The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior

During tumor progression, alternative splicing gives rise to different Mena protein isoforms. We analyzed how Mena11a, an isoform enriched in epithelia and epithelial-like cells, affects Mena-dependent regulation of actin dynamics and cell behavior. While other Mena isoforms promote actin polymerization and drive membrane protrusion, we find that Mena11a decreases actin polymerization and growth factor-stimulated membrane protrusion at lamellipodia. Ectopic Mena11a expression slows mesenchymal-like cell motility, while isoform-specific depletion of endogenous Mena11a in epithelial-like tumor cells perturbs cell:cell junctions and increases membrane protrusion and overall cell motility. Mena11a can dampen membrane protrusion and reduce actin polymerization in the absence of other Mena isoforms, indicating that it is not simply an inactive Mena isoform. We identify a phosphorylation site within 11a that is required for some Mena11a-specific functions. RNA-seq data analysis from patient cohorts demonstrates that the difference between mRNAs encoding constitutive Mena sequences and those containing the 11a exon correlates with metastasis in colorectal cancer, suggesting that 11a exon exclusion contributes to invasive phenotypes and leads to poor clinical outcomes.Virginia and D.K. Ludwig Fund for Cancer Research (Graduate Student Fellowship)National Institutes of Health (U.S.) (GM58801)Massachusetts Institute of Technology. Ludwig Center for Molecular OncologyDavid H. Koch Institute for Integrative Cancer Research at MIT (NCI Core Grant P30-CA14051

Extracting the late-time kinetic Sunyaev-Zel'dovich effect

We propose a novel technique to separate the late-time, post-reionization component of the kinetic Sunyaev Zeldovich (kSZ) effect from the contribution to it from a (poorly understood and probably patchy) reionization history. The kSZ effect is one of the most promising probe of the missing baryons in the Universe. We study the possibility of reconstructing it in three dimensions (3D), using future spectroscopic surveys such as the Euclid survey. By reconstructing a 3D template from galaxy density and peculiar velocity fields from spectroscopic surveys we cross-correlate the estimator against CMB maps. The resulting cross-correlation can help us to map out the kSZ contribution to CMB in 3D as a function of redshift thereby extending previous results which use tomographic reconstruction. This allows the separation of the late-time effect from the contribution owing to reionization. By construction, it avoids contamination from foregrounds, primary CMB, tSZ effect as well as from star-forming galaxies. Due to a high number density of galaxies the signal-to-noise ratio (S/N) for such cross-correlational studies is higher, compared to the studies involving CMB power-spectrum analysis. Using a spherical Bessel–Fourier (sFB) transform we introduce a pair of 3D power spectra: C⊥ℓ(k) and C⊥ℓ(k) that can be used for this purpose. We find that in a future spectroscopic survey with near all-sky coverage and a survey depth of z ≈ 1, reconstruction of C⊥ℓ(k) can be achieved in a few radial wave bands k ≈ (0.01–0.5 h−1 Mpc) with a S/N ratio of up to O(10) for angular harmonics in the range = (200–2000)

Current models of the observable consequences of cosmic reionization and their detectability

A number of large current experiments aim to detect the signatures of the cosmic reionization at redshifts z > 6. Their success depends crucially on understanding the character of the reionization process and its observable consequences and designing the best strategies to use. We use large-scale simulations of cosmic reionization to evaluate the reionization signatures at redshifted 21-cm and small-scale cosmic microwave background (CMB) anisotropies in the best current model for the background universe, with fundamental cosmological parameters given by Wilkinson Microwave Anisotropy Probe three-year results. We find that the optimal frequency range for observing the `global step of the 21-cm emission is 120150 MHz, while statistical studies should aim at 140160 MHz, observable by GMRT. Some strongly non-Gaussian brightness features should be detectable at frequencies up to ~190 MHz. In terms of sensitivity-signal trade-off relatively low resolutions, corresponding to beams of at least a few arcminutes, are preferable. The CMB anisotropy signal from the kinetic SunyaevZel'dovich effect from reionized patches peaks at tens of K at arcminute scales and has an rms of ~1 K, and should be observable by the Atacama Cosmology Telescope and the South Pole Telescope. We discuss the various observational issues and the uncertainties involved, mostly related to the poorly known reionization parameters and, to a lesser extend, to the uncertainties in the background cosmology

