Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice.</p> <p>Methods</p> <p>BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline.</p> <p>Results</p> <p>The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control.</p> <p>Conclusions</p> <p>Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.</p

Record linkage to obtain birth outcomes for the evaluation of screening biomarkers in pregnancy: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Linking population health data to pathology data is a new approach for the evaluation of predictive tests that is potentially more efficient, feasible and efficacious than current methods. Studies evaluating the use of first trimester maternal serum levels as predictors of complications in pregnancy have mostly relied on resource intensive methods such as prospective data collection or retrospective chart review. The aim of this pilot study is to demonstrate that record-linkage between a pathology database and routinely collected population health data sets provides follow-up on patient outcomes that is as effective as more traditional and resource-intensive methods. As a specific example, we evaluate maternal serum levels of PAPP-A and free <it>β</it>-hCG as predictors of adverse pregnancy outcomes, and compare our results with those of prospective studies.</p> <p>Methods</p> <p>Maternal serum levels of PAPP-A and free <it>β</it>-hCG for 1882 women randomly selected from a pathology database in New South Wales (NSW) were linked to routinely collected birth and hospital databases. Crude relative risks were calculated to investigate the association between low levels (multiples of the median ≤ 5^thpercentile) of PAPP-A or free <it>β</it>-hCG and the outcomes of preterm delivery (<37 weeks), small for gestational age (<10^thpercentile), fetal loss and stillbirth.</p> <p>Results</p> <p>Using only full name, sex and date of birth for record linkage, pregnancy outcomes were available for 1681 (89.3%) of women included in the study. Low levels of PAPP-A had a stronger association with adverse pregnancy outcomes than a low level of free <it>β</it>-hCG which is consistent with results in published studies. The relative risk of having a preterm birth with a low maternal serum PAPP-A level was 3.44 (95% CI 1.96–6.10) and a low free <it>β</it>-hCG level was 1.31 (95% CI 0.55–6.16).</p> <p>Conclusion</p> <p>This study provides data to support the use of record linkage for outcome ascertainment in studies evaluating predictive tests. Linkage proportions are likely to increase if more personal identifiers are available. This method of follow-up is a cost-efficient technique and can now be applied to a larger cohort of women.</p

Implementation of the external cephalic version in breech delivery. Dutch national implementation study of external cephalic version

<p>Abstract</p> <p>Background</p> <p>Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less.</p> <p>We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling.</p> <p>Method/design</p> <p>The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV.</p> <p>The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured.</p> <p>Discussion</p> <p>This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term.</p> <p>Trial Registration</p> <p>Dutch Trial Register (NTR): 1878</p

Depth-Sensing Indentation on REBa2Cu3O(7-\delta) Single Crystals obtained from Xenotime Mineral

A natural mixture of heavy rare earths oxides extracted from xenotime mineral have been used to prepare large single crystals of high-temperature REBa2Cu3O(7-\delta) superconductor grown using the CuO-BaO self-flux method. Its mechanical properties along the ab-plane were characterized using instrumented indentation. Hardness and elastic modulus were obtained by the Oliver and Pharr method and corresponds to 7.4 \pm 0.2 GPa and in range 135-175 GPa at small depths, respectively. Increasing the load promotes the nucleation of lateral cracks that causes a decrease in hardness and the measured elastic modulus by instrumented indentation at higher loads. The indentation fracture toughness was estimated by measuring the radial crack length from cube-corner indentations at various loads and was 0.8 \pm 0.2 MPa.m1/2. The observed slip systems of REBa2Cu3O(7-\delta) single crystals were [100](001) and [010](001), the same as for YBa2Cu3O(7-\delta) single crystals. The initial stages of deformation and fracture in the indentation process were investigated. The hardness and elastic modulus were not strongly modified by the crystallographic orientation in the ab-plane. This was interpreted in terms of the resolved shear stresses in the active slip systems. Evidence of cracking along the {100} and {110} planes on the ab-plane was observed. As a conclusion, the mechanical properties of REBa2Cu3O(7-\delta) single crystals prepared from xenotime are equivalent to those of YBa2Cu3O(7-\delta) single crystals produced by conventional rare earths oxides.Comment: The paper will appear in Volume 42 (2012) of the Brazilian Journal of Physic

Serum proteome analysis for profiling protein markers associated with carcinogenesis and lymph node metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), one of the most common cancers in population with Chinese or Asian progeny, poses a serious health problem for southern China. It is unfortunate that most NPC victims have had lymph node metastasis (LNM) when first diagnosed. We believe that the 2D based serum proteome analysis can be useful in discovering new biomarkers that may aid in the diagnosis and therapy of NPC patients. To filter the tumor specific antigen markers of NPC, sera from 42 healthy volunteers, 27 non-LNM NPC patients and 37 LNM NPC patients were selected for screening study using 2D combined with MS. Pretreatment strategy, including sonication, albumin and immunoglobulin G (IgG) depletion, was adopted for screening differentially expressed proteins of low abundance in serum. By 2D image analysis and MALDI-TOF-MS identification, twenty-three protein spots were differentially expressed. Three of them were further validated in the sera using enzyme-linked immunosorbent assay (ELISA). Our research demonstrates that HSP70, sICAM-1 and SAA, confirmed with ELISA at sera and immunohistochemistry, are potential NPC metastasis-specific serum biomarkers which may be of great underlying significance in clinical detection and management of NPC

Prevalence and determinants of unintended pregnancies amongst women attending antenatal clinics in Pakistan

Background: Unintended pregnancies are a global public health concern and contribute significantly to adverse maternal and neonatal health, social and economic outcomes and increase the risks of maternal deaths and neonatal mortality. In countries like Pakistan where data for the unintended pregnancies is scarce, studies are required to estimate its accurate prevalence and predictors using more specific tools such as the London Measure of Unplanned Pregnancies (LMUP). Methods: We conducted a hospital based cross sectional survey in two tertiary care hospitals in Pakistan. We used a pre tested structured questionnaire to collect the data on socio-demographic characteristics, reproductive history, awareness and past experience with contraceptives and unintended pregnancies using six item the LMUP. We used Univariate and multivariate analysis to explore the association between unintended pregnancies and predictor variables and presented the association as adjusted odds ratios. We also evaluated the psychometric properties of the Urdu version of the LMUP. Results: Amongst 3010 pregnant women, 1150 (38.2%) pregnancies were reported as unintended. In the multivariate analysis age \u3c 20 years (AOR 3.5 1.1-6.5), being illiterate (AOR 1.9 1.1-3.4), living in a rural setting (1.7 1.2-2.3), having a pregnancy interval of = \u3c 12 months (AOR 1.7 1.4-2.2), having a parity of \u3e2 (AOR 1.4 1.2-1.8), having no knowledge about contraceptive methods (AOR 3.0 1.7-5.4) and never use of contraceptive methods (AOR 2.3 1.4-5.1) remained significantly associated with unintended pregnancy. The Urdu version of the LMUP scale was found to be acceptable, valid and reliable with the Cronbach\u27s alpha of 0.85. Conclusions: This study explores a high prevalence of unintended pregnancies and important factors especially those related to family planning. Integrated national family program that provides contraceptive services especially the modern methods to women during pre-conception and post-partum would be beneficial in averting unintended pregnancies and their related adverse outcomes in Pakistan

Small Heat Shock Proteins Potentiate Amyloid Dissolution by Protein Disaggregases from Yeast and Humans

The authors define how small heat-shock proteins synergize to regulate the assembly and disassembly of a beneficial prion, and then they exploit this knowledge to identify the human amyloid depolymerase

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)