Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update

Introduction: Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse.

Areas covered: This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR.

Expert opinion: In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5–25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.     

Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques

ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E^?/? mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis.     

Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.     

Dual photoacoustic/ultrasound multi-parametric imaging from passion fruit-like nano-architectures

Ultrasound (US) imaging is a well-established diagnostic technique to image soft tissues in real time, while photoacoustic (PA) is an emerging imaging technique employed to collect molecular information. Integration of PA and US imaging provides complementary information enhancing diagnostic accuracy without employing ionizing radiations. The development of contrast agents able to combine PA and US features is pivotal to improve the significance of PAUS imaging and for PAUS-guided treatment of neoplasms. Here, we demonstrate in relevant ex-vivo models that disassembling passion fruit-like nano-architectures (pfNAs) can be employed in PAUS imaging. pfNAs are composed by silica nanocapsules comprising aggregates of commercial NIR-dyes-modified polymers and ultrasmall gold nanoparticles. The intrinsic US and PA features of pfNAs have been fully characterized and validated in tissue-mimicking materials and in ex vivo preparations. Moreover, the application of a multi-parametric approach has allowed the increase of information extrapolated from collected images for a fine texture analysis.     

Validación psicométrica de la Escala de gravedad de fatiga en médicos residentes mexicanos

Resident physicians are continually exposed to fatigue, which can lead to work, academic and personal problems, so it is important to have reliable and valid instruments to measure it. One of the most used is Fatigue Severity Scale, but, there are versions with different number of items in different populations. Therefore, the purpose of this work was to translate, adapt culturally relevant and compare versions with different numbers of items, to identify the most appropriate in Mexican resident physicians. With three different groups of participants; first one for translation by seven expert judges in the language, second for psychometric validation with 100 resident physicians, and third for confirmatory factor analysis and invariance test by type of program (specialty and high specialty) with 182 resident physicians. Distribution, discrimination, reliability and factor structure of the scale were tested in an exploratory and confirmatory analysis, leaving a final scale of 6 items with good fit (X²[9] = 9,39, p = 0,40; CFI = 0,99; RMSEA = 0,02), with a reliability = 0,91 and strict factorial invariance by type of residence program.     

Aprendizaje y prácticas clínicas

This collaboration briefly reviews the characteristics of professional learning. It pays special attention to the learning that takes place during clinical practices and to the fundamental role of reflection in the construction of knowledge and in the better understanding of the situation of the other (patients, family members, professionals) and oneself. It emphasizes the learning of values and attitudes, which are manifested in behaviors. Finally, it describes the characteristics of learning by role modeling and the influence of hidden curriculum on the development of professional competences.