Impact of ablation index settings on pulmonary vein reconnection.

PURPOSE: Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is still debated. We evaluated the incidence of acute and late PV reconnection (PVR) with different AI settings and its predictors. METHODS: The Ablation Index Registry is a multicenter study that included patients with paroxysmal/persistent atrial fibrillation (AF) who underwent first-time ablation. Each operator performed the ablation using his preferred ablation catheter (ThermoCool® SmartTouch or Surround Flow) and AI setting (380 posterior-500 anterior and 330 posterior-450 anterior). We divided the study population into two groups according to the AI setting used: group 1 (330-450) and group 2 (380-500). Incidence of acute PVR was validated within 30 min after PVI, whereas the incidence of late PVR was evaluated at repeat procedure. RESULTS: Overall, 490 patients were divided into groups 1 (258) and 2 (232). There was no significant difference in the procedural time, fluoroscopy time, and rate of the first-pass PVI between the two study groups. Acute PVR was observed in 5.6% PVs. The rate of acute PVR was slightly higher in group 2 (64/943, 6.8%, PVs) than in group 1 (48/1045, 4.6% PVs, p = 0.04). Thirty patients (6%) underwent a repeat procedure and late PVR was observed in 57/116 (49%) PVs (number of reconnected PV per patient of 1.9 ± 1.6). A similar rate of late PVR was found in the two study groups. No predictors of acute and late PVR were found. CONCLUSION: Ablation with a lower range of AI is highly effective and is not associated with a higher rate of acute and late PVR. No predictors of PV reconnection were found.

Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration.

BACKGROUND: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. OBJECTIVE: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. METHODS: The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. RESULTS: We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. CONCLUSION: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.

Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review.

Introduction: Disease modifying treatments are commonly used in the treatment of multiple sclerosis. As different opportunistic infections have been reported, concerns are also raised regarding the risk of invasive fungal infections.Areas covered: Both clinical trials and observational studies on safety and efficacy of diseases modifying treatment for multiple sclerosis were reviewed and data regarding the occurrence of invasive fungal infections were reported. Papers evaluating the following drugs were reviewed: rituximab, ocrelizumab, alemtuzumab, fingolimod, natalizumab, dimethyl fumarate, interferon, glatiramer acetate, cladribine, teriflunomide.Expert opinion: Overall, the occurrence of invasive fungal infections was low, with most infective events reported among patients treated with monoclonal antibodies and fingolimod. Aspergillosis and cryptococcal meningitidis were the most representative fungal infections. Although not common, these infections may be difficult to diagnose and their fatality rate is often high. For this reason, screening protocols for fungal infections must be implemented in the clinical practice when managing patients with MS.

Plasmonic directional couplers using channel waveguides in random arrays of metal nanoparticles.

Plasmonic directional couplers based on channel waveguides embedded in random arrays of metal nanoparticles (NPs) operating in near-infrared are fabricated using electron-beam lithography and investigated experimentally characterizing their performance with leakage-radiation microscopy. The power exchange between coupled waveguides, its spatial period and efficiency, along with the overall power transmission, are determined in the wavelength range from 700 to 800 nm. We introduce a simple coupled-mode approach based on three coupled waveguides. The composite system considers a waveguide consisting of NP-filled stripe with characteristics distinctly different from those of the channel waveguides. Using this model, we describe the performance of investigated composite plasmonic configurations and obtain good qualitative agreement with experimental observations.

Coping with the crisis: people with severe mental disorders acting for social change through sustainable energy.

BACKGROUND: The aim of the study was to examine the efficacy of a vocational training program on renewable energy sources in reducing disabilities of people with chronic psychosis (CP). The innovative element was that the project could produce major advantages regarding the economic needs of the whole area involved. METHODS: Experimental Cohort, 26 subjects with CP (EC); Control Cohort1, 130 subjects with CP following pharmacotherapy plus other rehabilitation activities (CIC); Control Cohort2, 101 subjects with CP following the usual treatment (pharmacotherapy) (CUC). Study tool: Health of the Nation Outcome Scales (HoNOS). Assessment made at the start of the study (T0) and after three months (T1). Statistical analysis made by MANOVA. RESULTS: Improvement in HoNOS total score in both groups (F=7.574, p=0.000) with non-significant differences between groups over time (F=1.336, p=0.252) was found comparing EC vs. CIC. Greater improvement in EC vs. CIC was shown in the HoNOS "impairment" scale (F=4.910, p=0.028). EC vs. CUC: both groups improved in HoNOS total score (F=9.440, p=0.000) but the improvement was greater in EC (F = 2.273, P=0.048). CONCLUSIONS: Work inclusion, as well as other rehabilitation treatments, reduces the social needs of people with chronic psychosis. Work inclusion in a project with real relevance for the area where these people live, produces more improvement of cognitive, physical and somatic disabilities, probably related to a better outcome in self-efficacy.

Modifications of the acidic soluble salivary proteome in human children from birth to the age of 48months investigated by a top-down HPLC-ESI-MS platform.

During the first year of life the infant oral environment undergoes dramatic changes. To investigate how the salivary proteome of human children evolves during infant development we have analyzed whole saliva of 88 children aged between 0 and 48months by a top-down platform based on RP-HPLC-ESI-MS. Children were divided according to their age into five groups (A, 0-6months, N=17; B, 7-12months, N=14; C, 13-24months, N=32; D, 25-36months, N=16; E, 37-48months, N=9). The proteins and peptides analyzed were histatins (histatin-1, histatin-3 1/24), acidic proline-rich proteins, statherin, P-B peptide, and salivary cystatins. Protein and peptide quantification based on the area of the RP-HPLC-ESI-MS extracted ion current peak evidenced that: (i) concentrations of the major salivary proteins/peptides showed a minimum in the 0-6-month-old group and increased with age; (ii) the level of histatin-1 reached a maximum in the 7-12-month-old group, a minimum in the 13-24-month-aged babies and it increased again in the 25-36-month-old group; (iii) S-type cystatins were almost undetectable in the 0-6-month-old group; (iv) P-B peptide concentration greatly increased with age; (v) histatin-3 1/24 and statherin concentrations did not show any age-related variation. BIOLOGICAL SIGNIFICANCE: The top-down proteomic approach undertaken in this work reveals that the salivary proteome of human children from birth to 48months of age shows important quantitative modifications. The concentrations of the major salivary proteins, with the exception of statherin and histatin-3 1/24, showed a minimum in the 0-6-month-old group when the expression in salivary glands is probably not fully activated. Concentrations of the salivary proteins slowly increased with age, with different trends. Only histatin-1 showed the highest concentration in the 7-12-month-old group, followed by a decrease in the 13-24-month-aged children. This particular trend could be related to the phenomenon of eruption of primary dentition. This study gives a contribution to the knowledge on the physiological variability occurring in human saliva during the early childhood. It could represent a strong and reliable basis for further investigation of saliva to develop diagnostic and prognostic biomarkers.

Exploring the diversity of Arctic eelpouts: first cytogenetic data on species of the genus Lycodes (Teleostei, Zoarcidae).

Zoarcidae (eelpouts), including 298 recognized valid species, is the most diverse family in the suborder Zoarcoidei (order Perciformes). Many of the species exhibit a great degree of phenotypic plasticity. In the present work, we analyze the genome of six Arctic species from the most diversified zoarcid genus Lycodes (L. eudipleurostictus, L. paamiuti, L. pallidus, L. seminudus, L. squamiventer, and L. reticulatus) providing the first information on the species-specific karyotype and pattern of major ribosomal genes chromosomal localization. The study revealed an unexpected consistency of the chromosomal features across species that apparently contrasts with the high level of inter-specific and intra-specific plasticity of morphological characters. The comparison between the chromosomal features of these Arctic eelpouts with those of the Antarctic species Lycodichthys dearborni (same subfamily, Lycodinae), suggests a conservative organization of the genome, at the level of gross architecture of chromosomes and karyotypes, within the family Zoarcidae.

Karyotyping and cytogenetic mapping of Atlantic cod (Gadus morhua Linnaeus, 1758).

The Atlantic cod (Gadus morhua) is an important natural resource for northern societies and is now also considered to be a promising candidate for aquaculture. In recent years, much effort has been directed towards the development of genomic tools, and genome initiatives for Atlantic cod have been established. Despite the growing attention devoted to the Atlantic cod genomics, basic aspects of its genome structure and organization remain unknown. Thus, the present work aims to study cytogenetic features of the Atlantic cod as a contribution to the knowledge of this species' genome. The Atlantic cod displays a diploid number of 46 chromosomes, with a karyotypic formula 16 m/sm + 30 st/t. Conventional karyotyping was improved by chromosomal mapping of two classes of repetitive sequences. 18S rDNA clusters were assigned to pairs 2 and 4; small amounts of 18S rDNA clusters were occasionally detected on pair 5. These findings could not be related to the geographical origin of the specimens, but were consistent with the variability of these repeated genes in fish in general. 5S ribosomal gene clusters, apparently corresponding to a single 5S rDNA class, were detected on twelve chromosomes (pairs 11, 12, 14, 17, 20 and 21). The present update of the existing but meagre information on the karyotype of Atlantic cod, plus the first physical mapping of repetitive genes in this species herein, opens the way for an integrated approach that combines genetic and physical mapping with the assembly of the genome of this commercially important species.

