Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease.

Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin.

One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study.

Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD.

A 66-year-old man with hydroxycarbamide induced pneumonitis.

Hydroxycarbamide is used in the treatment of myeloproliferative neoplasms. Hydroxycarbamide is known for its relative lack of severe side effects. Here we present a 66-year-old man with a severe pneumonitis within three weeks after starting him on hydroxycarbamide.

Temporal binding of interval markers.

How we estimate the passage of time is an unsolved mystery in neuroscience. Illusions of subjective time provide an experimental access to this question. Here we show that time compression and expansion of visually marked intervals result from a binding of temporal interval markers.

The functional role of time compression.

Multisensory integration provides continuous and stable perception from separate sensory inputs. Here, we investigated the functional role of temporal binding between the visual and the tactile senses. To this end we used the paradigm of compression that induces shifts in time when probe stimuli are degraded, e.