Texture-based characterization of subskin features by specified laser speckle effects at λ = 650 nm region for more accurate parametric 'skin age' modelling.

OBJECTIVE: The textural structure of 'skin age'-related subskin components enables us to identify and analyse their unique characteristics, thus making substantial progress towards establishing an accurate skin age model. METHODS: This is achieved by a two-stage process. First by the application of textural analysis using laser speckle imaging, which is sensitive to textural effects within the λ = 650 nm spectral band region. In the second stage, a Bayesian inference method is used to select attributes from which a predictive model is built. RESULTS: This technique enables us to contrast different skin age models, such as the laser speckle effect against the more widely used normal light (LED) imaging method, whereby it is shown that our laser speckle-based technique yields better results. CONCLUSION: The method introduced here is non-invasive, low cost and capable of operating in real time; having the potential to compete against high-cost instrumentation such as confocal microscopy or similar imaging devices used for skin age identification purposes.

Optimized parametric skin modelling for diagnosis of skin abnormalities by combining light back-scatter and laser speckle imaging.

BACKGROUND/PURPOSE: Optical and parametric skin imaging methods which can efficiently identify invisible sub-skin features or subtle changes in skin layers are very important for accurate optical skin modelling. In this study, a hybrid method is introduced that helps develop a parametric optical skin model by utilizing interdisciplinary techniques including light back-scatter analysis, laser speckle imaging, image-texture analysis and Bayesian inference methods. The model aims to detect subtle skin changes and hence very early signs of skin abnormalities/diseases. METHODS: Light back-scatter and laser speckle image textural analysis are applied onto the normal and abnormal skin regions (lesions) to generate set of attributes/parameters. These are then optimized by Bayesian inference method in order to build an optimized parametric model. RESULTS: The attributes selected by Bayesian inference method in the optimization stage were used to build an optimized model and then successfully verified. It was clearly proven that Bayesian inference based optimization process yields good results to build an optimized skin model. CONCLUSION: The outcome of this study clearly shows the applicability of this hybrid method in the analysis of skin features and is therefore expected to lead development of non-invasive and low-cost instrument for early detection of skin changes.

Novel clues for ultrasonographic diagnosis of reflux in pregnant women: a pilot study.

The aim of the present study was to define some novel radiological clues that may aid in the ultrasonographic diagnosis of gastroesophageal reflux in pregnant women. A total of 84 pregnant women, consisting of 42 reflux patients and 42 controls were included in the study. Reflux and control groups were compared in terms of age and our novel ultrasonographic landmarks related to oesophageal structure. While the two groups did not differ in terms of age, they were significantly different from each other with respect to: single layer, single wall oesophageal thickness; double layer, double wall oesophageal thickness; oesophageal hiatal diameter; perioesophageal fat pad thickness; hypoechogenic single wall muscularis mucosa and lamina propria thickness. Owing to our newly defined radiological clues, ultrasonography may have a 'greater than expected' role in the diagnosis of gastroesophageal reflux in pregnant women. However, further studies must be performed to document the actual diagnostic potential of these radiological tips.

Prediction of skin ages by means of multi-spectral light sources.

Assessment of skin aging is a complex biological process that depends on various internal and external factors but has become important due to personalized skin health and cosmetic treatments. Although there are a small number of attempts to assess the skin aging, they identify only one of the previously classified skin aging groups. The methods used to achieve it are also based generally on highly expensive measurement devices. This work therefore proposes novel low-cost skin aging assessment apparatus by using light back-scatter intensity level of Red, Blue, Green and Infrared bands. This is further enhanced by using a machine learning method to accurately predict actual skin age. The proposed method appears to be highly capable of capturing multi-layer cellular changes exhibited by the biological skin aging process and predicting skin ages with a root-mean-square error of as low as 0.160 by using only four features based on the four multi-spectral light sources. This assessment kit seems to be the first of its kind, which is expected to bring great benefit to both personalized skin healthcare and cosmetic sectors.

Predicting clinical outcomes for newborns using two artificial intelligence approaches.

Two different approaches, based on artificial neural networks (ANN) and fuzzy logic, were used to predict a number of outcomes of newborns: How they would be delivered, their 5 minute Apgar score, and neonatal mortality. The goal was to assess whether the methods would be comparable or whether they would perform differently for different outcomes. The results were comparable for Correct Classification Rate (CCR) and Specificity (true negative cases). Sensitivity (true positive cases) was slightly higher for the back-propagation feed-forward ANN than using the Fuzzy-Logic Classifier (FLC). Since this is one single database and a very large one, it is possible that the FLC would perform better than the ANN for very small databases, as shown by some of the co-authors in the past. The next step will be to test a small database with both methods to assess strengths and weaknesses with the intent to use both if needed with some medical data in the future.

Functional significance of XPD polymorphic variants: attenuated apoptosis in human lymphoblastoid cells with the XPD 312 Asp/Asp genotype.

Recent molecular epidemiological studies have identified polymorphisms in the XPD gene that are associated with increased risk of brain gliomas and head, neck, lung, and skin cancers. However, the functional significance of these polymorphic variants in altering cell processes such as cell cycle checkpoints, DNA repair, and apoptosis is uncertain. We have cloned the XPD variants Lys751Gln, Asp312Asn, and Lys751Gln-Asp312Asn into a pcDNA-3.1-expression vector. Using these constructs, we did not find any detectable difference in either in vitro binding with wild-type p53 or in DNA repair proficiency as measured by host cell reactivation assay. We then genotyped 34 different lymphoblastoid cell lines from six Centre d'Etude du Polymorphisme Humaine (CEPH)/Utah pedigree families and a CEPH/French pedigree family for polymorphisms at codons 751 and 312 and assessed their apoptotic response after either UV or ionized radiation exposure. The lymphoblastoid cell lines with homozygous or heterozygous Asp at codon 312 have similar apoptotic rates, whereas cell lines with homozygous Asn at codon 312 showed a 2.5-fold increased response to UV (P = 0.005; Student's t test). This is the first report known to us of a functional polymorphism in a gene involved in DNA damage-induced apoptosis. However, the presence of Lys or Gln at codon 751 did not influence the apoptotic response to UV. The diminished apoptotic response of cells containing the 312 Asp allele could both allow the survival and selective clonal expansion of carcinogen-damaged cells and be a mechanistic explanation for the increased risk of cancer at diverse tissue sites.

Compensatory fuzzy neural networks-based intelligent detection of abnormal neonatal cerebral Doppler ultrasound waveforms.

Compensatory fuzzy neural networks (CFNN) without normalization, which can be trained with a backpropagation learning algorithm, is proposed as a pattern recognition technique for intelligent detection of Doppler ultrasound waveforms of abnormal neonatal cerebral hemodynamics. Doppler ultrasound signals were recorded from the anterior cerebral arteries of 40 normal full-term babies and 14 mature babies with intracranial pathology. The features of normal and abnormal groups as inputs to pattern recognition algorithms were extracted from the maximum velocity waveforms by using principal component analysis. The proposed technique is compared with the CFNN with normalization and other pattern recognition techniques applied to Doppler ultrasound signals from various arteries. The results show that the proposed method is superior to the others, and can be a powerful technique to be used in analyzing Doppler ultrasound signals from various arteries.

Functional interaction of p53 and BLM DNA helicase in apoptosis.

The Bloom syndrome (BS) protein, BLM, is a member of the RecQ DNA helicase family that also includes the Werner syndrome protein, WRN. Inherited mutations in these proteins are associated with cancer predisposition of these patients. We recently discovered that cells from Werner syndrome patients displayed a deficiency in p53-mediated apoptosis and WRN binds to p53. Here, we report that analogous to WRN, BLM also binds to p53 in vivo and in vitro, and the C-terminal domain of p53 is responsible for the interaction. p53-mediated apoptosis is defective in BS fibroblasts and can be rescued by expression of the normal BLM gene. Moreover, lymphoblastoid cell lines (LCLs) derived from BS donors are resistant to both gamma-radiation and doxorubicin-induced cell killing, and sensitivity can be restored by the stable expression of normal BLM. In contrast, BS cells have a normal Fas-mediated apoptosis, and in response to DNA damage normal accumulation of p53, normal induction of p53 responsive genes, and normal G(1)-S and G(2)-M cell cycle arrest. BLM localizes to nuclear foci referred to as PML nuclear bodies (NBs). Cells from Li-Fraumeni syndrome patients carrying p53 germline mutations and LCLs lacking a functional p53 have a decreased accumulation of BLM in NBs, whereas isogenic lines with functional p53 exhibit normal accumulation. Certain BLM mutants (C1055S or Delta133-237) that have a reduced ability to localize to the NBs when expressed in normal cells can impair the localization of wild type BLM to NBs and block p53-mediated apoptosis, suggesting a dominant-negative effect. Taken together, our results indicate both a novel mechanism of p53 function by which p53 mediates nuclear trafficking of BLM to NBs and the cooperation of p53 and BLM to induce apoptosis.

Mechanistic aspects of the cytotoxic activity of glufosfamide, a new tumour therapeutic agent.

Beta-D-glucosyl-ifosfamide mustard (D 19575, glc-IPM, INN = glufosfamide) is a new agent for cancer chemotherapy. Its mode of action, which is only partly understood, was investigated at the DNA level. In the breast carcinoma cell line MCF7 glufosfamide inhibited both the synthesis of DNA and protein in a dose-dependent manner, as shown by the decreased incorporation of [3H-methyl]-thymidine into DNA and [14C]-methionine into protein of these cells. Treatment of MCF7 cells with 50 microM glufosfamide was sufficient to trigger poly(ADP-ribose) polymerase (PARP) activation, as revealed by immunofluorescence analysis. Both CHO-9 cells, which are O6-methylguanine-DNA methyltransferase (MGMT)-deficient, and an isogenic derivative, which has a high level of MGMT, showed the same cytotoxic response to beta-D-glc-IPM, indicating that the O6 position of guanine is not the critical target for cytotoxicity. By contrast, a sharp decrease in survival of cross-link repair deficient CL-V5 B cells was observed already at concentrations of 0.1 mM beta-D-glc-IPM, whereas the wild-type V79 cells showed a 90% reduction in survival only after treatment with 0.5 mM of this compound. The therapeutically inactive beta-L-enantiomer of glufosfamide also showed genotoxic effects in the same assays but at much higher doses. This was probably due to small amounts of ifosfamide mustard formed under the conditions of incubation. The results indicate that the DNA crosslinks are the most critical cytotoxic lesions induced by beta-D-glc-IPM.