Potential applications of human saliva as diagnostic fluid.

The use of human saliva as a diagnostic and prognostic fluid has until recently been somewhat disregarded. Although sample collection is non-invasive, physiological and genetic variations were largely responsible for its infrequent application in the past. Recently, several proteomic studies contributed to partial elucidation of the salivary proteome (more than 2400 protein components have been characterized), both in terms of composition, contributions to whole saliva and genetic/physiological variability. On this basis, is not too optimistic to believe that in the near future human saliva could become a relevant diagnostic fluid. In this review, the characterization by proteomic approaches of new salivary markers in oncology, head and neck carcinoma (oral cavity, oropharynx, larynx, and salivary glands), breast and gastric cancers, salivary gland function and disease, Sjögren syndrome, systemic sclerosis, dental and gingival pathology, systemic, psychiatric and neurological diseases, is described.

Characterization of diffraction-enhanced imaging contrast in breast cancer.

Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that has been shown to enhance contrast between normal and cancerous breast tissues. In this study, diffraction-enhanced imaging in computed tomography (DEI-CT) mode was used to quantitatively characterize the refraction contrasts of the organized structures associated with invasive human breast cancer. Using a high-sensitivity Si (3 3 3) reflection, the individual features of breast cancer, including masses, calcifications and spiculations, were observed. DEI-CT yields 14, 5 and 7 times higher CT numbers and 10, 9 and 6 times higher signal-to-noise ratios (SNR) for masses, calcifications and spiculations, respectively, as compared to conventional CT of the same specimen performed using the same detector, x-ray energy and dose. Furthermore, DEI-CT at ten times lower dose yields better SNR than conventional CT. In light of the recent development of a compact DEI prototype using an x-ray tube as its source, these results, acquired at a clinically relevant x-ray energy for which a pre-clinical DEI prototype currently exists, suggest the potential of clinical implementation of mammography with DEI-CT to provide high-contrast, high-resolution images of breast cancer (Parham 2006 PhD Dissertation University of North Carolina at Chapel Hill).

alpha-Defensin levels in whole saliva of totally edentulous subjects.

Salivary levels of alpha-defensins 1-4 and histatins 1, 3 and 5 were determined in 11 totally edentulous patients, 11 younger healthy adults with normal gingival mucosa (Control group I) and 8 subjects, age-matched with edentulous patients, having a minimum of 25 teeth (Control group II). Whole saliva was treated with trifluoroacetic acid and the acidic soluble fraction analyzed by High Performance Liquid Chromatography-Mass Spectrometry. The area of the extracted ion current peaks was used for peptide quantification. Levels of alpha-defensins1-4, but not of histatins, were significantly lower in totally edentulous patients with respect to both Control group I and Control group II. The two control groups did not show significant differences. The reduced level of oral alpha-defensins, which are mainly of crevicular origin, is most likely due to the absence of the gingival sulcus in the edentulous subjects. The near absence of alpha- defensins might be in part responsible for the higher vulnerability of the oral cavity to oral pathogen infections observed in totally edentulous patients.

Mass density images from the diffraction enhanced imaging technique.

Conventional x-ray radiography measures the projected x-ray attenuation of an object. It requires attenuation differences to obtain contrast of embedded features. In general, the best absorption contrast is obtained at x-ray energies where the absorption is high, meaning a high absorbed dose. Diffraction-enhanced imaging (DEI) derives contrast from absorption, refraction, and extinction. The refraction angle image of DEI visualizes the spatial gradient of the projected electron density of the object. The projected electron density often correlates well with the projected mass density and projected absorption in soft-tissue imaging, yet the mass density is not an "energy"-dependent property of the object, as is the case of absorption. This simple difference can lead to imaging with less x-ray exposure or dose. In addition, the mass density image can be directly compared (i.e., a signal-to-noise comparison) with conventional radiography. We present the method of obtaining the mass density image, the results of experiments in which comparisons are made with radiography, and an application of the method to breast cancer imaging.

Diffraction enhanced imaging contrast mechanisms in breast cancer specimens.

We have investigated the contrast mechanisms of the refraction angle, and the apparent absorption images obtained from the diffraction enhanced imaging technique (DEI) and have correlated them with the absorption contrast of conventional radiography. The contrast of both the DEI refraction angle image and the radiograph have the same dependence on density differences of the tissues in the visualization of cancer; in radiography these differences directly relate to the contrast while in the DEI refraction angle image it is the density difference and thickness gradient that gives the refraction angle. We show that the density difference of fibrils in breast cancer as measured by absorption images correlate well with the density difference derived from refraction angle images of DEI. In addition we find that the DEI apparent absorption image and the image obtained with the DEI system at the top of the reflectivity curve have much greater contrast than that of the normal radiograph (x8 to 33-fold higher). This is due to the rejection of small angle scattering (extinction) from the fibrils enhancing the contrast.

