Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure.

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure.

Breaking the Glass Ceiling in Simulation and Modeling: Women in Pharmaceutical Discovery.

The topic of gender equality within the United States workforce is receiving a great deal of attention. The field of chemistry is no exception and is increasingly focused on taking steps to achieve gender diversity within the chemistry workforce. Over the past several years, many computational chemistry groups within large pharmaceutical companies have realized growth in the number of women, and here we discuss the key factors that we believe have played a role in attracting and retaining the authors of this review as computational chemists in pharma.

Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties.

A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG.