2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

Objectives: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs.

Classification Criteria in Axial Spondyloarthritis: What Have We Learned; Where Are We Going?

Spondyloarthritis (SpA) is a chronic inflammatory condition that can have a predominately peripheral or axial presentation. Axial SpA (axSpA) affects the axial skeleton with either radiographic (r-axSpA) or nonradiographic (nr-axSpA) changes. Radiographic changes are a late disease feature and earlier disease stages can be identified by incorporating other imaging methods.

An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum.

The intraerythrocytic malaria parasite exerts tight control over its ionic composition. In this study, a combination of fluorescent ion indicators and (36)Cl(-) flux measurements was used to investigate the transport of Cl(-) and the Cl(-)-dependent transport of "H(+)-equivalents" in mature (trophozoite stage) parasites, isolated from their host erythrocytes. Removal of extracellular Cl(-), resulting in an outward [Cl(-)] gradient, gave rise to a cytosolic alkalinization (i.

A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites.

Chloroquine resistance in the malaria parasite Plasmodium falciparum has made malaria increasingly difficult to control. Chloroquine-resistant parasites accumulate less chloroquine than their chloroquine-sensitive counterparts; however, the mechanism underlying this remains unclear. The primary site of accumulation and antimalarial action of chloroquine is the internal acidic digestive vacuole of the parasite, the acidity of which is maintained by inwardly-directed H+ pumps, working against the (outward) leak of H+.

The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance.

Chloroquine resistance in the human malaria parasite, Plasmodium falciparum, arises from decreased accumulation of the drug in the ;digestive vacuole' of the parasite, an acidic compartment in which chloroquine exerts its primary toxic effect. It has been proposed that changes in the pH of the digestive vacuole might underlie the decreased accumulation of chloroquine by chloroquine-resistant parasites. In this study we have investigated the digestive vacuole pH of a chloroquine-sensitive and a chloroquine-resistant strain of P.

pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum.

Efforts to control malaria worldwide have been hindered by the development and expansion of parasite populations resistant to many first-line antimalarial compounds. Two of the best-characterized determinants of drug resistance in the human malaria parasite Plasmodium falciparum are pfmdr1 and pfcrt, although the mechanisms by which resistance is mediated by these genes is still not clear. In order to determine whether mutations in pfmdr1 associated with chloroquine resistance affect the capacity of the parasite to persist when drug pressure is removed, we conducted competition experiments between P.

Mutations in pfmdr1 modulate the sensitivity of Plasmodium falciparum to the intrinsic antiplasmodial activity of verapamil.

As well as having the ability to reverse chloroquine resistance in the human malaria parasite Plasmodium falciparum, verapamil has itself an innate antiplasmodial activity. We show here that mutations in Pgh1, the product of the malaria parasite's pfmdr1 gene, influence the parasite's susceptibility to the toxic effects of verapamil.