1,170 research outputs found

    Postural changes in women with chronic pelvic pain: a case control study

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    <p>Abstract</p> <p>Background</p> <p>Chronic pelvic pain (CPP) is a lower abdominal pain lasting at least 6 months, occurring continuously or intermittently and not associated exclusively with menstruation or intercourse. Although the musculoskeletal system has been found to be involved in CPP, few studies have assessed the contribution of posture in women with CPP. We aimed to determine if the frequency of postural changes was higher in women with CPP than healthy subjects.</p> <p>Methods</p> <p>A case-control study included 108 women with CPP of more than 6 months' duration (CPP group) who consecutively attended at the Hospital of the University of São Paulo and 48 healthy female volunteers (control group). Postural assessment was noninvasive and performed in the standing position, with the reference points of Kendall used as normal parameters. Factors associated with CPP were assessed by logistic regression analysis.</p> <p>Results</p> <p>Logistic regression showed that the independent factors associated with CPP were postural changes in the cervical spine (OR 4.1; 95% CI 1.6–10.7; p < 0.01) and scapulae (OR 2.9; 95% CI 1.1–7.6; p < 0.05).</p> <p>Conclusion</p> <p>Musculoskeletal changes were associated with CPP in 34% of women. These findings suggest that a more detailed assessment of women with CPP is necessary for better diagnosis and for more effective treatment.</p

    Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

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    BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

    The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

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    Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

    Novel, synergistic antifungal combinations that target translation fidelity

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    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8 fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone

    Improving Fecal Occult Blood Testing Compliance Using a Mailed Educational Reminder

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    Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the United States. Randomized controlled trials have shown that annual screening fecal occult blood testing (FOBT) reduces CRC mortality and incidence. However, patient compliance with FOBT is low. To determine whether a mailed educational reminder increases FOBT card return rates and to examine predictors of FOBT compliance. Blinded, randomized, controlled trial at the Veteran Affairs Medical Center, San Diego, California. Seven hundred and seventy-five consecutive patients ≥50 years of age referred by their primary care physicians for FOBT. Patients were randomly assigned to the usual care group or the intervention group. Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group only. The primary outcome was proportion of returned FOBT cards after 6 months. Patient demographic, clinical characteristics and prior FOBT completed were collected for multivariate regression analysis. At 6 months after card distribution, 64.6% of patients in the intervention group returned cards compared with 48.4% in the control group (P &lt; 0.001). Patients who received a mailed reminder (OR 2.02; 95% CI: 1.48–2.74) or have a prior history of returning the FOBT cards (OR 1.87; 95% CI: 1.29–2.70) were more likely to return the FOBT cards. Patients with current or recent illicit drug use were less likely to return the FOBT cards (OR 0.26; 95% CI: 0.13–0.50). A simple mailed educational reminder significantly increases compliance with FOBT for CRC screening
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