RNA binding properties of the US11 protein from four primate simplexviruses

<p>Abstract</p> <p>Background</p> <p>The protein encoded by the Us11 gene of herpes simplex viruses is a dsRNA binding protein which inhibits protein kinase R activity, thereby preventing the interferon-induced shut down of protein synthesis following viral infection. Us11 protein is not essential for infectivity <it>in vitro </it>and in mice in herpes simplex virus type 1 (HSV1), however this virus has a second, and apparently more important, inhibitor of PKR activity, the γ₁34.5 protein. Recently sequenced simian simplexviruses SA8, HVP2 and B virus do not have an ORF corresponding to the γ₁34.5 protein, yet they have similar, or greater, infectivity as HSV1 and HSV2.</p> <p>Methods</p> <p>We have expressed the US11 proteins of the simplexviruses HSV1, HSV2, HVP2 and B virus and measured their abilities to bind dsRNA, in order to investigate possible differences that could complement the absence of the γ₁34.5 protein. We employed a filter binding technique that allows binding of the Us11 protein under condition of excess dsRNA substrate and therefore a measurement of the true Kd value of Us11-dsRNA binding.</p> <p>Results and Conclusions</p> <p>The results show a Kd of binding in the range of 0.89 nM to 1.82 nM, with no significant difference among the four Us11 proteins.</p

Fluticasone furoate nasal spray in the treatment of allergic rhinitis

Allergic rhinitis (AR) is a prevalent disease with great morbidity and significant societal and economic burden. Intranasal corticosteroids are recommended as first-line therapy for patients with moderate-to-severe disease, especially when nasal congestion is a major component of symptoms. To compare the efficacy and safety profile of different available intranasal corticosteroids for the treatment of AR, it is important to understand their different structures and pharmacokinetic and pharmacodynamic properties. Knowledge of these drugs has increased tremendously over the last decade. Studies have elucidated mechanisms of action, pharmacologic properties, and the clinical impact of these drugs in allergic respiratory diseases. Although the existing intranasal corticosteroids are already highly efficient, the introduction of further improved formulations with a better efficacy/safety profile is always desired. Fluticasone furoate nasal spray is a new topical corticosteroid, with enhanced-affinity and a unique side-actuated delivery device. As it has high topical potency and low potential for systemic effects, it is a good candidate for rhinitis treatment

Asma persistente em adultos: comparação da tomografia computadorizada de tórax de alta resolução após um ano de seguimento

OBJECTIVE: The aims of this study were to evaluate the role of high resolution computed tomography of the torax in detecting abnormalities in chronic asthmatic patients and to determine the behavior of these lesions after at least one year. METHOD: Fourteen persistent asthmatic patients with a mean forced expiratory volume in 1-second that was 63% of predicted and a mean forced expiratory volume in 1-second /forced vital capacity of 60% had two high resolution computed tomographys separated by an interval of at least one year. RESULTS: All 14 patients had abnormalities on both scans. The most common abnormality was bronchial wall thickening, which was present in all patients on both computed tomographys. Bronchiectasis was suggested on the first computed tomography in 5 of the 14 (36%) patients, but on follow-up, the bronchial dilatation had disappeared in 2 and diminished in a third. Only one patient had any emphysematous changes; a minimal persistent area of paraseptal emphysema was present on both scans. In 3 patients, a "mosaic" appearance was observed on the first scan, and this persisted on the follow-up computed tomography. Two patients had persistent areas of mucoid impaction. In a third patient, mucus plugging was detected only on the second computed tomography. CONCLUSIONS: We conclude that there are many abnormalities on the high resolution computed tomography of patients with persistent asthma. Changes suggestive of bronchiectasis, namely bronchial dilatation, frequently resolve spontaneously. Therefore, the diagnosis of bronchiectasis by high resolution computed tomography in asthmatic patients must be made with caution, since bronchial dilatation can be reversible or can represent false dilatation. Nonsmoking chronic asthmatic subjects in this study had no evidence of centrilobular or panacinar emphysema.OBJETIVO: Avaliar o papel da tomografia computadorizada de tórax de alta resolução em detectar alterações estruturais pulmonares em pacientes asmáticos persistentes e determinar o comportamento destas lesões após pelo menos um ano de seguimento. MÉTODO: Foram avaliados 14 pacientes asmáticos persistentes em que eram disponíveis duas tomografias computadorizadas de tórax de alta resolução realizadas com um intervalo de pelo menos um ano. O valor médio do volume expiratório forçado no primeiro segundo foi de 63% do predito e o da relação volume expiratório forçado no primeiro segundo/capacidade vital forçada foi de 60%. RESULTADOS: Alterações estruturais foram detectadas em todos os pacientes em ambas tomografias. A anormalidade mais comumente observada foi espessamento brônquico, presente em todos os pacientes nos dois exames. Bronquectasias foram sugeridas na primeira tomografia em cinco dos 14 (36%) pacientes, mas no segundo exame a dilatação brônquica tinha desaparecido em dois e reduzido em um. Enfisema paraseptal foi detectado em um paciente. Em três, havia padrão "em mosaico " no primeiro exame, que persistiu no segundo exame. Em dois pacientes foram detectadas áreas persistentes de impactação mucóide. Em um terceiro, a impactação foi observada somente na segunda tomografia. CONCLUSÕES: Pacientes com asma persistente apresentam múltiplas anormalidades na tomografia computadorizada de tórax de alta resolução. Imagens sugestivas de bronquectasias freqüentemente têm resolução espontânea. Desta forma, é necessária precaução ao fazer o diagnóstico de bronquectasias através de tomografia computadorizada de tórax de alta resolução em pacientes asmáticos, uma vez que a dilatação brônquica pode ser reversível ou representar uma falsa dilatação. Enfisema centrilobular ou panacinar não foi detectado em nenhum paciente deste estudo

Exploring the relationship between autism spectrum disorder traits and metacognition sensitivity

Given the large amounts of data that are currently acquired and manipulated, a new field called Computational Psychiatry has emerged. One of the best examples where computational psychiatry has contributed to neurodevelopmental syndromes comes from the study on Autism Spectrum Disorder (ASD). One of the current problems to which attention has recently begun to be paid is whether or not people with ASD have altered metacognition. The importance of exploring metacognition in ASD lies in practical and theoretical implications. However, the results found by studies exploring metacognition in people with ASD are inconsistent with each other. Only one study has utilized a bias-free measure of metacognition as in the present study. The main objective of this study was to contribute to the debate, through the study of metacognition in ASD traits in a sample of neurotypical people in an online experiment with a perceptual task. The results have not shown a statistically significant relationship between ASD traits and metacognition. These results are consistent with some of the previous studies.Sociedad Argentina de Informática e Investigación Operativ

Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety

OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients

Cirurgia de revascularização do miocárdio: complicações pleuro-pulmonares agudas caracterizadas por tomografia computadorizada de tórax

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75% of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5%) was higher (P < 0.05) than in the internal mammary artery group (52.3%). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7% (day 2) to 26.7% (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion.INTRODUÇÃO: O comprometimento pleuro-pulmonar é freqüente após cirurgia de revascularização do miocárdio independente do uso de veia safena ou de artéria mamária interna. A presença de atelectasias e derrame pleural tem sido atribuída ao trauma torácico. OBJETIVOS: Definir a incidência do comprometimento pleuro-pulmonar observado através de tomografia computadorizada, analisando a influência do trauma no desenvolvimento destas complicações. MÉTODOS: Trinta pacientes foram submetidos a cirurgia eletiva de revascularização do miocárdio (8 safena e 22 também mamária com pleurotomia). Foi drenada a cavidade pleural esquerda de todos os pacientes do grupo mamária. Realizada Tomografia Computadorizada do tórax no 2º e 7º dias pós-op, avaliando-se o derrame pleural (0: sem líquido e 4: derrame em mais de 75% do hemitórax) e atelectasias (laminar: 1, segmentar: 3 e lobar: 10 pontos). RESULTADOS: Todos os pacientes apresentaram derrame pleural ou atelectasia. Entre o 2º e o 7º dia, o número de pacientes com derrame ou com atelectasia, no lado direito, diminuiu (p < 0.05). A prevalência de derrames, no 2º dia, no grupo safena, (87.5%) foi maior (p < 0.05) do que no grupo mamária (52.3%). A prevalência de atelectasias no lobo inferior direito diminuiu (p < 0.05) de 86.7% (2º dia) para 26.7% (7º dia). O grau de atelectasias, em ambos os lados, não diferiu no dia 2 (p = 0,42) mas sim no dia 7 (p < 0.0001). Houve diminuição das atelectasias do dia 2 para o 7, à direita (p < 0.001), mas não à esquerda (p = 0.21). Houve correlação (dia 2) entre as atelectasias e os derrames à direita (p = 0.04), mas não à esquerda (p = 0.113). CONCLUSÃO: Este estudo evidencia alta prevalência de derrame pleural e atelectasias após cirurgia de revascularização do miocárdio, que se reduz à direita no 7º dia de pós-operatório. Os fatores envolvidos na persis-tência das alterações à esquerda incluem o maior trauma torácico, ressaltando-se a drenagem e a presença de derrame pericárdico

Comparison between breathing and aerobic exercise on clinical control in patients with moderate-to-severe asthma: protocol of a randomized trial