Using the Web to aid biochemists and microbiologists: an example of computer-based learning using PCR as an example.

The aim of this study was two-fold: to make available to the medical community a fast, efficient tool for troubleshooting PCR problems, and to demonstrate that hypermedia allow one to approach this kind of problem in a new, more useful way. The Web provides access to an enormous amount of information in the medical area, and in particular enables troubleshooting of new techniques in the medical laboratory. Currently it is possible to find textual information but it is not always easy to find hypermedia information. In many cases authors change only the means of dissemination of a book or paper to the Web, but do not adapt the information to the features of this new medium. The prototype of our hypermedia application was developed using Director and Flash programs (Macromedia), the application was developed from a decision tree built as a result of information compiled from expert PCR users and the existing literature. It was implemented on a website using Dreamweaver (Macromedia). The usefulness and possibilities of this application have been tested with physicians, medical laboratory technicians, and health science students, and have been proven to be more effective than traditional methods, both in education processes and in helping researchers and medical laboratory technicians in their daily work. The advance and popularization of the Internet in the medical profession requires information on the Web to adapt to the advantages offered by hypermedia. This new step must be taken, and the Web must offer medical users not only a different medium of information distribution but also a new way of handling and obtaining information.

Improving the detection of simulated masses in mammograms through two different image-processing techniques.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether contrast-limited adaptive histogram equalization (CLAHE) or histogram-based intensity windowing (HIW) improves the detection of simulated masses in dense mammograms. MATERIALS AND METHODS: Simulated masses were embedded in portions of mammograms of patients with dense breasts; the mammograms were digitized at 50 microm per pixel, 12 bits deep. In two different experiments, images were printed both with no processing applied and with related parameter settings of two image-processing methods. A simulated mass was embedded in a realistic background of dense breast tissue, with its position varied. The key variables in each trial included the position of the mass, the contrast levels of the mass relative to the background, and the selected parameter settings for the image-processing method. RESULTS: The success in detecting simulated masses on mammograms with dense backgrounds depended on the parameter settings of the algorithms used. The best HIW setting performed better than the best fixed-intensity window setting and better than no processing. Performance with the best CLAHE settings was no different from that with no processing. In the HIW experiment, there were no significant differences in observer performance between processing conditions for radiologists and nonradiologists. CONCLUSION: HIW should be tested in clinical images to determine whether the detection of masses by radiologists can be improved. CLAHE processing will probably not improve the detection of masses on clinical mammograms.

Factors affecting phantom scores at annual mammography facility inspections by the U.S. Food and Drug Administration.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the factors affecting phantom image score at the annual inspection of mammography facilities. MATERIALS AND METHODS: In 1997, three U.S. Food and Drug Administration (FDA)-trained inspectors performed inspections of all mammography facilities in North Carolina. All federal and state inspection data were collected and evaluated by using linear regression analysis. Factors affecting the American College of Radiology phantom scores were assessed. RESULTS: Phantom score was affected by inspector identity, view box luminance, and optical density. All of these factors had a statistically significant effect on mass score (P < .05). Inspector identity yielded a statistically significant effect on speck group score, fibril score, and total score. Luminance yielded a statistically significant effect on both speck group score and total score. CONCLUSION: Phantom scoring should be automated to allow for more consistent interobserver scoring. In addition, radiology facilities can improve the likelihood of receiving a passing phantom score by reducing the ambient light and increasing the view box luminance in the location where the images are evaluated and the phantom is scored routinely. Radiologists should also consider increasing phantom and clinical image optical density to allow for improved phantom testing outcomes.

What every surgical oncologist should know about digital mammography.

This article reviews the available information on digital mammography for surgeons who care for patients with breast cancer. The limitations of the current film-based technology and why digital mammography promises to improve breast cancer detection and breast lesion diagnosis are described. The basics of digital imaging technology are reviewed, including a description of image contrast and spatial resolution and its variance from currently available clinical digital mammography systems. The results of clinical trials completed to date are reported. An upcoming large screening trial for digital mammography, sponsored by the National Cancer Institute, is described. Future technological developments, including improvements in softcopy display, image processing, computer-aided detection and diagnosis (CADD), tomosynthesis, and digital subtraction mammography (DSM), are briefly discussed.