Efficient quantitative assessment of facial paralysis using iris segmentation and active contour-based key points detection with hybrid classifier

BACKGROUND: Facial palsy or paralysis (FP) is a symptom that loses voluntary muscles movement in one side of the human face, which could be very devastating in the part of the patients. Traditional methods are solely dependent to clinician’s judgment and therefore time consuming and subjective in nature. Hence, a quantitative assessment system becomes apparently invaluable for physicians to begin the rehabilitation process; and to produce a reliable and robust method is challenging and still underway. METHODS: We introduce a novel approach for a quantitative assessment of facial paralysis that tackles classification problem for FP type and degree of severity. Specifically, a novel method of quantitative assessment is presented: an algorithm that extracts the human iris and detects facial landmarks; and a hybrid approach combining the rule-based and machine learning algorithm to analyze and prognosticate facial paralysis using the captured images. A method combining the optimized Daugman’s algorithm and Localized Active Contour (LAC) model is proposed to efficiently extract the iris and facial landmark or key points. To improve the performance of LAC, appropriate parameters of initial evolving curve for facial features’ segmentation are automatically selected. The symmetry score is measured by the ratio between features extracted from the two sides of the face. Hybrid classifiers (i.e. rule-based with regularized logistic regression) were employed for discriminating healthy and unhealthy subjects, FP type classification, and for facial paralysis grading based on House-Brackmann (H-B) scale. RESULTS: Quantitative analysis was performed to evaluate the performance of the proposed approach. Experiments show that the proposed method demonstrates its efficiency. CONCLUSIONS: Facial movement feature extraction on facial images based on iris segmentation and LAC-based key point detection along with a hybrid classifier provides a more efficient way of addressing classification problem on facial palsy type and degree of severity. Combining iris segmentation and key point-based method has several merits that are essential for our real application. Aside from the facial key points, iris segmentation provides significant contribution as it describes the changes of the iris exposure while performing some facial expressions. It reveals the significant difference between the healthy side and the severe palsy side when raising eyebrows with both eyes directed upward, and can model the typical changes in the iris region

Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l−1, 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers

Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes

The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects