Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid

Although singlet oxygen (1O2) has long been proposed as the primary reactive oxygen species in photodynamic therapy (PDT), it has only recently been possible to detect it in biological systems by its luminescence at 1270 nm. Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the 1O2 luminescence in cell suspensions over a wide range of treatment parameters. Here, we extend this to test the hypothesis that the photobiological response in vivo is also correlated with 1O2 generation, independent of individual treatment parameters. The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm−2 of pulsed 523 nm light at 50 mW cm−2, or to 50 J cm−2 at 15 or 150 mW cm−2. 1O2 luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment. As observed by other authors, a strong irradiance dependence of the PDT effect was observed. However, in all cases the responses increased with the 1O2 luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between 1O2 generation and photobiological response

Diagnosing delirium in elderly Thai patients: Utilization of the CAM algorithm

<p>Abstract</p> <p>Background</p> <p>Delirium is a common illness among elderly hospitalized patients. However, under-recognition of the condition by non-psychiatrically trained personnel is prevalent. This study investigated the performance of family physicians when detecting delirum in elderly hospitalized Thai patients using the Thai version of the Confusion Assessment Method (CAM) algorithm.</p> <p>Methods</p> <p>A Thai version of the CAM algorithm was developed, and three experienced Thai family physicians were trained in its use. The diagnosis of delirium was also carried out by four fully qualified psychiatrists using DSM-IV TR criteria, which can be considered the gold standard. Sixty-six elderly patients were assessed with MMSE Thai 2002, in order to evaluate whether they had dementia upon admission. Within three days of admission, each patient was interviewed separately by a psychiatrist using DSM-IV TR, and a family physician using the Thai version of the CAM algorithm, with both sets of interviewers diagnosing for delirium.</p> <p>Results</p> <p>The CAM algorithm tool, as used by family physicians, demonstrated a sensitivity of 91.9% and a specificity of 100.0%, with a PPV of 100.0% and an NPV of 90.6%. Interrater agreement between the family physicians and the psychiatrists was good (Cohen's Kappa = 0.91, p < 0.0001). The mean of the time the family physicians spent using CAM algorithm was significantly briefer than that of the psychiatrists using DSM-IV TR.</p> <p>Conclusions</p> <p>Family physicians performed well when diagnosing delirium in elderly hospitalized Thai patients using the Thai version of the CAM algorithm, showing that this measurement tool is suitable for use by non-psychiatrically trained personnel, being short, quick, and easy to administer. However, proper training on use of the algorithm is required.</p

Mortality and causes of death among violent offenders and victims-a Swedish population based longitudinal study

<p>Abstract</p> <p>Background</p> <p>Most previous studies on mortality in violent offenders or victims are based on prison or hospital samples, while this study analyzed overall and cause specific mortality among violent offenders, victims, and individuals who were both offenders and victims in a general sample of 48,834 18-20 year-old men conscripted for military service in 1969/70 in Sweden.</p> <p>Methods</p> <p>Each person completed two non-anonymous questionnaires concerning family, psychological, and behavioral factors. The cohort was followed for 35 years through official registers regarding violent offenses, victimization, and mortality. The impact of violence, victimization, early risk factors and hospitalization for psychiatric diagnosis or alcohol and drug misuse during follow up on mortality was investigated using Cox proportional hazard regression analyses.</p> <p>Results</p> <p>Repeat violent offenses were associated with an eleven fold higher hazard of dying from a substance-related cause and nearly fourfold higher hazard of dying from suicide. These figures remained significantly elevated also in multivariate analyses, with a 3.03 and 2.39 hazard ratio (HR), respectively. Participants with experience of violence and inpatient care for substance abuse or psychiatric disorder had about a two to threefold higher risk of dying compared to participants with no substance use or psychiatric disorder.</p> <p>Conclusions</p> <p>Violent offending and being victimized are associated with excess mortality and a risk of dying from an alcohol or drug-related cause or suicide. Consequently, prevention of violent behavior might have an effect on overall mortality and suicide rates. Prevention of alcohol and drug use is also warranted.</p

Early Events Associated with Infection of Epstein-Barr Virus Infection of Primary B-Cells

Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to introduce an expression cassette of green fluorescent protein (GFP) by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6–7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6–12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection