In the mammalian genome, 5‟-CpG-3‟ dinucleotides are frequently methylated, correlating with transcriptional silencing. Genome-wide waves of demethylation are thought to occur only twice during development, in primordial germ cells and in the pre-implantation embryo. They are followed by de novo methylation, setting up a pattern that is inherited throughout development. No global methylation changes are thought to occur during further somatic development, although methylation does alter at gene-specific loci, contributing to tissue-specific patterns of gene expression. Here we studied DNA methylation in differentiating mouse erythroblasts in vivo using several approaches including genomic-scale, reduced representation bisulfite sequencing (RRBS). Surprisingly, demethylation at the erythroid-specific β-globin locus was coincident with a wave of global DNA demethylation at most genomic elements, including repetitive elements and genes silenced in erythropoiesis. Over 30% of total methylation is irreversibly lost during erythroid differentiation. Demethylation occurred through a passive mechanism, requiring the rapid DNA replication triggered with the onset of erythroid terminal differentiation. Global loss of DNA methylation was not associated with a global increase in transcription, as determined by GeneChip analysis. We propose that global demethylation is a consequence of cellular mechanisms required for the rapid demethylation and induction of β-globin and other erythroid genes. Our findings demonstrate that, contrary to previously held dogma, DNA demethylation can occur globally during somatic cell differentiation, providing a new experimental model for the study of global demethylation in development and disease.

<p><strong>Introduction</strong></p> <p>The airway epithelium, which acts as a protective barrier, is impaired in asthmatic patients and may contribute to abnormal airway function. Chronic inflammation, a feature of asthma, is associated with structural changes in the airway epithelium including the transformation of columnar epithelial cells into mucin secreting goblet cells. Human epithelial cells exposed to Interleukin-13 (IL-13) <em>in vitro</em> resulted in goblet cell metaplasia and a significant drop in transepithelial resistance, indicating that barrier function is impaired.</p> <p><strong>Aim</strong></p> <p>We sought to determine whether goblet cell metaplasia alone is sufficient to impair airway epithelial barrier function <em>in vivo</em>.</p> <p><strong>Methods</strong></p> <p>Female BALB/c mice were infected with an adenovirus to overexpress IL-13, a control adenovirus, or no virus. Barrier integrity was assessed via single-photon emission computed tomography (SPECT) imaging by measuring the dispersion of technetium-labeled diethylene triamine pentaacetic acid (^99mTc-DTPA) out of the lungs over time. Lung sections were stained by Periodic acid-Schiff to detect the presence of mucin-containing goblet cells.</p> <p><strong>Results</strong></p> <p>IL-13 exposure resulted in goblet cell metaplasia and associated airway hyperresponsiveness to methacholine. However, there was no significant increase in dispersion of ^99mTc-DTPA over time from the airways in IL-13 overexpressed mice compared to control mice.</p> <p><strong>Conclusion</strong></p> <p>IL-13 induced goblet cell metaplasia did not impair the airway epithelial barrier to ^99mTc-DTPA in our <em>in vivo</em> mouse model. Therefore, we conclude that epithelial dysfunction to DTPA observed in human asthmatics and in animal models of asthma are not due to IL-13 induced goblet cell metaplasia.</p> / Master of Science (MSc)

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers. Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such as infections and certain medications, consequently leading to false positive diagnoses and unnecessary concern and over treatment with dire outcomes for the patient. Even worse, are the chances of false negative diagnoses, which result in prostate cancer not being diagnosed until its later stages. Therefore, although the use of the PSA level has had its uses in the clinic, it has failed to sufficiently bridge the gap or to distinguish indolent from aggressive disease. It has long been suggested in the literature that microRNAs are drastically altered throughout the course of cancer progression. Here, RNA sequencing was used to identify changes in miR expression profiles diagnostic for prostate cancer patients compared to non-patient controls. The RNA sequencing results were also used to identify normalization miRs to be used as endogenous controls. Confirmatory qRT-PCR was then used to corroborate these results for the top seven dysregulated miRs found from the RNA sequencing data. Data analysis of the Area Under the Curve (AUC) of the Receiver Operating Curves (ROC) of the selected miRs exhibited a better correlation with prostate cancer (AUC Range= 0.819- 0.950) than PSA (AUC of PSA=0.667). In summary, a panel of seven miRs are proposed, many of which have prostate specific targets, which would represent a significant improvement over current testing methods.

Introdução: A assistência ventilatória adequada é imprescindível para o tratamento do paciente ventilado artificialmente. A busca por parâmetros para realizar o ajuste ótimo e que tenham aplicação fácil a beira leito como, por exemplo, métodos não-invasivos, são desejáveis. Objetivo: analisar a acurácia diagnóstica das variáveis do padrão respiratório, da P0.1 esofágica e traqueal, para o ajuste da assistência ventilatória em pressão de suporte. Métodos: Vinte e sete pacientes internados em unidade de terapia intensiva foram consecutivamente incluídos no estudo. Todos pacientes estavam no modo de pressão de suporte, que foi aumentada para 20 cmH2O e diminui em passos de 3 cmH2O, até 2 cmH2O ou antes se o paciente apresentasse sinais de desconforto respiratório. Os pacientes foram monitorizados com cateteres para medidas de pressão esofágica e gástrica, com uma peça proximal ao tubo para mensurar a pressão traqueal a partir da oclusão da via aérea e com um pneumotacógrafo para medidas de fluxo. Durante todos níveis de suporte, foram gravados os dados dos cateteres esofágicos, gástricos, da traquéia, dados hemodinâmicos e do padrão respiratório. O ajuste da assistência ventilatória foi classificado como adequado, insuficiente e excessivo de acordo com critérios pré-estabelecidos. Resultados: Foram analisados 210 períodos com diferentes pressões de suporte e em 49% destes períodos a assistência foi excessiva, enquanto em 3,8% a assistência foi insuficiente. No início do estudo, enquanto os pacientes ainda estavam com a assistência ventilatória ajustada pela equipe assistente, 48,2% apresentavam assistência ventilatória excessiva. Pela pequena incidência de períodos com assistência ventilatória insuficiente, não foi avaliado a acurácia das variáveis para diagnóstico de assistência insuficiente. Para diagnosticar assistência ventilatória excessiva, a variável do padrão respiratório que se mostrou mais acurada foi a frequência respiratória, com sensibilidade de 90% e especificidade de 88% quando a frequência respiratória foi menor que 17 incursões por minuto. Outras variáveis do padrão respiratório não mostraram elevada acurácia. Também para o diagnóstico de assistência excessiva, foi elevada a acurácia da P0.1 esofágica (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 1,9) e da P0.1 traqueal (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 2,1). Conclusão: A ocorrência de assistência ventilatória excessiva foi significativamente maior que a assistência ventilatória insuficiente. A frequência respiratória menor que 17 foi a variável do padrão respiratório com maior acurácia para diagnosticar assistência ventilatória excessiva. As P0.1 esofágica e traqueal também tiveram acurácia elevas, mas menores que a frequência respiratória . / Introdution: The adequate assistance is essential for the treatment of mechanically ventilated patient. The search of parameters to achieve the optimal adjustment and with easy application to bedside, for example, non-invasive methods. Objective: Analyze the diagnostic accuracy of the breathing pattern variables, esophageal and tracheal P0.1 for adjustment of mechanical ventilation in pressure support ventilation. Methods: Twenty-seven patients in intensive care unit were consecutively included in the study. All patients were in the pressure support mode, which was raised to 20 cmH2O and decreased in steps of 3 cmH2O up to 2 cmH2O or earlier if the patient had signs of respiratory distress. Patients were monitored with catheters for esophageal and gastric pressure measurements, with the T-piece was used close to the tube to measure tracheal pressure during an airway occlusion and a pneumotachograph for flow measurements. Data was recorded for all support levels to esophageal, gastric, and tracheal pressures, also hemodynamic data and ventilatory pattern. The adjustment of mechanical ventilation was classified as adequate assistance, overassistance and underassistance according to pre-established criteria. Results: Two hundred and ten periods were analyzed with different pressures of support and 49% of these periods were overassistance, while 3,8% these periods were underassistance. At baseline, while patients were still ventilatory assistance set by assistance staff, 48,2% had overassistance. Due to the low incidence of periods with underassistance, the variables accurancy has not been evaluated. The variable breathing pattern that was more accurate diagnosing overassistance was the respiratory rate (90% sensitivity and specificity of 88 % when the respiratory rate was less than 17 breaths per minute). Other variables of the breathing pattern did not show high accuracy although esophageal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 1,9) and tracheal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 2,1) were high accuracy diagnosing overassistance. Conclusion: The occurrence of overassistance was significantly higher than underassistance. The respiratory rate below 17 was the variable breathing pattern more accurate to predict overassistance. The esophageal and tracheal P0.1 also had high accuracy but lower than the respiratory rate

