Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial.

Malaria and HIV co-infection are prevalent in sub-Saharan Africa causing significant drug interactions with co-treatment. We previously reported a 30%-70% reduction in exposure to the standard 3-day (6-dose) artemether-lumefantrine (AL) treatment for malaria when given with efavirenz-based HIV therapy, impacting malaria reinfection risk. We conducted a prospective, randomized study comparing the 3-day regimen to an extended 5-day (10-dose) regimen with pharmacokinetic sampling for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine (DBL) over 42 days.

The Kinesin Kar3 is Required for Endoplasmic Reticulum-Associated Degradation.

Degradation of aberrant, excess, and regulatory proteins at the endoplasmic reticulum (ER) is a conserved feature of eukaryotic cells, disruption of which contributes to disease. While remarkable progress has been made in recent years, mechanisms and genetic requirements for ER-Associated Degradation (ERAD) remain incompletely understood. We recently conducted a screen for genes required for turnover of a model ER translocon-associated substrate of the Hrd1 ubiquitin ligase in .

Human HKU1-reactive CD4 T cells are enriched for cytolytic potential that persists in older adults.

The emergence of SARS-CoV-2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using PBMC from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine Elispot assays. Unexpectedly, cytotoxic potential was uniquely enriched amongst HKU1-reactive CD4 T cells, as measured by quantification of granzyme producing cells.

Preconditions for Including the Effects of Urease and Nitrification Inhibitors in Emission Inventories.

Urease and nitrification inhibitors can reduce ammonia and greenhouse gas emissions from fertilizers and manure but their effectiveness depends on the conditions under which they are used. Consequently, it is essential for the credibility of emission reductions reported in regulatory emission inventories that their effectiveness is assessed under real-world conditions and not just in the laboratory. Here, we specify the criteria we consider necessary before the effects of inhibitors are included in regulatory emission inventories.