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Find video protocols related to scientific articles indexed in Pubmed.
Unbounded dynamics in dissipative flows: Rössler model.
Chaos
PUBLISHED: 07-03-2014
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Transient chaos and unbounded dynamics are two outstanding phenomena that dominate in chaotic systems with large regions of positive and negative divergences. Here, we investigate the mechanism that leads the unbounded dynamics to be the dominant behavior in a dissipative flow. We describe in detail the particular case of boundary crisis related to the generation of unbounded dynamics. The mechanism of the creation of this crisis in flows is related to the existence of an unstable focus-node (or a saddle-focus) equilibrium point and the crossing of a chaotic invariant set of the system with the weak-(un)stable manifold of the equilibrium point. This behavior is illustrated in the well-known Rössler model. The numerical analysis of the system combines different techniques as chaos indicators, the numerical computation of the bounded regions, and bifurcation analysis. For large values of the parameters, the system is studied by means of Fenichel's theory, providing formulas for computing the slow manifold which influences the evolution of the first stages of the orbit.
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Macro- and micro-chaotic structures in the Hindmarsh-Rose model of bursting neurons.
Chaos
PUBLISHED: 07-03-2014
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We study a plethora of chaotic phenomena in the Hindmarsh-Rose neuron model with the use of several computational techniques including the bifurcation parameter continuation, spike-quantification, and evaluation of Lyapunov exponents in bi-parameter diagrams. Such an aggregated approach allows for detecting regions of simple and chaotic dynamics, and demarcating borderlines-exact bifurcation curves. We demonstrate how the organizing centers-points corresponding to codimension-two homoclinic bifurcations-along with fold and period-doubling bifurcation curves structure the biparametric plane, thus forming macro-chaotic regions of onion bulb shapes and revealing spike-adding cascades that generate micro-chaotic structures due to the hysteresis.
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Surgical site infection: an observer-blind, randomized trial comparing electrocautery and conventional scalpel.
Int J Surg
PUBLISHED: 05-15-2014
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To evaluate the incidence of surgical site infection (SSI) based on the type of scalpel used for incisions in the skin and in subcutaneous tissues.
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HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
PLoS Pathog.
PUBLISHED: 05-01-2014
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A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
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Functionally defective high-density lipoproteins are related to heightened T-cell activation in vertically HIV-infected adolescents.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-16-2014
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We assessed high-density lipoprotein (HDL) anti-inflammatory properties in a cohort of vertically HIV-infected adolescents. We hypothesized that proatherogenic mechanisms related to inflammation and immune activation during HIV infection may impair HDL functionality and impact on the atherosclerotic burden. Compared with healthy controls, HDL from HIV-infected adolescents presented impaired functionality, as determined by its ability to inhibit monocyte chemotaxis in vitro, which correlated with detectable viral loads (P = 0.044), lower CD4 nadir (P = 0.043), increased levels of CD4 T-cell activation (P = 0.018), higher C-reactive protein (P = 0.009), and a tendency toward thicker carotid intima-media thickness (P = 0.071).
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WHO-histological criteria for myeloproliferative neoplasms: reproducibility, diagnostic accuracy and correlation with gene mutations and clinical outcomes.
Br. J. Haematol.
PUBLISHED: 03-31-2014
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Bone marrow histology is included in the diagnostic criteria of myeloproliferative neoplasms (MPNs). However, some concerns have emerged about its reproducibility. To evaluate the diagnostic accuracy of histology and to assess its correlation with presence of mutations and clinical outcomes, two pathologists reviewed the bone marrow biopsies corresponding to 211 patients with MPN. Despite the low agreement in the evaluation of individual histopathological characteristics, the concordance among pathologists when establishing the diagnosis was good (Kappa index 0·67). The specificity of histology was 100%, 98·5% and 98% in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), respectively, whereas the sensitivity of histological diagnosis was low in PV and ET (32·5% and 54% respectively) and acceptable in PMF (75%). Thirteen out of 146 (9%) patients with clinical ET were diagnosed as prefibrotic PMF. No histological agreement or MPN otherwise unspecified was more frequently observed in JAK2 V617F-positive ET than in CALR-mutated cases, whereas megakaryocytic abnormalities and prefibrotic PMF were more frequently observed in CALR-mutated ET. In conclusion, histological criteria of MPN have a limited diagnostic accuracy due to low sensitivity. Patients with JAK2 V617F-positive MPN have a heterogeneous histology while CALR-positive ET is associated with megakaryocyte abnormalities and prefibrotic PMF.
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Cardiovascular biomarkers in vertically HIV-infected children without metabolic abnormalities.
Atherosclerosis
PUBLISHED: 01-10-2014
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Early cardiovascular disease is a major concern for ART-suppressed vertically HIV-infected children; however, evidence is lacking regarding specific preventive measures. In this study, a complete panel of biomarkers was determined together with carotid intima-media thickness (IMT), in a cohort of 64 HIV-infected children and 30 controls. Mean age of participants was 14.1±5 years. HIV-infected patients showed normal lipid profile, with only slightly higher triglycerides, and no differences between groups were found regarding IMT. HIV-infected patients displayed higher levels of soluble CD14 (sCD14) and soluble vascular cell adhesion molecule-1 (sVCAM) (all p<0.05). However, levels of C-reactive protein, interleukin-6, myeloperoxidase, monocyte chemoattractant protein-1, P-selectin and tissue plasminogen activator were similar between groups. Vertically HIV-infected subjects on ART with no significant metabolic disturbances displayed increased sCD14 and sVCAM but not up-regulation of proinflammatory pathways. Larger studies are warranted to assess the impact of a strict metabolic control on cardiovascular risk and to define specific cardiovascular disease preventive strategies in this population.
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Regional Groundwater Flow in the Louisville Aquifer.
Ground Water
PUBLISHED: 01-07-2014
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The unconfined alluvial aquifer at Louisville, Kentucky, is an important source of water for domestic and industrial uses. It has been the object of several modeling studies in the past, particularly via the application of classical analytical solutions, and numerical solutions (finite differences and finite elements). A new modeling procedure of the Louisville aquifer is presented based on a modification of Adomian's Decomposition Method (ADM) to handle irregularly shaped boundaries. The new approach offers the simplicity, stability, and spatial continuity of analytical solutions, in addition to the ability to handle irregular boundaries typical of numerical solutions. It reduces to the application of a simple set of algebraic equations to various segments of the aquifer. The calculated head contours appear in reasonably agreement with those of previous studies, as well as with those from measured head values from the U.S. Geological Survey field measurement program. A statistical comparison of the error standard deviation is within the same range as that reported in previous studies that used complex numerical solutions. The present methodology could be easily implemented in other aquifers when preliminary results are needed, or when scarce hydrogeologic information is available. Advantages include a simple approach for preliminary groundwater modeling; an analytic description of hydraulic heads, gradients, fluxes, and flow rates; state variables are described continuously over the spatial domain; complications from stability and numerical roundoff are minimized; there is no need for a numerical grid or the handling of large sparse matrices; there is no need to use specialized groundwater software, because all calculations may be done with standard mathematics or spreadsheet programs. Nonlinearity, the effect of higher order terms, and transient simulations could be included if desired.
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Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio.
PLoS ONE
PUBLISHED: 01-01-2014
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A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events.
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Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry.
Clin. Cancer Res.
PUBLISHED: 12-18-2013
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According to current diagnostic criteria, mantle cell lymphoma (MCL) encompasses the usual, aggressive variants and rare, non-nodal cases with monoclonal asymptomatic lymphocytosis, cyclin D1-positive (MALD1). We aimed to understand the biology behind this clinical heterogeneity and to identify markers for adequate identification of MALD1 cases.
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Dynamics of the HIV-1 latent reservoir after discontinuation of the intensification of antiretroviral treatment: results of two clinical trials.
AIDS
PUBLISHED: 11-11-2013
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Antiretroviral therapy (ART) intensification has been shown to reduce the reservoir of latently infected CD4 T cells. However, it is currently unknown whether this effect is maintained after discontinuation of the intensifying drug.
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Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial.
Lancet Oncol.
PUBLISHED: 11-08-2013
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Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone.
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Neutropenia during therapy with peginterferon and ribavirin in HIV-infected subjects with chronic hepatitis C and the risk of infections.
Clin. Infect. Dis.
PUBLISHED: 04-10-2013
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It is unclear whether pegylated interferon (peg-IFN) -induced neutropenia in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with increased risk of serious infections.
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AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer.
J. Clin. Oncol.
PUBLISHED: 04-08-2013
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PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of the 424 patients were balanced between treatment arms. Most patients had visceral metastases, 43% had a disease-free interval less than 12 months, and 85% had measurable disease. Median follow-up was 26 months. The hazard ratio for investigator-assessed PFS was 0.82 (95% CI, 0.65 to 1.02; P = .0775; median PFS, 13.7 v 16.5 months in the non-bevacizumab and bevacizumab arms, respectively; PFS events in 72%). The Independent Review Committee-assessed PFS hazard ratio was 0.72 (95% CI, 0.54 to 0.94; P = .0162; median PFS, 13.9 v 16.8 months, respectively; PFS events in 53%). The RR was 70% versus 74%, respectively (P = .3492). Grade ? 3 febrile neutropenia and hypertension were more common with bevacizumab-containing therapy. High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.
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The CD4/CD8 ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.
AIDS
PUBLISHED: 02-26-2013
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We explored the associations of the CD4/CD8 ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 ratio may identify patients with higher immunoactivation despite ART.
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Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors.
Gastric Cancer
PUBLISHED: 01-03-2013
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There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer.
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Primary monophasic synovial sarcoma of the kidney: a case report and review of literature.
Clin Med Insights Oncol
PUBLISHED: 01-01-2013
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Primary synovial sarcoma (SS) of the kidney is a rare neoplasm and its presenting features are similar to other common renal tumors, making early diagnosis difficult. To date, few cases have been reported in the literature. Primary renal SSs can exist in either a monophasic or a biphasic pattern, the former being more common and tending to have a better prognosis than the biphasic variant. Herein we describe a case of primary renal SS that was diagnosed based on histopathology and immunohistochemistry after radical nephrectomy. Fusion gene product analysis was also done by FISH and RT-PCR. Patient follow-up and literature review are presented, focused on systemic therapy. We highlight that these tumors should be correctly diagnosed as clinical results and specific treatment are distinct from primary epithelial renal cell carcinoma. Adjuvant chemotherapy should be tailored for each patient in the management of disease, although its role still remains unclear.
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Automated screening of gynecologic cytology: a comparison of results.
Anal. Quant. Cytol. Histol.
PUBLISHED: 12-01-2011
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To compare the results among conventional gynecologic cytology liquid-based cytology and manual screening and liquid-based cytology automatically screened.
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Cell and tissue interactions of Treponema pallidum in primary and secondary syphilitic skin lesions: an ultrastructural study of serial sections.
Ultrastruct Pathol
PUBLISHED: 07-07-2011
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There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.
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High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy.
Haematologica
PUBLISHED: 05-05-2011
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Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy.
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Increased ALK gene copy number and amplification are frequent in non-small cell lung cancer.
J Thorac Oncol
PUBLISHED: 04-29-2011
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Translocation of the anaplastic lymphoma kinase (ALK) gene is involved in the tumorigenesis of a subset of non-small cell lung carcinomas (NSCLCs) and identifies patients sensitive to ALK inhibitors. ALK copy number changes and amplification, which plays an oncogenic role in tumors such as neuroblastoma, are poorly characterized in NSCLC. We aimed to study the prevalence of ALK copy number changes and their correlation to ALK protein expression, epidermal growth factor receptor (EGFR) status, and clinicopathological data in patients with NSCLC.
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Global organization of spiral structures in biparameter space of dissipative systems with Shilnikov saddle-foci.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 03-17-2011
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We reveal and give a theoretical explanation for spiral-like structures of periodicity hubs in the biparameter space of a generic dissipative system. We show that organizing centers for "shrimp"-shaped connection regions in the spiral structure are due to the existence of Shilnikov homoclinics near a codimension-2 bifurcation of saddle-foci.
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Molecular characteristics of mantle cell lymphoma presenting with clonal plasma cell component.
Am. J. Surg. Pathol.
PUBLISHED: 01-26-2011
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The normal counterparts of mantle cell lymphoma (MCL) are naive, quiescent B cells that have not been processed through the germinal center (GC). For this reason, although lymphomas arising from GC or post-GC B cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from 6 centers and were studied by immunohistochemistry, fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms analysis, capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis of microdissections of each of the MCL and PC populations to assess their clonal relationship. The clinical presentation was rather unusual compared with typical MCL, with 2 cases arising from the extranodal soft tissues of the head. All MCL cases were morphologically and immunohistochemically typical, bearing the t(11;14)(q13;q32). In all cases, the PC population was clonal. In 5 of the 7 cases, the MCL and PC clones showed identical restriction fragments, indicating a common clonal origin of the neoplastic population. The 2 cases with clonal diversity denoted the coexistence of 2 different tumors in a composite lymphoma/PC neoplasm. Our findings suggest that MCL can present with a PC component that is often clonally related to the lymphoma, representing a rare but unique biological variant of this tumor.
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PI3K signaling pathway is activated by PIK3CA mRNA overexpression and copy gain in prostate tumors, but PIK3CA, BRAF, KRAS and AKT1 mutations are infrequent events.
Mod. Pathol.
PUBLISHED: 11-26-2010
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The phosphatidylinositol 3-kinase (PI3K)-AKT and RAS-MAPK pathways are deregulated in a wide range of human cancers by gain or loss of function in several of their components. Our purpose has been to identify genetic alterations in members of these pathways in prostate cancer. A total of 102 prostate tumors, 79 from prostate cancer alone (group G1) and 23 from bladder and prostate cancer patients (G2), are the subject of this study. In 20 of these 23, the bladder tumors were also analyzed. PIK3CA, KRAS, BRAF and AKT1 mutations were analyzed by direct sequencing, and BRAF also by pyrosequencing. PIK3CA quantitative mRNA expression and fluorescence in situ hybridization (FISH) gains were tested in 25 and 32 prostate tumors from both groups (G1 and G2), respectively. Immunohistochemistry for pAKT was performed in 55 prostate tumors. Of 25 prostate tumors, 10 (40%) had PIK3CA mRNA overexpression that was statistically associated with Gleason score ? 7 (P=0.018). PIK3CA copy gain was detected in 9 of 32 (28%) prostate tumors. Of 20 bladder tumors, 3 (15%) displayed mutations in PIK3CA, KRAS and AKT1, the corresponding prostate tumors being wt. We also detected a previously not reported PIK3CA polymorphism (IVS9+91) in two prostate tumors. In all, 56% of prostate tumors overexpressed pAKT. There is a statistical association (P<0.0001) of strong pAKT immunostaining with high Gleason score, and with PIK3CA alterations (mRNA overexpression and/or FISH gains). PIK3CA gene is deregulated by mRNA overexpression and DNA gain in ? 40 and 28% of prostate tumors, respectively. High-grade prostate tumors are associated with PIK3CA mRNA overexpression, but not with FISH status. PIK3CA, BRAF, KRAS and AKT1 mutations are very infrequent events in prostate tumors. However, PI3K signaling pathway is activated by PIK3CA FISH gain and/or mRNA overexpression, leading to an increased pAKT protein expression.
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Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group.
Blood
PUBLISHED: 05-17-2010
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We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.
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A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma.
Blood
PUBLISHED: 05-17-2010
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Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease. Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022). This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).
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Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO Foundation study.
Clin. Cancer Res.
PUBLISHED: 04-06-2010
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To assess the pharmacodynamic effects of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody with intermediate affinity for the receptor, in skin and tumor tissues from head and neck cancer patients. Experimental design: Pharmacodynamic study in patients with advanced squamous cell carcinoma of the head and neck, unsuitable for chemoradiotherapy, enrolled in a single-center trial. Patients received 8 weekly infusions of nimotuzumab. The first nimotuzumab infusion was administered 1 week before starting radiation, whereas the remaining doses were administered concomitantly with irradiation. Paired biopsies were taken from skin and primary tumors, before (pretherapy) and 1 week (on single-agent therapy) after first infusion. Immunohistochemistry was conducted to assay the effects of nimotuzumab on total and phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), p-AKT, and proliferation (Ki-67).
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Molecular alterations of EGFR and PTEN in prostate cancer: association with high-grade and advanced-stage carcinomas.
Mod. Pathol.
