instruction:
Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Context: Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH.', 'A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA.', 'Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release.
Answer: LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing aPL-induced trophoblast inflammation and reversing LMWH-induced sFlt-1 secretion.
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Does vitamin D reverse aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast?


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Context: The Tonnis radiographic classification of developmental dysplasia of the hip (DDH) has been used as a prognostic indicator for patients with walking-age DDH. The International Hip Dysplasia Institute (IHDI) classification, a new radiographic classification system, has been proposed to be more reliable by its creators. We sought to validate its reliability using independent observers, to compare it to the Tonnis method, and to assess its prognostic significance in a large cohort of patients.', 'A consecutive series of walking-age DDH patients were examined radiographically and classified by the Tonnis and IHDI schemes by 3 independent observers. Interobserver agreement was determined using the Kappa method. Clinical data were collected on patients with regard to success of closed reduction, need for later pelvic osteotomy, and presence of subsequent radiographic avascular necrosis (AVN). The prognostic value of the Tonnis and IHDI classifications to predict these clinical outcomes was determined.', 'A total of 287 hips were available for analysis of the classification schemes. In total, 235 hips underwent attempted closed reduction and were eligible for analysis of successful closed reduction, and 131 hips had >4-year follow-up and were utilized for analysis of late pelvic osteotomy and AVN. Both classifications showed excellent interobserver reliability and in general, there was nonstatistically significant better reliability for the IHDI versus the Tonnis classification. In multivariate analysis, both IHDI and Tonnis classifications were found to be predictive of successful closed reduction and need for late pelvic osteotomy. Both methods showed trends toward being predictive of AVN rate, without statistical significance.
Answer: The IHDI classification is subjectively more facile to use and has excellent interrelater agreement for classifying the radiographic severity of DDH. It is also reliable in predicting success of closed reduction and need for late pelvic osteotomy.
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Is a New Radiographic Classification System for Developmental Hip Dysplasia Reliable and Predictive of Successful Closed Reduction and Late Pelvic Osteotomy?


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Context: Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities. Our previous findings showed that oleuropein exhibits leishmanicidal effects against three Leishmania spp. in vitro, and minimizes the parasite burden in L. donovani-infected BALB/c mice. The aim of the present study is to investigate the possible mechanism(s) that mediate this leishmanicidal activity.', 'We determined the efficacy of oleuropein in elevating ROS and NO production in L. donovani-infected J774A.1 macrophages and in explanted splenocytes and hepatocytes obtained from L. donovani-infected BALB/c mice. We also assessed the expression of genes that are related to inflammation, T-cell polarization and antioxidant defense, in splenocytes. Finally, we determined the ratios of specific IgG2a/IgG1 antibodies and DTH reactions in L. donovani-infected BALB/c mice treated with oleuropein.', "Oleuropein was able to elevate ROS production in both in vitro and in vivo models of visceral leishmaniasis and raised NO production in ex vivo cultures of splenocytes and hepatocytes. The extensive oxidative stress found in oleuropein-treated mice was obviated by the upregulation of the host's antioxidant enzyme (mGCLC) and the simultaneous downregulation of the corresponding enzyme of the parasite (LdGCLC). Moreover, oleuropein was able to mount a significant Th1 polarization characterized by the expression of immune genes (IL-12β, IL-10, TGF-β1, IFN-γ) and transcription factors (Tbx21 and GATA3). Moreover, this immunomodulatory effect was also correlated with an inhibitory effect on IL-1β gene expression, rather than with the expression of IL-1α, IL-1rn and TNF-α. Furthermore, oleuropein-treated BALB/c mice mounted a delayed-type hypersensitivity (DTH) response and an elevated Leishmania-specific IgG2a/IgG1 ratio that clearly demonstrated an in vivo protective mechanism.
Answer: The ability of Oleuropein to promote a Th1 type immune response in L. donovani-infected BALB/c mice points towards the candidacy of this bioactive compound as an immunomodulatory agent that may complement therapeutic approaches to leishmaniasis.
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Is the leishmanicidal activity of oleuropein selectively regulated through inflammation- and oxidative stress-related genes?