Comparative Disease Assessment: a multi-causal approach for estimating the burden of mortality

Journal of Public Health - The Comparative Risk Assessment (CRA) framework comprehensively evaluates the impact of exposure to risk factors on health populations using the counterfactual causal...     

Mutation of murine adenylate kinase 7 underlies a primary ciliary dyskinesia phenotype

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder, characterized by progressive development of bronchiectasis, inflammation, and features characteristic of chronic obstructive pulmonary disease. We report here that a murine mutation of the evolutionarily conserved adenylate kinase 7 (Ak7) gene results in animals presenting with pathological signs characteristic of PCD, including ultrastructural ciliary defects and decreased ciliary beat frequency in respiratory epithelium. The mutation is associated with hydrocephalus, abnormal spermatogenesis, mucus accumulation in paranasal passages, and a dramatic respiratory pathology upon allergen challenge. Ak7 appears to be a marker for cilia with (9 + 2) microtubular organization. This is suggested by its tissue specificity of expression and also the stringent conservation of Ak7 ortholog structure only in protozoans and metazoans possessing motile (9 + 2) cilia. Collectively, our results indicate an ancestral and crucial role of Ak7 in maintaining ciliary structure and function, and suggest that mutations of the human ortholog may underlie a subset of genetically uncharacterized PCD cases.     

Quantitative Image Analysis in Mammary Gland Biology

In this paper we present a summary of recent quantitative approaches used for the analysis of macro and microscopic images in mammary gland biology. The advantages and disadvantages of whole mount analysis, reconstruction of serial tissue sections and nucleus/cell segmentation of either conventional and confocal images are discussed, as are applications of quantitative image analysis, such as quantification of protein levels or vasculature measurements in normal tissue and cancer. Integration of quantitative imaging into the further study of the mammary gland holds the promise of better understanding its tissue complexity that evolves during development, differentiation and disease.     

Contasure-needleless® compared with Monarc® for the treatment of stress urinary incontinence

Introduction and hypothesis

For the treatment of stress urinary incontinence (SUI), various retropubic and transobturator techniques have demonstrated high cure rates. Single-incision tapes, such as Contasure-Needleless® (C-NDL), have demonstrated similar cure rates to the inside-out transobturator sling (TVT-O®).The aim of this study was to analyse if C-NDL® is equally as effective as an outside-in transobturator sling (Monarc®) for the treatment of SUI.

Methods

We carried out a prospective, single-centre, randomised trial. The results were analysed for a non-inferiority test with a minimum postoperative follow-up of 12 months. The objective and subjective cure rates were evaluated by a stress test and a postoperative Sandvik Severity Index respectively. Patient satisfaction and operative complications were registered. The cure was defined by a negative stress test and SSI 0.

Results

A total of 187 patients were included, 89 and 98 undergoing C-NDL® and Monarc® respectively. Epidemiological and clinical data did not show and significant differences between both groups except a high prevalence of women who smoke (15.7% C-NDL® vs 6.1% Monarc®, p 0.03). The negative stress test was negative in 72 patients (80.9%) in C-NDL® compared with 85 (88.5%) in Monarc® (p 0.082). The SSI was 0 in 47 (66.2%) for C-NDL® and 61 (70.1%) for the Monarc® group (p 0.01). There were 14 (16.1%) and 8 (8.3%) dissatisfied patients for the C-NDL® and Monarc® groups respectively (p 0.068). The rate of complications was similar in both groups.

Conclusions

According to the non-inferiority test, C-NDL® is not inferior to Monarc® (post-surgical SSI test), but it is inferior in the comparison of a negative stress test and patient satisfaction.

     

Peripheral neuropathy: an underdiagnosed cause of erectile dysfunction

OBJECTIVES

? To assess the prevalence of peripheral neuropathy in patients with erectile dysfunction (ED). ? To evaluate the reliability of clinical tests such as the five‐item version of the International Index of Erectile Function (IIEF‐5) and the Neuropathy Symptom Score (NSS) classification system in predicting the concurrence of peripheral neuropathy.

PATIENTS AND METHODS

? We studied 90 patients who were consecutively recruited from the Department of Andrology of the Central Hospital of Asturias. ? Anamnesis included questions about risk factors related to ED. ? The severity of ED was classified according to IIEF‐5 scores and symptoms of peripheral neuropathy were assessed using the NSS. ? Neurophysiological tests included electromyography, nerve conduction studies, evoked potentials from pudendal and tibial nerves as well as bulbocavernosus reflex. ? Small fibre function was assessed using quantitative sensory tests and sympathetic skin response. Statistical analysis was performed using the SPSS‐11 program.

RESULTS

? Patients with more severe symptoms of peripheral neuropathy showed lower (worse) IIEF‐5 scores (P= 0.015) and required more aggressive therapies (P < 0.001). ? Neurophysiological exploration confirmed neurological pathology in 68.9% of patients, of whom 7.8% had myelopathy and 61.1% peripheral neuropathy. ? Polyneuropathy was found in 37.8% of the patients, of whom 8.9% had pure small fibre polyneuropathy, and pudendal neuropathy was diagnosed in 14.4%. ? No association between neurophysiological diagnosis and IIEF‐5 score was detected, but a statistical association was found between neuropathy and NSS scores.

CONCLUSIONS

? Up to now, the impact of peripheral neuropathy in the pathogenesis of ED has been underestimated. The combination of anamnesis and an ad hoc neurophysiological protocol showed its high prevalence and provided a more accurate prognosis. ? In future, clinical practice should optimize the assessment of pelvic small fibre function.     

Automatic segmentation of histological structures in mammary gland tissue sections

Real-time three-dimensional (3-D) reconstruction of epithelial structures in human mammary gland tissue blocks mapped with selected markers would be an extremely helpful tool for diagnosing breast cancer and planning treatment. Besides its clear clinical application, this tool could also shed a great deal of light on the molecular basis of the initiation and progression of breast cancer. We present a framework for real-time segmentation of epithelial structures in two-dimensional (2-D) images of sections of normal and neoplastic mammary gland tissue blocks. Complete 3-D rendering of the tissue can then be done by surface rendering of the structures detected in consecutive sections of the blocks. Paraffin-embedded or frozen tissue blocks are first sliced and sections are stained with hematoxylin and eosin. The sections are then imaged using conventional bright-field microscopy and their background corrected using a phantom image. We then use the fast-marching algorithm to roughly extract the contours of the different morphological structures in the images. The result is then refined with the level-set method, which converges to an accurate (subpixel) solution for the segmentation problem. Finally, our system stacks together the 2-D results obtained in order to reconstruct a 3-D representation of the entire tissue block under study. Our method is illustrated with results from the segmentation of human and mouse mammary gland tissue samples.