PUBLISHED: 03-05-2010
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Prostate cancer is the second cause of cancer-related death in men of the Western world. The potential prognostic role of the combined alterations in EGFR and PTEN in prostate cancer is not well established. It was the aim of the study to investigate this role. Prevalence of EGFR and PTEN somatic mutations, EGFR amplification and EGFR protein expression were investigated in a series of prostate adenocarcinomas, classified according to the current Gleason grading system. Mutational analysis revealed eight EGFR and three PTEN mutations in 98 (8%) and 92 (3%) prostate adenocarcinomas, respectively. The combined prevalence of EGFR-PTEN mutations was 11%. EGFR overexpression was present in 31% of adenocarcinomas, with a marginally significant difference (P=0.068) between Gleason grade < or =7 adenocarcinomas and Gleason grade > or =8 and metastatic adenocarcinomas. Four cases (4 of 31; 13%) had an EGFR gene gain due to chromosome 7 polysomy. In 35% of adenocarcinomas we found some type of EGFR-PTEN alteration, with a tendency to be associated with advanced-stage prostate adenocarcinomas (P=0.04). The IVS18+19 polymorphism was also associated with more advanced prostate adenocarcinomas. This is the first study reporting mutations of EGFR and PTEN in the same series of prostate adenocarcinomas. Protein overexpression is the most frequent EGFR abnormality. Mutations in EGFR and PTEN genes are a minor event, although prostate cancer represents the third neoplasm in which the EGFR gene mutations are more prevalent. Alterations in the EGFR-PTEN signaling pathway are present in a third of prostate adenocarcinomas, particularly affecting the more advanced cases.
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[Etravirine drug interactions].
Enferm. Infecc. Microbiol. Clin.
PUBLISHED: 10-05-2009
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Etravirine (ETR) belongs to the family of non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs), with antiviral activity in patients with resistance to first-generation NNRTIs. The drug interactions caused by ETR are due to its dual effect on the CYP450 system. ETR acts as an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19. This drug shows few clinically significant drug interactions, the most important of which involve the unboosted protease inhibitors, the NNRTIs efavirenz and nevirapine, full-dose ritonavir and tipranavir/ritonavir. Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir.
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Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.
J. Invest. Dermatol.
PUBLISHED: 09-17-2009
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Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.
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FGFR3 mutations in prostate cancer: association with low-grade tumors.
Mod. Pathol.
PUBLISHED: 04-17-2009
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Prostate cancer is the second cause of cancer-related death in men of the Western World. The role of FGFR3 and its abnormalities in prostate cancer are not known. FGFR3 mutations have been reported in some human tumors. Few studies have analyzed the mutations of FGFR3 in prostate tumors, and no mutations have been previously reported. Prevalence of FGFR3 somatic mutations was investigated in a series of prostate tumors. The presence of other tumors in these patients, including urothelial, skin, colon, and lung neoplasms, was recorded. Mutational analysis of exons 7, 10, and 15 of FGFR3 revealed 9 mutations in the 112 prostate tumors studied (8%). Most of them consisted of the missense change S249C. The prevalence of mutations in tumors with combined Gleason score=6 is 18% (8/45) compared to 3% (1/36) for tumors with grade=7, and 0% (0/31) for those with grade >or=8 and metastases (P=0.007). The frequency of FGFR3 mutations in autopsy and biopsy samples was 6 and 9%, respectively. The prevalence of FGFR3 mutations in prostate tumors from patients with only prostate cancer was 2% compared to 23% in prostate tumors from patients with other associated neoplasms (P=0.001). This is the first report of molecular changes of FGFR3 in prostate cancer. This gene does not seem to be central to the pathogenesis of prostate cancer, but it is significantly associated with a subgroup of low-grade prostate tumors, and with the finding of other tumors, mainly arising in bladder and skin.
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CXCR4 mRNA overexpression in high grade prostate tumors: lack of association with TMPRSS2-ERG rearrangement.
Cancer Biomark
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The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n=44), ERG protein by IHC (n=84), and CXCR4 by quantitative RT-PCR (n=44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index=0.954). Seventy percent of Gleason ? 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p=0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement.
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The role of artesunate for the treatment of urinary schistosomiasis in schoolchildren: a systematic review and meta-analysis.
Pathog Glob Health
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Efficacy of artemisinin derivatives alone or in combination compared to praziquantel alone for the treatment of urinary schistosomiasis in schoolchildren.
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Response of vegetation to drought time-scales across global land biomes.
Proc. Natl. Acad. Sci. U.S.A.
