Ligand-based virtual screening procedure for the prediction and the identification of novel β-amyloid aggregation inhibitors using Kohonen maps and Counterpropagation Artificial Neural Networks

In this work we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of 62 N-phenylanthranilic acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence.     

Survival from breast cancers managed by surgeons participating in the National Breast Cancer Audit of the Royal Australasian College of Surgeons

Background: The National Breast Cancer Audit (NBCA) of the Royal Australasian College of Surgeons has collected data on early breast cancer since 1998. In this project, deaths were traced by linkage of NBCA patient identifiers (first three digits of surname and date of birth) with the National Death Index that covers all deaths in Australia. Methods: Death data were traced to 31 December 2007. Invasive cancers diagnosed in 1998–2005 were included in survival analyses to allow enough follow‐up for assessment. Survivals were compared with survivals for similar stages recorded by the New South Wales (NSW) Cancer Registry and USA Surveillance Epidemiology and End Results (SEER) programme. Survivals were analysed by conventional clinical risk factors to see if expected differences presented. Results: The 5‐year survival from breast cancer of 93% for NBCA cases was the same as the SEER figure for local and regional cases combined in 1996–2004. The NBCA figure for localized cases was 97%, which was the same as for NSW. Node‐positive NBCA cancers had a 5‐year survival of 89%, which was slightly higher than the corresponding 86% for NSW, which may reflect exclusion from the NBCA of some cases with a poorer prognosis, including those with positive fixed nodes. As expected, lower survivals presented for older cases and those with conventional clinical risk factors. Conclusions: These survivals are credible both overall and by clinical risk factor. Opportunities present to use these data for survival monitoring and to investigate survival by socio‐demographic characteristic, treatment protocol, case volume and provider characteristics.     

Unattended versus attended automated office blood pressure: Systematic review and meta‐analysis of studies using the same methodology for both methods

There is increasing interest in unattended automated office blood pressure (OBP) measurement, which gives lower blood pressure values than the conventional auscultatory OBP. Whether unattended automated OBP differs from standardized attended automated OBP performed using the same device and measurement protocol remains uncertain. A systematic review and meta‐analysis of studies (aggregate data) comparing unattended vs attended automated OBP using the same device and measurement protocol (conditions, number of measurements, visits) was performed. Ten eligible studies (n = 1004, weighted age 60.8 ± 4.2 [SD] years, 55% males) were analyzed. Unattended OBP (pooled systolic/diastolic 133.9 [95% CI: 129.7, 138]/80.6 [95% CI: 77, 84.2] mm Hg) did not differ from attended OBP (135.3 [95% CI: 130.9, 139.6]/81 [95% CI: 77.6, 84.3] mm Hg); pooled systolic OBP difference −1.3, 95% CI: −4.3, 1.7 mm Hg and diastolic −0.4, 95% CI: −1.2, 0.3 mm Hg. Nine of ten studies achieved high quality score and no publication bias was identified. Meta‐regression analysis did not reveal any effect of age, gender, or attended systolic OBP on the unattended‐attended systolic OBP difference (P = NS for all). However, there was a trend toward higher attended than unattended OBP at higher OBP levels. These data suggest that, when the same device and measurement protocol are used, attended automated OBP provides similar blood pressure values as unattended automated OBP. Although unattended automated OBP is theoretically advantageous as it ensures that standardized conditions and measurement protocol are used, attended automated OBP, if carefully performed, appears to be a reasonable and practical alternative.     

Animal models for arthritis: innovative tools for prevention and treatment

The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in 'omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology.     

Dermoids of the eustachian tube: CT and MR findings with histologic correlation.

Two patients with congenital dermoids of the eustachian tube presented with recurrent otitis media and chronic otorrhea resistant to antimicrobial therapy. CT demonstrated fat density, homogeneous lesions, filling and expanding the eustachian tube. On MR, signal from the lesions was consistent with fat, and the relationship with the internal carotid artery was better delineated than by CT. Microscopically, the masses consisted of a conglomeration of ectodermal and mesodermal elements.     

MR findings in kernicterus.

We describe the MR appearance of kernicterus (bilirubin encephalopathy). T2-weighted images show high signal bilaterally in the globus pallidus, a known area of cerebral deposition of bilirubin.