Hipermovilidad articular determinada por el Test de Beighton en estudiantes universitarios

Introduction: Joint hypermobility (JHM) implies an increased range of motion that exceeds what is considered normal for the examined joint. Objetive: To determine the frequency of JHM in first-year medical students of the Facultad de Ciencias Médicas of Universidad Nacional de Asunción (FCM-UNA) and its association to gender. Methods: Cross-sectional observational study. A physical examination was performed using the Beighton scoring system. Individuals who scored 4 or more points were considered to have JHM. Results: 100 students were included. 38% scored at least 4 points to diagnose them with JHM. 1% met all criteria. The item that evaluates forward bending of the spine was the most frequent among students. 84.2% of the individuals with criteria for JHM were women. There is a significant difference between the presence of JHM between women and men (p = 0.001). Conclusion: There is a substantial amount of individuals who meet JHM criteria among first-year medical students of the FCM-UNA. Women were identified with JHM more frequently than men.Introducción: La hipermovilidad articular (HMA), implica un aumento del rango de movilidad de las articulaciones que excede lo considerado normal para la articulación examinada. Objetivo: Determinar la frecuencia de HMA en estudiantes de primer curso de la carrera de medicina de la Universidad Nacional de Asunción y su asociación según el sexo de los individuos incluidos. Metodología: Estudio observacional de corte transversal. Se realizó un examen físico con el test de Beighton, que consiste en un sistema de puntos y se consideró a los individuos con HMA a aquel que sumara 4 o más puntos en el test. Resultados: se incluyeron 100 estudiantes, de los cuales el 38% cumplió como mínimo con 4 puntos suficientes para diagnosticarlos con HMA. El 1% cumplió con todos los criterios. El item que evalúa la flexión de la columna, fue el más frecuentemente identificado entre los estudiantes. El 84,2% de los individuos con criterio para HMA fueron mujeres. Existe una diferencia significativa entre la presencia de HMA entre mujeres y hombres (p=0.001). Conclusión: Existe una frecuencia importante de individuos que cumplen con criterios de HMA en el primer curso de la carrera de medicina de la FCM-UNA. Las mujeres fueron identificadas con HMA con mayor frecuencia en relación a los hombres

Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling

The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration

Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression

Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo. Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and Mena, an actin regulator, and involves increases in focal complex signaling and tumor-cell-mediated extracellular matrix (ECM) remodeling. Compared to Mena, higher levels of the pro-metastatic MenaINV isoform associate with α5, which enables 3D haptotaxis of tumor cells towards the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MenaINV and FN levels were correlated in two breast cancer cohorts, and high levels of MenaINV were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor-cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM guided directional migration

Interleukin 6 Dependence of Anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6–deficient (−/−) and –intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, –double-stranded (ds)DNA, and -chromatin antibodies in IL-6+/+, but not IL-6−/− mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not −/−, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6−/− and IL-6+/+ mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses

Dense gas in the Galactic central molecular zone is warm and heated by turbulence

The Galactic center is the closest region in which we can study star formation under extreme physical conditions like those in high-redshift galaxies. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H$_2$CO) transitions. We used the $3_{2,1} - 2_{2,0} / 3_{0,3} - 2_{0,2}$ line ratio to determine the gas temperature in $n \sim 10^4 - 10^5$cm$^{-3}$ gas. We have produced temperature maps and cubes with 30" and 1 km/s resolution and published all data in FITS form. Dense gas temperatures in the Galactic center range from ~60 K to > 100 K in selected regions. The highest gas temperatures T_G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km/s and 50 km/s clouds, and in "The Brick" (G0.253+0.016). We infer an upper limit on the cosmic ray ionization rate ${\zeta}_{CR} < 10^{-14}$ 1/s. The dense molecular gas temperature of the region around our Galactic center is similar to values found in the central regions of other galaxies, in particular starburst systems. The gas temperature is uniformly higher than the dust temperature, confirming that dust is a coolant in the dense gas. Turbulent heating can readily explain the observed temperatures given the observed line widths. Cosmic rays cannot explain the observed variation in gas temperatures, so CMZ dense gas temperatures are not dominated by cosmic ray heating. The gas temperatures previously observed to be high in the inner ~75 pc are confirmed to be high in the entire CMZ

Mechanistic Basis of Branch-Site Selection in Filamentous Bacteria

Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed