Antifolate Agents Against Wild and Mutant Strains of Plasmodium falciparum

Plasmodium falciparum dihydrofolate reductase is an important target for antimalarial chemotherapy. The emergence of resistance has significantly reduced the efficacy of the classic antifolate drugs cycloguanil and pyrimethamine. In this paper we report new dihydrofolate reductase inhibitors identified using molecular modelling principles with the goal of designing new antifolate agents active against both wild and tetramutant dihydrofolate reductase strains three series of trimethoprim analogues were designed, synthesised and tested for biological activity. Pyrimethamine and cycloguanil have been reported to loose efficacy because of steric repulsion in the active site pocket produced due to mutation in Plasmodium falciparum dihydrofolate reductase. The synthesised molecules have sufficient flexibility to withstand this steric repulsion to counteract the resistance. The molecules have been synthesised by conventional techniques and fully characterised by spectroscopic methods. The potency of these molecules was evaluated by in vitro enzyme specific assays. Some of the molecules were active in micromolar concentrations and can easily be optimised to improve binding and activity.     

A Qualitative Analysis of Father–Son Relationships among HIV-Positive Young Black Men Who Have Sex with Men

Young black men who have sex with men (YBMSM) are experiencing high and rising rates of HIV infection, more than any other age-risk group category in the USA. Contributors to HIV risk in this group remain incompletely elucidated. We conducted exploratory qualitative interviews with 20 HIV-positive YBMSM aged 17–24 and found that father–son relationships were perceived to be important sociocontextual influences in participants’ lives. Participants discussed the degree of their fathers’ involvement in their lives, emotional qualities of the father–son relationship, communication about sex, and masculine socialization. Participants also described pathways linking father–son relationships to HIV risk, which were mediated by psychological and situational risk scenarios. Our thematic analysis suggests that father–son relationships are important to the psychosocial development of YBMSM, with the potential to either exacerbate or attenuate sexual risk for HIV. Interventions designed to strengthen father–son relationships may provide a promising direction for future health promotion efforts in this population.     

What is patient adherence? A terminology overview

It is well known that patient adherence to appropriately prescribed medications is essential for treatment efficacy and positive therapeutic outcomes. It is also understood that patients who are prescribed medications do not necessarily take them as prescribed. Indeed, variation in patients' medication-taking is an age old conundrum which remains the focus of much interest amongst researchers and clinicians owing to its far-reaching consequences. Despite the extensive adherence-related research over the last four decades and a recent surge in this field, there remains a lack of uniformity in the terminology used to describe adherence and its related concepts. In turn, it is often difficult to conduct comparisons between adherence-related studies, which may be associated with the non-cumulative nature of work in this field. The purpose of this commentary is to provide an overview of key terminology relating to the field of adherence research.