Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Virologic Failures on Initial Boosted-PI Regimen Infrequently Possess Low-Level Variants with Major PI Resistance Mutations by Ultra-Deep Sequencing

It is unknown whether HIV-positive patients experiencing virologic failure (VF) on boosted-PI (PI/r) regimens without drug resistant mutations (DRM) by standard genotyping harbor low-level PI resistant variants. CASTLE compared the efficacy of atazanavir/ritonavir (ATV/r) with lopinavir/ritonavir (LPV/r), each in combination with TVD in ARV-naïve subjects.To determine if VF on an initial PI/r-based regimen possess low-level resistant variants that may affect a subsequent PI-containing regimen.Patients experiencing VF on a Tenofovir/Emtricitabine+PI/r regimen were evaluated by ultra deep sequencing (UDS) for mutations classified/weighted by Stanford HIVdb. Samples were evaluated for variants to 0.4% levels. 36 VF subjects were evaluated by UDS; 24 had UDS for PI and RT DRMs. Of these 24, 19 (79.2%) had any DRM by UDS. The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11), TAMs(7) & K65R(4); PI DRMs were detected in 9 subjects: M46I/V(5), F53L(2), I50V(1), D30N(1), and N88S(1). The remaining 12 subjects, all with VLs<10,000, had protease gene UDS, and 4 had low-level PI DRMs: F53L(2), L76V(1), I54S(1), G73S(1). Overall, 3/36(8.3%) subjects had DRMs identified with Stanford-HIVdb weights >12 for ATV or LPV: N88S (at 0.43% level-mutational load 1,828) in 1 subject on ATV; I50V (0.44%-mutational load 110) and L76V (0.52%-mutational load 20) in 1 subject each, both on LPV. All VF samples remained phenotypically susceptible to the treatment PI/r.Among persons experiencing VF without PI DRMs with standard genotyping on an initial PI/r regimen, low-level variants possessing major PI DRMs were present in a minority of cases, occurred in isolation, and did not result in phenotypic resistance. NRTI DRMs were detected in a high proportion of subjects. These data suggest that PIs may remain effective in subjects experiencing VF on a PI/r-based regimen when PI DRMs are not detected by standard or UDS genotyping

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed

Holographic Geometry of Entanglement Renormalization in Quantum Field Theories

We study a conjectured connection between the AdS/CFT and a real-space quantum renormalization group scheme, the multi-scale entanglement renormalization ansatz (MERA). By making a close contact with the holographic formula of the entanglement entropy, we propose a general definition of the metric in the MERA in the extra holographic direction, which is formulated purely in terms of quantum field theoretical data. Using the continuum version of the MERA (cMERA), we calculate this emergent holographic metric explicitly for free scalar boson and free fermions theories, and check that the metric so computed has the properties expected from AdS/CFT. We also discuss the cMERA in a time-dependent background induced by quantum quench and estimate its corresponding metric.Comment: 42pages, 9figures, reference added, minor chang

Cytogenetical studies in five Atlantic Anguilliformes fishes

The order Anguilliformes comprises 15 families, 141 genera and 791 fish species. Eight families had at least one karyotyped species, with a prevalence of 2n = 38 chromosomes and high fundamental numbers (FN). The only exception to this pattern is the family Muraenidae, in which the eight species analyzed presented 2n = 42 chromosomes. Despite of the large number of Anguilliformes species, karyotypic reports are available for only a few representatives. In the present work, a species of Ophichthidae, Myrichthys ocellatus (2n = 38; 8m+14sm+10st+6a; FN = 70) and four species of Muraenidae, Enchelycore nigricans (2n = 42; 6m+8sm+12st+16a; FN = 68), Gymnothorax miliaris (2n = 42; 14m+18sm+10st; FN = 84), G. vicinus (2n = 42; 8m+6sm+28a; FN = 56) and Muraena pavonina (2n = 42; 6m+4sm+32a; FN = 52), collected along the Northeastern coast of Brazil and around the St Peter and St Paul Archipelago were analyzed. Typical large metacentric chromosomes were observed in all species. Conspicuous polymorphic heterochromatic regions were observed at the centromeres of most chromosomes and at single ribosomal sites. The data obtained for Ophichthidae corroborate the hypothesis of a karyotypic diversification mainly due to pericentric inversions and Robertsonian rearrangements, while the identification of constant chromosome numbers in Muraenidae (2n = 42) suggests a karyotype diversification through pericentric inversions and heterochromatin processes