Le maintien de la PCO2 et du pH du sang artériel est vital. Le principal mécanisme de cette régulation, chez les mammifères, est le chémoréflexe respiratoire central au CO2, une hyperventilation en réponse à l’hypercapnie, dont les bases neurales sont l’enjeu d’un débat persistant. Notre travail s’intéresse aux rôles supposés d’un groupe d’interneurones du niveau facial du tronc cérébral, le « noyau rétrotrapézoïde », dans le chémoréflexe au CO2 et l’accélération du rythme respiratoire autour de la naissance. Notre approche est inspirée par la symptomatologie respiratoire du syndrome d’Ondine ou CCHS (apnées et abrogation du chémoréflexe) et son gène causal, codant le facteur de transcription Phox2b, exprimé par les neurones du RTN. Nous avons disséqué le rôle du RTN dans le chémoréflexe central en étudiant les propriétés anatomiques et fonctionnelles in vitro chez l’embryon, et in vivo chez l’animal postnatal, de modèles murins - perte et gain de fonction –ciblant le RTN de la manière la plus sélective possible par génétique intersectionnelle. Ces modèles sont basés (i) sur l’historique d’expression des facteurs de transcription Phox2b, Lbx1, Atoh1 spécifiant les neurones du RTN au cours du développement et (ii) sur la transposition, chez la souris, de mutations humaines, Phox2b27Ala/+ et Lbx1fs/fs affectant ces facteurs, et qui sont respectivement, diagnostique, et proposé comme telle, du CCHS. L’ensemble des mutants étudiés récapitulent chez la souris, des traits phénotypiques exclusifs chez l’embryon et à la naissance: l’abrogation anatomique du RTN, le ralentissement du rythme respiratoire et la perte complète du chémoréflexe. Nos travaux montrent donc que le RTN est un composant obligatoire du circuit chémoréflexe. Nous montrons de plus, que le chémoréflexe n’est pas requis pour la survie des souriceaux à la naissance, cette dernière pourrait être liée au déficit conjoint d’une autre structure de même identité que le RTN, son homologue segmentaire au niveau trigéminal du tronc cérébral: le groupe péri-trigéminal. / The maintenance of PCO2 and pH in arterial blood is vital. The principal mechanism through which this is achieved in mammals is the respiratory chemoreflex, a hyperventilation response to hypercapnia, whose circuitry is still elusive and the matter of a persistent debate. Our work deals with the putative roles of a group of interneurons at facial level of the brainstem, the “retrotrapezoïd nucleus”, in the CO2 chemoreflex and in the acceleration of breathing around birth. Our approach is inspired by the respiratory symptoms of Ondine’s curse or CCHS (apneas and abrogation of the chemoreflex) and its causal gene, encoding the transcription facteur Phox2b, expressed in RTN neurons. We have dissected the role of the RTN by studying the anatomical and functional properties in vitro in embryos and in vivo at birth and postnatally, of gain and loss of function mutant mouse models, as selective as possible towards the RTN through intersectional strategies. Our models are based (i) on the history of expression of the transcription factors Phox2b, Lbx1, Atoh1 that specify RTN neurons during development and (ii) on the transfer into the mouse of the human mutations Phox2b27Ala/+ and Lbx1fs/fs that target these factors and are respectively diagnostic and candidate diagnostic for CCHS. Compoundly, the mutants recapitulate exclusive phenotypic traits in the embryo and at birth: anatomical abrogation of the RTN, a slowed down respiratory rhythm and the complete loss of chemoreflex. Our work demonstrates that the RTN is an obligatory component of the chemoreflex circuit. Furthermore, we show that the chemoreflex is not required for survival at birth and that the latter may be put at risk by the joint deficiency of another structure sharing the same molecular identity with the RTN, in fact its segmental homologue at trigeminal level of the brainstem: the peri-trigeminal group.

Introdução: A assistência ventilatória adequada é imprescindível para o tratamento do paciente ventilado artificialmente. A busca por parâmetros para realizar o ajuste ótimo e que tenham aplicação fácil a beira leito como, por exemplo, métodos não-invasivos, são desejáveis. Objetivo: analisar a acurácia diagnóstica das variáveis do padrão respiratório, da P0.1 esofágica e traqueal, para o ajuste da assistência ventilatória em pressão de suporte. Métodos: Vinte e sete pacientes internados em unidade de terapia intensiva foram consecutivamente incluídos no estudo. Todos pacientes estavam no modo de pressão de suporte, que foi aumentada para 20 cmH2O e diminui em passos de 3 cmH2O, até 2 cmH2O ou antes se o paciente apresentasse sinais de desconforto respiratório. Os pacientes foram monitorizados com cateteres para medidas de pressão esofágica e gástrica, com uma peça proximal ao tubo para mensurar a pressão traqueal a partir da oclusão da via aérea e com um pneumotacógrafo para medidas de fluxo. Durante todos níveis de suporte, foram gravados os dados dos cateteres esofágicos, gástricos, da traquéia, dados hemodinâmicos e do padrão respiratório. O ajuste da assistência ventilatória foi classificado como adequado, insuficiente e excessivo de acordo com critérios pré-estabelecidos. Resultados: Foram analisados 210 períodos com diferentes pressões de suporte e em 49% destes períodos a assistência foi excessiva, enquanto em 3,8% a assistência foi insuficiente. No início do estudo, enquanto os pacientes ainda estavam com a assistência ventilatória ajustada pela equipe assistente, 48,2% apresentavam assistência ventilatória excessiva. Pela pequena incidência de períodos com assistência ventilatória insuficiente, não foi avaliado a acurácia das variáveis para diagnóstico de assistência insuficiente. Para diagnosticar assistência ventilatória excessiva, a variável do padrão respiratório que se mostrou mais acurada foi a frequência respiratória, com sensibilidade de 90% e especificidade de 88% quando a frequência respiratória foi menor que 17 incursões por minuto. Outras variáveis do padrão respiratório não mostraram elevada acurácia. Também para o diagnóstico de assistência excessiva, foi elevada a acurácia da P0.1 esofágica (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 1,9) e da P0.1 traqueal (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 2,1). Conclusão: A ocorrência de assistência ventilatória excessiva foi significativamente maior que a assistência ventilatória insuficiente. A frequência respiratória menor que 17 foi a variável do padrão respiratório com maior acurácia para diagnosticar assistência ventilatória excessiva. As P0.1 esofágica e traqueal também tiveram acurácia elevas, mas menores que a frequência respiratória . / Introdution: The adequate assistance is essential for the treatment of mechanically ventilated patient. The search of parameters to achieve the optimal adjustment and with easy application to bedside, for example, non-invasive methods. Objective: Analyze the diagnostic accuracy of the breathing pattern variables, esophageal and tracheal P0.1 for adjustment of mechanical ventilation in pressure support ventilation. Methods: Twenty-seven patients in intensive care unit were consecutively included in the study. All patients were in the pressure support mode, which was raised to 20 cmH2O and decreased in steps of 3 cmH2O up to 2 cmH2O or earlier if the patient had signs of respiratory distress. Patients were monitored with catheters for esophageal and gastric pressure measurements, with the T-piece was used close to the tube to measure tracheal pressure during an airway occlusion and a pneumotachograph for flow measurements. Data was recorded for all support levels to esophageal, gastric, and tracheal pressures, also hemodynamic data and ventilatory pattern. The adjustment of mechanical ventilation was classified as adequate assistance, overassistance and underassistance according to pre-established criteria. Results: Two hundred and ten periods were analyzed with different pressures of support and 49% of these periods were overassistance, while 3,8% these periods were underassistance. At baseline, while patients were still ventilatory assistance set by assistance staff, 48,2% had overassistance. Due to the low incidence of periods with underassistance, the variables accurancy has not been evaluated. The variable breathing pattern that was more accurate diagnosing overassistance was the respiratory rate (90% sensitivity and specificity of 88 % when the respiratory rate was less than 17 breaths per minute). Other variables of the breathing pattern did not show high accuracy although esophageal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 1,9) and tracheal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 2,1) were high accuracy diagnosing overassistance. Conclusion: The occurrence of overassistance was significantly higher than underassistance. The respiratory rate below 17 was the variable breathing pattern more accurate to predict overassistance. The esophageal and tracheal P0.1 also had high accuracy but lower than the respiratory rate

Introdução: O envelhecimento está associado com a diminuição de uma série de funções, incluindo a função pulmonar, a variabilidade da freqüência cardíaca, o barorreflexo espontâneo, a qualidade de vida e de sono, assim como com o aumento de níveis de estresse. Estudos recentes sugerem que os exercícios respiratórios do Yoga podem melhorar as funções respiratória e cardiovascular, além de aumentar a qualidade de vida e de sono e reduzir os sintomas de estresse em populações de pacientes com doença pulmonar. A hipótese testada no presente trabalho é de que o treinamento respiratório do Yoga pode melhorar a função respiratória, a variabilidade da freqüência cardíaca, a qualidade de vida e de sono e os sintomas de estresse de idosos saudáveis. Objetivo: Investigar os efeitos do treinamento de técnica respiratória do Yoga na função pulmonar, na variabilidade da freqüência cardíaca e no barorreflexo espontâneo, assim como na qualidade de vida, na qualidade de sono e nos sintomas de estresse de idosos saudáveis. Métodos: Vinte e nove voluntários idosos saudáveis (idade: 68±6 anos, homens: 34%, índice de massa corporal=25±3 kg/m2) foram aleatorizados para 4 meses de treinamento constituído por 2 aulas/semana, acrescidas de exercícios em casa 2 vezes por dia de alongamento (Controle, n=14) ou exercícios respiratórios (Yoga, n=15). Os exercícios respiratórios do Yoga (bhastrika) são constituídos de uma seqüência de exercícios que se iniciam por expirações rápidas e forçadas (kapalabhati), seguidas por inspiração pela narina direita, apnéia inspiratória com a geração de pressão negativa intratorácica e expiração pela narina esquerda (surya bedhana). Foram realizadas medidas de função pulmonar, pressões expiratória e inspiratória máximas (PEmax e PImax, respectivamente), variabilidade da freqüência cardíaca e da pressão arterial para a determinação do barorreflexo espontâneo no início do estudo (basal) e ao final, após 4 meses de treinamento (4 meses). Também foram aplicados questionários de qualidade de vida, qualidade de sono e sintomatologia de estresse no início e no final do estudo. Resultados: Os indivíduos de ambos os grupos foram semelhantes quanto aos parâmetros demográficos. As variáveis fisiológicas não se alteraram após 4 meses no grupo controle. No grupo Yoga, houve um aumento significante na PEmax (34%, p<0.0001) e na PImax (26%, p<0.0001), assim como também houve uma diminuição significante no componente de baixa freqüência (marcador da modulação simpática cardíaca) e uma diminuição significante da razão baixa freqüência/alta freqüência (marcador do equilíbrio simpatovagal) da variabilidade da freqüência cardíaca (40%, p<0.001). A sensibilidade do barorreflexo espontâneo não se alterou no grupo Yoga. Ocorreram aumentos marginais no grupo Yoga, que não atingiram significância estatística na qualidade de vida e nos sintomas de estresse. Não houve alteração da qualidade de sono. Conclusão: O treinamento respiratório do Yoga pode ser benéfico para a população idosa saudável, pois pode melhorar a fisiologia respiratória e o equilíbrio simpatovagal / Introduction: Aging is associated with a decline of many functions, including pulmonary function, heart rate variability, spontaneous baroreflex, quality of life, quality of sleep, and with the increase of stress symptoms. Recent studies suggest that Yoga respiratory exercises may improve respiratory and cardiovascular function, increase quality of life, quality of sleep and decrease stress symptoms in patients with pulmonary disease. The hypothesis tested in the present study is that Yoga respiratory training may improve respiratory function, heart rate variability, quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Objective: To investigate the effects of a respiratory Yoga training on respiratory function, heart rate variability and spontaneous baroreflex, as well as on quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Methods: Twenty-nine healthy elderly volunteers (age: 68±6 years, males: 34%, body mass index=25±3 kg/m2) were randomized into a 4-month training program composed of 2 classes/week plus home exercises twice a day of either stretching (Control, n=14) or respiratory exercises (Yoga, n=15). Yoga respiratory exercises (bhastrika) are composed by a sequence of exercises which begins with rapid forced expirations (kapalabhati), followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril (surya bedhana). Pulmonary function test, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate and blood pressure variability for spontaneous baroreflex determination were measured at baseline and after 4 months. Quality of life, quality of sleep, and stress symptoms questionnaires were also applied in the beginning and at the end of the study. Results: Subjects from both groups were similar for demographic parameters. Physiological variables did not change after 4 months in the Control group. In the Yoga group, there was a significant increase in PEmax (34%, p<0.0001) and in PImax (26%, p<0.0001), and a significant decrease in the low-frequency component (marker of cardiac sympathetic modulation) and a significant decrease in low frequency/high frequency (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex sensitivity did not change in the Yoga group. There were only marginal increases in quality of life, and in stress symptoms in the Yoga group, with no statistical significance, and no changes in quality of sleep. Conclusion: Respiratory Yoga training may be beneficial to the elderly healthy population, for it may improve respiratory physiology and sympathovagal balance

Introdução: O envelhecimento está associado com a diminuição de uma série de funções, incluindo a função pulmonar, a variabilidade da freqüência cardíaca, o barorreflexo espontâneo, a qualidade de vida e de sono, assim como com o aumento de níveis de estresse. Estudos recentes sugerem que os exercícios respiratórios do Yoga podem melhorar as funções respiratória e cardiovascular, além de aumentar a qualidade de vida e de sono e reduzir os sintomas de estresse em populações de pacientes com doença pulmonar. A hipótese testada no presente trabalho é de que o treinamento respiratório do Yoga pode melhorar a função respiratória, a variabilidade da freqüência cardíaca, a qualidade de vida e de sono e os sintomas de estresse de idosos saudáveis. Objetivo: Investigar os efeitos do treinamento de técnica respiratória do Yoga na função pulmonar, na variabilidade da freqüência cardíaca e no barorreflexo espontâneo, assim como na qualidade de vida, na qualidade de sono e nos sintomas de estresse de idosos saudáveis. Métodos: Vinte e nove voluntários idosos saudáveis (idade: 68±6 anos, homens: 34%, índice de massa corporal=25±3 kg/m2) foram aleatorizados para 4 meses de treinamento constituído por 2 aulas/semana, acrescidas de exercícios em casa 2 vezes por dia de alongamento (Controle, n=14) ou exercícios respiratórios (Yoga, n=15). Os exercícios respiratórios do Yoga (bhastrika) são constituídos de uma seqüência de exercícios que se iniciam por expirações rápidas e forçadas (kapalabhati), seguidas por inspiração pela narina direita, apnéia inspiratória com a geração de pressão negativa intratorácica e expiração pela narina esquerda (surya bedhana). Foram realizadas medidas de função pulmonar, pressões expiratória e inspiratória máximas (PEmax e PImax, respectivamente), variabilidade da freqüência cardíaca e da pressão arterial para a determinação do barorreflexo espontâneo no início do estudo (basal) e ao final, após 4 meses de treinamento (4 meses). Também foram aplicados questionários de qualidade de vida, qualidade de sono e sintomatologia de estresse no início e no final do estudo. Resultados: Os indivíduos de ambos os grupos foram semelhantes quanto aos parâmetros demográficos. As variáveis fisiológicas não se alteraram após 4 meses no grupo controle. No grupo Yoga, houve um aumento significante na PEmax (34%, p<0.0001) e na PImax (26%, p<0.0001), assim como também houve uma diminuição significante no componente de baixa freqüência (marcador