A study of non-steroidal anti-inflammatory drugs on human neutrophil toxic oxygen metabolite production

A study was carried out on the effect of a wide range of nonsteroidal anti-inflammatory drugs (NSAIDs) on the receptor- and postreceptor-mediated respiratory burst in human neutrophils. Superoxide (O2-) - which can give rise to toxic oxygen metabolites known to cause tissue damage - was measured spectrophotometrically by the reduction of ferricytochrome C. It was found that the NSAIDs fell into three categories: 1) those that increased production, 2) those that had no effect and 3) those that decreased production. These findings could have clinical relevance for the therapy of chronic inflammatory diseases such as rheumatoid arthritis. In order to investigate the mode of action of those drugs which potentiated 01 release, a pharmacological study of the transduction mechanisms of the respiratory burst was undertaken. A number of cyclooxygenase and 5-lipoxygenase inhibitors had no effect on the stimulated response, implying that the enhancing effect of the NSAIDs was independent of their effect on arachidonic metabolism. Putative "specific" inhibitors of the diacylglycerol (DAG) metabolizing enzyme, DAG kinase, gave similar results to those obtained with the potentiating NSAIDs (with the exception of RAF), indicating that the NSAID effect could involve increased DAG/protein kinase C (PKC) activity. The role of the DAG/PKC pathway in the respiratory burst was addressed using a novel series of potent PKC inhibitors reported to be selective for PKC over other protein kinases. It was found that these agents inhibited 01 production induced by both receptor and postreceptor stimuli, and also in activation sequences that are reported to be Ca2+-independent. Differences in the order of potency of the PKC inhibitors within the range of stimuli used indicated that there might be different PKC isoenzymes, differentially affected by the inhibitors. The potentiating NSAIDs were tested for an effect on isolated PKC, but none were found to directly activate the enzyme. Inhibition by wortmannin of the response to some stimuli may suggest a role for the phospholipase D pathway of DAG generation. This study supports a role for the DAG/PKC pathway in signal- transduction for the neutrophil respiratory burst

The motivation of shorthand

This item was digitized by the Internet Archive. Thesis (Ed.M.)--Boston Universityhttps://archive.org/details/motivationofshor00two

Relationship between teacher checklist, parent rating scale, and California Test of Personality in grades I, II, and III

Thesis (Ed.M.)--Boston Universit

Reduced duration mismatch negativity in adolescents with psychotic symptoms: further evidence for mismatch negativity as a possible biomarker for vulnerability to psychosis

Background: Deficits in the mismatch negativity (MMN) and P3a components are the most reliable and robust findings in schizophrenia. These abnormalities have also been recently documented in individuals clinically at risk for psychosis, indicating that the MMN may be a potential biomarker for psychosis. However, the at risk samples included in MMN studies are characterised by pre-existing clinical symptomatology and significant functional decline which are related to MMN amplitude. These factors may be potential confounds in determining whether deficient MMN is present prior to clinical manifestation of the disorder. Therefore, investigating the MMN in the extended psychosis phenotype comprising adolescents with psychotic symptoms from the general population may provide important information on whether abnormal MMN is apparent in the earliest stages of risk. Methods: Thirty six adolescents completed a duration deviant MMN task. Fourteen adolescents with psychotic symptoms comprised the at risk group and 22 with no psychotic symptoms comprised the Controls. The task consisted of 85% standard tones (25 ms) and 15% deviant tones (50 ms). The groups were compared on MMN and P3a amplitude and latency across frontocentral and temporal electrodes. Results: Adolescents with psychotic symptoms were characterised by a reduction in MMN amplitude at frontal and temporal regions compared to the controls. Conclusions: This is the first study to demonstrate impaired auditory discrimination for duration deviant tones in nonclinical adolescents with psychotic symptoms. These findings suggest that MMN amplitude may be a possible biomarker for vulnerability to psychosis

Five-Year Follow Up of a Low Glycaemic Index Dietary Randomised Controlled Trial in Pregnancy—No Long-Term Maternal Effects of a Dietary Intervention

Objective: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. Design: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. Setting: Dublin, Ireland (2007–2016). Population: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. Methods: Fasting glucose was measured at 13 and 28 weeks’ gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. Outcome: Maternal diet, HbA1c, and weight retention at 5 years post-intervention. Results: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36–3.04) and parity ≥3 (B 1.04, 95% CI 0.09–1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B −0.06, 95% CI −0.11 to −0.02), gestational weight gain (B 0.19, 95% CI 0.00–0.38), and GI (B 0.26, 95% CI 0.06–0.46) at 5 years. Conclusions: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. Tweetable abstract: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later

Optimizing parameters of an open-source airway segmentation algorithm using different CT images.

Background: Computed tomography (CT) helps physicians locate and diagnose pathological conditions. In some conditions, having an airway segmentation method which facilitates reconstruction of the airway from chest CT images can help hugely in the assessment of lung diseases. Many efforts have been made to develop airway segmentation algorithms, but methods are usually not optimized to be reliable across different CT scan parameters. Methods: In this paper, we present a simple and reliable semi-automatic algorithm which can segment tracheal and bronchial anatomy using the open-source 3D Slicer platform. The method is based on a region growing approach where trachea, right and left bronchi are cropped and segmented independently using three different thresholds. The algorithm and its parameters have been optimized to be efficient across different CT scan acquisition parameters. The performance of the proposed method has been evaluated on EXACT’09 cases and local clinical cases as well as on a breathing pig lung phantom using multiple scans and changing parameters. In particular, to investigate multiple scan parameters reconstruction kernel, radiation dose and slice thickness have been considered. Volume, branch count, branch length and leakage presence have been evaluated. A new method for leakage evaluation has been developed and correlation between segmentation metrics and CT acquisition parameters has been considered. Results: All the considered cases have been segmented successfully with good results in terms of leakage presence. Results on clinical data are comparable to other teams’ methods, as obtained by evaluation against the EXACT09 challenge, whereas results obtained from the phantom prove the reliability of the method across multiple CT platforms and acquisition parameters. As expected, slice thickness is the parameter affecting the results the most, whereas reconstruction kernel and radiation dose seem not to particularly affect airway segmentation. Conclusion: The system represents the first open-source airway segmentation platform. The quantitative evaluation approach presented represents the first repeatable system evaluation tool for like-for-like comparison between different airway segmentation platforms. Results suggest that the algorithm can be considered stable across multiple CT platforms and acquisition parameters and can be considered as a starting point for the development of a complete airway segmentation algorithm

Determination of a suitable low-dose abdominopelvic CT protocol using model-based iterative reconstruction through cadaveric study.

Introduction: Cadaveric studies provide a means of safely assessing new technologies and optimizing scanning prior to clinical validation. Reducing radiation exposure in a clinical setting can entail incremental dose reductions to avoid missing important clinical findings. The use of cadavers allows assessment of the impact of more substantial dose reductions on image quality. Our aim was to identify a suitable low‐dose abdominopelvic CT protocol for subsequent clinical validation. Methods: Five human cadavers were scanned at one conventional dose and three low‐dose settings. All scans were reconstructed using three different reconstruction algorithms: filtered back projection (FBP), hybrid iterative reconstruction (60% FBP and 40% adaptive statistical iterative reconstruction (ASIR40)), and model‐based iterative reconstruction (MBIR). Two readers rated the image quality both quantitatively and qualitatively. Results: Model‐based iterative reconstruction images had significantly better objective image noise and higher qualitative scores compared with both FBP and ASIR40 images at all dose levels. The greatest absolute noise reduction, between MBIR and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62% compared with conventional dose studies reconstructed with ASIR40, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artefact scores. Conclusion: This cadaveric study demonstrates that MBIR reduces image noise and improves image quality in abdominopelvic CT images acquired with dose reductions of up to 62%

Relational autonomy: an example from breast cancer nursing

This article is an exploration of how the concept of relational autonomy might be applied in practice. The discussion uses the example of breast cancer nursing as a lens through which to consider how a view of autonomy as relational might affect the ways in which practitioners work with their clients