Photodynamic opening of blood-brain barrier

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2 ) and photosensitizer (5-aminolevulinic acid – 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5- ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumo

The multi-modality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging

The term 'athlete's heart' refers to a clinical picture characterized by a slow heart rate and enlargement of the heart. A multi-modality imaging approach to the athlete's heart aims to differentiate physiological changes due to intensive training in the athlete's heart from serious cardiac diseases with similar morphological features. Imaging assessment of the athlete's heart should begin with a thorough echocardiographic examination. Left ventricular (LV) wall thickness by echocardiography can contribute to the distinction between athlete's LV hypertrophy and hypertrophic cardiomyopathy (HCM). LV end-diastolic diameter becomes larger (>55 mm) than the normal limits only in end-stage HCM patients when the LV ejection fraction is <50%. Patients with HCM also show early impairment of LV diastolic function, whereas athletes have normal diastolic function. When echocardiography cannot provide a clear differential diagnosis, cardiac magnetic resonance (CMR) imaging should be performed. With CMR, accurate morphological and functional assessment can be made. Tissue characterization by late gadolinium enhancement may show a distinctive, non-ischaemic pattern in HCM and a variety of other myocardial conditions such as idiopathic dilated cardiomyopathy or myocarditis. The work-up of athletes with suspected coronary artery disease should start with an exercise ECG. In athletes with inconclusive exercise ECG results, exercise stress echocardiography should be considered. Nuclear cardiology techniques, coronary cardiac tomography (CCT) and/or CMR may be performed in selected cases. Owing to radiation exposure and the young age of most athletes, the use of CCT and nuclear cardiology techniques should be restricted to athletes with unclear stress echocardiography or CMR

Исследование желаемого образа семьи молодежи, проживающей в больших, средних и малых городах

Funding: EPSRC EP/J01771X, Royal Society Wolfson Research Merit AwardBackground Topical Photodynamic therapy (PDT) is an effective treatment for superficial non-melanoma skin cancers (NMSC) and dysplasia. During PDT light activates the photosensitiser (PpIX), metabolised from a topical pro-drug. A combination of PpIX, light and molecular oxygen results in inflammation and cell death. However, the outcomes of the treatment could be better. Insufficient biosynthesis of PpIX may be one of the causes of incomplete response or recurrence. Measuring surface fluorescence is usually employed as a means of studying PpIX formation. The aim of this work was to develop a device and a method for convenient fluorescence imaging in clinical settings to gather information on PpIX metabolism in healthy skin and NMSC with a view to improving PDT regimes. Methods A handheld fluorescence camera and a time course imaging method was developed and used in healthy volunteers and patients diagnosed with basal cell carcinoma (BCC) and actinic keratosis (AK). The photosensitiser (precursor) creams used were 5-aminolaevulinic acid (ALA; Ameluz®) and methyl aminolevulinate (MAL; Metvix®). Pain was assessed using a visual analogue score immediately after the PDT. Results Fluorescence due to PpIX increases over three hours incubation in healthy skin and in lesional BCC and AK. Distribution of PpIX fluorescence varies between the lesion types and between subjects. There was no significant correlation between PpIX fluorescence characteristics and pro-drug, diagnosis or pain experienced. However, there was a clear dependence on body site. Conclusion The device and the method developed can be used to assess the characteristics of PpIX fluorescence, quantitative analysis and time course. Our findings show that body site influences PpIX fluorescence which we suggest may be due to the difference in skin temperature at different body sites.PostprintPeer reviewe

Imported Malaria in Children in Industrialized Countries, 1992–2002

Children account for a considerable proportion of cases imported to the United States and Europe

When Institutional Work Backfires: Organizational Control Of Professional Work In The Pharmaceutical Industry

Integrating institutional and role theories, this paper develops a Logics–Roles– Action (LRA) framework for understanding how for-profit organizations structure institutional work to managerially control the work of professionals they employ. Structurally, this institutional work involves three elements: (1) internalizing pluralistic logics (logics); (2) institutionalizing distinct roles embedded in these logics (roles); and (3) scripting goal-oriented role enactment plans (action). An empirical examination of the LRA framework in the pharmaceutical industry evidences four distinct organizational strategies that script role enactments of sales professionals in their interactions with physicians. Each strategy is intended to reaffirm prevailing institutional logics, but eventually backfires by disrupting the very institutional structures that it seeks to maintain and replicate. We show that this disruptive effect is mediated by changes in the social knowledge of institutional work. We close with theoretical and managerial implications for organizational structuring of institutional work and dynamics of institutional change

Why we need easy access to all data from all clinical trials and how to accomplish it

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation