Success in eliminating malaria will depend on whether parasite evolution outpaces control efforts. Here, we show that Plasmodium falciparum parasites (the deadliest of the species causing human malaria) found in low-transmission-intensity areas have evolved to invest more in transmission to new hosts (reproduction) and less in within-host replication (growth) than parasites found in high-transmission areas. At the cellular level, this adaptation manifests as increased production of reproductive forms (gametocytes) early in the infection at the expense of processes associated with multiplication inside red blood cells, especially membrane transport and protein trafficking. At the molecular level, this manifests as changes in the expression levels of genes encoding epigenetic and translational machinery. Specifically, expression levels of the gene encoding AP2-G-the transcription factor that initiates reproduction-increase as transmission intensity decreases. This is accompanied by downregulation and upregulation of genes encoding HDAC1 and HDA1-two histone deacetylases that epigenetically regulate the parasite's replicative and reproductive life-stage programmes, respectively. Parasites in reproductive mode show increased reliance on the prokaryotic translation machinery found inside the plastid-derived organelles. Thus, our dissection of the parasite's adaptive regulatory architecture has identified new potential molecular targets for malaria control.

In individuals with MI, delirium was associated with increased inpatient mortality.

Background: As the use of left atrial appendage closure (LAAC) becomes more widespread, improvements in resource utilization and cost-effectiveness are necessary. Currently, there are limited data on same-day discharge (SDD) after LAAC. We aimed to evaluate the safety and feasibility of SDD versus non-SDD in patients with nonvalvular atrial fibrillation who underwent LAAC. Methods: We retrospectively studied 211 patients who underwent the WATCHMAN procedure in a tertiary hospital (June 2016 to June 2019). The primary safety outcome was the composite of stroke, systemic embolism, major bleeding requiring transfusion, vascular complications requiring endovascular intervention, or death through 7 days (periprocedural) and 45 days post-procedure. The secondary outcomes were the individual components of the primary outcome and all-cause readmission. We compared the clinical outcomes of patients who had SDD and non-SDD post-procedure. Results: Patients with procedure-related complications on the day of LAAC and patients who were admitted for acute clinical events before LAAC were excluded. One hundred ninety patients were included in the final analysis. Seventy-two of 190 (38%) patients had SDD, and 118 of 190 (62%) had non-SDD. There were no statistically significant differences in the primary safety outcome through 7 days (1.4% versus 5.9%; P =0.26) and 45 days post-procedure (2.8% versus 9.3%; P =0.14) between the two groups. The secondary outcomes were similar in both groups. No patients had device-related thrombus on transesophageal echocardiography at 45 days. Only 1 patient from the non-SDD group had clinically significant peri-device flow (>5 mm) at 45 days. Conclusions: In a selected cohort of patients who underwent successful elective LAAC with WATCHMAN without same-day procedure-related complications, the primary safety outcome and secondary outcomes through 7 and 45 days post-procedure were similar in the SDD and non-SDD groups. Our findings are hypothesis generating and warrant further investigation in prospective trials.