Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy

<p>Abstract</p> <p>Background-</p> <p>Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA.</p> <p>Methods-</p> <p>Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895). Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol), and quality of life (QOL) were measured at various time points from 0 to 12 months. PSA outcome was evaluated.</p> <p>Results-</p> <p>Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (<it>p </it>= 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.</p> <p>Conclusion-</p> <p>Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.</p

Closing the Mind's Eye: Incoming Luminance Signals Disrupt Visual Imagery

Mental imagery has been associated with many cognitive functions, both high and low-level. Despite recent scientific advances, the contextual and environmental conditions that most affect the mechanisms of visual imagery remain unclear. It has been previously shown that the greater the level of background luminance the weaker the effect of imagery on subsequent perception. However, in these experiments it was unclear whether the luminance was affecting imagery generation or storage of a memory trace. Here, we report that background luminance can attenuate both mental imagery generation and imagery storage during an unrelated cognitive task. However, imagery generation was more sensitive to the degree of luminance. In addition, we show that these findings were not due to differential dark adaptation. These results suggest that afferent visual signals can interfere with both the formation and priming-memory effects associated with visual imagery. It follows that background luminance may be a valuable tool for investigating imagery and its role in various cognitive and sensory processes

A sensitive flow cytometric methodology for studying the binding of L. chagasi to canine peritoneal macrophages

BACKGROUND: The Leishmania promastigote-macrophage interaction occurs through the association of multiple receptors on the biological membrane surfaces. The success of the parasite infection is dramatically dependent on this early interaction in the vertebrate host, which permits or not the development of the disease. In this study we propose a novel methodology using flow cytometry to study this interaction, and compare it with a previously described "in vitro" binding assay. METHODS: To study parasite-macrophage interaction, peritoneal macrophages were obtained from 4 dogs and adjusted to 3 × 10(6 )cells/mL. Leishmania (Leishmania) chagasi parasites (stationary-phase) were adjusted to 5 × 10(7 )cells/mL. The interaction between CFSE-stained Leishmania chagasi and canine peritoneal macrophages was performed in polypropylene tubes to avoid macrophage adhesion. We carried out assays in the presence or absence of normal serum or in the presence of a final concentration of 5% of C5 deficient (serum from AKR/J mice) mouse serum. Then, the number of infected macrophages was counted in an optical microscope, as well as by flow citometry. Macrophages obtained were stained with anti-CR3 (CD11b/CD18) antibodies and analyzed by flow citometry. RESULTS: Our results have shown that the interaction between Leishmania and macrophages can be measured by flow cytometry using the fluorescent dye CFSE to identify the Leishmania, and measuring simultaneously the expression of an important integrin involved in this interaction: the CD11b/CD18 (CR3 or Mac-1) β2 integrin. CONCLUSION: Flow cytometry offers rapid, reliable and sensitive measurements of single cell interactions with Leishmania in unstained or phenotypically defined cell populations following staining with one or more fluorochromes

Are we losing the battle against cardiometabolic disease? The case for a paradigm shift in primary prevention

Kraushaar LE, Krämer A. Are we losing the battle against cardiometabolic disease? The case for a paradigm shift in primary prevention. BMC Public Health. 2009;9(1):64.Background: Cardiovascular and diabetic disease are the leading and preventable causes of death worldwide. The currently prognosticated dramatic increase in disease burden over the next two decades, however, bespeaks a low confidence in our prevention ability. This conflicts with the almost enthusiastic reporting of study results, which demonstrate substantial risk reductions secondary to simple lifestyle changes. Discussion: There is a case to be made for a disregard of the difference between statistical significance and clinical relevance of the reported data. Nevertheless, lifestyle change remains the main weapon in our battle against the epidemic of cardiometabolic disease. But along the way from risk screening to intervention to maintenance the compound inefficiencies of current primary preventive strategies marginalize their impact. Summary: Unless we dramatically change the ways in which we deploy preventive interventions we will inevitably lose the battle. In this paper we will argue for three provocative strategy changes, namely (a) the disbanding of screening in favor of population-wide enrollment into preventive interventions, (b) the substitution of the current cost utility analysis for a return-on-investment centered appraisal of interventions, and (c) the replacement of standardized programs modeled around acute care by individualized and perpetual interventions

Effects of clinical pathways in the joint replacement: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>A meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs.</p> <p>Methods</p> <p>Medline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2.</p> <p>Results</p> <p>Twenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home.</p> <p>Conclusion</p> <p>The results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way, teams critically analyse the actual organisation of the process and the multidisciplinary team is highly involved in the re-organisation. Further studies should focus on the evaluation of pathways as complex interventions to help to understand which mechanisms within the clinical pathways can really improve the quality of care. With the need for knee and hip joint replacement on the rise, the use of clinical pathways might contribute to better quality of care and cost-effectiveness.</p

Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion