Consistency and Standardization of Color in Medical Imaging: a Consensus Report

This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8–9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group

Characterization of the global network of optical magnetometers to search for exotic physics (GNOME)

The Global Network of Optical Magnetometers to search for Exotic physics (GNOME) is a network of geographically separated, time-synchronized, optically pumped atomic magnetometers that is being used to search for correlated transient signals heralding exotic physics. The GNOME is sensitive to nuclear- and electron-spin couplings to exotic fields from astrophysical sources such as compact dark-matter objects (for example, axion stars and domain walls). Properties of the GNOME sensors such as sensitivity, bandwidth, and noise characteristics are studied in the present work, and features of the network’s operation (e.g., data acquisition, format, storage, and diagnostics) are described. Characterization of the GNOME is a key prerequisite to searches for and identification of exotic physics signatures

Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum

Key message In plants, phosphorylated MAPKs display constitutive nuclear localization; however, not all studied plant species show co-localization of activated MAPKs to mitotic microtubules. Abstract The mitogen-activated protein kinase (MAPK) signaling pathway is involved not only in the cellular response to biotic and abiotic stress but also in the regulation of cell cycle and plant development. The role of MAPKs in the formation of a mitotic spindle has been widely studied and the MAPK signaling pathway was found to be indispensable for the unperturbed course of cell division. Here we show cellular localization of activated MAPKs (dually phosphorylated at their TXY motifs) in both interphase and mitotic root meristem cells of Lupinus luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization of activated MAPKs has been found in all species. Colocalization of these kinases to mitotic microtubules was most evident in L. esculentum, while only about 50 % of mitotic cells in the root meristems of P. sativum and V. faba displayed activated MAPKs localized to microtubules during mitosis. Unexpectedly, no evident immunofluorescence signals at spindle microtubules and phragmoplast were noted in L. luteus. Considering immunocytochemical analyses and studies on the impact of FR180204 (an inhibitor of animal ERK1/2) on mitotic cells, we hypothesize that MAPKs may not play prominent role in the regulation of microtubule dynamics in all plant species

Performance adaptive training control strategy for recovering wrist movements in stroke patients: a preliminary, feasibility study

<p>Abstract</p> <p>Background</p> <p>In the last two decades robot training in neuromotor rehabilitation was mainly focused on shoulder-elbow movements. Few devices were designed and clinically tested for training coordinated movements of the wrist, which are crucial for achieving even the basic level of motor competence that is necessary for carrying out ADLs (activities of daily life). Moreover, most systems of robot therapy use point-to-point reaching movements which tend to emphasize the pathological tendency of stroke patients to break down goal-directed movements into a number of jerky sub-movements. For this reason we designed a wrist robot with a range of motion comparable to that of normal subjects and implemented a self-adapting training protocol for tracking smoothly moving targets in order to facilitate the emergence of smoothness in the motor control patterns and maximize the recovery of the normal RoM (range of motion) of the different DoFs (degrees of Freedom).</p> <p>Methods</p> <p>The IIT-wrist robot is a 3 DoFs light exoskeleton device, with direct-drive of each DoF and a human-like range of motion for Flexion/Extension (FE), Abduction/Adduction (AA) and Pronation/Supination (PS). Subjects were asked to track a variable-frequency oscillating target using only one wrist DoF at time, in such a way to carry out a progressive splinting therapy. The RoM of each DoF was angularly scanned in a staircase-like fashion, from the "easier" to the "more difficult" angular position. An Adaptive Controller evaluated online performance parameters and modulated both the assistance and the difficulty of the task in order to facilitate smoother and more precise motor command patterns.</p> <p>Results</p> <p>Three stroke subjects volunteered to participate in a preliminary test session aimed at verify the acceptability of the device and the feasibility of the designed protocol. All of them were able to perform the required task. The wrist active RoM of motion was evaluated for each patient at the beginning and at the end of the test therapy session and the results suggest a positive trend.</p> <p>Conclusion</p> <p>The positive outcomes of the preliminary tests motivate the planning of a clinical trial and provide experimental evidence for defining appropriate inclusion/exclusion criteria.</p

Identification and differential expression dynamics of peach small GTPases encoding genes during fruit development and ripening

The function of monomeric GTPases of the RAS superfamily in fruit development and ripening has been partially characterized. Here the identification of peach (Prunus persica) small GTPases of the RAS superfamily expressed in fruit and the characterization of their expression profiles during fruit development are described. Extensive searches on expressed sequence tag (EST) databases led to the selection of a total of 24 genes from peach encoding proteins with significant similarity to Arabidopsis small GTPases. Sequence similarity analyses and identification of conserved motifs, diagnostic of specific RAS families and subfamilies, enabled bona fide assignment of fourteen PpRAB, seven PpARF/ARL/SAR, two PpROP and one PpRAN GTPases. Transcriptional expression profiles of peach monomeric GTPases, analysed by real-time quantitative reverse transcription-PCR, were obtained for mesocarp samples, collected in two consecutive years. Reproducible patterns of expression could be identified for five peach RAB-encoding genes (PpRABA1-1, PpRABA2, PpRABD2-1, PpRABD2-2, and PpRABC2), two ARFs (PpARFA1-1 and PpARLB1), and two ROPs (PpROP3 and PpROP4). Interestingly, the transient transcriptional up-regulation of PpARF genes and of PpRAB genes of the A and D clades, putatively controlling the exocytic delivery of cell wall components and modifying enzymes, appeared to coincide with peaks of growth speed and sugar accumulation and with the final phases of ripening. To our knowledge, this is the first description of the co-ordinated differential expression of a set of genes encoding small GTPases of the ARF and RAB families which takes place during key moments of fruit development and maturation

Interleukin 6, lipopolysaccharide-binding protein and interleukin 10 in the prediction of risk and etiologic patterns in patients with community-acquired pneumonia: results from the German competence network CAPNETZ

<p>Abstract</p> <p>Background</p> <p>The aim of our study was to investigate the predictive value of the biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10) and lipopolysaccharide-binding protein (LBP) compared with clinical CRB and CRB-65 severity scores in patients with community-acquired pneumonia (CAP).</p> <p>Methods</p> <p>Samples and data were obtained from patients enrolled into the German CAPNETZ study group. Samples (blood, sputum and urine) were collected within 24 h of first presentation and inclusion in the CAPNETZ study, and CRB and CRB-65 scores were determined for all patients at the time of enrollment. The combined end point representative of a severe course of CAP was defined as mechanical ventilation, intensive care unit treatment and/or death within 30 days. Overall, a total of 1,000 patients were enrolled in the study. A severe course of CAP was observed in 105 (10.5%) patients.</p> <p>Results</p> <p>The highest IL-6, IL-10 and LBP concentrations were found in patients with CRB-65 scores of 3-4 or CRB scores of 2-3. IL-6 and LBP levels on enrollment in the study were significantly higher for patients with a severe course of CAP than for those who did not have severe CAP. In receiver operating characteristic analyses, the area under the curve values for of IL-6 (0.689), IL-10 (0.665) and LPB (0.624) in a severe course of CAP were lower than that of CRB-65 (0.764) and similar to that of CRB (0.69). The accuracy of both CRB and CRB-65 was increased significantly by including IL-6 measurements. In addition, higher cytokine concentrations were found in patients with typical bacterial infections compared with patients with atypical or viral infections and those with infection of unknown etiology. LBP showed the highest discriminatory power with respect to the etiology of infection.</p> <p>Conclusions</p> <p>IL-6, IL-10 and LBP concentrations were increased in patients with a CRB-65 score of 3-4 and a severe course of CAP. The concentrations of IL-6 and IL-10 reflected the severity of disease in patients with CAP. The predictive power of IL-6, IL-10 and LBP for a severe course of pneumonia was lower than that of CRB-65. Typical bacterial pathogens induced the highest LBP, IL-6 and IL-10 concentrations.</p

Coherent Raman Scattering microscopy: technology developments and biological applications

Optical microscopy is an indispensable tool that is driving progress in cell biology, and is still the only practical means of obtaining spatial and temporal resolution within living cells and tissues. Coherent Raman Scattering (CRS) microscopy has emerged in the last decade as a powerful multiphoton microscopy technique which overcomes the need for fluorescent labelling and yet retains biomolecular specificity and intrinsic 3D resolution. We have developed several home-built CRS microscopes featuring innovative excitation/detection schemes and quantitative image analysis. Our second-generation multimodal CRS instrument is based on a single 5fs Ti:Sa laser source with 350nm bandwidth capable of exciting a wide vibrational range from 1200 cm -1 to 3800 cm -1 , thus enabling hyperspectral microscopy. Alongside CRS, it also features simultaneous detection of two-photon fluorescence and second harmonic generation for correlative studies. Our latest technology developments include high-content high-throughput label-free quantitative chemical imaging via Bessel beam illumination and sparse sampling. Our latest biological applications feature quantitative imaging of i) intra-cellular lipid droplets in live mouse oocytes and early embryos, ii) cancer organoids and their responses to drugs, iii) freshwater microalgae as potential food supplements for omega-3 fatty acids

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

<p>Abstract</p> <p>Background</p> <p>Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.</p> <p>Methods</p> <p>We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.</p> <p>Results</p> <p>In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.</p> <p>Conclusion</p> <p>PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.</p

Progastrin Represses the Alternative Activation of Human Macrophages and Modulates Their Influence on Colon Cancer Epithelial Cells

Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influence of these peptides on the phenotype of macrophages differentiated from human peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was similar in tumoral and normal surrounding tissue, but the number of M2 macrophages (CD206+ cells) was significantly higher in the tumor. However, the number of these tumor-associated M2 macrophages correlated negatively with the immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages differentiated from human peripheral monocytes in the presence of progastrin showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers (CD86, IL12). Progastrin induced similar effects in mature macrophages treated with IL4 to obtain a M2-phenotype or with LPS plus IFNγ to generate M1-macrophages. Macrophages differentiated in the presence of progastrin presented a reduced expression of Wnt ligands and decreased the number and increased cell death of co-cultured colorectal cancer epithelial cells. Our results suggest that progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This effect exerted on tumor associated macrophages may modulate cancer progression and should be taken into account when analyzing the therapeutic value of gastrin immunoneutralization

Factors affecting glomerular filtration rate, as measured by iohexol disappearance, in men with or at risk for HIV infection

Objective: Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design: Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(-)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods: iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results: Median iGFR was higher among HIV(+) than HIV(-) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(-) men; predictors of CKD were similar using iGFR and eGFR. Conclusions: iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR. © 2014 Margolick et al