Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.     

ON SAMPLE SIZE CALCULATION BASED ON ODDS RATIO IN CLINICAL TRIALS

Sample size calculation formulas for testing equality, noninferiority, superiority, and equivalence based on odds ratio were derived under both parallel and one-arm crossover designs. An example concerning the study of odds ratio between a test compound (treatment) and a standard therapy (control) for prevention of relapse in subjects with schizophrenia and schizoaffective disorder is presented to illustrate the derived formulas for sample size calculation for various hypotheses under both a parallel design and a crossover design. Simulations were performed to assess the adequacy of the sample size calculation formulas. Simulation results were given at the end of the paper.     

(Em)placing recovery: Sites of health and wellness for individuals with serious mental illness in supported housing

This study used photo-elicitation methodology to explore how the move from supervised to supported housing affects recovery and community connections for individuals living with serious mental illness (SMI) in four Canadian cities. Qualitative interviews conducted in 2015 revealed five themes: (1) the characteristics distinguishing home from housing; (2) the importance of amenities offered by supported housing; (3) the connections between accessibility, mobility, and wellbeing; (4) the role of certain places in facilitating aspects of recovery such as offering hope or facilitating social connectedness; and (5) the concrete and metaphorical impact of changing vantage points on identity (re)construction. Utilizing therapeutic landscapes as an analytical framework, and combining insights from the health geography, and mental health (MH) housing and recovery literatures, this study deepens current understanding of how everyday places—conceptualized as therapeutic landscapes—directly and indirectly support MH recovery for individuals with SMI. Implications for research on housing, and on the spatial aspects of recovery processes are discussed.     

Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Atypical Developmental Venous Anomaly Associated with Single Arteriovenous Fistula and Intracerebral Hemorrhage: a Case Demonstrated by Superselective Angiography

We present a case of developmental venous anomaly associated with arteriovenous fistula supplied by a single arterial feeder adjacent to a large acute intracerebral hemorrhage. The arteriovenous fistula was successfully obliterated by superselective embolization while completely preserving the developmental venous anomaly. Two similar cases, including superselective angiographic findings, have been reported in the literature; however, we describe herein superselective angiographic findings in more detail and demonstrate the arteriovenous shunt more clearly than the previous reports. In addition, a literature review was performed to discuss the association of a developmental venous anomaly with vascular lesions.     

The Effect of Therapeutic Ultrasound on Pain and Physical Function in Patients with Knee Osteoarthritis

Osteoartritis (OA) is one of the most frequent causes of pain, loss of function and disability in adults. The prevalence of OA is expected to increase substantially in the future. Knee OA is the most common subset of OA. Therapeutic ultrasound (US) is one of several physical therapy modalities suggested for the management of pain and loss of function due to OA. The purpose of our study was to investigate the efficacy of US therapy in reducing pain and functional loss and improving the quality of life in patients with knee OA in comparison to sham US therapy. The study involved 62 patients. The patients were randomly divided into two groups. The patients in group 1 (n = 30) were administered 1 W/cm², 1 MHz continuous US, and the patients in group 2 (n = 32) were administered sham US. The US treatment was applied for 8 min to each knee, 16 min in total, 5 d a wk, for a total of 10 sessions during 2 wk. The patients were evaluated immediately after treatment and 1 mo after therapy according to the visual analog scale (VAS), night pain, range of motion, morning stiffness, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne and Short Form-36 (SF-36) scales and 6 min walking distance. Improvement in pain and joint functions was observed in both groups according to the evaluation immediately after treatment and at 1 mo after the therapy. According to the evaluation results immediately after treatment, there was significant improvement in all pain scales (VAS, WOMAC, Lequesne, SF-36), morning stiffness and 6 min walking distance in patients receiving real US treatment (p < 0.05), but only in some pain scales (VAS, WOMAC) and functions in the group receiving sham US (p < 0.05). Significantly better improvement was observed in some pain scales (SF-36), functions (WOMAC, SF-36) and 6 min walking distance in the real US group. At 1 mo after therapy, no significant difference was observed between groups except for improvement in night pain in the real US group. In conclusion, US therapy has been found to be effective in reducing pain and improving physical function in the short term, but this positive effect was not persistent in the long term. However, we believe that the results of our study may contribute to ongoing research for the treatment of patients with knee OA, and further systematic investigation on larger patient populations may delineate the role of US in knee OA treatment.