da modulação simpática cardíaca) e uma diminuição significante da razão baixa freqüência/alta freqüência (marcador do equilíbrio simpatovagal) da variabilidade da freqüência cardíaca (40%, p<0.001). A sensibilidade do barorreflexo espontâneo não se alterou no grupo Yoga. Ocorreram aumentos marginais no grupo Yoga, que não atingiram significância estatística na qualidade de vida e nos sintomas de estresse. Não houve alteração da qualidade de sono. Conclusão: O treinamento respiratório do Yoga pode ser benéfico para a população idosa saudável, pois pode melhorar a fisiologia respiratória e o equilíbrio simpatovagal / Introduction: Aging is associated with a decline of many functions, including pulmonary function, heart rate variability, spontaneous baroreflex, quality of life, quality of sleep, and with the increase of stress symptoms. Recent studies suggest that Yoga respiratory exercises may improve respiratory and cardiovascular function, increase quality of life, quality of sleep and decrease stress symptoms in patients with pulmonary disease. The hypothesis tested in the present study is that Yoga respiratory training may improve respiratory function, heart rate variability, quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Objective: To investigate the effects of a respiratory Yoga training on respiratory function, heart rate variability and spontaneous baroreflex, as well as on quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Methods: Twenty-nine healthy elderly volunteers (age: 68±6 years, males: 34%, body mass index=25±3 kg/m2) were randomized into a 4-month training program composed of 2 classes/week plus home exercises twice a day of either stretching (Control, n=14) or respiratory exercises (Yoga, n=15). Yoga respiratory exercises (bhastrika) are composed by a sequence of exercises which begins with rapid forced expirations (kapalabhati), followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril (surya bedhana). Pulmonary function test, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate and blood pressure variability for spontaneous baroreflex determination were measured at baseline and after 4 months. Quality of life, quality of sleep, and stress symptoms questionnaires were also applied in the beginning and at the end of the study. Results: Subjects from both groups were similar for demographic parameters. Physiological variables did not change after 4 months in the Control group. In the Yoga group, there was a significant increase in PEmax (34%, p<0.0001) and in PImax (26%, p<0.0001), and a significant decrease in the low-frequency component (marker of cardiac sympathetic modulation) and a significant decrease in low frequency/high frequency (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex sensitivity did not change in the Yoga group. There were only marginal increases in quality of life, and in stress symptoms in the Yoga group, with no statistical significance, and no changes in quality of sleep. Conclusion: Respiratory Yoga training may be beneficial to the elderly healthy population, for it may improve respiratory physiology and sympathovagal balance

Atherosclerosis, characterized by the build-up of cholesterol, immune cells and cellular debris within arterial walls, is accelerated following myocardial infarction by poorly understood mechanisms. Ubiquitin, a small, well-studied intracellular protein involved in protein turnover via the proteasome pathway, has recently been shown to exert extracellular effects on cardiac myocytes, in vitro, and in mice undergoing myocardial remodeling. This study investigates the potential role of extracellular ubiquitin in atherosclerosis by determining its effects on two critical atherosclerotic processes: the migration of vascular smooth muscles cells and the uptake of modified LDL by monocyte/macrophages in foam cell formation. In the presence of ubiquitin, smooth muscle cell migration was accelerated and foam cell formation was enhanced, suggesting that ubiquitin has an active role in atherosclerosis.

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting blood glucose, and attenuated cardiac diastolic dysfunction after WD compared to wild-type mice. Collectively, the metabolic and cardiac phenotypes of NCCKO mice resembled that of the IL-18KO mice, indicating that NCC may mediate IL-18 signaling in a mouse model of diet-induced obesity and cardiac dysfunction.