Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti

3D Visualisation and Quantification by Microcomputed Tomography of Late Gestational Changes in the Arterial and Venous Feto-Placental Vasculature of the Mouse

This study evaluates microcomputed tomography (micro-CT) as a method to obtain quantitative three-dimensional (3D) information on the arterial and venous vasculature of the mouse placenta. Surface renderings at embryonic days (E) 13.5, 15.5, and 18.5 (full term) revealed that the arterial and venous vasculature branched within the chorionic plate whereas only the arterial vasculature deeply penetrated the placenta. Umbilical vessel diameters measured by micro-CT did not significantly differ from those measured non-invasively in vivo by ultrasound biomicroscopy. Variability in umbilical diameters, and surface area and volume measurements of arterial and venous vascular trees due to experimental error was low relative to biological variability, and significant inter-litter differences within gestational ages were detected. Furthermore, umbilical vessel diameter increased significantly and incrementally to an arterial diameter of 0.631 ± 0.009 mm and a venous diameter of 0.690 ± 0.018 mm at E18.5. Umbilical vein diameter was 3–9% greater than the artery, and both were significantly correlated with embryonic body weight ( R ≥ 0.96). Surface area and volume were determined for vessels greater than the minimum resolvable diameter of 0.03 mm which therefore excluded capillaries. Arterial surface area and volume were unchanged from E13.5–15.5 but then more than doubled at E18.5 (to 170 ± 13 mm 2 and 7.2 ± 0.8 mm 3, respectively). Venous surface areas and volumes changed similarly with development although surface areas were lower than their arterial counterparts. We conclude that micro-CT has sufficient accuracy and precision to quantify late gestational changes in the 3D structure of the arterial and venous vasculature of the mouse placenta

Simultaneous Segmentation and Grading of Hippocampus for Patient Classification with Alzheimer’s Disease

Abstract. Purpose: To propose an innovative approach to better detect Alzheimer’s Disease (AD) based on a finer detection of hippocampus (HC) atrophy patterns. Method: In this paper, we propose a new approach to simultaneously perform segmentation and grading of the HC to better capture the patterns of pathology occurring during AD. Based on a patch-based framework, the novel proposed grading measure estimates the similarity of the patch surrounding the voxel under study with all the patches present in different training populations. The training library used during our experiments was composed by 2 populations, 50 Cognitively Normal subjects (CN) and 50 patients with AD. Tests were completed in a leave-one-out framework. Results: First, the evaluation of HC segmentation accuracy yielded a Dice’s Kappa of 0.88 for CN and 0.84 for AD. Second, the proposed HC grading enables detection of AD with a success rate of 89%. Finally, a comparison of several biomarkers was investigated using a linear discriminant analysis. Conclusion: Using the volume and the grade of the HC at the same time resulted in an efficient patient classification with a success rate of 90%

Automatic Generation of Training Data for Brain Tissue Classification from MRI

A novel fully automatic procedure for brain tissue classification from 3D magnetic resonance head images (MRI) is described. The procedure uses feature space proximity measures, and does not make any assumptions about the tissue intensity distributions. As opposed to existing methods, which are often sensitive to anatomical variability and pathology (such as atrophy), the proposed procedure is robust against morphological deviations from the model. Starting from a set of samples generated from prior tissue probability maps (the "model") in a standard, brain-based coordinate system ("stereotaxic space"), the method reduces the fraction of incorrectly labeled samples in this set from 25% down to 5%. The corrected set of samples is then used by a supervised classifier for classifying the entire 3D image. Validation experiments were performed on both real and simulated MRI data; the Kappa similarity measure increased from 0.83 to 0.94