Search

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Marina Elena Cazzaniga,1 Laura Biganzoli,2 Laura Cortesi,3 Sabino De Placido,4 Michela Donadio,5 Alessandra Fabi,6 Antonella Ferro,7 Daniele Generali,8,9 Vito Lorusso,10 Andrea Milani,11 Emilia Montagna,12 Elisabetta Munzone,12 Laura Orlando,13 Laura Pizzuti,6 Edda Simoncini,14 Claudio Zamagni,15 Giovanni L Pappagallo16 On behalf of the “Metronomic Chemotherapy in Advanced Breast Cancer” Study Group 1Medical Oncology Unit & Phase 1 Research Unit, ASST Monza, Monza, Italy; 2Medical Oncology Division, Hospital of Prato, Azienda USL Toscana Centro, Prato, Italy; 3Haematology and Oncology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy; 4Clinical Medicine and Surgery Department, University of Naples Federico II, Naples, Italy; 5Medical Oncology Breast Unit, AOU Città della Salute e della Scienza, Turin, Italy; 6Oncology Unit 1, Regina Elena National Cancer Institute, Rome, Italy; 7Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy; 8Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 9UO Multidisciplinare di Patologia Mammaria e Ricerca Traslazionale, ASST di Cremona, Cremona, Italy; 10Operative Unit of Medical Oncology, Oncology Institute of Bari, Bari, Italy; 11Division of Investigative Clinical Oncology, Candiolo Cancer Institute – FPO, IRCCS, Candiolo, Italy; 12Division of Medical Senology, IEO, European Institute of Oncology, IRCCS, Milan, Italy; 13Medical Oncology & Breast Unit, “Antonio Perrino” Hospital, Brindisi, Italy; 14Breast Unit, ASST Spedali Civili di Brescia, Brescia, Italy; 15SSD Medical Oncology Addarii, Policlinico Sant’Orsola Malpighi, Bologna, Italy; 16Medical Oncology Unit, Azienda ULSS 3 Serenissima, Mirano-Dolo, ItalyAbstract: The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2–4years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%–50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life. Oral chemotherapeutic agents such as capecitabine and vinorelbine have demonstrated efficacy in patients with mBC, with prolonged disease control and good tolerability. Use of oral chemotherapy reduces the time and cost associated with treatment and is often more acceptable to patients than intravenous drug delivery. Metronomic administration of oral chemotherapy is therefore a promising treatment strategy for some patients with mBC and inhibits tumor progression via multiple mechanisms of action. Ongoing clinical trials are investigating metronomic chemotherapy regimens as a strategy to prolong disease control with favorable tolerability. This article provides an overview of metronomic chemotherapy treatment options in mBC, with perspectives on this therapy from a panel of experts. Keywords: advanced breast cancer, metronomic chemotherapy, vinorelbine, tolerability, quality of life

International audience

Aims and background Project RIGHT (Research for the Identification of the most effective and hIGHly accepted clinical guidelines for cancer Treatment) is promoted by the Italian Association of Medical Oncology (AIOM) to evaluate the concordance between AIOM breast cancer guidelines and clinical practice in Italy. In RIGHT-1, feasibility and the appropriateness of indicators were assessed in patients with early breast cancer. RIGHT-2 evaluated the compliance with guidelines in a nationwide program. Methods Thirty-five Italian centers participated in the RIGHT-2 survey. Ten indicators were evaluated to verify an agreement between 2005 AIOM breast cancer guidelines and practice. Patients with clinical stage I-II invasive breast cancer, age ≤70 years, who had their first visit at the oncology center between October 2005 and November 2006 were included. Results In RIGHT-2, ≥90% adherence for the diagnosis indicator and three therapy indicators were observed. The lowest degree of compliance (0%) was observed for the follow-up indicator in asymptomatic patients. Conclusions In RIGHT-2, compliance to the 2005 AIOM breast cancer guidelines was 64%. When the follow-up indicator was eliminated, overall adherence to AIOM guidelines was 71%. The results highlight the need to continue improving the already good standards of breast cancer care.

Background The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. Patients and methods A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. Results Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. Conclusions The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

We have studied the photoinduced transformation of small rings (3-membered) in amorphous silica by Car-Parrinello simulations. The process of ring opening leading to the formation of a couple of paramagnetic centers, namely an E' and a non-bridging-oxygen hole center (NBOHC), has been proposed experimentally to occur in silica exposed to F2 laser irradiation (at 7.9 eV). By using a new scheme for the simulation of rare events in ab-initio molecular dynamics (Iannuzzi, Laio and Parrinello, Phys. Rev. Lett. 90, 238303 (2003)), we have identified the transformation path for the opening of a 3-membered ring induced by a self-trapped triplet exciton, the migration of NBOHC and formation of a couple of stable E' and NBOHC paramagnetic defects.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m(-2) on days 1 and 15, PTX 60 mg m(-2) on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m(-2) every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization ( WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable.

Introdu??o: O estresse cr?nico provoca altera??es fisiol?gicas. Quando ele ocorre no per?odo gestacional, que ? um momento sens?vel a diversos fatores internos e externos, com alta plasticidade e que pode implicar no desenvolvimento fetal, ele pode aumentar os riscos de doen?as respirat?rias, neuroend?crinas e inflamat?rias que est?o associadas com o aumento da ativa??o do eixo hipot?lamo-hip?fise-adrenal (HPA). O eixo HPA ? importante para as fun??es metab?licas, neurais, para a matura??o pulmonar e para a modula??o da secre??o de citocinas pr?-inflamat?rias. Por outro lado, ? relevante a busca por m?todos de preven??o para os efeitos gerados pelo estresse, sendo o exerc?cio f?sico uma das estrat?gias poss?veis, j? que apresenta efeitos terap?uticos e protetores, ajudando na redu??o de sintomas gerados pelo estresse e na preven??o de diversas doen?as. Objetivo: Avaliar os efeitos do exerc?cio f?sico antes e durante o per?odo gestacional sobre altera??es em marcadores do processo inflamat?rio e do eixo HPA de camundongos neonatos estressados no per?odo pr?-natal. M?todos: Foram utilizados f?meas e machos Balb/cByJ. As f?meas prenhas foram divididas em tr?s grupos: controle (CONT), estresse pr?-natal por conten??o (PNS) e exerc?cio f?sico antes e durante o per?odo gestacional e estresse pr?-natal por conten??o (PNS+EX). Ap?s a divis?o foi iniciado o protocolo de exerc?cio com dura??o de 3 semanas. No oitavo dia de gesta??o as f?meas retornaram ao protocolo de exerc?cio e foi iniciado o protocolo de estresse at? o 21? dia de gesta??o (G21/PND0). As f?meas foram submetidas ? cesariana e os filhotes removidos para a retirada do enc?falo e pulm?o (PND0). Em outra coorte de animais, as mesmas an?lises foram realizadas no 10? dia de vida (PND10). Ap?s a coleta de tecido foram analisados, por meio de express?o g?nica, os marcadores de GR, MR, IL-6, IL-10 e TNF no enc?falo e no pulm?o, e atrav?s de express?o proteica foi avaliado MMP-2 somente no pulm?o. Resultados: Os animais do grupo PND0 demostraram um efeito do exerc?cio com a redu??o de IL-6 e aumento de IL-10 no enc?falo. No pulm?o o exerc?cio n?o reverteu os efeitos do estresse que diminuiu a express?o de todos os marcadores avaliados. O exerc?cio nos animais do PND10 reverteu os efeitos gerados pelo estresse com a redu??o de MR, IL-6 e IL-10 no hipocampo. Observou-se um efeito positivo do exerc?cio no pulm?o com a redu??o de GR. Os animais do sexo masculino, no hipocampo, apresentaram uma redu??o de GR mostrando somente um efeito do estresse. No pulm?o tamb?m foi apresentado um efeito do estresse em GR com sua diminui??o e efeito do exerc?cio com a redu??o de MR. Na express?o proteica de MMP-2, n?o houve diferen?a significativa em ambos os grupos, sexos ou dia de vida. Conclus?o: O estresse pr?-natal alterou a resposta inflamat?ria e de marcadores de regula??o do eixo HPA, tanto no pulm?o como no enc?falo de ambos os dias analisados. O exerc?cio f?sico conseguiu reverter os efeitos do estresse sobre alguns dos marcadores estudados. Introduction: Chronic stress causes physiological changes. When it occurs in the gestational period, which is a time sensitive to several internal and external factors, with high plasticity and which can affect fetal development, it can increase the risks of respiratory, neuroendocrine and inflammatory diseases that are associated with increased activation of the hypothalamic-pituitaryadrenal (HPA) axis. The HPA axis is important for metabolic and neural functions, for lung maturation and for the modulation of pro-inflammatory cytokine secretion. On the other hand, the search for prevention methods for the effects generated by stress is relevant, with physical exercise being one of the possible strategies, since it has therapeutic and protective effects, helping to reduce symptoms generated by stress and preventing various diseases. Objective: To evaluate the effects of physical exercise before and during the gestational period on changes in markers of the inflammatory process and the HPA axis in the brain and lungs of prenatally stressed newborn mice. Methods: Balb/cByJ females and males were used. The pregnant females were divided into three groups: control (CONT); prenatal stress by restraint (PNS); and physical exercise before and during the gestational period and prenatal stress by restraint (PNS+EX). After the division, a 3-week exercise protocol was initiated. On the eighth day of gestation, the females returned to the exercise protocol and the stress protocol was started until the 21st day of gestation (G21/PND0). The females underwent cesarean section and the pups were removed for brain and lung removal (PND0). In another cohort of animals, the same analyzes were performed on the 10th day of life (PND10). After tissue collection, the markers of GR, MR, IL-6, IL-10 and TNF were analyzed through gene expression in the brain and in the lungs, and MMP-2 was evaluated through protein expression only in the lungs. Results: The animals in the PND0 group demonstrated effect of exercise with reduction in IL-6 and an increase in IL-10 in the brain. In the lung, the exercise did not reverse the effects of stress that reduced the expression of all evaluated markers. The exercise in PND10 animals reversed the effects generated by stress with the reduction of MR, IL-6 and IL-10 in the hippocampus. A positive effect of exercise on the lung was observed with the reduction of GR. Male animals in the hippocampus showed a reduction in GR showing only an effect of stress. In the lung, an effect of stress was also observed on GR with its decrease and effect of exercise with the reduction of MR. In the protein expression of MMP-2, there was no significant difference in both groups, sex or day of life. Conclusion: Prenatal stress altered the inflammatory response and regulatory markers of the HPA axis, both in the lung and in the brain on both days analyzed. Physical exercise was able to reverse the effects of stress on some of the studied markers. Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq

Introdu??o: A Fibrose C?stica (FC) ? uma doen?a cr?nica que afeta gravemente o sistema respirat?rio. Uma das causas de morbimortalidade destes pacientes ? a exacerba??o pulmonar, que normalmente ? avaliada atrav?s de escores espec?ficos. Entretanto, n?o h? um consenso sobre a melhor forma de diagnostic?-la. Como o teste do degrau de tr?s minutos (TD3) ? um teste de f?cil aplica??o e boa reprodutibilidade, pode ser ?til na identifica??o de exacerba??es pulmonares nestes pacientes. Objetivo: Avaliar o uso do TD3 na identifica??o de exacerba??o pulmonar em crian?as e adolescentes com FC. M?todos: Estudo transversal no qual foram inclu?dos pacientes a partir de seis anos com FC confirmada por teste gen?tico. Foram exclu?dos aqueles pacientes que possuissem qualquer limita??o que impedissem a reasliza??o do TD3. A presen?a de exacerba??o pulmonar foi avaliada por meio da aplica??o do escore de Kanga, e a for?a muscular do quadr?ceps utilizando dinamometria. Ap?s, foi realizado o TD3, no qual o paciente subiu e desceu durante tr?s minutos um degrau com altura de 15 cm. Foram aferidas frequ?ncia card?aca (Fc), satura??o perif?rica de oxig?nio (SpO2) e sensa??o de dispneia e fadiga de membros inferiores utilizando a escala de Borg modificada, antes e ap?s o teste. Os valores obtidos foram comparados entre os pacientes exacerbados e n?o exacerbados e a sensibilidade/especificidade calculada. Resultados: Foram inclu?dos 62 pacientes com m?dia de idade de 11,1?4,25 anos. A fun??o pulmonar encontrou-se reduzida e a pontua??o m?dia do escore de Kanga na amostra ficou perto dos 16, sendo que a pontua??o acima de 20 no escore foi considerada exacerba??o pulmonar moderada/grave, e foi atingida por pelo menos um quarto dos pacientes. Escore de Kanga se correlacionou com idade, VEF1, Fc de recupera??o em 1 minuto, SpO2 ap?s o TD3 e SpO2 de recupera??o em 1 minuto. Ao comparar os pacientes com maior e menor pontua??o no escore de Kanga, a idade, Fc em repouso e Fc de recupera??o em 1 minuto, foram significativamente maiores no grupo com maior pontua??o. J? o VEF1, SpO2 em repouso, SpO2 ap?s o TD3 e SpO2 ap?s 1 minuto de recupera??o foram significativamente menores no grupo com maior pontua??o. A an?lise de uma curva ROC mostrou que a Fc de recupera??o ap?s 1 minuto de realiza??o do TD3 foi a melhor vari?vel para predizer a exacerba??o pulmonar, sendo sens?vel e espec?fica para um ponto de corte de 111 bpm. Conclus?o: O TD3 demonstrou uma boa sensibilidade para detec??o da exacerba??o pulmonar moderada/grave em crian?as e adolescentes com FC, podendo ser considerado como um m?todo adicional para auxiliar a avalia??o e acompanhamento destes pacientes. Introduction: Cystic Fibrosis (CF) is a chronic disease that affects the respiratory system. One of the causes of patient morbidity and mortality is a pulmonary exacerbation, which is evaluated by the use of specific scores. However, there is no consensus on the best form of diagnosis. Considering that the three-minute step test (TD3) is a test of easy application and good reproducibility, it may be useful in identifying pulmonary exacerbations in these patients. Objective: To evaluate the use of TD3 in the identification of pulmonary exacerbation in children and adolescents with CF. Methods: Cross-sectional study in which patients aged six years and older with CF confirmed by genetic testing were included. Those patients who had any limitation that prevented the realization of the TD3 were excluded. The presence of pulmonary exacerbation was assessed using the Kanga score, and quadriceps muscle strength using dynamometry. Afterwards, the TD3 was performed and the patient went up and down a step with a height of 15 cm for three minutes. Heart rate (HR), peripheral oxygen saturation (SpO2) and sensation of dyspnea and lower limb fatigue were measured using the modified Borg scale, before and after the test. The values obtained were compared between exacerbated and non-exacerbated patients and the sensitivity/specificity calculated. Results: Sixty-two patients with a mean age of 11.1?4.25 years were included. Pulmonary function was found to be reduced and the mean Kanga score in the sample was around 16, with a score above 20, which is considered moderate/severe pulmonary exacerbation, achieved by at least a quarter of the patients. Kanga score correlated with age, FEV1, 1-minute recovery HR, SpO2 after TD3, and 1-minute recovery SpO2. When comparing patients with the highest and lowest scores on the Kanga score, age, resting HR and 1-minute recovery HR were significantly higher in the group with the highest scores. On the other hand, FEV1, SpO2 at rest, SpO2 after TD3 and SpO2 after 1 minute of recovery were significantly lower in the group with the highest score. The analysis of the ROC curve showed that the HR recovery after 1 minute of performing the TD3 was the best variable to predict pulmonary exacerbation, with good sensitivity and specificity for a cut-off value of 111 bpm. Conclusion: The TD3 demonstrated good sensitivity in detecting moderate/severe pulmonary exacerbation in children and adolescents with CF and may be considered as an additional method to assist in the evaluation and follow-up of these patients. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Os estressores compreendem uma gama de potenciais for?as adversas que podem ser emocionais ou f?sicas. Em situa??es basais ou de estresse, o eixo hipot?lamo-hip?fise-adrenal (HPA) ? o centro controlador da produ??o e secre??o de corticosteroides. O conceito fisiol?gico de programa??o tem sido utilizado amplamente para explicar as associa??es entre eventos estressores pr?-natais, crescimento fetal alterado e o aumento da vulnerabilidade a doen?as metab?licas, cognitivas e neuroend?crinas ao longo da vida. Ainda, estudos t?m demonstrado que indiv?duos fisicamente aptos e que praticam frequentemente atividades f?sicas exibem um menor ?ndice de problemas de sa?de, especialmente quando se deparam com situa??es de estresse. Desta forma, o principal objetivo desse trabalho foi avaliar as repercuss?es comportamentais, inflamat?rias e de regula??o central do eixo HPA em resposta ao estresse pr?-natal e ? pr?tica de exerc?cio f?sico maternal em camundongos Balb/c. No primeiro estudo identificamos que o modelo experimental de estresse por conten??o utilizado ? capaz de promover altera??es no metabolismo de glicose cerebral. Esses achados foram observados, por meio de microPET, a partir da diminui??o na absor??o de 18F-FDG em diferentes regi?es encef?licas de machos e f?meas. No segundo estudo observamos que o estresse por conten??o, quando aplicado durante a gesta??o, promove altera??es significativas no comportamento maternal e na express?o g?nica e proteica de mediadores inflamat?rios no bulbo olfat?rio durante a lacta??o. No terceiro estudo verificamos que esse modelo de estresse, quando aplicado durante a gesta??o, podem influenciar a mortalidade celular, a autofagia, a express?o g?nica, o estresse oxidativo e a inflama??o em neur?nios corticais da prole de camundongos neonatos. O quarto estudo demonstrou que o exerc?cio f?sico possui efeitos protetores sobre o comportamento materno e a regula??o dos marcadores respons?veis pela resposta ao estresse na placenta e no c?rebro de camundongos neonatos estressados no per?odo pr?-natal. Os resultados obtidos com esses trabalhos demonstram que o estresse durante a gesta??o gera diversas altera??es comportamentais, inflamat?rias e em marcadores envolvidos com a modula??o do eixo HPA. Al?m disso, o exerc?cio f?sico maternal demonstrou possuir um papel importante na modula??o da sa?de materno-fetal, contribuindo na preven??o de altera??es no neurodesenvolvimento induzidas pelo estresse pr?-natal. Stressors comprise a range of adverse abilities that can be emotional or physical. The hypothalamic-pituitary-adrenal (HPA) axis is the controlling center for the production and secretion of corticosteroids during basal or stressful situations. The physiological concept of programming has been used extensively to explain the associations between prenatal stressful events, altered fetal growth, and increased vulnerability to metabolic, cognitive, and neuroendocrine disorders throughout life. In addition, studies have demonstrated that individuals physically fit and that frequently practice physical activities exhibit a lower rate of health problems, especially when faced with stressful situations. Thus, the main objective of present work was to evaluate behavioral, inflammatory, and central regulatory repercussions of the HPA axis in response to prenatal stress and to the practice of maternal physical exercise in Balb/c mice. In the first study, we have identified that the experimental model of restraint stress used was able to promote alterations in the brain glucose metabolism. These findings were observed from the decreased 18F-FDG absorption in different brain regions of males and females evaluated through microPET. In the second study, we have observed that restraint stress, when applied during pregnancy, promoted significant changes in maternal behavior and gene/protein expression of inflammatory mediators in the olfactory bulb during lactation. In the third study, we have found that the same stress model, when applied during pregnancy, altered cell mortality, autophagy, gene expression, oxidative stress, and inflammation in cortical neurons in the neonatal period. The fourth study indicated that physical exercise has a protective effect on both maternal behavior and the regulation of markers responsible for the stress response in the placenta and brain of prenatally stressed neonatal mice. The results obtained from these studies demonstrate that stress during pregnancy generated several alterations on behavior, inflammation, and in the regulation of markers involved in the modulation of the HPA axis. In addition, maternal physical exercise plays an important role in the modulation of maternal-fetal health, contributing to the prevention of neurodevelopmental changes induced by prenatal stress. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Introdu??o: Elevadas quantidades de DNA extracelular est?o presentes no escarro de pacientes com fibrose c?stica (FC), sendo derivadas de neutr?filos necr?ticos/apopt?ticos e principalmente das redes extracelulares de neutr?filos (NETs), um mecanismo de defesa recentemente descrito. O DNA altera a viscosidade do muco e contribui para a obstru??o das vias a?reas, o que favorece ? coloniza??o e infec??o por bact?rias, exacerba??es frequentes e consequente perda progressiva da fun??o pulmonar. At? o momento, s?o escassos os estudos investigando a associa??o do DNA extracelular e da libera??o das NETs com a gravidade da doen?a. Objetivo: Avaliar a associa??o da quantidade de DNA extracelular com a fun??o pulmonar, uso de antibi?ticos e hospitaliza??o por exacerba??es em pacientes com FC. M?todos: Trata-se de um estudo transversal, incluindo pacientes com FC maiores de cinco anos de idade, clinicamente est?veis e capazes de expectorar de forma espont?nea. O escarro foi coletado durante a visita ambulatorial e posteriormente processado para quantifica??o do DNA extracelular. As redes extracelulares de DNA no escarro foram visualizadas por microscopia de imunofluoresc?ncia e tamb?m foi analisado o perfil de morte celular. Foram coletados dados de fun??o pulmonar, coloniza??o das vias a?reas, n?mero de dias de antibi?tico e de interna??o hospitalar nos 12 meses anteriores. Os pacientes foram divididos em dois grupos pelo valor da mediana da quantidade de DNA extracelular no escarro. Os pacientes ou pais/respons?veis assinaram um termo de consentimento e o estudo foi aprovado pelo comit? de ?tica da Universidade. Resultados: Foram inclu?dos 33 pacientes, m?dia de idade de 16,3?6,2 anos, volume expirat?rio for?ado no primeiro segundo (VEF1) de 67,0?26,7% e DNA 241,9?147,2?g/mL. Foi observada uma correla??o significativa entre DNA e o VEF1 (r=-0,60; p243,0?g/mL), foi observada uma diminui??o significativa do VEF1 (52,1?27,8% vs. 81,1?16,2%; p=0,001) e uma maior necessidade de interna??o hospitalar (68,8% vs. 35,3%; p=0,05). N?o foram encontradas diferen?as significativas em rela??o ao n?mero de exacerba??es, dias de antibi?tico e coloniza??o cr?nica por Pseudomonas aeruginosa. Foi poss?vel observar ainda a presen?a de redes extracelulares de DNA e um baixo percentual de necrose e apoptose no escarro. Conclus?o: A quantidade elevada de DNA extracelular no escarro de pacientes com FC est? associada com redu??o da fun??o pulmonar e necessidade de interna??o hospitalar, o que pode estar relacionado ?s redes extracelulares liberadas pelos neutr?filos. Introduction: High levels of extracellular DNA are present in the sputum of cystic fibrosis (CF) patients, originated from necrotic/apoptotic neutrophils and neutrophil extracellular traps (NETs), a defense mechanism recently described. DNA alters mucus viscosity and contributes to airway obstruction, which predisposes to infections and colonization by bacteria, recurrent exacerbations and lung function decline. However, there are few studies investigating the association between extracellular DNA and NETs release with the disease severity in CF. Objectives: To evaluate the association of the levels of extracellular DNA with lung function, use of antibiotics and hospitalization for pulmonary exacerbation. Methods: This is a cross-sectional study. CF patients older than 5 years old, clinically stable and able to spontaneously expectorate were included. Sputum was collected during the outpatient visit and subsequently processed for quantitation of extracellular DNA. The extracellular DNA traps in sputum were visualized by immunofluorescence microscopy and cellular death profile was determined. Lung function data, airway colonization, number of antibiotic days and hospital stay in the previous 12 months were collected. For the analysis, patients were allocated into two groups according to the median levels of DNA in sputum. Patients or parents signed a consent form and the study was approved by the research ethics committee of the University. Results: We have included 33 patients in the study, mean age 16.3?6.2 years, forced expiratory volume in the first second (FEV1) of 67.0?26.7% and DNA level of 241.9?147.2?g/mL. A significant correlation was observed between DNA and FEV1 (r=-0.60; p 243.0?g/mL). No significant differences were found in the number of exacerbations, days of antibiotics and chronic colonization by Pseudomonas aeruginosa. It was also possible to observe the presence of extracellular DNA traps and a low percentage of necrosis and apoptosis in the sputum. Conclusions: The results of the present study demonstrated that the higher levels of extracellular DNA in the sputum of CF patients is associated with lower lung function and hospitalization, which may be related to the extracellular traps released by neutrophils. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Introdu??o: H? evid?ncias que dist?rbios do sono, inclusive hipoxemia noturna s?o comuns em indiv?duos com fibrose c?stica (FC), por?m o diagn?stico geralmente n?o ? realizado em fase inicial, piorando o progn?stico. Da mesma forma, sabe-se que existe correla??o entre a variabilidade da frequ?ncia card?aca (VFC) e mortalidade em diversas condi??es cl?nicas. Evid?ncias demonstram altera??o da VFC como consequ?ncia de alguns dist?rbios do sono, por?m poucos estudos relacionam tais altera??es em crian?as e adolescentes com FC. Objetivo: Avaliar a associa??o da VFC com os achados de dist?rbios do sono em crian?as e adolescentes com FC. M?todos: Trata-se de um estudo transversal, com indiv?duos diagnosticados com FC, idade entre 6 e 18 anos atendidos em um Centro de Refer?ncia de Vit?ria, Esp?rito Santo. Foram registradas informa??es referentes ao perfil sociodemogr?fico e cl?nico da amostra, escore de Shwachman-Kulczycki (SK), avalia??o da fun??o pulmonar, estado nutricional e n?vel de atividade f?sica di?ria, atrav?s da aplica??o da vers?o curta do Question?rio Internacional de Atividade F?sica (IPAQ). Para avalia??o da variabilidade da frequ?ncia card?aca foi utilizado o cardiofrequenc?metro Polar RS800CX (Polar Electro Oy, Finland) durante 25 minutos de repouso e para avalia??o do sono, a polissonografia basal noturna tipo II. Para an?lise, os dados da VFC foram transmitidos para um computador utilizando o software Polar ProTrainer 5 e convertidos em arquivos de texto que foram analisados no Software Kubios HRV Standard. Os 5 minutos iniciais foram exclu?dos para fins de estabiliza??o dos par?metros e foi realizada filtragem manual para elimina??o de batimentos ect?picos e aplicado filtro digital de baixa intensidade para eliminar os intervalos RR anormais considerando no m?ximo 5% de corre??o. Como crit?rios de avalia??o do sono, a hipoxemia noturna foi considerada nos indiv?duos com satura??o de oxi-hemoglobina (SpO2) inferior a 90% por mais que 5% do tempo total do sono (TTS), e s?ndrome de apneia obstrutiva do sono (SAOS) quando o ?ndice de apneia e hiponeia obstrutiva fosse maior ou igual a 2 por hora. Resultados: A amostra foi composta por 30 indiv?duos, com m?dia de idade de 11,2 anos, maioria do sexo feminino (66,6%) e com volume expirat?rio for?ado no primeiro segundo (VEF1) de 62,77?27,62%. Foi identificado uma efici?ncia do sono reduzida, com m?dia de 66,49%, ?ndice de dist?rbios respirat?rios do sono (IDR) com mediana de 2,5 (1,85-3,9), hipoxemia noturna 26,67% e presen?a de SAOS (IAHO?2/h) em 30%. Na an?lise da VFC encontramos SDNN m?dio de 60,76?45,85 e no dom?nio frequ?ncia, m?dia de 60,35?17,20 para LF (nu) e de 38,90?17,24 para HF (nu). Houve correla??o significativa entre o ?ndice de modula??o global da VFC (LF/HF) e a SpO2 m?nima durante o sono nos pacientes com menor fun??o pulmonar (VEF1?60%) (r=0,7134; p=0,02). A preval?ncia de dist?rbios do sono e anormalidade da VFC foi maior nos indiv?duos com menor fun??o pulmonar (VEF1?60%). Conclus?o: Os resultados obtidos indicam uma correla??o isolada de dist?rbios do sono com par?metros de VFC apenas em indiv?duos com fun??o pulmonar reduzida. Al?m disso, esses pacientes apresentam uma maior preval?ncia de dist?rbios do sistema nervoso aut?nomo, hipoxemia noturna e presen?a de SAOS. Introduction: There is evidence that sleep disorders, including nocturnal hypoxemia, are common in individuals with cystic fibrosis (CF), but diagnostic tests are not routinely performed at an early stage, leading to late detection and worse prognosis. Similarly, it is known that there is a correlation between heart rate variability (HRV) and mortality in several clinical conditions. Evidence demonstrates changes in HRV as a consequence of some sleep disorders, but few studies relate such changes in patients with CF. Objective: To correlate HRV with findings of sleep disorders in CF children and adolescents. Methods: This is a cross-sectional study, with individuals diagnosed with CF, aged between 6 and 18 years, attended at a Reference Center in Vit?ria, Esp?rito Santo. Information regarding the sociodemographic and clinical profile of the sample, Shwachman Kulczycki (SK) score, evaluation of lung function, nutritional status and daily physical activity levels were recorded through the aplication of the short version of the International Physical Activity Questionnaire? IPAQ. To assess the heart rate variability, a Polar RS800CX cardiofrequency meter (Polar Electro Oy, Finland) was used for 25 minutes while at rest and to evaluate possible sleep disorders, basal nocturnal polysomnography was performed. For the analysis, HRV data were transmitted to a computer using a Polar ProTrainer 5 software and converted to text files that were analyzed using the Kubios HRV Standard Software. The initial 5 minutes were excluded for parameters stabilization purposes and manual filtering was performed to eliminate ectopic beats and a low intensity digital filter was applied to eliminate abnormal RR intervals, considering a maximum of 5% correction. As a sleep evaluation criteria, nocturnal hypoxemia was considered in individuals with an oxyhemoglobin saturation (SpO2) less than 90% for more than 5% of the total sleep time (TST), and obstructive sleep apnea syndrome (OSAS) when the rate of obstructive apnea and hypopnea was greater than or equal to 2 per hour. Results: The sample consisted of 30 individuals, with a mean age of 11.2 years, mostly female (66.6%). Reduced sleep efficiency was identified in 66.49% of patients, respiratory disorder index (RDI) with a median of 2.5 (1.85-3.9) and a presence of OSAS (rate of obstructive apnea and hypopnea ?2 / h) oft 30% (n=9). In the HRV analysis we have found a mean SDNN of 60.76?45.85 and, in the frequency domain, a mean of 60.35?17.20 for LF (nu) and 38.90?17.24 for HF (nu). There was a significant correlation between the overall LF/HF modulation index and the minimum SpO2 during the sleep of patients in the group with lower pulmonary function (r=0.7134; p=0.02). The prevalence of sleep disorders and HRV abnormities was higher in individuals with lower pulmonary function (FEV1?60%). Conclusion: The results obtained indicate an isolated correlation of sleep disorders with HRV parameters only in individuals with reduced pulmonary function. In addition, these patients have a higher prevalence of autonomic nervous system disorders, nocturnal hypoxemia, and OSAS.

Introdu??o: A asma ? uma doen?a inflamat?ria cr?nica das vias a?reas inferiores, caracterizada por limita??o do fluxo a?reo e pela hiperresponsividade br?nquica. Um subgrupo de crian?as com asma grave n?o responde adequadamente ao tratamento, sendo classificados como asma grave resistente ? terapia (AGRT). Devido a fatores como sibilos recorrentes, tosse, falta de ar, uso cont?nuo de medica??es, bronconstri??o induzida pelo exerc?cio (BIE) e hiperinsufla??o pulmonar din?mica, esses pacientes podem apresentar limita??es na capacidade de exerc?cio. Objetivo: Avaliar a capacidade de exerc?cio e o efeito do uso de press?o positiva cont?nua nas vias a?reas (CPAP) sobre a toler?ncia ao exerc?cio em crian?as e adolescentes com AGRT. M?todos: Esta tese est? dividida em dois artigos. Ambos os estudos inclu?ram crian?as e adolescentes com diagn?stico de AGRT, com idade entre seis e 18 anos. O artigo 1 consiste em um estudo do tipo transversal. Foram realizados teste de fun??o pulmonar (espirometria), teste de exerc?cio cardiopulmonar (TECP) e teste de BIE. A associa??o entre as vari?veis foi avaliada. J? o artigo 2 constituiu em um estudo do tipo ensaio cl?nico, controlado, randomizado, com crossover. Os participantes utilizaram, em ordem aleat?ria, CPAP (PEEP 10cmH2O e FiO2 0,21) ou placebo (controle - CPAP com PEEP m?nima), ambos por um per?odo de 40 minutos. Ap?s cada uma das interven??es, os pacientes realizaram o TECP. Em visita subsequente, ap?s per?odo de washout, os pacientes participaram do procedimento oposto ao inicial. Todos os testes seguiram as recomenda??es internacionais. Resultados: No estudo 1 foram inclu?dos 24 pacientes com AGRT e m?dia de idade de 11,5?2,6 anos. A m?dia do volume expirat?rio for?ado no primeiro segundo (VEF1) foi de 91,3?9,2%. O BIE ocorreu em 54,2% dos pacientes. No TECP, o consumo m?ximo de oxig?nio (VO2) foi de 34,1?7,8 mL.kg-1.min-1. Ao correlacionar as vari?veis do TECP e da espirometria encontramos correla??o significativa da reserva ventilat?ria com o VEF1 (r=0,57; p=0,003). Da mesma forma, houve correla??o significativa do TECP com o percentual de queda do VEF1 no teste de BIE, tanto para o VEVO2 (r=0,47; p=0,02), como para o VEVCO2 (r=0,46; p=0,02). Pacientes com VEF1

Fibrose pulmonar (FP) ? o resultado de um processo de les?o cr?nica no qual fibroblastos se tornam ativados e passam a secretar e depositar grandes quantidades de matriz extracelular (ECM). Este fato leva uma dificuldade na degrada??o da ECM, seguido por rigidez tecidual, perda de fun??o tecidual e morte. A frutose-1,6-bisfosfato ? um metab?lito intermedi?rio da rota glicol?tica que vem sendo estudada h? v?rios anos e tem demonstrado a??es protetoras em diferentes tipos celulares e tecidos. H? evid?ncias de que a FBP ? capaz de prevenir o desenvolvimento da FP induzida por bleomicina (BLM) em camundongos, mas o mecanismo pelo qual isso acontece ainda ? desconhecido. Assim, o objetivo deste estudo foi avaliar os efeitos da FBP sobre a preven??o e/ou regula??o do processo fibr?tico em um modelo experimental de FP in vivo e em c?lulas pulmonares in vitro. Para isso, tratamos animais que receberam BLM intratraqueal com FBP por 14 dias. Ainda, utilizamos culturas prim?rias de fibroblastos e miofibroblastos pulmonares extra?dos de camundongos saud?veis e fibr?ticos, respectivamente. Analisamos, a fun??o pulmonar, a express?o g?nica de subtipos de col?genos e outros componentes importantes no processo fibrotico, assim como as taxas de prolifera??o, contra??o e migra??o celular, al?m das prote?nas envolvidas na degrada??o da ECM. No modelo de FP, a FBP foi capaz de melhorar significativamente a fun??o pulmonar, como demonstrado pela redu??o do dep?sito de col?geno e diminui??o da express?o de genes relacionados ? ECM, como col?geno e fibronectina. In vitro, miofibroblastos tratados com FBP por 3 dias demonstraram uma menor taxa de prolifera??o, contra??o e migra??o, o que s?o ind?cios de desativa??o e revers?o fenot?pica. Al?m disso, a FBP tamb?m diminui a express?o de genes e prote?nas relacionados ? ECM, como col?geno, fibronectina e actina de m?sculo liso ? em cultura prim?ria de miofibroblastos. MMP1, uma colagenase respons?vel pela degrada??o da ECM, teve sua express?o aumentada, enquanto a TIMP-1, um inibidor da MMP1, diminuiu. MMP2, que est? associada ao aumento da invas?o do tecido por miofibroblastos, tamb?m teve sua express?o diminu?da. Nossos resultados demonstram que a FBP pode prevenir o desenvolvimento de FP induzida por BLM atrav?s da redu??o da produ??o e dep?sito de col?geno e outros componentes de ECM e isso pode ser mediado atrav?s do aumento da produ??o de MMP1 e diminui??o da TIMP-1, o que promoveria uma degrada??o efetiva da ECM depositada no tecido. Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired ECM degradation followed by tissue stiffness, loss of lung function and death. Fructose-1,6-bisphosphate is a metabolite from glycolytic pathway that has been studied for many years and showing beneficial actions in different cell lines and tissues. In a recent study from our laboratory, FBP was able to prevent the development of FP bleomycin (BLM)-induced on mice, but the underlying mechanism is still unknown. In this way, the objective of this study was to evaluate the effects of FBP under prevention and regulation of fibrotic process in PF mouse model and lung fibroblasts. In this way, we treated mice that received BLM intratracheally with FBP for 14 days. We also extracted lung fibroblasts and myofibroblasts from healthy and fibrotic animals, respectively. We analyzed lung function, gene expression of collagen subtypes and other important components of ECM, as well proliferation, contraction and migration rates, and proteins involved in ECM degradation. In PF mice model, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Myofibroblasts treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and ?-smooth muscle actin, were downregulated in FBP-treated myofibroblasts in vitro. Moreover, MMP1, responsible for ECM degradation, and TIMP-1, a MMP1 inhibitor, were up and down regulated, respectively. MMP2, which is associated with fibroblast invasion on tissue, also was downregulated. These results demonstrate that FBP may prevent bleomycininduced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and increased MMP1 production, which would allow a better ECM degradation. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Introdu??o: A fibrose c?stica (FC) ? uma doen?a gen?tica que afeta diversos sistemas e ?rg?os e necessita de um tratamento regular e complexo. A recomenda??o para a pr?tica de exerc?cio f?sico ? parte importante do tratamento. No entanto, j? ? conhecida a baixa ades?o a estas recomenda??es, o que pode influenciar na qualidade de vida e sobrevida dos pacientes. A fim de melhorar a ades?o ? pr?tica de exerc?cio, o uso de videogames interativos (VG) pode ser uma importante ferramenta. Objetivo: Avaliar se a utiliza??o de VG por indiv?duos com FC e saud?veis gera a demanda cardiorrespirat?ria necess?ria para treinamento f?sico aer?bico tendo como par?metro o desempenho no teste de exerc?cio cardiopulmonar (TECP). M?todos: Estudo transversal incluindo sujeitos com FC (grupo FC) e saud?veis (grupo controle ? CON), pareados por idade e sexo, com idade maior do que 6 anos. Sujeitos que n?o conseguiram realizar o TECP foram exclu?dos. O estudo foi divido em 2 visitas, sendo que na primeira foram realizadas medidas antropom?tricas, espirometria e o TECP para ambos. Ainda, nesta visita, foi aplicado um question?rio de sa?de respirat?ria com o grupo CON. J? na visita 2 foi aplicado o question?rio de atividade f?sica (IPAQ-A/IPAQ-C) e realizados os testes com os VG Nintendo Wii (Wii Fit Plus: (1) Obstacle Course, (2) Rhythm Boxing e (3) Free Run) e Xbox One (Just Dance 2015: (1) Love Me Again, (2) Summer e (3) Happy), 10 minutos cada console. Durante o TECP e o uso de VG foi utilizado um analisador de gases para mensura??o das vari?veis cardiorrespirat?rias. Ainda, durante o VG, utilizou-se um aceler?metro (wGT3X-BT) e foi quantificado o grau de esfor?o f?sico e satisfa??o. Utilizou-se estat?stica descritiva, o teste t de Student e ANOVA de uma via (p?s-teste de Bonferroni). O estudo foi aprovado pelo comit? de ?tica em pesquisa. Resultados: Foram recrutados 25 sujeitos para o grupo CON e 30 para o FC, com m?dia de idade de 16,2?5,0 e 16,9?5,1, respectivamente. A m?dia (%) do VEF1 no grupo FC foi de 73,3?24 e da CVF de 81,2?19,6, valores menores (p0,05). Tamb?m n?o houve diferen?as entre grupos no pico do exerc?cio (TECP) para a frequ?ncia card?aca (Fc) (186,0?9,0 vs 180,0?12,6 bpm), VO2 (36,7?8,50 vs 36,9?6,40 mL/kg/min) e VE (54,2?16,3 vs 50,0?17,2 L/min). No grupo CON os jogos 2 e 3 (Xbox) e o jogo 3 (Nintendo) elevaram a Fc a valores similares (p>0,05) ao limiar anaer?bico (LA - TECP), enquanto no grupo FC isso ocorreu para o jogo 2 (Xbox) e 3 (Nintendo). Quanto ao VO2 e VE, ambos grupos obtiveram respostas similares (p>0,05) ao LA no jogo 2 do Xbox e no jogo 3 do Nintendo. N?o houve diferen?as (p>0,05) entre os VG no n?mero de passos e no grau de esfor?o/satisfa??o. Conclus?o: O uso de jogos espec?ficos de VG foi capaz elevar a resposta cardiorrespirat?ria a n?veis similares ao LA, demonstrando que os VG podem ser uma alternativa para o treinamento de indiv?duos saud?veis e com FC. Introduction: Cystic fibrosis (CF) is a genetic disease that affects several systems and organs and requires a regular and complex treatment. Physical exercise is recommended as an important part of the treatment. However, the low adherence of patients to this recommendation is already known, which may influence quality of life survival. In order to improve adherence to exercise, the use of interactive video games (VG) may emerge as an important tool. Objective: To assess whether the use of VG by CF and healthy individuals generates the cardiorespiratory demand necessary for aerobic physical training, using as a parameter the performance in the cardiopulmonary exercise test (CPET). Methods: Cross-sectional study with CF and healthy subjects (control group - CON), matched by age and gender, aged over 6 years old. Subjects who were unable to perform CPET were excluded. The study was divided into 2 visits: on the first visit, anthropometric measures, spirometry, and CPET were performed for both groups. In addition, during this visit, a respiratory health questionnaire was applied to the CON group. On the second visit, a physical activity questionnaire (IPAQ-A/IPAQ-C) was applied and the VG tests were performed using Nintendo Wii (Wii Fit Plus: (1) Obstacle Course, (2) Rhythm Boxing, and (3) Free Run) and Xbox One (Just Dance 2015: (1) Love Me Again, (2) Summer and (3) Happy), 10 minutes for each console. During both CPET and the use of VG, a gas analyzer was used to measure cardiorespiratory variables. In addition, during VG use, an accelerometer (wGT3X-BT) was used and the degree of physical effort and satisfaction was quantified. Descriptive statistics, Student's t-test and one-way ANOVA (with Bonferroni post hoc test) were used. The study was approved by the Research Ethics Committee. Results: Twenty-five subjects were recruited for the CON and 30 for the CF group, with a mean age of 16.2?5.0 and 16.9?5.1, respectively. The mean (%) FEV1 in the CF group was 73.3?24 and the FVC was 81.2?19.6, which represents lower values (p0.05). There were also no differences between groups at peak exercise (CPET) for heart rate (HR) (186.0?9.0 vs 180.0?12.6 bpm), VO2 (36.7?8.50 vs 36.9?6.40 mL/kg/min) and VE (54.2?16.3 vs 50.0?17.2 L/min). In the CON group, games 2 and 3 (Xbox) and game 3 (Nintendo) raised the HR to values similar (p>0.05) to the anaerobic threshold (AT - CPET), while in the CF group this occurred for games 2 (Xbox) and 3 (Nintendo). As for VO2 and VE, both groups obtained similar responses (p>0.05) to the AT in games 2 (Xbox) and 3 (Nintendo). There were no differences (p>0.05) between VG regarding the number of steps and the degree of effort/satisfaction. Conclusion: The use of specific VG was able to raise the cardiorespiratory response to levels similar to the anaerobic threshold, showing that VG may be an alternative for the training of healthy and CF individuals. Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq

INTRODU??O: A asma induzida pelo exerc?cio (AIE) ? definida como uma obstru??o transit?ria das vias a?reas durante e ap?s o exerc?cio, podendo ser evidenciada pela queda no volume expirat?rio for?ado no primeiro segundo (VEF1). Embora v?rios instrumentos tenham sido criados e testados para detectar a AIE, a maioria possui baixo poder diagn?stico. Nesse sentido, considerando a ampla utiliza??o da Global Initiative for Asthma (GINA) na pr?tica cl?nica e que o mesmo possui uma quest?o espec?fica de atividade f?sica, torna-se relevante a avalia??o do seu desempenho na detec??o de AIE. OBJETIVO: Avaliar o desempenho diagn?stico da quest?o relacionada ? atividade f?sica do GINA na detec??o de AIE em crian?as e adolescentes com asma. M?TODOS: Trata-se de um estudo observacional, do tipo transversal, realizado no Laborat?rio de Atividade F?sica em Pediatria. Foram inclu?das crian?as e adolescentes (6 e 18 anos) com diagn?stico cl?nico de asma. Excluiu-se pacientes com sinais de exacerba??o pulmonar e aqueles que apresentassem limita??es motoras. Os pacientes foram divididos em 2 grupos de acordo com a classifica??o da gravidade: asma leve/moderada (ALM) e asma grave resistente ? terapia (AGRT). Tanto a avalia??o da gravidade como do controle da doen?a seguiram os crit?rios da GINA. Dados antropom?tricos e cl?nicos foram coletados. Al?m disso, foi avaliada a fun??o pulmonar e realizado o teste de broncoprovoca??o induzida por exerc?cio (BIE). O teste de BIE foi realizado em uma esteira, com aumentos de velocidade e inclina??o, de acordo com recomenda??es internacionais. Utilizou-se a quarta quest?o do GINA (Alguma limita??o de atividade f?sica por asma?) para avaliar o poder diagn?stico do instrumento. Para fins estat?sticos, as compara??es foram realizadas pelo teste t de Student e pelo teste de qui-quadrado de Pearson. A an?lise do desempenho diagn?stico da quest?o espec?fica do question?rio da GINA para a detec??o da BIE foi avaliada pela curva ROC. O estudo foi aprovado pelo Comit? de ?tica em Pesquisa e todos os pais e/ou respons?veis assinaram um termo de consentimento livre e esclarecido e os participantes o termo de assentimento do estudo. RESULTADOS: Foram avaliados 40 pacientes, sendo 17 do grupo ALM e 23 do grupo AGRT. A m?dia de idade foi de 11,25 anos, com o VEF1 (escore-z) de 0,33 e 32,5% classificados como doen?a n?o controlada. Destes, 19 (47,5%) apresentaram queda do VEF1 no teste de BIE, sendo 13 (56,5%) do grupo AGRT e 6 (35,2%) no grupo ALM. Houve uma frequ?ncia de AIE significativamente maior (p=0,05) nos sujeitos com VEF1 mais baixo (escore-z -1,0. No entanto, n?o houve diferen?as significativas na frequ?ncia de BIE quando avaliada a influ?ncia da gravidade e do controle da doen?a. Da mesma forma, n?o foi encontrada associa??o da quest?o 4 da GINA com os resultados da AIE (p>0,05). A sensibilidade encontrada foi de 57,9% e a especificidade de 57,1% (n=40). A ?rea sob a curva ROC n?o demonstrou um poder discriminativo da quarta quest?o do GINA para a detec??o de AIE em crian?as e adolescentes com asma (p=0,35). CONCLUS?O: Os resultados do presente estudo demonstraram que a quarta quest?o do question?rio da GINA (atividade f?sica) possui um poder diagn?stico insuficiente do ponto de vista cl?nico para a detec??o de AIE em crian?as e adolescentes com asma (ALM e AGRT). Desta forma, recomenda-se que a avalia??o da AIE seja ainda realizada pelo teste de broncoprovoca??o induzida por exerc?cio, evitando assim, subestimativas e/ou superestimativas nos resultados da avalia??o. INTRODUCTION: Exercise-induced asthma (EIA) is defined as transient airway obstruction during and after exercise and may be evidenced by a decrease in forced expiratory volume in the first second (FEV1). Although several instruments have been designed and tested to detect EIA, most have low diagnostic power. Thus, considering the wide use of the Global Initiative for Asthma (GINA) in clinical practice and that it has a specific question for physical activity, it is relevant to evaluate its performance in the detection of EIA. OBJECTIVES: To evaluate the diagnostic performance of the physical activity related question of GINA in the detection of EIA in children and adolescents with asthma. METHODS: This is a cross-sectional, observational, study performed in the Laboratory of Pediatric Physical Activity. Children and adolescents (6 to 18 years old) with clinical diagnosis of asthma were included. Patients with signs of pulmonary exacerbation and those with motor limitations were excluded. Patients were divided into 2 groups according to severity classification: mild/moderate asthma (MMA) and severe therapy-resistant asthma (STRA). Both the assessment of severity and disease control followed GINA criteria. Anthropometric and clinical data were collected. In addition, pulmonary function was evaluated and the exercise-induced bronchoprovocation test (EIB) was performed. The EIB test was performed on a treadmill, with increases in speed and inclination, in accordance with international recommendations. We have used the fourth question of GINA (Any activity limitation due to asthma?) to evaluate the diagnostic power of the instrument. For statistical purposes, the comparisons were performed using the Student t test and the Pearson's chi-square test. The analysis of the diagnostic performance of the GINA questionnaire specific question for the detection of EIB was evaluated using the ROC curve. The study was approved by the Research Ethics Committee and all parents and/or guardians signed a free and informed consent form and the participants the study assent term. RESULTS: We have evaluated 40 patients, 17 of the MMA group and 23 of the STRA group. The mean age was 11.25 years, with a FEV1 (z-score) of 0.33 and 32.5% classified as uncontrolled disease. Of these, 19 (47.5%) presented a decrease in FEV1 in the EIB test, 13 (56.5%) in the STRA group and 6 (35.2%) in the MMA group. There was a significantly higher EIA frequency (p=0.05) in subjects with lower FEV1 (z-score -1.0. However, there were no significant differences in the frequency of EIB when evaluating the influence of disease severity and control. Likewise, no association of question 4 of GINA was found with the EIA results (p>0.05). The sensitivity found was 57.9% and the specificity was 57.1% (n=40). The area under the ROC curve did not demonstrate a discriminative power of the fourth GINA question for the detection of EIA in children and adolescents with asthma (p=0.35). CONCLUSION: The results of the present study demonstrated that the fourth question of the GINA questionnaire (physical activity) has a clinically insufficient diagnostic power for the detection of EIA in children and adolescents with asthma (MMA and STRA). Thus, it is recommended that the evaluation of EIA to be performed by the EIB test, avoiding underestimation and/or overestimation resulting from this evaluation. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P P P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). Conclusions The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. Trial registration EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

A obesidade ? uma doen?a cr?nica crescente mundialmente e, em decorr?ncia da sua abrang?ncia, vem configurando-se quase como uma epidemia e tornando-se um dos problemas mais relevantes de sa?de p?blica na atualidade, uma vez que ? um fator de risco que pode desencadear diversas doen?as. Assim, este estudo teve como objetivo avaliar o efeito da interven??o interdisciplinar com abordagem motivacional sobre a capacidade de exerc?cio e o n?vel de atividade f?sica di?ria em adolescentes com sobrepeso e obesidade. Este estudo trata-se de um ensaio cl?nico controlado, randomizado, com cegamento ?nico dos indiv?duos. Foram inclu?dos adolescentes com idade entre 15 e 18 anos e ?ndice de massa corporal (IMC) compat?vel com sobrepeso ou obesidade (? percentil 85 e ? percentil 99,9). O presente estudo foi aprovado pelo Comit? de ?tica em Pesquisa da Universidade (CAAE: 36209814.6.0000.5336) e todos os pais e/ou respons?veis assinaram o termo de consentimento livre e esclarecido (TCLE) e os escolares o termo de assentimento (TA). Ap?s o interesse inicial, os indiv?duos foram convidados por telefone para participar de uma triagem e ap?s randomizados atrav?s do software Random Allocation Software (vers?o 2.0) para participar de um dos dois grupos a seguir: abordagem tradicional (controle) ou entrevista motivacional (interven??o) visando ? modifica??o do estilo de vida. No grupo controle (GC) o foco foi o desenvolvimento de habilidades por meio de a??es educativas em sa?de utilizando a pedagogia da transmiss?o. No grupo interven??o (GI) foi utilizado o Modelo Transte?rico de Mudan?a juntamente com a Entrevista Motivacional para tentar desenvolver habilidades por meio de a??es educativas em sa?de que proporcionassem o desenvolvimento da autonomia e do empoderamento para a mudan?a de comportamento, com base em estrat?gias motivacionais interdisciplinares. Posteriormente, foram agendadas as avalia??es iniciais que inclu?ram o teste de exerc?cio cardiopulmonar (TECP) e a aferi??o do n?vel de atividade f?sica habitual por meio de um question?rio curto e de uma medida objetiva (ped?metro). As avalia??es foram realizadas em dois momentos para ambos os grupos, no tempo zero (momento da inclus?o no estudo) e ap?s tr?s meses (t?rmino da interven??o). De um total de 43 adolescentes com sobrepeso e obesidade, 05 foram exclu?dos, resultando em uma amostra de 37 participantes, sendo 18 no GC e 19 no GI. A m?dia de idade foi em torno de 17 anos, com predom?nio do sexo feminino. A m?dia do IMC (escore-z) foi cerca de 2, sendo 17 classificados com sobrepeso e 20 com obesidade. N?o houve diferen?as significativas nos dados basais de caracter?sticas demogr?ficas, antropom?tricas e de atividade f?sica habitual entre os grupos. A interven??o motivacional n?o provocou diferen?as significativas (p>0,05) na compara??o das vari?veis de capacidade de exerc?cio e atividade f?sica habitual (question?rio e ped?metro) entre o GC e o GI. A m?dia do VO2m?x (mL/kg/min) no pico do exerc?cio foi cerca de 26,0, enquanto o VO2m?x (mL/kg/min) no limiar anaer?bico (LA) foi perto de 22,0. Todas as vari?veis cardiovasculares, metab?licas, ventilat?rias e subjetivas no pico do exerc?cio foram semelhantes em ambos os grupos, com exce??o da VEm?x que foi significativamente maior (p=0,001) no GI em compara??o ao GC. Quando se testou o efeito da entrevista motivacional sobre o estado nutricional (peso e IMC) e a aptid?o f?sica avaliada pelo TECP (VEm?x, VO2m?x, VO2m?x no LA e os equivalentes ventilat?rios) novamente n?o foram observadas altera??es significativas. Os resultados permitem concluir que a interven??o com abordagem motivacional n?o alterou a aptid?o f?sica e os n?veis de atividade f?sica habituais em adolescentes com sobrepeso e obesidade. Obesity is a chronic disease that is growing worldwide and, as a result of its coverage, has developed almost an epidemic and it is becoming one of the most relevant public health problems nowadays, since it is a risk factor that can trigger diseases. Thus, this study aimed to evaluate the effect of an interdisciplinary intervention with a motivational approach on exercise capacity and habitual physical activity levels in overweight and obese adolescents. This is a randomized controlled trial with single blinding of individuals. Adolescents aged 15 to 18 years and body mass index (BMI) compatible with overweight or obesity (? 85th percentile and ?99.9th percentile) were included. The present study was approved by the Research Ethics Committee of the University (CAAE: 36209814.6.0000.5336) and all parents and/or guardians signed the informed consent form (ICF) and the students signed the assent form (AF). After the initial interest, individuals were invited by telephone to participate in a screening and then randomized through the Random Allocation Software (version 2.0) to participate in one of the following two groups: traditional approach (control) or motivational interview (intervention) aiming at the modification of lifestyle. In the control group (GC) the focus was the development of skills through educational health actions using the transmission pedagogy. In the intervention group (GI) the Transtheoric Model of Change was used along with the Motivational Interview to try to develop skills through educational actions in health that provided the development of autonomy and empowerment for behavior change, based on interdisciplinary motivational strategies. Subsequently, the initial evaluations, including the cardiopulmonary exercise test (CPET) and the levels of physical activity were assessed using a short questionnaire and an objective measure (pedometer). The evaluations were performed in two moments for both groups, at time zero (time of inclusion in the study) and after three months (end of intervention). Of a total of 43 overweight and obese adolescents, 05 were excluded, resulting in a sample of 37 participants, 18 in the GC and 19 in the GI. The mean age was around 17 years, with a predominance of females. The mean BMI (z score) was about 2, with 17 being overweight and 20 being obese. There were no significant differences in the baseline demographic, anthropometric and physical activity characteristics between groups. The motivational intervention did not cause significant differences (p>0.05) in the comparison of the variables of exercise capacity and habitual physical activity (questionnaire and pedometer) between GC and GI. The mean VO2max (mL/kg/min) at peak exercise was about 26.0, while the VO2max (mL/kg/min) at the anaerobic threshold (LA) was close to 22.0. All cardiovascular, metabolic, ventilatory and subjective variables at peak exercise were similar in both groups, except for Vmax that was significantly higher (p=0.001) in GI compared to GC. When we tested the effect of the motivational interview on nutritional status (weight and BMI) and physical fitness assessed by CPET (VEmax, VO2max, VO2max in AT and ventilatory equivalents) again no significant changes were observed. The results allow us to conclude that the intervention with a motivational approach did not alter physical fitness and habitual physical activity levels in overweight and obese adolescents. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

INTRODU??O: Potenciais amea?as para a homeostasia podem ocorrer durante a vida in utero, promovendo efeitos de programa??o tanto no desenvolvimento neurol?gico quanto na fun??o do eixo hipot?lamo-pituit?ria-adrenal (HPA). O eixo HPA ? o centro controlador e regulador do organismo que conecta o sistema nervoso central com o sistema hormonal. Este eixo responde ao est?mulo estressor e auxilia o organismo a manter a homeostasia, al?m de ser essencial para auxiliar no funcionamento fisiol?gico normal. Indiv?duos fisicamente aptos e que praticam frequentemente atividades f?sicas exibem um menor ?ndice de problemas de sa?de, especialmente quando se deparam com situa??es de estresse, contribuindo na redu??o dos n?veis de ansiedade e depress?o. OBJETIVO: Avaliar os efeitos do exerc?cio f?sico antes do per?odo gestacional sobre altera??es decorrentes do estresse pr?-natal em camundongos adultos. METODOLOGIA: F?meas e machos Balb/c foram divididos em tr?s grupos: controle (CTLE), estresse pr?-natal por conten??o (PNS) e exerc?cio f?sico antes do per?odo gestacional e estresse pr?-natal por conten??o (EX+PNS). O peso dos animais foi avaliado durante a gesta??o, e nos dias 1, 10 e 21 de vida e na vida adulta. Esses animais foram mantidos at? a idade adulta (60 dias de vida) quando foram avaliados os comportamentos de medo/ansiedade, no aparato de labirinto em cruz elevada, e depress?o, por meio do teste de prefer?ncia e ingest?o de sacarose. Al?m disso, foi avaliada a express?o g?nica, atrav?s da t?cnica de PCR em tempo real, do receptor tipo 1 do horm?nio liberador de corticotrofina (CRHR1) no c?rtex pr?-frontal, do receptor de glicocorticoide (GR) e do receptor de mineralocorticoide (MR) no hipocampo e as concentra??es plasm?ticas de corticosterona foram avaliadas. RESULTADOS: Durante a gesta??o, as f?meas do grupo EX+PNS apresentaram maior peso em rela??o ao grupo CTLE. Em rela??o ao peso da prole, os animais do grupo EX+PNS exibiram um aumento no peso nos dias 1, 10 e 21 de vida, comparados com o grupo PNS. Durante a vida adulta, os animais estressados no per?odo pr?-natal apresentaram menor peso, enquanto o exerc?cio pr?-gestacional promoveu um aumento no peso da prole, em rela??o ao grupo CTLE. Em rela??o aos testes comportamentais, houve uma diminui??o significativa no tempo gasto no bra?o aberto do aparato de labirinto em cruz elevada nos animais dos grupos PNS e EX+PNS, em ambos os sexos, demonstrando um aumento no comportamento de medo/ansiedade. O estresse pr?-natal aumentou a prefer?ncia por sacarose em f?meas e a ingest?o de sacarose em ambos os sexos. No entanto, o exerc?cio promoveu uma diminui??o significativa na ingest?o de sacarose, em machos e f?meas. A express?o de CRHR1 diminuiu no c?rtex pr?-frontal de f?meas do grupo EX+PNS em rela??o ao grupo PNS. Por outro lado, o exerc?cio antes da gesta??o n?o foi capaz de reverter a diminui??o significativa nas concentra??es basais de GR provocadas pelo estresse pr?-natal em f?meas adultas. N?o houve diferen?as significativas entre os grupos na express?o g?nica de GR em machos e de MR e corticosterona em f?meas e machos. CONCLUS?O: O exerc?cio f?sico em esteira antes do per?odo gestacional parece ser capaz de reduzir os efeitos do estresse pr?-natal em marcadores importantes da resposta do eixo HPA de uma maneira dependente do sexo. INTRODUCTION: Potential threats to homeostasis may occur during the in utero period, promoting programming effects on both neurological development and hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis acts as a control and regulatory center of the body that connects the central nervous system to the hormonal system. The axis responds to the stressor stimulus and assists the body to maintain homeostasis, as well as being essential to the normal regulatory physiological functioning. Physically fit and physically active individuals exhibit a lower rate of health problems, especially when faced with stressful situations, contributing to reduced levels of anxiety and depression. OBJECTIVE: To evaluate the effects of physical exercise before the gestational period on changes due to prenatal stress in adult mice. METHODS: Balb/c female and male mice were divided into three groups: control (CTLE), prenatal restraint stress (PNS) and physical exercise before the gestational period and prenatal restraint stress (EX+PNS). The weight of the animals was evaluated during gestation, days 1, 10 and 21 of life and also as adults. Animals were then maintained until adulthood (60 days of life) when fear/anxiety behaviors were evaluated in the elevated plus maze, and depression was evaluated using the preference for sucrose and the ingestion of sucrose test. In addition, real-time PCR gene expression of corticotrophin releasing hormone (CRHR1) type 1 receptor in the prefrontal cortex, glucocorticoid receptor (GR) and mineralocorticoid (MR) receptor in the hippocampus, as well as plasmatic concentrations of corticosterone were evaluated. RESULTS: During gestation, females of the EX+PNS group presented greater weight in relation to the CTLE group. Regarding the offspring weight, animals of the EX+PNS group showed an increase in weight on days 1, 10 and 21 of life, compared to the PNS group. During the adult life, animals stressed in the prenatal period presented lower weight, while the pregestational exercise promoted an increase in the offspring weight in relation to the CTLE group. In relation to behavioral tests, there was a significant decrease in the time spent in the open arms of the elevated plus maze in the PNS and EX+PNS groups, in both sexes, demonstrating an increase in fear/anxiety behavior. Prenatal stress increased the preference for sucrose in females and sucrose intake in both sexes. However, exercise promoted a significant decrease in sucrose intake in males and females. CRHR1 expression decreased in the prefrontal cortex of EX+PNS females compared to the PNS group. On the other hand, pregestational exercise was not able to reverse the significant decrease in basal GR concentrations caused by prenatal stress in adult females. There were no significant differences between groups in GR gene expression in males, as well as in MR and corticosterone in both females and males. CONCLUSION: Physical exercise on the treadmill before the gestational period seems to be able to reduce the effects of prenatal stress on important markers of the HPA axis response in a sex-dependent manner. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Introdu??o: Indiv?duos com paralisia cerebral (PC) frequentemente apresentam comprometimento do membro superior levando a limita??es na funcionalidade. A avalia??o do membro superior apenas com o exame f?sico tradicional pode ser limitada nesses indiv?duos. O uso de escalas e avalia??es espec?ficas e validadas auxiliam os profissionais da sa?de no entendimento dessas limita??es e no planejamento do tratamento. No entanto, no Brasil n?o se tem a disposi??o uma escala validada que avalie a fun??o do membro superior e direcione o plano de tratamento em indiv?duos com PC. Objetivo: Esta tese teve como objetivo geral validar o instrumento de avalia??o do membro superior, Shriners Hospital Upper Extremity Evaluation (SHUEE), para indiv?duos com PC hemipl?gica da popula??o brasileira. Material e m?todos: Estudo transversal, de valida??o, no qual foi realizada a tradu??o do manual e do instrumento. As propriedades psicom?tricas avaliadas foram confiabilidade e validade convergente. A confiabilidade foi determinada atrav?s da consist?ncia interna (coeficiente ? de Cronbach, ?-C), efeito teto e ch?o, sensibilidade ? mudan?a e concord?ncia intra e inter-observador. A validade convergente foi realizada utilizando-se o Pediatric Motor Activity Log (PMAL), a escala de autocuidados do Pediatric Evaluation of Disability Inventory (PEDI) e o Manual Ability Classification System (MACS). Resultados: Foram avaliados 21 indiv?duos com PC hemipl?gica e idade m?dia de 8,73?3,98 anos. Ap?s a tradu??o do instrumento, n?o houve necessidade de adapta??o cultural. O coeficiente ?-C total do SHUEE foi de 0,887 (IC 95% 0,745- 0,970). A sensibilidade ? mudan?a foi calculada em 5 indiv?duos que realizaram aplica??o de Toxina Botul?nica tipo A e fisioterapia, apresentando diferen?a significativa entre a avalia??o pr? e p?s-tratamento na An?lise Posicional Din?mica. A validade convergente mostrou correla??o significativa da An?lise Funcional Espont?nea e An?lise Posicional Din?mica com o PMAL, PEDI e MACS. Todos os itens do SHUEE apresentaram concord?ncias fortes, tanto na avalia??o intra quanto na inter-observador (ICC maior do que 0,9). Conclus?o: Os resultados apresentados na tese nos permitem concluir que a vers?o do SHUEE em portugu?s do Brasil demonstrou um bom desempenho em rela??o ? confiabilidade e validade convergente, sugerindo ser uma ferramenta adequada e confi?vel para os indiv?duos com PC hemipl?gica da popula??o brasileira. Introduction: Individuals with cerebral palsy (CP) often have upper limb impairment leading to limitations in functionality. The use of specific and validated scales assists health professionals in the understanding of these limitations and treatment planning. However, Brazil does not have available validated scales to assess the upper limb function and direct the treatment plan in individuals with CP. Objective: This thesis aimed at validating the upper limb assessment tool, Shriners Hospital Upper Extremity Evaluation (SHUEE), for individuals with hemiplegic CP of the Brazilian population. Methods: Cross-sectional validation study in which the translation of the manual and instrument was performed. The evaluated psychometric properties were reliability and convergent validity. Reliability was determined by internal consistency (Cronbach ? coefficient, ?-C), ceiling and floor effect, sensitivity to change and intra and interobserver agreement. Convergent validity was performed using the Pediatric Motor Activity Log (PMAL), the self-care scale of the Pediatric Evaluation of Disability Inventory (PEDI) and the Manual Ability Classification System (MACS). Results: A total of 21 individuals with hemiplegic CP, mean age of 8.73?3.98 years, were evaluated. The instrument was translated and there was no need for cultural adaptation. The total ?-C coefficient of the SHUEE was 0.887 (95% CI 0.745 to 0.970). Sensitivity to change was calculated in 5 subjects who underwent application of Botulinum Toxin Type A and physical therapy, with a significant difference in the Dynamic Positional Analysis between pre and post-treatment evaluations. The convergent validity showed significant correlation of Spontaneous Functional Analysis and Dynamic Positional Analysis with PMAL, PEDI and MACS. All items of SHUEE showed high intra and inter-observer agreement (ICC greater than 0.9). Conclusion: The results presented in this thesis allow us to conclude that the Brazilian Portuguese version of SHUEE demonstrated a good reliability and convergent validity, suggesting that it is a reliable tool for the upper limb evaluation of Brazilian children and adolescents with hemiplegic CP.

Objetivos: Gerar valores de refer?ncia para dois protocolos de resist?ncia muscular inspirat?ria (RMI) em crian?as e adolescentes saud?veis. M?todos: Estudo observacional, transversal, em crian?as e adolescentes saud?veis de 4 a 18 anos. Foram realizadas as mensura??es de peso, altura, press?o inspirat?ria m?xima (PIMAX) e RMI, utilizando-se dois protocolos. No protocolo de carga incremental foi utilizada uma carga fixa de 30% da PIMAX com incremento de 10% a cada 2 minutos. J? no protocolo de carga m?xima foi utilizada uma carga fixa de 70% da PIMAX e mensurado o tempo limite (Tlim) alcan?ado at? a exaust?o. Resultados: Foram inclu?dos 462 participantes, sendo 281 correspondentes ao protocolo de carga incremental e 181 ao de carga m?xima. No protocolo de carga incremental, houve correla??es moderadas e positivas entre a RMI e a idade, PIMAX, peso e altura. No entanto, o modelo de regress?o demonstrou que a PIMAX e a idade foram as melhores vari?veis para predi??o da RMI. J? no protocolo de carga m?xima, foram encontradas correla??es fracas e positivas com a idade, peso e altura. No modelo de regress?o, apenas a idade e altura influenciaram na endurance. A for?a de predi??o (R2) do protocolo de carga incremental foi de 0,65, enquanto o de carga m?xima foi de 0,15. A reprodutibilidade mensurada pelo coeficiente de correla??o intraclasse (ICC) foi maior no protocolo incremental (0,96) em compara??o ao de carga m?xima (0,69). Conclus?o: A RMI em crian?as e adolescentes saud?veis pode ser explicada em fun??o da idade, altura e PIMAX. O protocolo de carga incremental apresentou melhores resultados e deve ser o modelo de escolha para avalia??o da RMI na faixa et?ria pedi?trica. Objectives: To generate reference values for two inspiratory muscle endurance protocols (IME) in healthy children and adolescents. Methods: An observational, cross-sectional study was conducted including healthy children and adolescents between 4 and 18 years old. Body weight, height, maximal inspiratory pressure (MIP) and IME (using two protocols) measurements were performed. In the incremental threshold loading a fixed load of 30% of the MIP with an increase of 10% every 2 minutes was used. In the a fixed load of 70% of the MIP was used and the time limit (Tlim) to exhaustion was measured. Results: In total, 462 participants were included, 281 performed the incremental threshold loading and 181 the maximum load protocol. There were moderate and positive correlations between IME and age, MIP, height and weight in the incremental threshold loading. However, the regression model showed that MIP and age were the best variables to predict RMI. In the maximum load protocol, weak and positive correlations with age, weight and height were found. In the regression model for this protocol, only age and height influenced the endurance. The prediction power (R2) for the incremental threshold loading was 0.65, while for the maximum load protocol was 0.15. Reproducibility measured by the intraclass correlation coefficient (ICC) was higher in the incremental threshold loading (0.96) compared to the maximum load protocol (0.69). Conclusion: The IME in healthy children and adolescents can be explained by age, height and MIP. The incremental threshold loading showed better results and should be the model of choice when evaluating IME in the pediatric age group. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Objetivos: Avaliar a capacidade funcional de crian?as e adolescentes obesas em compara??o com indiv?duos eutr?ficos e verificar poss?veis correla??es com par?metros bioqu?micos no sangue. Materiais e m?todos: Foram inclu?das crian?as e adolescentes, entre 6 e 18 anos, divididos em grupos controle (eutr?fico) e obeso de acordo com o ?ndice de massa corporal (IMC). Coletaram-se dados referentes ?s caracter?sticas demogr?ficas, antropom?tricas, circunfer?ncia abdominal e capacidade funcional atrav?s do Shuttle Walk Test (SWT). No grupo de obesos, foram avaliados par?metros bioqu?micos no sangue (colesterol total, HDL, LDL, triglicer?deos e glicemia), al?m da aplica??o de um question?rio de atividade f?sica. Para an?lise estat?stica, utilizaram-se os testes de qui-quadrado, t de Student para amostras independentes e o teste de correla??o de Pearson. Resultados: Foram inclu?dos 77 participantes, sendo 27 no grupo controle e 50 obesos. N?o houve diferen?a significativa entre os dois grupos em rela??o ?s caracter?sticas da amostra, exceto quanto ao peso corporal, IMC e circunfer?ncia abdominal. A maioria dos obesos apresentaram resultados dos exames bioqu?micos dentro do limite desej?vel, por?m nenhum foi considerado ativo. Houve redu??o significativa (p

Introdu??o: Adversidades enfrentadas no per?odo pr?-natal podem estar implicadas na programa??o fetal e no surgimento de doen?as na vida adulta. No entanto, pouco se sabe sobre os efeitos do estresse neste per?odo sobre o sistema respirat?rio. Objetivos: Avaliar os efeitos do estresse pr?-natal por conten??o, em dois diferentes momentos da prenhez, sobre a fun??o pulmonar e o perfil inflamat?rio em camundongos machos e f?meas, expostos a um modelo de asma induzida por ovalbumina (OVA). Materiais e m?todos: Foram utilizados camundongos BALB/c machos e f?meas divididos em tr?s diferentes grupos controle (CON), estresse pr?-natal a partir da 2? semana (PNS1) e estresse pr?-natal na ?ltima semana (PNS2). A pesagem da prole foi feita em 3 diferentes momentos (dias 1, 10 e 21). Quando adultos, foi avaliado o comportamento de medo/ansiedade no campo aberto (entre o 50? e 54? dia). No 56? dia foi realizada a aplica??o do modelo de asma por ovalbumina com posterior an?lise do teste de fun??o pulmonar (resist?ncia das vias a?reas, amortecimento do tecido e elast?ncia), al?m da coleta de lavado broncoalveolar para contagem total e diferencial de c?lulas e avalia??o de citocinas inflamat?rias. O pulm?o esquerdo foi retirado e processado para an?lise histol?gica. Resultados: Houve diminui??o significativa (p

A exposi??o neonatal ao lipopolissacar?deo (LPS) gera um estimulo estressor capaz de afetar o desenvolvimento de importantes sistemas, dando origem a altera??es comportamentais e neuroend?crinas duradoras. O objetivo desta disserta??o ? avaliar a resposta a um est?mulo inflamat?rio em camundongos Balb/c submetidos ? estresse neonatal por LPS em diferentes idades e sexos. Os camundongos receberam, no 3? e 10? dias de vida, inje??o i.p. de LPS (100?g /Kg) ou solu??o salina. Ap?s 21 ou 60 dias de vida, os mesmos foram submetidos ? inje??o de solu??o salina ou a um est?mulo inflamat?rio atrav?s da inje??o de carragenina 1%. Foram mensurados no lavado peritoneal citocinas inflamat?rias, esp?cies reativas de oxig?nio e produ??o de Redes Extracelulares de Neutr?filos (NETs). Os resultados encontrados demonstram que o estresse neonatal por LPS diminui a libera??o de citocinas inflamat?rias nos animais jovens machos e f?meas. J? nos adultos, somente as f?meas apresentaram a mesma resposta. Foi encontrado um aumento na produ??o de NETs nos animais do grupo nLPS com 60 dias quando comparado com animais nLPS com 21 dias, em ambos os sexos, indicando um efeito do estresse neonatal sobre a ontogenia da forma??o de NETs. A produ??o de ROS n?o sofreu influ?ncia do estresse neonatal, por?m foi encontrada uma maior produ??o na idade adulta, independente da interven??o neonatal. Os resultados do presente estudo indicam que o estresse neonatal por LPS altera a produ??o de citocinas em resposta a um est?mulo inflamat?rio em diferentes idades, em um efeito dependente do sexo. Al?m disso, parece que a forma??o de NETs ao longo da vida tamb?m ? influenciada pelas altera??es no per?odo neonatal. Neonatal exposure to lipopolysaccharides (LPS) generates a stressful stimulus capable of affecting the development of important systems, which causes lasting behavioral and neuroendocrine alterations. The aim of this study is to evaluate the response to an inflammatory stimulus in Balb/c mice exposed to LPS-induced neonatal stress at different ages and genders. Mice underwent intraperitonial injections on postnatal days 3 and 10 with either LPS (100ug/Kg) or saline solution. After 21 or 60 days of age, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species and NETs production were measured in the peritoneal lavage. Our findings indicate that LPS-induced neonatal stress can reduce inflammatory cytokines in young animals, males and females. In adults, however, only females showed the same response pattern. In nLPS group, an increase in NETs production was observed in animals that were 60-days-old when compared to 21-days-old in both genders, which indicates an effect of neonatal stress on the ontogeny of NETs formation. The production of ROS was not affected by neonatal stress, even though an increased production was found among adults regardless of neonatal intervention. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a gender dependent way. Moreover, it seems like the formation of NETs throughout life is also influenced by alterations undergone during the neonatal period. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul - FAPERGS

Introdu??o: Nas ?ltimas d?cadas, vem ocorrendo um r?pido crescimento das taxas de preval?ncia de asma, obesidade e sedentarismo na popula??o infantil. Al?m disso, a intera??o entre estas doen?as cr?nicas pode causar um comprometimento na capacidade muscular ventilat?ria, na qualidade de vida e nos n?veis de atividade f?sica. No entanto, ainda s?o escassas as informa??es sobre a influ?ncia do estado nutricional sobre esses par?metros na faixa et?ria pedi?trica. Objetivos: Esta tese teve como objetivo geral avaliar o impacto da asma sobre qualidade de vida, sedentarismo e capacidade muscular ventilat?ria e a influ?ncia do sobrepeso/obesidade em crian?as e adolescentes. Materiais e m?todos: Foram inclu?dos participantes com ou sem diagn?stico de asma, idade entre 6 e 18 anos, recrutados em duas escolas p?blicas de Porto Alegre-RS. Os sujeitos asm?ticos foram selecionados atrav?s dos crit?rios do ISAAC e os participantes do grupo controle, a partir da aus?ncia de sintomas respirat?rios. Foram coletados dados de antropometria, question?rio de qualidade de vida, avalia??o do n?vel de atividade f?sica (question?rio e aceler?metro) e testes de capacidade muscular ventilat?ria. A classifica??o do ?ndice de massa corporal foi realizada utilizando-se o escore-z: eutr?fico (≥-2 e ≤+1), sobrepeso (>+1 e ≤+2) e obeso (>+2). Resultados: Os resultados obtidos foram separados em dois artigos. O primeiro artigo demonstrou uma redu??o significativa da qualidade de vida nos adolescentes do grupo asm?tico com sobrepeso/obesidade. No entanto, n?o foram encontradas diferen?as significativas nos n?veis de atividade f?sica entre os grupos, independente do ?ndice de massa corporal/faixa et?ria. O segundo artigo demonstrou que a resist?ncia muscular inspirat?ria apresentou-se reduzida somente nos adolescentes com sobrepeso/obesidade no grupo asm?tico em compara??o ao controle. Conclus?o: De uma maneira geral, os resultados apresentados nesta tese nos permitem concluir que os adolescentes asm?ticos com sobrepeso/obesidade apresentam uma redu??o da qualidade de vida e da resist?ncia muscular inspirat?ria. Al?m disso, n?o foram encontradas altera??es nos n?veis de atividade f?sica, apesar da elevada taxa de inatividade/sedentarismo demonstrada. Introduction: In the last decades, there has been a fast growth in prevalence rates of asthma, obesity and physical inactivity in children. In addition, interaction between these chronic illnesses can cause impairment in respiratory muscle capacity, quality of life and physical activity levels. However, there is still little information on the nutritional status influence in pediatric patients. Objectives: This thesis aimed evaluating the impact of asthma on quality of life, physical activity levels and the influence of overweight/obesity in children and adolescents. Methods: Participants with or without asthma diagnosis, 6 to 18 years old, recruited from two public schools in Porto Alegre-RS were included. The individuals with asthma were selected through ISAAC criteria and the participants in the control group based on the absence of respiratory symptoms. Anthropometric data, quality of life questionnaire, physical activity levels (questionnaire and accelerometer) and respiratory muscle capacity tests were also collected. The classification of body mass index was performed through z-score: eutrophic (≥-2 and ≤+1), overweight (>+1 and ≤+2) and obese (>+2). Results: The obtained results were separated in two articles. The first article showed a significant reduction in quality of life of the overweight/obesity adolescents from the asthmatic group. No significant differences were found in levels of physical activity between both groups, regardless of body mass index/age range. The second article showed that inspiratory muscle endurance was reduced only in overweight/obese adolescents in the asthmatic group compared to the control group. Conclusion: Overall, the results presented in this thesis allow us to conclude that overweight/obese asthmatic adolescents have a reduced quality of life and inspiratory muscle endurance. In addition, no change in physical activity levels was found, despite the high rate of inactivity/sedentary demonstrated.

M?todos : Estudo observacional, transversal, em pacientes com FC (6 a 18 anos) e indiv?duos saud?veis pareados na propor??o de 1:2 por sexo, idade, altura e peso. Foram realizados espirometria, oscilometria de impulso, pletismografia, manovacuometria e protocolo de endurance muscular inspirat?ria. Para an?lise de dados utilizou-se os testes t de student e a correla??o linear de Pearson. Resultados : Foram inclu?dos 34 pacientes com FC, m?dia de idade de 14,0?2,7, sendo 20 pacientes (58,8%) do sexo masculino, com m?dia de press?o inspirat?ria m?xima percentual (PIMAX%) de 118,5?25,8 e de endurance (percentual da PIMAX) de 60,9?13,3. Tamb?m foram inclu?dos 68 indiv?duos saud?veis com m?dia de PIMAX% de 105,8?18,0 e de endurance de 65,3?12,3. Os pacientes com FC apresentaram maior PIMAX% do que os saud?veis e n?o apresentaram diferen?a significativa na endurance. Ao analisar separadamente os pacientes com FC sem coloniza??o por Pseudomonas aeruginosa e com volume expirat?rio for?ado no primeiro segundo (VEF1) maior do que 80% do previsto a PIMAX% foi significativamente maior nos pacientes com FC e a endurance muscular inspirat?ria foi menor em compara??o com os saud?veis. A PIMAX se correlacionou com capacidade vital for?ada (r=0,44; p=0,01) e com VEF1 (r=0,41; p=0,01) e a endurance se correlacionou com resist?ncia total das vias a?reas (r=0,35; p=0,04) e com a resist?ncia central das vias a?reas (r=0,48; p=0,04). Conclus?o : Crian?as e adolescentes com FC apresentam altera??es da for?a e da endurance muscular inspirat?ria que s?o distintas em diferentes n?veis de comprometimento pulmonar. Al?m disso, a for?a parece estar mais relacionada com par?metros da fun??o pulmonar e a endurance com a resist?ncia das vias a?reas. Objectives : To evaluate inspiratory muscle strength and endurance in children and adolescents with cystic fibrosis (CF) in comparison with healthy subjects. Methods : This cross-sectional observational study evaluated CF patients (6 to 18 years old) and healthy subjects paired in a 1:2 proportion, for sex, age, height and weight. Spirometry, impulse oscillometry, plethysmography, manovacuometry and a protocol of inspiratory muscle endurance were performed. Data were analyzed using Student s t test and Pearson correlation coefficient. Results : Thirty four patients with CF were included in the study with a mean age of 12.6?2.9 years and twenty of them were boys (58.8%). The mean percentage of maximal inspiratory pressure (MIP%) was 118.5?25.8 and the endurance (percentage of MIP) was 60.9?13.3. Sixty eight healthy subjects were included and they presented a mean MIP% of 105.8?18.0 and an endurance of 65.3?12.3 of. CF patients had higher MIP% than healthy subjects and no significant difference in the endurance was shown. When restricting the analysis to CF patients without colonization by Pseudomonas aeruginosa and with forced expiratory volume in one second (FEV1) greater than 80% of predicted values, MIP% values were significantly higher and inspiratory muscle endurance was lower, in comparison with the control group. MIP correlated more significantly with forced vital capacity (r=0.44, p=0.01) and FEV1 (r=0.41, p=0.01), while endurance correlated better with total airway resistance (r=0.35, p=0.04) and with central airway resistance (r=0.48, p=0.04). Conclusion : Children and adolescents with CF present changes in inspiratory muscle strength and endurance that are associated differently with levels of pulmonary impairment. Furthermore, the significant strength associations are better related to pulmonary function parameters, while endurance is to airway resistance.

A administra??o de lipopolissacar?deo (LPS) no per?odo neonatal gera um est?mulo imunol?gico estressante capaz de estimular a express?o de citocinas no sistema nervoso central e causar altera??es cerebrais em certas regi?es do hipocampo de ratos adultos, al?m de ativar o eixo hipot?lamo-pituit?ria-adrenal (HPA) em neonatos. O objetivo deste estudo ? avaliar os efeitos em longo prazo da inflama??o no per?odo neonatal sobre o perfil inflamat?rio e oxidativo na sepse experimental na vida adulta. No d?cimo dia ap?s o nascimento, camundongos Balb/c receberam diferentes tratamentos: nLPS, recebeu 100 L de solu??o 100 g/Kg de LPS i.p. ou nSal em que foi administrado 100 L de solu??o salina i.p. Quando adultos, os animais foram submetidos ? administra??o i.p. de solu??o salina ou LPS e, 12 horas ap?s, foram coletados o soro para mensura??o das citocinas inflamat?rias e o f?gado para determina??o dos complexos mitocondriais e estresse oxidativo. Houve aumento do comportamento de medo/ansiedade no grupo nLPS. Os complexos II e II-III aumentaram nos machos nLPS-salina quando comparados ao controle. A administra??o de LPS nas f?meas adultas provocou uma diminui??o da atividade da enzima glutationa reduzida. N?o houve diferen?as em rela??o ?s citocinas inflamat?rias. Os resultados indicam que a inflama??o no per?odo neonatal foi efetiva na indu??o do programming. O metabolismo da cadeia respirat?ria mitocondrial parece ser influenciado pela inflama??o neonatal em animais machos. O estresse neonatal por LPS parece n?o alterar o perfil inflamat?rio das citocinas no modelo de sepse experimental. During the neonatal period, the administration of lipopolysaccharide (LPS) generates a stressful immune stimulation resulting in the expression of cytokines in the central nervous system. As result, brain changes in certain regions of the hippocampus of adult rats, as well as activation of the hypothalamic-pituitary-adrenal axis (HPA) in neonates is observed. The objective of this study is to evaluate the long-term effects of neonatal inflammation on the oxidative and inflammatory status during experimental sepsis in adult life. On day ten after birth, Balb/c mice received different treatments: nLPS, received 100 μL of a 100 μg/kg i.p. LPS solution or nSal, received 100 μL of i.p. saline solution. As adults, animals were submitted to i.p. administration of saline solution or LPS. After 12 hours, serum samples and liver were collected to measure inflammatory cytokines and to determine mitochondrial complexes and oxidative stress, respectively. There was an increase in the fear/anxiety behavior in the nLPS group. The complexes II and II-III increased in the nLPS saline group when compared to control. The LPS administration in the adult females induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results indicate that the neonatal inflammation was effective in inducing programming. The mitochondrial respiratory chain metabolism seems to be influenced by the neonatal inflammation in males. LPS neonatal stress seems not to change the cytokine inflammatory profile in an experimental model of sepsis

Objetivos : Avaliar as poss?veis altera??es posturais e a distribui??o das press?es plantares em pacientes com FC. Al?m disso, buscou-se avaliar os efeitos de um programa de orienta??es para a pr?tica de exerc?cio f?sico em crian?as e adolescentes com FC. M?todo : Este estudo foi dividido em duas fases, sendo realizado em um centro de FC com crian?a e adolescentes entre sete e 20 anos. A primeira fase constitui um estudo de corte transversal, em que indiv?duos saud?veis foram selecionados com objetivo de obter um padr?o de normalidade para avalia??o postural e baropodometria visando ? compara??o com pacientes com FC. Na segunda fase, foi realizado um ensaio clinico controlado e randomizado, de orienta??es para o exerc?cio f?sico a partir dos resultados obtidos na fase I. Os pacientes foram alocados em dois grupos, sendo 17 no grupo controle (G1) e 17 no grupo interven??o (G2). A interven??o utilizada foi um manual de orienta??es com exerc?cios f?sicos aer?bicos e alongamentos. Para an?lise de dados utilizou-se o teste de Kolmogorov-Smirnov e o teste t de student . O tamanho de efeito (TE) foi calculado utilizando-se a ferramenta Effect Size Calculator, considerando-se n?vel de signific?ncia de 5%. Resultados : Na fase I foram inclu?das 34 crian?as e adolescentes com FC, m?dia de idade de 12,6?2,9 anos, sendo 20 pacientes (58,8%) do sexo masculino. Para o pareamento, foram inclu?das 34 crian?as saud?veis, com m?dia de idade de 12,8?3,3. Como esperado, n?o houve diferen?a significativa entre os grupos quanto ? caracteriza??o da amostra. Crian?as com FC apresentaram maiores desvios posturais em compara??o com crian?as saud?veis. Foram observadas diferen?as significativas quanto ao alinhamento da cabe?a (p=0,001), cintura escapular (p=0,015) e pelve (p=0,001), assim como aumento da lordose cervical (p=0,001) e dist?ncia latero-lateral do t?rax ( p=0,002). Crian?as com FC tamb?m apresentaram maiores graus de cifose tor?cica, embora essa diferen?a n?o tenha sido significativa (p=0,068). Os resultados da baropodometria n?o demonstraram diferen?as estatisticamente significativas. Na fase II (n= 34), n?o houve diferen?as na avalia??o inicial entre os grupos interven??o e controle. Por outro lado, os resultados demonstram que a interven??o provocou uma diminui??o na lordose cervical (p=0,0003; TE=1,41), na cifose tor?cica (p=0,01; TE=0,89), na lordose lombar (p=0,05; TE=0,71), na dist?ncia lateral do t?rax (p=0,01; TE=0,91) e na protus?o abdominal (p=0,04; TE=0,75). Na avalia??o baropodom?trica, houve diferen?a significativa na press?o m?dia (p=0,001; TE=1,25) e na ?rea de contato (p=0,01; TE=1,02). Conclus?o : Crian?as e adolescentes com FC apresentam altera??es posturais quando comparados com indiv?duos saud?veis. Al?m disso, o estudo demonstrou que a orienta??o para a pr?tica de exerc?cios contribui para a melhora da postura em crian?as e adolescentes com FC, evitando a progress?o de algumas desordens posturais. Objectives : To evaluate possible postural changes and the distribution of plantar pressures in patients with CF. Furthermore, were sought to evaluate the effects of an educational guideline for physical activity in children and adolescents with CF. Method : This study was divided into two phases, being held in a CF center with children and adolescents between seven and 20 years. The first phase is a cross-sectional study in which healthy subjects were selected in order to obtain a normality pattern for postural assessment and baropodometry, aiming to later comparison with patients CF. In the second phase, we performed a randomized controlled clinical trial to access the influence of the exercise guideline on the postural alterations seen in the results of phase I. Patients were assigned to two groups, 17 in the control group (G1) and 17 in the intervention group (G2). The intervention evaluated consisted of a manual with instructions for aerobic exercise and stretching. Data was analyzed using the Kolmogorov-Smirnov and the student t test. The effect size was calculated using the Effect Size Calculator tool, considering a significance level of 5%. Results : In phase I, thirty four patients with CF were included in the study with a mean age of 12.6?2.9 years and twenty of them were boys (58.8%). Thirty four healthy children with a mean age of 12.8?3.3 years were selected and paired to the CF patients. No significant baseline differences between groups were identified, as expected. CF children presented more postural deviations compared to healthy subjects. Significant differences were observed as to alignment of the head (p=0.001), shoulder girdle (p=0.015) and pelvis (p=0.001), as well as increased cervical lordosis (p=0.001) and lateral chest distance (p=0.002). Children with CF also showed higher degrees of thoracic kyphosis, although this difference was not significant (p=0.068). No significant differences were demonstrated in the baropodometry. In phase II (n=34), there were no baseline differences between both intervention and control groups. On the other hand, results demonstrate that the intervention caused a decrease in cervical lordosis (p=0.0003; ES=1.41), thoracic kyphosis (p=0.01; ES=0.89), lumbar lordosis (p=0.05; ES=0.71), lateral chest distance (p=0.01; ES=0.91) and abdominal protrusion (p=0.04; ES=0.75). In the baropodometric evaluation, there were significant differences in the mean pressure (p=0.001; ES=1.25) and in the contact area (p=0.01; ES=1.02). Conclusions : CF children and adolescents present postural changes when compared to healthy individuals. Furthermore, the study demonstrated that the educational guideline for exercise practice helped to improve posture in children and adolescents with CF, preventing the progression of some postural disorders.

Introdu??o : O per?odo pr?-natal ? de suma import?ncia para o desenvolvimento e a matura??o de diversos sistemas e ?rg?os essenciais. Objetivo : Avaliar os efeitos do estresse pr?-natal sobre as respostas comportamentais, assim como poss?veis altera??es estruturais e do padr?o celular no pulm?o em um modelo experimental com camundongos Balb/c. Materiais e M?todos: Foram utilizadas f?meas Balb/c prim?paras. Ap?s a identifica??o da prenhez, os animais foram divididos em 3 grupos: CTLE (controle), PNS 1 (estresse em dias intercalados a partir do 8? dia da prenhez) e PNS 2 (estresse a partir do 15? dia da prenhez at? o nascimento). O estresse pr?-natal foi realizado atrav?s de conten??o. Os animais foram pesados ao nascimento, dia 10 e no desmame (dia 21). Quando adultos, foram analisados o comportamento de medo/ansiedade por meio dos testes de campo aberto (CA) e labirinto em cruz elevada (LCE) e foi realizado lavado broncoalveolar (LBA) e an?lise histopatol?gica do pulm?o. Resultados : N?o foram encontradas diferen?as em rela??o ao peso dos animais entre os tr?s grupos. A an?lise comportamental dos machos no teste do CA e LCE, n?o apresentou diferen?a significativa entre os grupos PNS 1 e PNS 2 em rela??o ao CTLE. Na an?lise do teste CA, as f?meas do grupo PNS 1 apresentaram uma diminui??o da dist?ncia total percorrida (p

A avalia??o da for?a muscular respirat?ria ? um m?todo n?o invasivo e de f?cil aplicabilidade, utilizado para a mensura??o da press?o inspirat?ria m?xima (PIMAX) e da press?o expirat?ria m?xima (PEMAX). No entanto, ainda n?o existem valores de refer?ncia para crian?as em idade pr?-escolar, impossibilitando a normaliza??o dos resultados obtidos e dificultando a avalia??o da fun??o muscular respirat?ria. Assim, o objetivo deste estudo foi gerar valores de refer?ncia para a for?a muscular respirat?ria em crian?as e adolescentes saud?veis de tr?s a doze anos de idade. Os participantes foram recrutados atrav?s de tr?s escolas e selecionados ap?s an?lise do question?rio de doen?as respirat?rias e assinatura do termo de consentimento pelos pais ou respons?veis. Todos os participantes inclu?dos no estudo possu?am exame espirom?trico normal e medidas de peso e altura no dia da mensura??o. A avalia??o da for?a muscular respirat?ria foi realizada por um ?nico avaliador seguindo as diretrizes para testes de fun??o pulmonar. A associa??o entre os valores de PIMAX e PEMAX com as potenciais vari?veis preditoras foram analizadas utilizando-se um modelo de regress?o linear m?ltipla. Um total de 171 participantes foram selecionados e distribu?dos uniformemente por faixa et?ria. A idade, altura, peso e CVF apresentaram correla??es de moderada ? forte com ambas as press?es respirat?rias. No entanto, o modelo de regress?o demonstrou que a altura e o peso foram as melhores vari?veis para predi??o da PIMAX em ambos os sexos e o peso e a idade para a PEMAX. A for?a de predi??o (R2) variou de 46 a 58%. O coeficiente de correla??o intraclasse foi utilizado em um subgrupo e demonstrou excelente reprodutibilidade entre os testes. Em conclus?o, os resultados do presente estudo demonstram que o comportamento da for?a muscular respirat?ria em pr?-escolares e escolares saud?veis pode ser explicado em fun??o da idade, altura e peso. The evaluation of respiratory muscle strength is a noninvasive and easily applicable method, used for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). However, there are no reference values for children in preschool age, which makes it difficult to standardize the results and complicates the assessment of respiratory muscle function. Thus, the objective of present study was to generate reference values for respiratory muscle strength in healthy children and adolescents aged between three to twelve years old. Participants were recruited from three schools and selected after a respiratory disease questionnaire analysis and attainment of informed and written consent by parents or guardians. All participants included in the study had normal spirometry and measures of height and weight were performed in the same day. The evaluation of respiratory muscle strength was performed by a single examiner following the guidelines for pulmonary function tests. The association between MIP and MEP values with the potential predictive variables was analyzed using a multiple linear regression model. A total of 171 participants were selected and distributed evenly by age. The age, height, weight and FVC showed moderate to strong correlations with both respiratory pressures. However, the regression model showed that the height and weight were the best variables to predict MIP in both sexes and age and weight to predict MEP. The power of prediction (R2) ranged from 46 to 58%. The intraclass correlation coefficient was used in a subgroup and demonstrated an excellent reproducibility between tests. In conclusion, the results of present study demonstrate that the behavior of respiratory muscle strength in healthy preschool and school children can be explained by age, height and weight.

Background: Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer is challenging. This study evaluated the activity and safety of a combination of cisplatin and capecitabine in this setting. Patients and Methods: Thirty-nine consecutive patients entered the study. All had experienced failures or relapse after previous treatment with anthracyclines and taxanes plus/minus other chemotherapeutic regimens. The present treatment consisted of intravenous cisplatin 20 mg/m2 every week for 6 weeks, followed by 1 week of rest, and oral capecitabine 1,000 mg/m2 twice daily for 14 days, followed by a 7-day rest period. Results: Objective response was obtained in 14 patients (35.9%), with complete remission in 3 (7.7%). Median time to progression was 5.2 months and survival was 10.9 months in the entire population and 8.7 and 16.5 months in the responding patients, respectively. The dose-limiting toxicity for the regimen was leucopenia, while gastrointestinal discomfort was the most frequent cause of capecitabine reduction or delay. Conclusions: The cisplatin and capecitabine combination regimen is active and manageable. It seems to be non-cross resistant to anthracyclines and taxanes.