Abstract: Introduction: The onset of the Covid-19 pandemic led global health institutions to recommend the adoption of restrictive measures such as the closure of educational facilities. Educational institutions were forced to suddenly adapt to emergency distance learning methods, with little time for preparation. The students also faced challenges such as relying on the internet and remaining isolated at home. Medical and health science schools also had to adapt to this new model to humanized practices. Objective: To evaluate the perceived use of emergency distance learning by students at a state university health sciences and medical school during the Covid-19 Pandemic. Method: This is a descriptive and exploratory study, with a cross-sectional design and quantitative approach, involving the application of a questionnaire containing closed questions. The questionnaire was divided into four topics: sample characterization, conditions for internet use, study site conditions, and student perception of the use of distance learning. Result: The study included 480 students from the nursing, medicine, and dentistry courses at the Amazonas State University. Most of these students used their home wifi, with regular signal quality. Students from smaller, inner state towns were the most disadvantaged by inconsistent internet connections. Students were mainly in their bedrooms when they attended the and pointed to losing concentration easily as the main detrimental factor of the remote classes. Most students disagreed with the effectiveness of assessments for this type of learning,and rated the experience with remote teaching as unsatisfactory. However, most students agreed that it is possible to learn theoretical content with quality through distance learning. Conclusion: The Covid-19 pandemic brought about a sudden change of scenery. The new educational model, using distance learning, has brought new challenges for teaching. The results show that the factors that hindered the students were the instability of their internet connection and difficulty in maintaining concentration during distance learning classes. Students found it easy to clarify doubts about the classes with the teachers; the system proved adequate for the teaching and learning of the theoretical content.

Resumo: Introdução: Com a pandemia de Covid-19, instituições globais de saúde recomendaram a adoção de medidas restritivas, como o fechamento de unidades de ensino. As instituições de ensino tiveram que se adaptar ao ensino remoto emergencial de forma abrupta e com pouco tempo para preparo. Os alunos também tiveram desafios a serem enfrentados, como uso da internet e isolamento dentro de casa. O ensino superior na área de saúde também teve que se adequar a esse novo modelo com adaptação a práticas humanizadas. Objetivo: Este estudo teve como objetivo avaliar a percepção da utilização do ensino remoto emergencial por discentes em uma universidade pública de saúde durante a pandemia da Covid-19. Método: Trata-se de uma pesquisa descritiva e exploratória, com delineamento transversal e abordagem quantitativa, realizada por meio de aplicação de um questionário com perguntas fechadas. O questionário foi dividido em quatro tópicos: caracterização da amostra, condições de uso da internet, condições do local do estudo e percepção do estudante acerca da utilização do ensino remoto. Resultado: Participaram do estudo 480 alunos dos cursos de Enfermagem, Medicina e Odontologia da Universidade do Estado do Amazonas. A maioria desses alunos utilizou wi-fi residencial, com qualidade de sinal regular, e aqueles que residem no interior do estado foram os mais prejudicados por conta da inconstância da internet. Os alunos assistiram predominantemente às aulas no quarto e apontaram a fácil desconcentração como o fator mais prejudicial das aulas remotas. A maioria dos alunos discorda da eficácia das avaliações para esse tipo de ensino, assim como avalia de forma insatisfatória a experiência com o ensino remoto. No entanto, a maioria concordou que é possível aprender o conteúdo teórico com qualidade no ensino remoto. Conclusão: A pandemia de Covid-19 acarretou uma mudança repentina de cenário. O novo modelo educacional, de educação a distância, trouxe novos desafios para o ensino. Os resultados evidenciam que os fatores que prejudicaram os estudantes foram a instabilidade da internet e a dificuldade em se concentrar durante a aprendizagem remota. Houve facilidade para os discentes esclarecerem as dúvidas das aulas com os docentes, o que corrobora o ensino e a aprendizagem da parte teórica por meio desse sistema.

ABSTRACT Objectives: Fragility fractures increase morbidity and mortality. Adding assessment of clinical risk factors independently or as a previous step to Bone Densitometry (BD) should provide better accuracy in fracture risk prediction. FRAX tool might be used to stratify patients in order to rationalize the need for BD and risk classification. The primary objective of this study is to describe and perform comparisons between the estimated risk of fractures in 10 years using the FRAX calculator based on clinical factors with and without BD results for women aged 40 or more with clinical diseases monitored in tertiary care service in internal medicine. Methods: Cross-sectional. Women over 40 years with BD in the previous year. After medical chart review, identification of risk factors and risk estimations using FRAX-BRAZIL with (FRAX BDI) and without (FRAX BDNI) the inclusion of T-score. Results: 239 women. Age 65 ± 10.35 years. BMI 29.68 ± 6.27kg/m2. Risk factors: 32(13.4%) previous fractures; 23 (9.6%) current smoking; 78 (32.6%) corticosteroids use; 44 (18.4%) rheumatoid arthritis; 38 (15.9%) secondary causes; FRAX scores were higher when BD was not included. Spearman correlation coefficients between FRAX BDNI and FRAX BDI for major fractures r = 0.793 (95% CI 0.7388‒0.836). For hip fractures r = 0.6922 (95% CI 0.6174‒0.75446) Conclusion: Using FRAX to estimate 10-year fracture risk without BD data might be a reliable tool for screening, even for patients with a high prevalence of risk factors, improving accessibility and equity in health systems. The present study’s data suggest an overestimation of fracture risk with FRAX BDNI, suggesting that it is safe to be widely used as a screening tool.

BACKGROUND: Even students with previous academic success may face challenges that affect their academic performance. Many medical schools offer programs to students at the risk of academic failure, to ensure that they succeed in the course. OBJECTIVE AND METHODS: In this report we describe a pioneering academic tutoring program developed at a Brazilian medical school and discuss the initial results of the program based on the feedback from tutors and data regarding the progression of students in the medical course. RESULTS: In 2018, 33 students enrolled into the program. Students' performance difficulties were mainly associated with mental health problems and socioeconomic vulnerability. Of the 33 students, 27 (81.8%) were assisted by the Mental Health Support Service and 16 (48.5%) were assisted by the Social Assistance Service. In addition to the planning academic activity class load, tutors were able to assist students in solving socioeconomic issues, carrying out personal support interventions with the promotion of self-esteem, and presenting suggestions for behavioral changes in their routine. For most students (72%), the action plan proposed by the tutors was successful. Eight of the 14 (57%) students in the fourth year progressed to the final two years of in-hospital practical training (internship). CONCLUSIONS: The Academic Tutoring Program showed positive results for most of the students. Close monitoring and tutor intervention allowed students with poor academic performance to overcome the low performance cycle. These important tasks demand time and energy from tutors, and institutional recognition of these professionals is essential for the successful maintenance of the program.

Resumo Justificativa e objetivos: Em videolaparoscopias, a associação de pneumoperitônio e obesidade pode contribuir para complicações pulmonares, mas não está bem definida em grupos específicos de obesos. Avaliamos os efeitos do pneumoperitônio na mecânica respiratória dos obesos Grau I em comparação aos não obesos. Métodos: Estudo prospectivo envolvendo 20 pacientes submetidos à colecistectomia videolaparoscópica, com espirometria normal, separados em não-obesos (IMC ≤ 25 kg.m-2) e obesos (IMC > 30 kg.mg-2), excluídos obesos Grau II e III. Mensuramos dados da mecânica ventilatória pulmonar antes do pneumoperitônio basal, após cinco, quinze e trinta minutos da insuflação peritoneal e quinze minutos após a desinsuflação final. Resultados: O IMC médio dos não obesos foi de 22,72 ± 1,43 kg.m-2 e dos obesos 31,78 ± 1,09 kg.m-2, p < 0,01. A duração da anestesia e da insuflação peritoneal foram semelhantes entre os grupos. A complacência pulmonar (Crs) basal dos obesos (38,3 ± 8,3 mL.cm H2O-1) foi inferior aos não obesos (47,4 ± 5,7 mL.cm H2O-1), p = 0,01. Após a insuflação, a Crs diminuiu nos dois grupos e permaneceu ainda mais baixa nos obesos em todos os momentos avaliados (GLM p < 0,01). A pressão de pico e a pressão de platô do sistema respiratório foram mais elevadas nos obesos, mas apresentaram semelhantes variações nos momentos analisados (GLM p > 0,05). O mesmo ocorreu com a pressão elástica, mais elevada nos obesos em todos tempos (GLM p = 0,04), e a pressão resistiva apresentou diferenças nas variações entre os grupos durante o pneumoperitônio (GLM p = 0,05). Conclusão: Obesos Grau I apresentam maiores alterações na mecânica pulmonar que os não obesos em videolaparoscopias e este fato recomenda cuidados relacionados a ventilação mecânica.

Abstract Introduction and objectives: The association pneumoperitoneum and obesity in video laparoscopy can contribute to pulmonary complications, but has not been well defined in specific groups of obese individuals. We assessed the effects of pneumoperitoneum in respiratory mechanics in Grade I obese compared to non-obese. Methods: Prospective study including 20 patients submitted to video laparoscopic cholecystectomy, normal spirometry, divided into non-obese (BMI ≤ 25 kg.m-2) and obese (BMI > 30 kg.mg-2), excluding Grade II and III obese. We measured pulmonary ventilation mechanics data before pneumoperitoneum (baseline), and five, fifteen and thirty minutes after peritoneal insufflation, and fifteen minutes after disinflation (final). Results: Mean BMI of non-obese was 22.72 ± 1.43 kg.m-2 and of the obese 31.78 ± 1.09 kg.m-2, p < 0.01. Duration of anesthesia and of peritoneal insufflation was similar between groups. Baseline pulmonary compliance (Crs) of the obese (38.3 ± 8.3 mL.cm H2O-1) was lower than of the non-obese (47.4 ± 5.7 mL.cm H2O-1), p = 0.01. After insufflation, Crs decreased in both groups and remained even lower in the obese at all moments assessed (GLM p < 0.01). Respiratory system peak pressure and plateau pressure were higher in the obese, albeit variations were similar at moments analyzed (GLM p > 0.05). The same occurred with elastic pressure, higher in the obese at all times (GLM p = 0.04), and resistive pressure showed differences in variations between groups during pneumoperitoneum (GLM p = 0,05). Conclusions: Grade I obese presented more changes in pulmonary mechanics than the non-obese during video laparoscopies and the fact requires mechanical ventilation-related care.

OBJECTIVES: This study aimed to analyze the efficiency of physiotherapy techniques in sputum induction and in the evaluation of pulmonary inflammation in asthmatic children and adolescents. Although hypertonic saline (HS) is widely used for sputum induction (SI), specific techniques and maneuvers of physiotherapy (P) may facilitate the collection of mucus in some asthmatic children and adolescents. METHODS: A randomized crossover study was performed in patients with well-controlled asthma, and 90 sputum samples were collected. Children and adolescents were assessed using spirometry and randomized at entry into one of three sputum induction techniques: (i) 3% hypertonic saline – HS technique; (ii) physiotherapy (oscillatory positive expiratory pressure, forced expiration, and acceleration of expiratory flow) – P technique; and (iii) hypertonic saline + physiotherapy – HSP technique. ClinicalTrials.gov: NCT03136042. RESULTS: The total cells (mL) and the percentage (%) of differential inflammatory cells were similar in all techniques. The sputum weight (g) in the HSP technique was significantly higher than that in the HS technique. In all techniques, the percentage of viable cells was >50%, and there was no difference between the HS and P techniques. Moreover, sputum induction did not cause any alterations in the pulmonary function of patients. CONCLUSION: The physiotherapy sputum collection technique was effective in obtaining viable cells from mucus samples and yielded the same amount of sputum as the gold standard technique (hypertonic saline). In addition, the physiotherapy maneuvers were both safe and useful for sputum induction in asthmatic children and adolescents with well-controlled asthma.

The COVID-19 pandemic demanded a quick shift from presential to e-learning processes. Unlike planned e-learning programs, medical schools have had to quickly deliver the entire medical curriculum using remote strategies. This study aimed to perform a meta-synthesis of previous pandemic situations and describe the experience of the São Paulo University School of Medicine. We searched the Cochrane Central Register of Controlled Trials, Medline, EMBASE, Lilacs, Scopus, Web of Science, and ERIC, using the following keywords: (“SARS” OR “severe acute respiratory syndrome” OR “severe acute respiratory syndrome” OR “Middle East Respiratory Syndrome Coronavirus” OR “middle east respiratory syndrome*” OR “MERS-CoV” OR “Mers” OR “Middle Eastern Respiratory Syndrome*” OR “MERS-CoV*” OR “coronavirus” OR “Coronavirus Infections” OR “coronavirus*” OR “COVID-19” OR “2019-nCoV” OR “SARS-CoV-2”) AND (“online education” OR “Education, Distance” OR “e-learning” OR “course online” OR “flipped classroom”) AND (“lockdown” OR “social distance” OR “quarantine”). The endpoints were the online platforms used for online learning, the model of class, recorded versus online interaction, duration of online lectures, and students' and teachers' perceptions of online learning. We retrieved 38 records; only seven articles studied online education methods related to the pandemic and social distancing rules. The most frequently used online platform was Zoom®. The studies examined both synchronous and asynchronous approaches. There was no evidence regarding duration and students’ and teachers' attitude. This study suggests that the online learning shift was feasible; however, because of the nature of the education shift (pandemic), future studies must further analyze the educational structure.

RESUMO Diversas doenças respiratórias são caracterizadas por hipersecreção com necessidade de higiene brônquica (HB). Osciladores orais de alta frequência (OOAF) são dispositivos que promovem HB diária; entretanto, seu custo pode ser inviável para aquisição por pacientes com baixa renda. Os objetivos deste estudo foram: desenvolver um OOAF de baixo custo (OOAF-BC) e comparar suas propriedades físicas com as dos disponíveis comercialmente (Shaker e Flutter). O OOAF-BC foi desenvolvido com material de polivinil clorido e uma esfera de aço inoxidável. As pressões e frequências foram mensuradas nos fluxos de 4, 6, 8, 10 e 15 L/min. As pressões nos bocais foram medidas por um transdutor conectado ao computador. As frequências de oscilação foram derivadas do gráfico de pressão. A comparação dos dispositivos foi feita por Anova com post hoc de Tukey, p≤0.05. Não houve diferença entre as frequências dos três dispositivos em todos os fluxos testados. O OOAF-BC apresentou pressão mais alta comparado ao Shaker em todos os fluxos testados (4 L/min: 4,7±1,2 vs. 1,0±0,2 cmH2O; 6 L/min: 8,6±1,5 vs. 3,5±0,5 cmH2O; 8 L/min: 10,8±1,6 vs. 5,4±0.2 cmH2O; 10 L/min: 13,5±1,2 vs. 7,7±0.4 cmH2O; 15 L/min: 14,3±1,1 vs. 7,8±0,2 cmH2O; OOAF-BC vs. Shaker; p≤0.05) e nos fluxos de 10 e 15 L/min comparado ao Flutter (10 L/min: 13,5±1,2 vs. 7,5±1,2 cmH2O; 15 L/min: 14,3±1,1 vs. 8,2±1,2 cmH2O; OOAF-BC vs. Flutter, p≤0.05). O custo do OOAF-BC foi pelo menos seis vezes menor. O OOAF-BC apresentou frequências similares e pressões mais altas que os outros OOAF comercialmente disponíveis. Estudos futuros são necessários para avaliar sua eficácia clínica.

ABSTRACT Several respiratory diseases are characterized by hypersecretion, requiring airway clearance therapy (ACT). Oral high-frequency oscillation (OHFO) devices are effective to enable daily ACT; however, they are still too expensive to become available for low-income patients. We sought to develop a low-cost device (OHFO-LC) and compare its physical properties with those OHFO commercially available (Shaker and Flutter). The OHFO-LC was developed from polyvinyl chloride material and one stainless steel sphere. Pressures and frequencies were measured at flows of 4, 6, 8, 10 and 15L/min. Pressures at the mouthpieces were measured by a transducer connected to a microcomputer. The oscillation frequencies were obtained from the graph of the pressure. The frequencies and pressures were compared among groups using one-way Anova and Tukey’s post hoc tests, p≤0.05. There were no differences among the frequencies of the three devices in all tested flows. The OHFO-LC device showed a higher positive expiratory pressure compared with the Shaker at all tested flows (4 L/min: 4.7±1.2 vs. 1.0±0.2 cmH2O; 6 L/min: 8.6±1.5 vs. 3.5±0.5 cmH2O; 8 L/min: 10.8±1.6 vs. 5.4±0.2 cmH2O; 10 L/min: 13.5±1.2 vs. 7.7±0.4 cmH2O; 15 L/min: 14.3±1.1 vs. 7.8±0.2 cmH2O; OHFO-LC vs. Shaker; p≤0.05) and at 10 and 15 L/min compared with Flutter (10 L/min: 13.5±1.2 vs. 7.5±1.2 cmH2O; 15 L/min: 14.3±1.1 vs. 8.2±1.2 cmH2O; OHFO-LC vs. Flutter, p≤0.05). The cost of the OHFO-LC device was much lower than both the Shaker and the Flutter. Our results showed that the OHFO-LC had physical properties with similar frequencies but higher pressures than other OHFO devices that are commercially available. Future studies are necessary to evaluate its clinical efficacy.

