Learning to Read Better: Training Decoding, Comprehension and Perceptual Skills

The present study is a program evaluation designed to evaluate an elementary school remedial reading instructional program using Carr\u27s model (1982) of reading ability. The Learning to Read Better program evolved from Anes\u27 (1979a, 1979b, 1981) study and experience In teaching children with reading problems. The program is structured according to the components of the reading process, with time in the reading room and teaching responsibility allocated so that learning in each component occurs during every remedial session. Four key components of the reading process emphasized in this program are: visual-perceptual training, decoding, oral reading, and comprehension

Exosomal Hsp70 Induces a Pro-Inflammatory Response to Foreign Particles Including Mycobacteria

© 2010 Anand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Exosomes are endosome-derived vesicles that are released when multi-vesicular bodies (MVBs) fuse with the plasma membrane. Exosomes released from mycobacteria-infected cells have recently been shown to be pro-inflammatory. A prominent host molecule that is found within these exosomes is Hsp70, a member of the heat-shock family of proteins. Methodology/Principal Findings: We first characterized the exosomes purified from control and mycobacteria-infected cells. We found that relative to uninfected cells, macrophages infected with M. smegmatis and M. avium release more exosomes and the exosomes they released had more Hsp70 on their surface. Both exosomes and exogenous Hsp70 treatment of macrophages led to NF-kB activation and TNFa release in uninfected macrophages; Hsp70 levels were elevated in mycobacteria-infected cells. Macrophage treatment with Hsp70 also led to increase in the phagocytosis and maturation of latex-bead phagosomes. Finally, Hsp70 pre-incubation of M. smegmatis- and M. avium-infected cells led to increased phago-lysosome fusion, as well as more killing of mycobacteria within macrophages. Conclusions/Significance: Our results fit into an emerging concept whereby exosomes-containing Hsp70 are effective inducers of inflammation, also in response to mycobacterial infection.E.A. was supported by Fundação para a Ciência e a Tecnologia (FCT) Grant PIC/IC/82859/2007 and PTDC/SAU-MII/098024/2008. P.K.A was supported by a post-doctoral research grant from Alexander von Humboldt foundation, Germany and Marie-Curie fellowship from European Union, FP6 programme MIF1-CT- 2006-039351. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Esters of pyrazinoic acid are active against pyrazinamide-resistant strains of Mycobacterium tuberculosis and other naturally resistant mycobacteria in vitro and ex vivo within macrophages.

Pyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M. tuberculosis, M. africanum, and M. microti) but not against M. bovis and M. avium. The latter two are mycobacterial species involved in human and cattle tuberculosis and in HIV coinfections, respectively. PZA is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to form the active metabolite pyrazinoic acid (POA). As a result of this mechanism, resistance to PZA, as is often found in tuberculosis patients, is caused by point mutations in pyrazinamidase. In previous work, we have shown that POA esters and amides synthesized in our laboratory were stable in plasma (M. F. Simões, E. Valente, M. J. Gómez, E. Anes, and L. Constantino, Eur J Pharm Sci 37:257–263, 2009, http://dx.doi.org/10.1016/j.ejps.2009.02.012). Although the amides did not present significant activity, the esters were active against sensitive mycobacteria at concentrations 5- to 10-fold lower than those of PZA. Here, we report that these POA derivatives possess antibacterial efficacy in vitro and ex vivo against several species and strains of Mycobacterium with natural or acquired resistance to PZA, including M. bovis and M. avium. Our results indicate that the resistance probably was overcome by cleavage of the prodrugs into POA and a long-chain alcohol. Although it is not possible to rule out that the esters have intrinsic activity per se, we bring evidence here that long-chain fatty alcohols possess a significant antimycobacterial effect against PZA-resistant species and strains and are not mere inactive promoieties. These findings may lead to candidate dual drugs having enhanced activity against both PZA-susceptible and PZA-resistant isolates and being suitable for clinical development

The smaller the market, the better the rent capturing: electrification in North Portugal during the Interwar Period

This article analyses the origin of the persistently high level of electricity prices that hampered the expansion of electricity consumption during the interwar period in Porto. Initially, the rent-seeking behaviour of both the supply firm and the City Hall at the local level affected the expansion of the local electricity market. During the 1930s, this collusion at municipal level coincided with unpredictable energy policies at state level. This circumstance impeded the indispensable increase of scale and the building of a regional market of electricity in north Portugal. The literature on regulation and institutional analysis has proved very useful. Finally, though equally important, primary sources from company archives and institutional bodies were also employed.Este artículo analiza el origen de los elevados precios de la electricidad en Oporto entre las dos guerra mundiales y su secuela, su lenta electrificación. La colusión entre la compañía suministradora y el municipio limitó la expansión al comenzar el servicio hidroeléctrico; luego, la expectativa reiteradamente frustrada de una mayor intervención gubernamental fue en detrimento de mayores inversiones. Se impidió así el necesario aumento de escala, la plena integración del mercado eléctrico del Norte de Portugal y, en consecuencia, los precios eléctricos se mantuvieron elevados y la electrificación sufrió un persistente atraso. La adopción de una perspectiva institucional se ha revelado muy útil para esclarecer el funcionamiento de este mercado, que se ha examinado consultando fuentes empresariales, municipales y gubernamentales.This research has been financed by the Fundaçao Ciência e Tecnologia de Portugal

Cyanoacrylate closure for peripheral veins: Consensus document of the Australasian College of Phlebology

Background: Cyanoacrylates are fast-acting adhesives used in procedural medicine including closure of superficial wounds, embolization of truncal vessels pre-operatively, vascular anomalies, visceral false aneurysms, endoleaks, gastrointestinal varices and gastrointestinal bleeding. More recently, catheter-directed cyanoacrylate adhesive closure was introduced as an alternative to endovenous thermal ablation (ETA) to occlude superficial veins of the lower limbs. Objectives: To formulate policies for the safe and effective delivery of cyanoacrylate adhesive closure procedures in Australasia, based on current experience and evidence. Methods: A panel of phlebologists including vascular surgeons, interventional radiologists, dermatologists and research scientists systematically reviewed the available data on cyanoacrylate products used in medicine and shared personal experience with the procedure. The reviewed material included bibliographic and biomedical data, material safety data sheets and data requested and received from manufacturers. Results and recommendations: Cyanoacrylate adhesive closure appears to be an effective treatment for saphenous reflux with occlusion rates at 36 months of 90–95%. We recommend a maximum dose of 10 mL of cyanoacrylate per treatment session. Serious complications are rare, but significant. Hypersensitivity to acrylates is reported in 2.4% of the population and is an important absolute contraindication to cyanoacrylate adhesive closure.1 Post-procedural inflammatory reactions, including hypersensitivity-type phlebitis, occur in 10–20% of patients.2 In the long term, cyanoacrylate adhesive closure results in foreign-body granuloma formation within 2–12 months of the procedure. We recommend against the use of cyanoacrylate adhesive closure in patients with uncontrolled inflammatory, autoimmune or granulomatous disorders (e.g. sarcoidosis). Caution should be exercised in patients with significant active systemic disease or infection and alternative therapies such as thermal ablation and foam sclerotherapy should be considered. Conclusions: Cyanoacrylate adhesive closure appears to be an effective endovenous procedure, with short-term closure rates comparable to ETA and therefore greater efficacy than traditional surgery for treating superficial veins of the lower limbs. Ongoing data collection is required to establish the long-term safety

Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Identification of a Novel Gene Product That Promotes Survival of Mycobacterium smegmatis in Macrophages

BACKGROUND: Bacteria of the suborder Corynebacterineae include significant human pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in mycobacteria is increasingly common making identification of new antimicrobials a priority. Mycobacteria replicate intracellularly, most commonly within the phagosomes of macrophages, and bacterial proteins essential for intracellular survival and persistence are particularly attractive targets for intervention with new generations of anti-mycobacterial drugs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified a novel gene that, when inactivated, leads to accelerated death of M. smegmatis within a macrophage cell line in the first eight hours following infection. Complementation of the mutant with an intact copy of the gene restored survival to near wild type levels. Gene disruption did not affect growth compared to wild type M. smegmatis in axenic culture or in the presence of low pH or reactive oxygen intermediates, suggesting the growth defect is not related to increased susceptibility to these stresses. The disrupted gene, MSMEG_5817, is conserved in all mycobacteria for which genome sequence information is available, and designated Rv0807 in M. tuberculosis. Although homology searches suggest that MSMEG_5817 is similar to the serine:pyruvate aminotransferase of Brevibacterium linens suggesting a possible role in glyoxylate metabolism, enzymatic assays comparing activity in wild type and mutant strains demonstrated no differences in the capacity to metabolize glyoxylate. CONCLUSIONS/SIGNIFICANCE: MSMEG_5817 is a previously uncharacterized gene that facilitates intracellular survival of mycobacteria. Interference with the function of MSMEG_5817 may provide a novel therapeutic approach for control of mycobacterial pathogens by assisting the host immune system in clearance of persistent intracellular bacteria

Incorporation of a Dietary Omega 3 Fatty Acid Impairs Murine Macrophage Responses to Mycobacterium tuberculosis

by creating an immunosuppressive environment. We hypothesized that incorporation of n-3 PUFA suppresses activation of macrophage antimycobacterial responses and favors bacterial growth, in part, by modulating the IFNγ-mediated signaling pathway.. The fatty acid composition of macrophage membranes was modified significantly by DHA treatment. DHA-treated macrophages were less effective in controlling intracellular mycobacteria and showed impaired oxidative metabolism and reduced phagolysosome maturation. Incorporation of DHA resulted in defective macrophage activation, as characterized by reduced production of pro-inflammatory cytokines (TNFα, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFNγ receptor with lipid rafts, without affecting surface expression of IFNγ receptor. in response to activation by IFNγ, by modulation of IFNγ receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis

Dendrimers as anti-inflammatory agents

Dendrimers constitute an intriguing class of macromolecules which find applications in a variety of areas including biology. These hyperbranched macromolecules with tailored backbone and surface groups have been extensively investigated as nanocarriers for gene and drug delivery, by molecular encapsulation or covalent conjugation. Dendrimers have provided an excellent platform to develop multivalent and multifunctional nanoconjugates incorporating a variety of functional groups including drugs which are known to be anti-inflammatory agents. Recently, dendrimers have been shown to possess anti-inflammatory properties themselves. This unexpected and intriguing discovery has provided an additional impetus in designing novel active pharmaceutical agents. In this review, we highlight some of the recent developments in the field of dendrimers as nanoscale anti-inflammatory agents