The role of CD180 in hematological malignancies and inflammatory disorders.

Toll-like receptors play a significant role in the innate immune system and are also involved in the pathophysiology of many different diseases. Over the past 35 years, there have been a growing number of publications exploring the role of the orphan toll-like receptor, CD180. We therefore set out to provide a narrative review of the current evidence surrounding CD180 in both health and disease. We first explore the evidence surrounding the role of CD180 in physiology including its expression, function and signaling in antigen presenting cells (APCs) (dendritic cells, monocytes, and B cells). We particularly focus on the role of CD180 as a modulator of other TLRs including TLR2, TLR4, and TLR9. We then discuss the role of CD180 in inflammatory and autoimmune diseases, as well as in hematological malignancies of B cell origin, including chronic lymphocytic leukemia (CLL). Based on this evidence we produce a current model for CD180 in disease and explore the potential role for CD180 as both a prognostic biomarker and therapeutic target. Throughout, we highlight specific areas of research which should be addressed to further the understanding of CD180 biology and the translational potential of research into CD180 in various diseases

A surveillance system to assess the need for updating systematic reviews.

BackgroundSystematic reviews (SRs) can become outdated as new evidence emerges over time. Organizations that produce SRs need a surveillance method to determine when reviews are likely to require updating. This report describes the development and initial results of a surveillance system to assess SRs produced by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program.MethodsTwenty-four SRs were assessed using existing methods that incorporate limited literature searches, expert opinion, and quantitative methods for the presence of signals triggering the need for updating. The system was designed to begin surveillance six months after the release of the original review, and then ceforth every six months for any review not classified as being a high priority for updating. The outcome of each round of surveillance was a classification of the SR as being low, medium or high priority for updating.ResultsTwenty-four SRs underwent surveillance at least once, and ten underwent surveillance a second time during the 18 months of the program. Two SRs were classified as high, five as medium, and 17 as low priority for updating. The time lapse between the searches conducted for the original reports and the updated searches (search time lapse - STL) ranged from 11 months to 62 months: The STL for the high priority reports were 29 months and 54 months; those for medium priority reports ranged from 19 to 62 months; and those for low priority reports ranged from 11 to 33 months. Neither the STL nor the number of new relevant articles was perfectly associated with a signal for updating. Challenges of implementing the surveillance system included determining what constituted the actual conclusions of an SR that required assessing; and sometimes poor response rates of experts.ConclusionIn this system of regular surveillance of 24 systematic reviews on a variety of clinical interventions produced by a leading organization, about 70% of reviews were determined to have a low priority for updating. Evidence suggests that the time period for surveillance is yearly rather than the six months used in this project

Maca (L. meyenii) for improving sexual function: a systematic review

<p>Abstract</p> <p>Background</p> <p>Maca (<it>Lepidium meyenii</it>) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction.</p> <p>Methods</p> <p>We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca <it/>compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors.</p> <p>Results</p> <p>Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects.</p> <p>Conclusion</p> <p>The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.</p

Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia

<p>Abstract</p> <p>Background</p> <p><it>Francisella tularensis</it>, the causative agent of tularemia, displays subspecies-specific differences in virulence, geographic distribution, and genetic diversity. <it>F. tularensis </it>subsp. <it>holarctica </it>is widely distributed throughout the Northern Hemisphere. In Europe, <it>F. tularensis </it>subsp. <it>holarctica </it>isolates have largely been assigned to two phylogenetic groups that have specific geographic distributions. Most isolates from Western Europe are assigned to the B.Br.FTNF002-00 group, whereas most isolates from Eastern Europe are assigned to numerous lineages within the B.Br.013 group. The eastern geographic extent of the B.Br.013 group is currently unknown due to a lack of phylogenetic knowledge about populations at the European/Asian juncture and in Asia. In this study, we address this knowledge gap by describing the phylogenetic structure of <it>F. tularensis </it>subsp. <it>holarctica </it>isolates from the country of Georgia, and by placing these isolates into a global phylogeographic context.</p> <p>Results</p> <p>We identified a new genetic lineage of <it>F. tularensis </it>subsp. <it>holarctica </it>from Georgia that belongs to the B.Br.013 group. This new lineage is genetically and geographically distinct from lineages previously described from the B.Br.013 group from Central-Eastern Europe. Importantly, this new lineage is basal within the B.Br.013 group, indicating the Georgian lineage diverged before the diversification of the other known B.Br.013 lineages. Although two isolates from the Georgian lineage were collected nearby in the Ukrainian region of Crimea, all other global isolates assigned to this lineage were collected in Georgia. This restricted geographic distribution, as well as the high levels of genetic diversity within the lineage, is consistent with a relatively older origin and localized differentiation.</p> <p>Conclusions</p> <p>We identified a new lineage of <it>F. tularensis </it>subsp. <it>holarctica </it>from Georgia that appears to have an older origin than any other diversified lineages previously described from the B.Br.013 group. This finding suggests that additional phylogenetic studies of <it>F. tularensis </it>subsp. <it>holarctica </it>populations in Eastern Europe and Asia have the potential to yield important new insights into the evolutionary history and phylogeography of this broadly dispersed <it>F. tularensis </it>subspecies.</p

Effectiveness of Terbutaline Pump for the Prevention of Preterm Birth. A Systematic Review and Meta-Analysis

Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following acute treatment of preterm contractions. The effectiveness and safety of this maintenance tocolysis have not been clearly established. We aimed to systematically evaluate the effectiveness and safety of subcutaneous (SQ) terbutaline infusion by pump for maintenance tocolysis.MEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews and Dissemination databases, post-marketing surveillance data and grey literature were searched up to April 2011 for relevant experimental and observational studies. Two randomized trials, one nonrandomized trial, and 11 observational studies met inclusion criteria. Non-comparative studies were considered only for pump-related harms. We excluded case-reports but sought FDA summaries of post-marketing surveillance data. Non-English records without an English abstract were excluded. Evidence of low strength from observational studies with risk of bias favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks, mean days of pregnancy prolongation, and neonatal death. Observational studies of medium to high risk of bias also demonstrated benefit for other surrogate outcomes, such as birthweight and neonatal intensive care unit (NICU) admission. Several cases of maternal deaths and maternal cardiovascular events have been reported in patients receiving terbutaline tocolysis.Although evidence suggests that pump therapy may be beneficial as maintenance tocolysis, our confidence in its validity and reproducibility is low, suggesting that its use should be limited to the research setting. Concerns regarding safety of therapy persist

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

Objectives: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL. Results: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04). Conclusion: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes

SYNTHESIS OF GOLD NANOPARTICLES BY BLUE-GREEN ALGAE Spirulina platensis

Kalabegishvili T. et al. E14-2012-31 Synthesis of Gold Nanoparticles by Blue-Green Algae Spirulina platensis The synthesis of gold nanoparticles by one of the many popular microorganisms Å blue-green algae Spirulina platensis was studied. The complex of optical and analytical methods was applied for investigation of experimental samples after exposure to chloroaurate (HAuCl4) solution at different doses and for different time intervals. To characterize formed gold nanoparticles UV-vis, TEM, SEM, EDAX, and XRD were used. It was shown that after 1.5Ä2 days of exposure the extracellular formation of nanoparticles of spherical form and the distribution peak within the interval of 20Ä30 nm took place. To determine gold concentrations in the Spirulina platensis biomass, neutron activation analysis (NAA) and atomic absorption spectrometry (AAS) were applied. The results obtained evidence that the concentration of gold accumulated by Spirulina biomass is rapidly growing in the beginning, followed by some increase for the next few days. The obtained substance of Spirulina biomass with gold nanoparticles may be used for medical, pharmaceutical, and technological purposes. The investigation has been performed a