Photosensitiser delivery for photodynamic therapy. Part 2: systemic carrier platforms

Background: The treatment of solid tumours and angiogenic ocular diseases by photodynamic therapy (PDT) requires the injection of a photosensitiser (PS) to destroy target cells through a combination of visible light irradiation and molecular oxygen. There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic PDT. Objective: This article aims to review recent developments in systemic carrier delivery platforms for PDT, with an emphasis on target specificity. Methods: Recent publications, spanning the last five years, concerning delivery carrier platforms for systemic PDT were reviewed, including PS conjugates, dendrimers, micelles, liposomes and nanoparticles. Results/conclusion: PS conjugates and supramolecular delivery platforms can improve PDT selectivity by exploiting cellular and physiological specificities of the targeted tissue. Overexpression of receptors in cancer and angiogenic endothelial cells allows their targeting by affinity-based moieties for the selective uptake of PS conjugates and encapsulating delivery carriers, while the abnormal tumour neovascularisation induces a specific accumulation of heavy weighted PS carriers by enhanced permeability and retention (EPR) effect. in addition, polymeric prodrug delivery platforms triggered by the acidic nature of the tumour environment or the expression of proteases can be designed. Promising results obtained with recent systemic carrier platforms will, in due course, be translated into the clinic for highly efficient and selective PDT protocols.

The relationship between counterfactual thinking and emotional reactions to event outcomes: Does one account fit all?

By enabling a comparison between what is and what might have been, counterfactual thoughts amplify our emotional responses to bad outcomes. Well-known demonstrations such as the action effect (the tendency to attribute most regret to a character whose actions brought about a bad outcome) and the temporal order effect (the tendency to undo the last in a series of events leading up to a bad outcome) are often explained in this way. An important difference between these effects is that outcomes are due to decisions in the action effect, whereas in the temporal order effect outcomes are achieved by chance. In Experiment 1, we showed that imposing time pressure leads to a significant reduction in the action but not in the temporal order effect. In Experiment 2, we found that asking participants to evaluate the protagonists (

Interpersonal Aspects of Thinking Skills in an Intercultural Language Learning Context

Asking and answering certain types of questions are thought to develop thinking skills in all types of classrooms. Previous research has demonstrated that asking higher order questions and answering with elaborated responses are associated with high achievement in first, second, and foreign language contexts. Typically more attention is paid to question frequency or achievements inferred from individual performances than to the dialogues in which asking and answering occurs. This paper argues for a focus on the construction of responses in interaction as an alternative to the investigation of questions, effects of training or individual measurements of performance. Drawing on interactional data from an adult English as a Second Language classroom, it is argued that constructing an answer to a critical question appears to be a highly collaborative and evaluative affair. The thinking skills literature suggests that responding to higher order questions is an individual higher cognitive function, however it is argued in this paper that in attempting to construct evaluative answers language learners are involved not only in a cognitive task, which may or may not be helpful to language learning, but also in a complex social task in which perspectives need to be negotiated, stances taken and identities navigated. It is suggested that higher order thinking cannot be separated from the social and cultural knowledge through which it is brought into being. It is argued that any implementation of thinking skills in an English language teaching context ought to consider interpersonal and social aspects, particularly in intercultural settings.

A Paradoxical Effect of Systemic IL-23 in EAE – Limitation of Autoimmune Inflammatory Demyelination

The heterodimeric cytokine IL-23 plays a non-redundant function in the development of cell-mediated, organspecific autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). To further characterize the mechanisms of action of IL-23 in autoimmune inflammation, we administered IL-23 systemically at different time points during both relapsing and chronic EAE. Surprisingly, we found suppression of disease in all treatment protocols. We observed a reduction in the number of activated macrophages and microglia in the CNS, while T cell infiltration was not significantly affected. Disease suppression correlated with reduced expansion of myelin-reactive T cells, loss of T-bet expression, loss of lymphoid structures, and increased production of IL-6 and IL-4. Here we describe an unexpected function of exogenous IL-23 in limiting the scope and extent of organ-specific autoimmunity.

Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

Abstract OBJECTIVE: Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. METHODS: In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. RESULTS: SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p

Impure Thinking Practices and Clinical Acts: The Sonorous Becomings of Heidi Fast

This article introduces the recent sound works of Heidi Fast, a Finnish voice and performance artist. Fast’s creative practice operates between art and philosophy, and articulates several ‘zones of becoming’: what Fast designates as ‘the clinical’, ‘the virtual’ and ‘vocal thought-material’. Using a methodology of routing, the article shows how these zones emerge as aesthetic, ethical and political concerns within Fast’s work. Since 2005, Fast’s sound works have variously taken shape as miniature concerts, social sculptures, imaginary soundscapes and environmental music performances. Drawing upon the writings of theorists who have helped shape her practice, this article argues that Fast uses sound and voice to propose an ‘actualising philosophy’. This philosophy actualises virtualities (unrealised potentials), affecting transformative shifts through tiny mutations in perceptions and behaviours.

Systemic Family Therapy for Families who have Experienced Trauma: A Randomised Controlled Trial

This paper describes a randomised controlled trial (RCT) investigation of the added value of systemic family therapy (SFT) over individually focused cognitive behavioural therapy (CBT) for families in which one or more members has suffered trauma and been referred to a community-based psychotherapy centre. The results illustrate how an apparently robust design can be confounded by high attrition rates, low average number of therapeutic sessions and poor protocol adherence. The paper highlights a number of general and specific lessons regarding the resources and processes involved that can act as a model for those planning to undertake studies of this type and scope. A key message is that the challenges of conducting RCTs in ‘real world’ settings should not be underestimated. The wider implications in relation to the place of RCTs within the creation of the evidence base for complex psycho-social interventions is discussed and the current movement towards a phased mixed-methods approach, including the appropriate use of RCTs, which some might argue is a return to the original vision of evidence-based practice (EBP), is affirmed.