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We evaluated the response of the Earth land biomes to drought by correlating a drought index with three global indicators of vegetation activity and growth: vegetation indices from satellite imagery, tree-ring growth series, and Aboveground Net Primary Production (ANPP) records. Arid and humid biomes are both affected by drought, and we suggest that the persistence of the water deficit (i.e., the drought time-scale) could be playing a key role in determining the sensitivity of land biomes to drought. We found that arid biomes respond to drought at short time-scales; that is, there is a rapid vegetation reaction as soon as water deficits below normal conditions occur. This may be due to the fact that plant species of arid regions have mechanisms allowing them to rapidly adapt to changing water availability. Humid biomes also respond to drought at short time-scales, but in this case the physiological mechanisms likely differ from those operating in arid biomes, as plants usually have a poor adaptability to water shortage. On the contrary, semiarid and subhumid biomes respond to drought at long time-scales, probably because plants are able to withstand water deficits, but they lack the rapid response of arid biomes to drought. These results are consistent among three vegetation parameters analyzed and across different land biomes, showing that the response of vegetation to drought depends on characteristic drought time-scales for each biome. Understanding the dominant time-scales at which drought most influences vegetation might help assessing the resistance and resilience of vegetation and improving our knowledge of vegetation vulnerability to climate change.
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Absence of TGF-?RII predicts bone and lung metastasis and is associated with poor prognosis in stage III breast tumors.
Cancer Biomark
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In the case of operated breast cancer (BC), prognostic markers help to determine if the patient needs additional treatment and predictive markers help the clinician to decide which treatment to use. Thus, a better knowledge of known predictive and prognostic markers and the identification of new markers, may improve the treatment of BC patients. The transforming growth factor-beta type II receptor (TGF-?RII), a main receptor of transforming growth factor beta pathway, is a potential new prognostic marker. The aims of the present study were to investigate both the predictive and prognostic impact of TGF-?RII in BC samples. TGF-?RII protein expression was evaluated using immunohistochemistry on a tissue microarray containing 110 TNM stage III BC samples obtained prior to doxorubicin-based neoadjuvant chemotherapy (NAC). Our results demonstrate that TGF-?RII did not predict the response to NAC. On the other hand, an association between TGF-?RII-negative tumor and higher risk of metastasis to lungs and bones was verified. TGF-?RII negativity was an independent prognostic factor for decreased disease-free and overall survival.
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A 12-gene expression signature is associated with aggressive histological in prostate cancer: SEC14L1 and TCEB1 genes are potential markers of progression.
Am. J. Pathol.
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The main challenge for clinical management of prostate cancer is to distinguish tumors that will progress faster and will show a higher tendency to recur from the more indolent ones. We have compared expression profiles of 18 prostate cancer samples (seven with a Gleason score of 6, eight with a Gleason score of 7, and three with a Gleason score of ?8) and five nonneoplastic prostate samples, using the Affymetrix Human Array GeneChip Exon 1.0 ST. Microarray analysis revealed 99 genes showing statistically significant differences among tumors with Gleason scores of 6, 7, and ?8. In addition, mRNA expression of 29 selected genes was analyzed by real-time quantitative RT-PCR with microfluidic cards in an extended series of 30 prostate tumors. Of the 29 genes, 18 (62%) were independently confirmed in the extended series by quantitative RT-PCR: 14 were up-regulated and 4 were down-regulated in tumors with a higher Gleason score. Twelve of these genes were differentially expressed in tumors with a Gleason score of 6 to 7 versus ?8. Finally, IHC validation of the protein levels of two genes from the 12-gene signature (SEC14L1 and TCEB1) showed strong protein expression levels of both genes, which were statistically associated with a high combined Gleason score, advanced stage, and prostate-specific antigen progression. This set of genes may contribute to a better understanding of the molecular basis of prostate cancer. TCEB1 and SELC14L1 are good candidate markers for predicting prognosis and progression of prostate cancer.
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The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression.
J. Infect.
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HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.
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[Temporal and spatial variation of shorebirds in Barra de Navidad lagoon, Jalisco, during three non-breeding seasons].
Rev. Biol. Trop.
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Resident and migratory shorebirds inhabit different kinds of wetlands such as lagoons, rivers and seashores among others. In recent years, these areas have been importantly affected by urban, agriculture and touristic activities, such as the Barra de Navidad lagoon, for which little information is available to support conservation programs. The aim of this work was to describe shorebirds temporal and spatial distribution in Barra de Navidad lagoon during three non-breeding seasons (1999-2000, 2006-2007 and 2008-2009). For this, monthly censuses were performed from November-April with the purpose of registering all the shorebirds species. We were able to identify 19 shorebirds species (three residents and 16 winter visitors), of which Charadrius wilsonia, Limosa fedoa and Tringa semipalmata were the most abundant. The greater number of species was registered for November, December and March of the first and third seasons. The greater number of individuals was registered when birds were feeding during low tides, mainly in December, January and February of the first and third seasons. At low tide, there was a great number of species and individuals in zone C. This area had muddy substrates that were exposed during low tides and were used to feed. Barra de Navidad lagoon provided suitable habitats for feeding and resting for resident and migratory birds. Twelve of the 19 species were considered as priority within the Mexican bird conservation strategy. However, these habitats are threatened by human activities performed in the nearby areas of the lagoon that may have negative consequences for the distribution, abundance and conservation of these species.
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[The evaluation of an instrument for pediatric oncology patient classification].
Rev Esc Enferm USP
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The objectives of this study were to assess the interrater reproducibility of the instrument to classify pediatric patients with cancer; verify the adequacy of the patient classification instrument for pediatric patients with cancer; and make a proposal for changing the instrument, thus allowing for the necessary adjustments for pediatric oncology patients. A total of 34 pediatric inpatients of a Cancer Hospital were evaluated by the teams of physicians, nurses and nursing technicians. The Kappa coefficient was used to rate the agreement between the scores, which revealed a moderate to high value in the objective classifications, and a low value in the subjective. In conclusion, the instrument is reliable and reproducible, however, it is suggested that to classify pediatric oncology patients, some items should be complemented in order to reach an outcome that is more compatible with the reality of this specific population.
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Topological changes in periodicity hubs of dissipative systems.
Phys. Rev. Lett.
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We reveal the existence of a new codimension-1 curve that involves a topological change in the structure of the chaotic invariant sets (attractors and saddles) in generic three-dimensional dissipative systems with Shilnikov saddle foci. This curve is related to the spiral-like structures of periodicity hubs that appear in the biparameter phase plane. We show how this curve configures the spiral structure (via the doubly superstable points) originated by the existence of Shilnikov homoclinics and how it separates two regions with different kinds of chaotic attractors or chaotic saddles. Inside each region, the topological structure is the same for both chaotic attractors and saddles.
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[Stroke in the very old: myths and realities].
Med Clin (Barc)
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The incidence of stroke in the very old is increasing. However, there are very few data regarding the differences in the management and outcomes in Spain.
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Association of HIV-Infection and antiretroviral therapy with levels of endothelial progenitor cells and subclinical atherosclerosis.
J. Acquir. Immune Defic. Syndr.
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Although in the general population circulating vascular progenitor cell levels have been implicated in the homeostasis of the vascular wall through differentiation into endothelium and/or smooth muscle cells, it has not yet been assessed in HIV-infected patients. We herein investigated the number of progenitor cell subpopulations in HIV-infected patients and its relationship to carotid intima-media thickness (c-IMT).
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Diagnosis of subclinical atherosclerosis in HIV-infected patients: higher accuracy of the D:A:D risk equation over Framingham and SCORE algorithms.
Eur J Prev Cardiol
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Aims: While the detection of subclinical atherosclerosis may provide an opportunity for the prevention of cardiovascular disease (CVD), which currently is a leading cause of death in HIV-infected subjects, its diagnosis is a clinical challenge. We aimed to compare the agreement and diagnostic performance of Framingham, SCORE and D:A:D equations for the recognition of subclinical atherosclerosis in HIV patients and to adjust the D:A:D equation using HIV and CVD variables.Methods and results: Atherosclerosis was evaluated in 203 HIV-infected individuals by measuring the carotid intima-media thickness (IMT). The CVD risk was calculated using the Framingham, SCORE and D:A:D risk equations. Framingham, SCORE and D:A:D equations showed a low agreement with the IMT (Kappa: 0.219, 0.298, 0.244, respectively; p = 0.743) and a moderate predictive performance, (area under the curve [AUC] = 0.686, 0.665 and 0.716, respectively; p = 0.048), with the D:A:D equation being the most accurate. Atherosclerosis was demonstrated in a significant proportion of subjects with low predicted CVD risk by all three algorithms (16.3%, 17.2%, 17.2%, respectively; p = 0.743). In patients with an estimated low CVD risk atherosclerosis was associated with older age (p = 0.012) and low CD4 counts (p = 0.021). A model was developed to adjust the D:A:D equation; a significant increase in accuracy was obtained when CD4 counts and low-grade albuminuria were included (AUC = 0.772; p < 0.001).Conclusion: The D:A:D equation overperforms Framingham and SCORE in HIV patients. However, all three equations underestimate the presence of subclinical atherosclerosis in this population. The accuracy of the D:A:D equation improves when CD4 counts and low-grade albuminuria are incorporated into the equation.
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[Clinical factors and biomarkers associated with subclinical atherosclerosis in the human immunodeficiency virus infection].
Med Clin (Barc)
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HIV-infected patients present accelerated cardiovascular disease (CVD) and CVD is among the most important causes of mortality in this population. We aimed to identify biomarkers and clinical factors associated with subclinical atherosclerosis in HIV-infected patients.
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Value of p16(INK4a) in the diagnosis of low-grade urothelial carcinoma of the urinary bladder in urinary cytology.
Cancer Cytopathol
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The sensitivity of urinary cytology for the diagnosis of urothelial carcinomas is low, particularly in low-grade carcinomas. The UroVysion test is a fluorescent in situ hybridization multiprobe assay that increases the sensitivity of urinary cytology. However, this test is not widely available. P16(INK4a) , a protein involved in cell cycle progression, is overexpressed in urothelial carcinoma. Immunocytochemical expression of p16(INK4a) has been examined in biopsy samples from urothelial carcinomas, but few studies have addressed this protein in urine cytology.
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Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer.
Hum. Pathol.
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Different members of the phosphoinositide 3 kinase--serine threonine protein kinase (PI3K-AKT) pathway are altered in bladder cancer. Fibroblast growth factor receptor 3 (FGFR3) mutations characterize the low-grade tumors, and RAS genes are mutated in approximately 13% of all bladder tumors. Interestingly, a percentage of bladder tumors have alterations in more than 1 PI3K-AKT or rat sarcoma viral oncogene homolog-RAF mitogen activated protein kinase (RAS-MAPK) pathway gene or their upstream regulators, but some combinations are mutually exclusive. We analyzed mutations in FGFR3, phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in 88 urothelial cell carcinomas and the immunohistochemical expression of phospho-v-akt murine thymoma viral oncogene homolog (AKT) and mitogen-activated protein kinase 1 and 2 (pERK1/2) in 80 and 77 urothelial cell carcinomas, respectively. Approximately 43% and 20.5% of tumors presented 1 and 2 mutated genes, respectively. FGFR3 mutations were more frequent alone, whereas PIK3CA mutations were associated with another mutated gene (FGFR3 and KRAS). Overall, mutated FGFR3 (FGFR3(mut)) and mutated FGFR3 (FGFR3(mut))-mutated PIK3CA (PIK3CA(mut)) genotypes were associated with low-grade bladder tumors and mutated PIK3CA (PIK3CA(mut))-mutated KRAS (KRAS(mut)) and mutated AKT1 (AKT1(mut)) were only present in high-grade tumors. There are no mutated FGFR3 (FGFR3(mut))-mutated RAS (RAS(mut)) nor mutated PIK3CA (PIK3CA(mut))-mutated AKT1 (AKT1(mut)) combinations. Fifty percent and 56% of tumors showed high levels of pAKT and pERK1/2, respectively. High levels of pAKT were associated with total mutations, FGFR3(mut), and PIK3CA(mut) tumors but not with tumor grade or stage. Wild-type tumors presented significantly higher pERK1/2 expression. Mutations in FGFR3 and FGFR3-PIK3CA but not single PIK3CA mutations characterize low-grade bladder tumors. Single FGFR3 or PIK3CA mutations and the different mutation combinations FGFR3-PIK3CA/AKT1 and PIK3CA-RAS can activate the AKT but not the MAPK pathway. Other genes different from FGFR3 may be related with the pERK activation in bladder tumors.
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Subclinical atherosclerosis and markers of immune activation in HIV-infected children and adolescents: The CaroVIH Study.
J. Acquir. Immune Defic. Syndr.
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HIV-infected adults display increased cardiovascular disease, probably driven by inflammation and immune activation. These relationships have not been addressed in vertically HIV-infected children and adolescents, a population at very high-risk for long-term non-AIDS complications.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.