Sequential Bilateral Vertebral Artery Dissections with Prompt Resolution of Initial Insult.

Vertebral arterial dissection is a known cause of stroke in young adults. There has been a multitude of cases of bilateral vertebral dissections, including progression from one vertebral artery to another. This case reports the curious sequential nature of the healing of a previously dissected vertebral artery with subsequent dissection of the collateral vertebral artery. Follow-up neuroimaging evaluation performed several months later showed healed bilateral vertebral artery. The potential trigger was neck cracking.

Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication.

Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. We show that acute lymphoblastic leukemia (ALL) cells avoid lethal replication stress after thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP-mediated dCTP production. The metabolic switch in dCTP production triggered by DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI-39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme dC kinase (dCK). Positron emission tomography (PET) imaging was useful for following both the duration and degree of dCK inhibition by DI-39 treatment in vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co-targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL models in mice, without detectable host toxicity. These findings advance our understanding of nucleotide metabolism in leukemic cells, and identify dCTP biosynthesis as a potential new therapeutic target for metabolic interventions in ALL and possibly other hematological malignancies.

A magnesiothermic reaction process for the scalable production of mesoporous silicon for rechargeable lithium batteries.

Mesoporous, 3-D, nanocrystalline Si has been synthesized via the magnesiothermic reduction of SiO particles at a peak temperature of only 500 °C in a scalable flow-through reactor setup. Such 3-D porous Si as an anode material exhibited high, reversible capacities (i.e., >900 mA h g(-1) after 160 charge-discharge cycles at 1000 mA g(-1)).