Light-Emitting Diode Therapy in Chemotherapy-Induced Mucositis

Background and Objective: Mucositis is the most common oral complication of cancer chemotherapy, which causes pain on mastication and swallowing, impairs patients` ability to eat and take oral drugs and may determine interruption of the treatment. The aim of this study was to evaluate the effect of light-emitting diode (LED) therapy on chemotherapy-induced mucositis in hamsters. Study Design/Materials and Methods: Animals of both experimental (Group 1; n = 32) and positive control (Group II; n = 32) groups received intraperitoneal injections of 5-fluorouracil on days 0 and 2. All animals had their right and left cheek pouch irritated by superficial scratching on days 3 and 4. In Group I, LED irradiation (630 nm +/- 10 nm, 160 mW, 12 J/cm(2)) was applied during 37.5 seconds at days 3, 4, 6, 8, 10, 12, and 14. In Group II, mucositis was induced, but LED therapy was not performed. The oral mucosa was photographed from day 4 to 14 at 2-day intervals. Photographs were randomly scored according to the severity of induced mucositis (0 to 5). In the negative control group (Group III; n = 6), no mucositis was induced. Biopsies of the cheek pouches of 8 animals (Group I and Group II) were surgically obtained on days 5, 9, 13 and 15 and processed for histological examination. Results: The statistical analysis showed significant differences between irradiated and non-irradiated groups (P < 0.05). However, muscular degeneration was observed in 18% of the samples of Group I. Conclusion: It may be concluded that the LED therapy protocol established for this in vivo study was effective in reducing the severity of oral mucositis, although the oral lesions were not completely prevented. Lasers Surg. Med. 40:625-633, 2008. (c) 2008Wiley-Liss, Inc.

Susceptibility of Staphylococcus aureus to porphyrin-mediated photodynamic antimicrobial chemotherapy: an in vitro study

The ability of Staphylococcus aureus to develop multidrug resistance is well documented, and the antibiotic resistance showed by an increasing number of bacteria has shown the need for alternative therapies to treat infections, photodynamic therapy (PDT) being a potential candidate. The aim of this study was to determine the effect of photodynamic therapy as a light-based bactericidal modality to eliminate Staphylococcus aureus. The study investigated a technique based on a combination of light and a photosensitizer that is capable of producing oxidative species to induce a cytotoxic effect. A Staphylococcus aureus suspension was exposed to a light emitting diode (LED) emitting at 628 nm, 14.6 mW/cm(2), and energy density of 20J/cm(2), 40J/cm(2), or 60 J/cm(2) in the presence of different porphyrin concentrations (PhotogemA (R)). Three drug concentrations were employed: 12 mu l/ml, 25 mu l/ml, and 50 mu l/ml. The treatment response was evaluated by the number of bacterial colony forming units (CFU) after light exposure. The results indicated that exposure to 60 J/cm(2) eliminated 100% (10 log(10) scales) of bacteria, on average. The best PDT response rate to eliminate Staphylococcus aureus was achieved with exposure to LED light in combination with the photosensitizer at concentrations ranging from 25 mu l/ml to 50 mu l/ml. These data suggest that PDT has the potential to eliminate Staphylococcus aureus in suspension and indicates the necessary drug concentration and light fluency.

A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system

The aim of this study was to evaluate the anti-tumor activity of Amblyomin-X, a serine protease Kunitz-type inhibitor. Amblyomin-X induced tumor mass regression and decreased number of metastatic events in a B16F10 murine melanoma model. Alterations on expression of several genes related to cell cycle were observed when two tumor cell lines were treated with Amblyomin-X. PSMB2, which encodes a proteasome subunit, was differentially expressed, in agreement to inhibition of proteasomal activity in both cell lines. In conclusion, our results indicate that Amblyomin-X selectively acts on tumor cells by inducing apoptotic cell death, possibly by targeting the ubiquitin-proteasome system. (C) 2010 Elsevier Ltd. All rights reserved.

Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

The ruthenium NO donors of the group trans-[Ru(NO)(NH(3))(4)L](n+), where the ligand (L) is N-heterocyclic H(2)O, SO(3)(2 -), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC(50)(try)) and cytotoxicity data on mammalian V-79 cells (IC(50)(V79)), the in vitro therapeutic indices (TIs) (IC(50)(V79)/IC(50)(try)) for these compounds were calculated. Compounds that exhibited an in vitro TI of >= 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC(50)(try/epi) of <= 100 mu M were assayed in a mouse model for acute Chagas` disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) (isn, isonicotinamide) and trans-[Ru(NO)(NH3) 4imN](BF4) 3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD(50)) for both compounds are higher than 125 mu mol/kg, the in vivo TIs (LD(50)/ED(50)) of the compounds are 1,453 for trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and 658 for trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3). Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi -glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

Lessons learned from stakeholders in a facilitation intervention targeting neonatal health in Quang Ninh province, Vietnam

BACKGROUND: In northern Vietnam the Neonatal health - Knowledge Into Practice (NeoKIP, Current Controlled Trials ISRCTN44599712) trial has evaluated facilitation as a knowledge translation intervention to improve neonatal survival. The results demonstrated that intervention sites, each having an assigned group including local stakeholders supported by a facilitator, lowered the neonatal mortality rate by 50% during the last intervention year compared with control sites. This process evaluation was conducted to identify and describe mechanisms of the NeoKIP intervention based on experiences of facilitators and intervention group members. METHODS: Four focus group discussions (FGDs) were conducted with all facilitators at different occasions and 12 FGDs with 6 intervention groups at 2 occasions. Fifteen FGDs were audio recorded, transcribed verbatim, translated into English, and analysed using thematic analysis. RESULTS: Four themes and 17 sub-themes emerged from the 3 FGDs with facilitators, and 5 themes and 18 sub-themes were identified from the 12 FGDs with the intervention groups mirroring the process of, and the barriers to, the intervention. Facilitators and intervention group members concurred that having groups representing various organisations was beneficial. Facilitators were considered important in assembling the groups. The facilitators functioned best if coming from the same geographical area as the groups and if they were able to come to terms with the chair of the groups. However, the facilitators' lack of health knowledge was regarded as a deficit for assisting the groups' assignments. FGD participants experienced the NeoKIP intervention to have impact on the knowledge and behaviour of both intervention group members and the general public, however, they found that the intervention was a slow and time-consuming process. Perceived facilitation barriers were lack of money, inadequate support, and the function of the intervention groups. CONCLUSIONS: This qualitative process evaluation contributes to explain the improved neonatal survival and why this occurred after a latent period in the NeoKIP project. The used knowledge translation intervention, where facilitators supported multi-stakeholder coalitions with the mandate to impact upon attitudes and behaviour in the communes, has low costs and potential for being scaled-up within existing healthcare systems.

Inflation targeting, credibility and confidence crises

We study the interplay between the central bank transparency, its credibility, and the ination target level. Based on a model developed in the spirit of the global games literature, we argue that whenever a weak central bank adopts a high degree of transparency and a low target level, a bad and self conrmed type of equilibrium may arise. In this case, an over-the-target ination becomes more likely. The central bank is considered weak when favorable state of nature is required for the target to be achieved. On the other hand, if a weak central bank opts for less ambitious goals, namely lower degree of transparency and higher target level, it may avoid condence crises and ensure a unique equilibrium for the expected ination. Moreover, even after ruling out the possibility of condence crises, less ambitious goals may be desirable in order to attain higher credibility and hence a better coordination of expectations. Conversely, a low target level and a high central bank transparency are desirable whenever the economy has strong fundamentals and the target can be fullled in many states of nature.

Inflation targeting in Brazil: a Keynesian approach

O Regime de Meta de Inflação se Tornou Dominante na Formulação de Políticas dos Bancos Centrais nos Últimos 15 Anos. a Teoria Subjacente, Particularmente a Regra de Taylor, Pode ser Vista como uma Competente Generalização Desse Comportamento. de um Ponto de Vista Keynesiano, Ele Será Aceitável se Encararmos a Taxa de Juros de Equilíbrio como Apenas uma Convenção Variável e se a Combinarmos ou com uma Taxa de Câmbio ou com uma Meta de Emprego. no Caso do Brasil, Porém, Além Dessa Ressalva Teórica e da Condição do Duplo Mandato, o Regime de Metas de Inflação Enfrenta um Problema de Incoerência. esta é uma Política que se Destinava a ser Utilizada na Administração da Política Monetária, não na Mudança do Regime de Política Monetária . a Política de Metas de Inflação foi Introduzida no Brasil em 1999 como um Substituto para a Âncora Cambial, que Havia Sido Usada Desastrosamente entre 1995 e 1998. Durante Muitos Anos, o País Havia Enfrentado uma Armadilha de Alta Taxa de Juros / Taxa de Câmbio Valorizada E, Portanto, Precisava Mudar seu Regime de Política Monetária Antes de Eventualmente Adotar o Regime de Meta de Inflação. Essa Mudança, que Começou com a Flutuação de Janeiro de 1999, Deveria ter Sido Completada com Reformas Específicas (Fim da Indexação dos Serviços Públicos e dos Próprios Juros Básicos). no Entanto, em Lugar de Desenvolver uma Estratégia para Reduzir a Taxa de Juros, o Governo Continuou a Definir a Inflação como o Principal Problema a ser Enfrentado e Adotou uma Política Formal de Metas de Inflação. a Conseqüência é que Desde 1999 Essa Política se Tornou o Obstáculo que a Economia Brasileira Enfrenta para Escapar da Armadilha da Taxa de Juros

Automatic layout generation of static CMOS circuits targeting delay and power

The evolution of integrated circuits technologies demands the development of new CAD tools. The traditional development of digital circuits at physical level is based in library of cells. These libraries of cells offer certain predictability of the electrical behavior of the design due to the previous characterization of the cells. Besides, different versions of each cell are required in such a way that delay and power consumption characteristics are taken into account, increasing the number of cells in a library. The automatic full custom layout generation is an alternative each time more important to cell based generation approaches. This strategy implements transistors and connections according patterns defined by algorithms. So, it is possible to implement any logic function avoiding the limitations of the library of cells. Tools of analysis and estimate must offer the predictability in automatic full custom layouts. These tools must be able to work with layout estimates and to generate information related to delay, power consumption and area occupation. This work includes the research of new methods of physical synthesis and the implementation of an automatic layout generation in which the cells are generated at the moment of the layout synthesis. The research investigates different strategies of elements disposition (transistors, contacts and connections) in a layout and their effects in the area occupation and circuit delay. The presented layout strategy applies delay optimization by the integration with a gate sizing technique. This is performed in such a way the folding method allows individual discrete sizing to transistors. The main characteristics of the proposed strategy are: power supply lines between rows, over the layout routing (channel routing is not used), circuit routing performed before layout generation and layout generation targeting delay reduction by the application of the sizing technique. The possibility to implement any logic function, without restrictions imposed by a library of cells, allows the circuit synthesis with optimization in the number of the transistors. This reduction in the number of transistors decreases the delay and power consumption, mainly the static power consumption in submicrometer circuits. Comparisons between the proposed strategy and other well-known methods are presented in such a way the proposed method is validated.

Targeting the poor: a macroeconomic analysis of cash transfer programs

This paper introduces cash transfers targeting the poor in an incomplete markets model with heterogeneous agents facing idiosyncratic risk. These transfers change the degree of insurance in the economy and affect precautionary motives asymmetrically, leading the poorest households to decrease savings proportionally more than their richer counterparts. In a model economy calibrated to Brazil, once the cash transfer program is adopted, wealth inequality and social welfare increase, poverty decreases, while employment and income inequality remain about the same. Imperfect access to financial markets is important for these results, whereas whether the program is funded with lump sum or distortive taxes is not.

Mobility, targeting and private school vouchers

This paper uses general equilibrium simulations to explore the role ofresidential mobility in shaping the impact of different types of private school voucher policies. In particular, general vouchers available to all residents in the state are compared to vouchers specifically targeted to either underprivileged school districts or underprivileged households. The simulations are derived from a three-community mo deI of low, middle and high income school districts (calibrated to New York data), where each school district is composed of multiple types of neighborhoods that may vary in house quality as well as the leveI of neighborhood extemalities. Households that differ in both their income and in the ability leveI of their children choose between school districts, between neighborhoods within their school district, and between the local public school or a menu of private school altematives.Local public school quality within a district is endogenously determined bya combination of the average peer quality of public school attending children as well as local property and state income tax supported spending. Financial support (above a required state minimum) is set by local majority rule. Finally, there exists the potential for a private school market composed of competitive schools that face production technologies similar to those ofpublic schools but who set tuition and admissions policies to maximize profits. In tbis model, it is demonstrated that school district targeted vouchers are similar in their impact to non-targeted vouchers but vastIy different from vouchers targeted to low income households. Furthermore, strong migration effects are shown to significantly improve the likely equity consequences of voucher programs.

Inflation targeting, credibility and coordination aspects

There are plenty of economic studies pointing out some requirements, like the inexistence of fiscal dominance, for inflation targeting framework be implemented in successful (credible) way. Essays on how public targets could be used in the absence of such requirements are unusual. In this papel' we appraise how central banks could use inflation targeting before soundness economic fundamentaIs have been achieved. First, based on concise framework, where confidence crises and imperfect information are neglected, we conclude that less ambitious (greater) target for inflation increases the credibility in the precommitment. Optimal target is higher than the one obtained using the Cukierman-Liviatan [7] model, where increasing credibility effect is not considered. Second, extending the model to make confidence crises possible, multiple equilibria solutions becomes possible too. In this case, to set greater targets for inflation may stimulate confidence crises and reduce the policymaker credibility. On the other hand, multiple (bad) equilibria may be avoided. The optimal target depends on the likelihood of each equilibrium be selected. Finally, when perturbing common knowledge uniqueness is restored even considering confidence crises, as in Morris-Shin[ 14]. The first result, i.e. less ambitious target for inflation increases credibility in precommitment, is also recovered. Adding a precise public signal, cOOl'dinated self-fulfilling actions and equilibrium multiplicity may still exist for some lack of common knowledge (as in Angeleto and Weming[l]). In this case, to set greater targets for inflation may stimulate confidence crisis again, reducing the policymaker credibility. From another aspect, multiple (bad) equilibria may be avoided. Optimal policy prescriptions depend on the likelihood of each equilibrium be selected. Results also indicate that more precise public information may open the door for bad equilibrium, contrary to the conventional wisdom that more central oank transparency is always good when considering inflation targeting framework.

Apresentação 10: “Inflation Targeting”, “Currency Regimes with Defaultable Debts” e Sistema Tributário na Presença de Informalidade e Evasão Fiscal…A disseminação internacional das pesquisas aplicadas relacionadas a agenda brasileira

Coordenadora: Goret P. Paulo

Tc-99m-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

To evaluate the tumor response to neoadjuvant chemotherapy, Tc-99m-sestamibi breast scintigraphy was proposed as a quantitative method Fifty-five patients with ductal carcinoma were studied They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation The ratio of these counts before to after neoadjuvant chemotherapy was assessed The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type Dunn's multiple comparison test was used to detect differences between histological types The Mann-Whitney test was used to compare means between quantitative and qualitative variables scintigraphic tumor response vs clinical response and uptake before chemotherapy vs scintigraphic tumor response The Spearman's test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response All of the variables compared presented significant differences The change in Tc-99m-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response