Symptoms in different severity degrees of bruxism: a cross-sectional study

Objective: The aim of the present study was to evaluate symptoms of the muscle pain, sleep quality, oral health, anxiety, stress and depression in individuals with different severity degrees of bruxism. Methods: Seventy-two individuals with bruxism were enrolled in the study, classified into: moderate (n=25) and severe (n=47) bruxism. Pain intensity was assessed using the Visual Analogical Scale, pain threshold with algometer, sleep quality by the Pittsburgh Sleep Quality Index, oral health by the Oral Health Impact Profile, anxiety by the State-Trait Anxiety Inventory, stress by the Perceived Stress Scale and depression using the Beck Depression Inventory. The significance level considered was 5%. Results: The results showed that individuals with severe bruxism presented greater muscle pain intensity, sleep disorder, worse oral health, high anxiety level and dysphoria with statistically significant differences (pObjetivo: Avaliar sintomas de dor muscular, qualidade de sono, saúde bucal, ansiedade, estresse e depressão em indivíduos com diferentes graus de severidade do bruxismo. Métodos: Setenta e dois indivíduos com bruxismo participaram do estudo e foram classificados com bruxismo moderado (n=25) e severo (n=47). A intensidade da dor foi avaliada pela Escala Visual Analógica, limiar de dor com o algômetro, qualidade de sono pelo Índice de Qualidade de Sono de Pittsburgh, saúde bucal pelo Perfil de Impacto de Saúde Bucal, ansiedade pelo Inventário de Ansiedade Traço-Estado, estresse pela Escala de Estresse Percebido e depressão pelo Inventário de Depressão de Beck. O nível de significância considerado foi 5%. Resultados: Os resultados demonstraram que indivíduos com bruxismo severo apresentaram maior intensidade de dor muscular, distúrbio do sono, pior qualidade de saúde bucal, elevado grau de ansiedade e disforia, com diferenças estatisticamente significantes (p;0,05). Conclusão: Os dados sugerem que indivíduos com bruxismo severo tem sintomas mais intensos. Eles apresentam maior intensidade de dor muscular, alterações na qualidade do sono e saúde bucal, ansiedade e depressão do que indivíduos com bruxismo moderado. Porém, ambos apresentam similaridade no estresse.Objetivo: Evaluar los síntomas dolor muscular, calidad de sueño, salud bucal, ansiedad, estrés y depresión en sujetos con diferentes niveles de gravedad del bruxismo. Método: Participaron del estudio 72 personas con bruxismo, clasificado según los niveles moderado (n=25) y grave (n=47). Se evaluaron la intensidad del dolor mediante la Escala Visual Analógica, umbral de dolor con algómetro, la calidad de sueño por el Índice de Calidad de Sueño de Pittsburgh, la salud bucal mediante el Perfil del Impacto de Salud Bucal, la ansiedad por el Inventario de Ansiedad Rasgo-Estado, el estrés mediante la Escala de Estrés Percibido y la depresión por el Inventario de Depresión de Beck. Se consideró el nivel de significación de 5%. Resultados: Los sujetos con bruxismo grave presentaron más intensamente dolor muscular, trastorno de sueño, peor calidad de salud bucal, alto grado de ansiedad y disforia, con diferencias estadísticamente significativas (p;0,05). Conclusión: Los datos mostraron que los sujetos con bruxismo grave sufren síntomas más intensos. A pesar de sufrir síntomas más intensos de dolor muscular, calidad de sueño y salud bucal alterada, ansiedad y depresión que los sujetos con bruxismo moderado, el estrés está presente en los dos niveles de bruxismo

The Anopheles gambiae Oxidation Resistance 1 (OXR1) Gene Regulates Expression of Enzymes That Detoxify Reactive Oxygen Species

OXR1 is an ancient gene, present in all eukaryotes examined so far that confers protection from oxidative stress by an unknown mechanism. The most highly conserved region of the gene is the carboxyl-terminal TLDc domain, which has been shown to be sufficient to prevent oxidative damage.OXR1 has a complex genomic structure in the mosquito A. gambiae, and we confirm that multiple splice forms are expressed in adult females. Our studies revealed that OXR1 regulates the basal levels of catalase (CAT) and glutathione peroxidase (Gpx) expression, two enzymes involved in detoxification of hydrogen peroxide, giving new insight into the mechanism of action of OXR1. Gene silencing experiments indicate that the Jun Kinase (JNK) gene acts upstream of OXR1 and also regulates expression of CAT and GPx. Both OXR1 and JNK genes are required for adult female mosquitoes to survive chronic oxidative stress. OXR1 silencing decreases P. berghei oocyst formation. Unexpectedly, JNK silencing has the opposite effect and enhances Plasmodium infection in the mosquito, suggesting that JNK may also mediate some, yet to be defined, antiparasitic response.The JNK pathway regulates OXR1 expression and OXR1, in turn, regulates expression of enzymes that detoxify reactive oxygen species (ROS) in Anopheles gambiae. OXR1 silencing decreases Plasmodium infection in the mosquito, while JNK silencing has the opposite effect and enhances infection

Observation of trapped light within the radiation continuum

The ability to confine light is important both scientifically and technologically. Many light confinement methods exist, but they all achieve confinement with materials or systems that forbid outgoing waves. These systems can be implemented by metallic mirrors, by photonic band-gap materials, by highly disordered media (Anderson localization) and, for a subset of outgoing waves, by translational symmetry (total internal reflection) or by rotational or reflection symmetry. Exceptions to these examples exist only in theoretical proposals. Here we predict and show experimentally that light can be perfectly confined in a patterned dielectric slab, even though outgoing waves are allowed in the surrounding medium. Technically, this is an observation of an ‘embedded eigenvalue’—namely, a bound state in a continuum of radiation modes—that is not due to symmetry incompatibility. Such a bound state can exist stably in a general class of geometries in which all of its radiation amplitudes vanish simultaneously as a result of destructive interference. This method to trap electromagnetic waves is also applicable to electronic and mechanical waves.United States. Army Research Office (Institute for Soldier Nanotechnologies under contract no. W911NF-07-D0004)United States. Department of Energy (grant no. DE-SC0001299)National Science Foundation (U.S.) (NSF grant no. DMR-0819762