Automatic Extraction of Dermatological Parameters from Nevi Using an Inexpensive Smartphone Microscope: A Proof of Concept

The evolution of smartphone technology has made their use more common in dermatological applications. Here we studied the feasibility of using an inexpensive smartphone microscope for the extraction of dermatological parameters and compared the results obtained with a portable dermoscope, commonly used in clinical practice. Forty-two skin lesions were imaged with both devices and visually analyzed by an expert dermatologist. The presence of a reticular pattern was observed in 22 dermoscopic images, but only in 10 smartphone images. The proposed paradigm segments the image and extracts texture features which are used to train and validate a neural network to classify the presence of a reticular pattern. Using 5-fold cross-validation, an accuracy of 100% and 95% was obtained with the dermoscopic and smartphone images, respectively. This approach can be useful for general practitioners and as a triage tool for skin lesion analysis

Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells

A novel cell-targeting, pH-sensitive polymeric carrier was employed in this study for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on facile conjugation of BTZ to catechol-containing polymeric carriers that are designed to be taken up selectively by cancer cells through cell surface receptor-mediated mechanisms. The polymer used as a building block in this study was poly(ethylene glycol), which was chosen for its ability to reduce nonspecific interactions with proteins and cells. The catechol moiety was exploited for its ability to bind and release borate-containing therapeutics such as BTZ in a pH-dependent manner. In acidic environments, such as in cancer tissue or the subcellular endosome, BTZ dissociates from the polymer-bound catechol groups to liberate the free drug, which inhibits proteasome function. A cancer-cell-targeting ligand, biotin, was presented on the polymer carriers to facilitate targeted entry of drug-loaded polymer carriers into cancer cells. Our study demonstrated that the cancer-targeting drug-polymer conjugates dramatically enhanced cellular uptake, proteasome inhibition, and cytotoxicity toward breast carcinoma cells in comparison with nontargeting drug-polymer conjugates. The pH-sensitive catechol-boronate binding mechanism provides a chemoselective approach for controlling the release of BTZ in targeted cancer cells, establishing a concept that may be applied in the future toward other boronic acid-containing therapeutics to treat a broad range of diseases

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

PVA-GTA Fricke gel dosimeters exposed to clinical photons beams: Nuclear Magnetic Resonance Relaxometry and Imaging

Fricke Gel (FXGs) dosimetric system is based on the radiation induced oxidation of ferrous to ferric ions. The application of Fricke gels for ionizing radiation dosimetry is continuously increasing worldwide due to their many favorable properties. However, one of their shortcomings is that ferrous and ferric ions diffuse in the gel matrix. To maintain the spatial integrity of the dose distribution, Fricke gels must be undergoing measurement within a few hours of their irradiation, so that ferric ions remain close to their point of production. Thus, the spatial integrity of the dose distribution in the Fricke gel is maintained (Schreiner, 2015). The gel matrix also contributes to the oxidation of ferrous ions during irradiation, increasing the chemical yield of ferric ions in aqueous solution and increasing the sensitivity of the dosimeter. The oxidation of ferrous ions also causes a reduction of the longitudinal nuclear magnetic relaxation time T1 which can be measured by means of Nuclear Magnetic Resonance Relaxometry (NMR) and Magnetic Resonance Imaging (MRI) (Marrale, 2014). The results here presented are related to an experimental investigation conducted on Fricke Gels characterized by gelatinous matrix of Polyvinyl alcohol (PVA) cross-linked with a Glutaraldehyde (GTA) (Marini, 2016). The main dosimetric features of the NMR signal were investigated. The gels were irradiated in the clinical dose range between 0 and 20 Gy. In order to assess the photon sensitivity we analyzed the dependence of NMR relaxation times on radiation dose with varying ferrous ammonium sulfate content inside FXGs. Furthermore, signal stability was followed for several days after irradiation. These measurements were preliminary to MRI analysis which can permit 3D dose mapping. In order to maximize the MRI response a systematic study was performed to optimize acquisition sequences and parameters. In particular, we analyzed for inversion recovery sequences the dependence of MRI signal on the repetition time TR and on the inversion time TI. The dose calibration curves are reported and discussed from the point of view of the dosimeter use in clinical radiotherapy. This work has highlighted that the optimization of additives inside gel matrix is fundamental for maximizing photon sensitivity of these detectors. We can conclude that FXG dosimeters with optimal ferrous ammonium sulfate content can be regarded as a valuable dosimetric tool to achieve fast information on spatial dose distribution

Attributes and definitions of locomotor capacity in older people: a World Health Organisation (WHO) locomotor capacity working group meeting report

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Genome Wide Identification of Recessive Cancer Genes by Combinatorial Mutation Analysis

We devised a novel procedure to identify human cancer genes acting in a recessive manner. Our strategy was to combine the contributions of the different types of genetic alterations to loss of function: amino-acid substitutions, frame-shifts, gene deletions. We studied over 20,000 genes in 3 Gigabases of coding sequences and 700 array comparative genomic hybridizations. Recessive genes were scored according to nucleotide mismatches under positive selective pressure, frame-shifts and genomic deletions in cancer. Four different tests were combined together yielding a cancer recessive p-value for each studied gene. One hundred and fifty four candidate recessive cancer genes (p-value<1.5×10−7, FDR = 0.39) were identified. Strikingly, the prototypical cancer recessive genes TP53, PTEN and CDKN2A all ranked in the top 0.5% genes. The functions significantly affected by cancer mutations are exactly overlapping those of known cancer genes, with the critical exception for the absence of tyrosine kinases, as expected for a recessive gene-set

Review of retrospective dosimetry techniques for external ionising radiation exposures

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. © The Author 2010. Published by Oxford University Press. All rights reserved

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

BACKGROUND: To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC). METHODS: Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment. RESULTS: Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR 2.62; 95 % CI 1.14–6.02; P 0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P 0.02). CONCLUSIONS: The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea