit and seed weight in a natural population of Campanula americana. Effects due to the maternal parent were large for all measures of fruit and seed production, while the paternal parent had a significant effect only upon mean seed weight. As the number of prior fruits on the maternal plant increased the probability that a flower would produce a mature fruit, the number of seeds per fruit, and total seed weight per fruit all decreased.