Abstract\ud \ud Background\ud Asthma is a chronic inflammatory airway disease characterized by reversible obstruction, inflammation and hyperresponsiveness to different stimulus. Aerobic and breathing exercises have been demonstrated to benefit asthmatic patients; however, there is no evidence comparing the effectiveness of these treatments.\ud \ud \ud Methods/design\ud This is a prospective, comparative, blinded, and randomized clinical trial with 2 groups that will receive distinct interventions. Forty-eight asthmatic adults with optimized medical treatment will be randomly divided into either aerobic (AG) or breathing exercises (BG). Patients will perform breathing or aerobic exercise twice a week for 3 months, totalizing 24 sessions of 40 minutes each. Before intervention, both groups will complete an educational program consisting of 2 educational classes. Before and after interventions, the following parameters will be quantified: clinical control (main outcome), health related quality of life, levels of anxiety and depression, daily living physical activity and maximal exercise capacity (secondary outcome). Hyperventilation syndrome symptoms, autonomic nervous imbalance, thoracoabdominal kinematics, inflammatory cells in the sputum, fraction of exhaled nitric oxide (FENO) and systemic inflammatory cytokines will also be evaluated as possible mechanisms to explain the benefits of both interventions.\ud \ud \ud Discussion\ud Although the benefits of breathing and aerobic exercises have been extensively studied, the comparison between both has never been investigated. Furthermore, the findings of our results will allow us to understand its application and suitability to patients that will have more benefits for every intervention optimizing its effect.\ud \ud \ud Trial registration\ud Clinicaltrials.gov; Identifier: \ud NCT02065258\ud \ud .This work was supported by São Paulo Research Foundation - FAPESP (grants\ud 2009/53904-9 and 2011/50071-6)

Efeito agudo do salbutamol no sistema cardiovascular durante o exercício físico em pacientes com asma moderada ou grave: estudo aleatorizado, duplo-cego e cruzado

Salbutamol é um β2-agonista de curta duração frequentemente utilizado em pacientes com asma para prevenir os sintomas durante ou após exercício físico. Alterações hemodinâmicas em repouso estão bem descritas. Contudo são escassos os dados sobre os efeitos na frequência cardíaca (FC) e pressão arterial (PA) durante o exercício e na fase de recuperação em pacientes com asma moderada ou grave. Foi realizado um estudo aleatorizado, duplo-cego e cruzado, em que foram inclusos 15 indivíduos com asma moderada e grave, com média de idade de 46,4±9,3 anos. Os pacientes realizaram um teste de esforço máximo em dois dias não consecutivos, com administração de 400mcg de salbutamol ou 4 “puffs” de placebo. Durante todo o protocolo foi monitorada a FC, a PA, a percepção de esforço e o pico de fluxo expiratório (PFE). Após o uso do salbutamol, o valor do PFE aumentou em média de 28,0±47,7L/m, permanecendo maior nos tempos de 5, 10 e 15 minutos de recuperação passiva em relação ao placebo (p;0,05). Esses resultados sugerem que o uso de salbutamol é seguro, e que a FC não necessita de ser ajustada para prescrever a intensidade do exercício após a administração de salbutamol em indivíduos com asma moderada ou grave.Salbutamol es un agonista β2 de corta duración frecuentemente utilizado en pacientes con asma para prevenir los síntomas durante o después del ejercicio físico. Los cambios hemodinámicos en descanso están bien descritos. Sin embargo, son escasos los datos sobre los efectos en la frecuencia cardíaca (FC) y la presión arterial (PA) durante el ejercicio y en la fase de recuperación en pacientes con asma moderada o grave. Se realizó un estudio aleatorizado, doble ciego y cruzado, donde fueron incluidos 15 individuos con asma moderada y grave, con una media de edad de 46,4 ± 9,3 años. Los pacientes realizaron una prueba de esfuerzo máximo en 2 días no consecutivos, con administración de 400mcg de salbutamol o 4 «puffs» de placebo. Durante el protocolo se supervisaron la FC, PA, percibe el esfuerzo y el Pico flujo espiratorio (PEF). Después del uso del salbutamol, el valor del PFE aumentó en promedio de 28,0 ± 47,7 L/m, permaneciendo mayor en los tiempos 5, 10 y 15 minutos de recuperación pasiva con relación al placebo (p ; 0,05). Los resultados sugieren que el uso de salbutamol es seguro y que la FC no necesita ser ajustada para prescribir la intensidad del ejercicio después de la administración de salbutamol en individuos con asma moderada o grave.Salbutamol is a β2-agonist of short duration commonly used in patients with asthma to prevent symptoms during or after exercise. Hemodynamic changes at rest are well described. However, there is little data on the effects on heart rate (HR) and blood pressure (BP) during exercise and recovery phase in patients with moderate or severe asthma A randomized, double-blind, cross-over study was conducted, including 15 individuals with moderate and severe asthma, mean age 46.4±9.3 years. Patients underwent a maximal 2-day exercise test with 400 mcg salbutamol or 4 placebo puffs. Throughout the protocol, HR, BP, perceived exertion and peak of expiratory flow (PEF) were monitored. After the use of salbutamol, the PEF value increased by a mean of 28.0±47.7L/m, remaining increased at 5, 10 and 15 minutes of passive recovery compared to placebo (p;0.05). These results suggest that the use of salbutamol is safe and that HR does not need to be adjusted to prescribe exercise intensity following salbutamol administration in subjects with moderate or severe asthma

The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial

Abstract\ud \ud Background\ud Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown.\ud \ud \ud Methods/Design\ud This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m2) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups.\ud \ud \ud Discussion\ud This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms.\ud \ud \ud Trial registration\ud \ud \ud NCT02188940The study was supported by the São Paulo Research Foundation (FAPESP;\ud Grants 2012/16700-9 and 2012/16134-3) and Conselho Nacional de Pesquisa (CNPq Grants 485065/2012-6)