Visualization of Abscess Formation in a Murine Thigh Infection Model of Staphylococcus aureus by 19F-Magnetic Resonance Imaging (MRI)

Background: During the last years, 19 F-MRI and perfluorocarbon nanoemulsion (PFC) emerged as a powerful contrast agent based MRI methodology to track cells and to visualize inflammation. We applied this new modality to visualize deep tissue abscesses during acute and chronic phase of inflammation caused by Staphylococcus aureus infection. Methodology and Principal Findings: In this study, a murine thigh infection model was used to induce abscess formation and PFC or CLIO (cross linked ironoxides) was administered during acute or chronic phase of inflammation. 24 h after inoculation, the contrast agent accumulation was imaged at the site of infection by MRI. Measurements revealed a strong accumulation of PFC at the abscess rim at acute and chronic phase of infection. The pattern was similar to CLIO accumulation at chronic phase and formed a hollow sphere around the edema area. Histology revealed strong influx of neutrophils at the site of infection and to a smaller extend macrophages during acute phase and strong influx of macrophages at chronic phase of inflammation. Conclusion and Significance: We introduce 19 F-MRI in combination with PFC nanoemulsions as a new platform to visualize abscess formation in a murine thigh infection model of S. aureus. The possibility to track immune cells in vivo by this modality offers new opportunities to investigate host immune response, the efficacy of antibacterial therapies and th

Selectivity of the photosensitiser Tookad® for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions

Ischemic Preconditioning in the Animal Kidney, a Systematic Review and Meta-Analysis

Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ≥24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments

Female Institutional Directors on Boards and Firm Value

The aim of this research is to examine what impact female institutional directors on boards have on corporate performance. Previous research shows that institutional female directors cannot be considered as a homogeneous group since they represent investors who may or may not maintain business relations with the companies on whose corporate boards they sit. Thus, it is not only the effect of female institutional directors as a whole on firm value that has been analysed, but also the impact of pressure-resistant female directors, who represent institutional investors (investment, pension and mutual funds) that only invest in the company, and do not maintain a business relation with the firm. We hypothesize that there is a non-linear association, specifically quadratic, between institutional and pressure-resistant female directors on boards and corporate performance. Our results report that female institutional directors on boards enhance corporate performance, but when they reach a certain threshold on boards (11.72 %), firm value decreases. In line with female institutional directors, pressure-resistant female directors on boards also increase firm value, but only up to a certain figure (12.71 % on boards), above which they have a negative impact on firm performance. These findings are consistent with an inverted U-shaped relationship between female institutional directors and pressure-resistant female directors and firm performance

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Perceived spirituality, mindfulness and quality of life in psychiatric patients

There is some evidence of the relationship between spirituality and quality of life, but there are few bibliographic references on these constructs for patients suffering from mental illness; thus, this study was aimed at revealing the possible role of spiritual outlooks as a protective factor in these individuals. The sample consisted of 96 Portuguese psychiatric patients, selected from a psychiatric hospital and assessed based on parameters for quality of life, spirituality and mindfulness. The data support some theories about the nature of the spirituality. Spiritual beliefs are poorly correlated with the quality of life index, and there is a moderate association between these beliefs and some aspects of mindfulness. It is suggested that a spiritual outlook of psychiatric patients should be taken into account in psychological interventions