RESUMEN Varias enfermedades respiratorias se caracterizan por hipersecreción, que requiere higiene bronquial (HB). Los osciladores orales de alta frecuencia (OOAF) son dispositivos que promueven la HB diaria; sin embargo, su costo puede no ser factible para la adquisición por parte de pacientes con bajos ingresos. Los objetivos de este estudio fueron desarrollar un OOAF de bajo costo (OOAF-BC) y comparar sus propiedades físicas con las de los disponibles comercialmente (Shaker y Flutter). El OOAF-BC se desarrolló con material de polivinilo clorado y una bola de acero inoxidable. Las presiones y frecuencias se midieron en flujos de 4, 6, 8, 10 y 15 L/min. Las presiones de la boquilla se midieron mediante un transductor conectado a la computadora. Las frecuencias de oscilación se derivaron del gráfico de presión. Se compararon los dispositivos con la utilización de Anova con post hoc de Tukey, p≤0,05. No hubo diferencias entre las frecuencias de los tres dispositivos en todos los flujos probados. El OOAF-BC mostró una presión más alta en comparación con Shaker en todos los flujos probados (4 L/min: 4,7±1,2 vs. 1,0±0,2 cmH2O; 6 L/min: 8,6±1,5 vs. 3,5±0,5 cmH2O; 8 L/min: 10,8±1,6 vs. 5,4±0,2 cmH2O; 10 L/min: 13,5±1,2 vs. 7,7±0,4 cmH2O; 15 L/min: 14,3±1,1 vs. 7,8±0,2 cmH2O; OOAF-BC vs. Shaker; p≤0,05) y con flujos de 10 y 15 L/min en comparación con Flutter (10 L/min: 13,5±1,2 vs. 7,5±1,2 cmH2O; 15 L/min: 14,3±1,1 vs. 8,2±1,2 cmH2O; OOAF-BC vs. Flutter, p≤0,05). El costo de OOAF-BC fue al menos seis veces menor. El OOAF-BC mostró frecuencias similares y presiones más altas que otros OOAF disponibles comercialmente. Se necesitan estudios futuros para evaluar su eficacia clínica.

Resumo Objetivo: Caracterizar o consumo de álcool e tabaco e correlacioná-lo às doenças em tratamento de pacientes de um ambulatório de clínica geral. Método: As perguntas do ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) foram respondidas por 300 pacientes escolhidos aleatoriamente e enquadrados em grupos conforme os diagnósticos das doenças em tratamento no Ambulatório Geral e Didático (AGD), Serviço de Clínica Geral do HC-FMUSP; o consumo das substâncias foi caracterizado e a sua correlação com as doenças em tratamento foi calculada por meio do método do Qui-quadrado e teste de Pearson. Resultados: O consumo de tabaco mostrou-se mais prevalente, mais intenso e maior causa de complicações (de saúde, sociais, legais ou financeiras) do que o do álcool; o consumo de tabaco apresentou correlação positiva e significante (p<0,0001) com a referência de doença respiratória no prontuário médico. De acordo com o critério proposto no questionário, poucos consumidores de bebida alcoólica seriam encaminhados para intervenção preventiva, ao contrário do que ocorreria com os fumantes. Conclusão: A aplicação do ASSIST permitiu caracterizar e correlacionar positivamente o uso de tabaco com doenças respiratórias em tratamento. A importância do questionário como instrumento preventivo das consequências do tabagismo ficou mais evidente do que em relação às associadas ao consumo de bebida alcoólica.

Summary Objective: To characterize the use of alcohol and tobacco and correlate both to the diseases of outpatients in a general practice outpatient clinic. Method: The ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) questionnaire was answered by 300 randomly chosen subjects assigned to different groups according to the diseases being treated at the Outpatient General and Teaching Clinic of the Department of Internal Medicine, Hospital das Clínicas of the University of São Paulo's School of Medicine (HC-FMUSP, in the Portuguese acronym), São Paulo, Brazil. The consumption of tobacco and alcohol was characterized and its correlation with the groups of diseases being treated was calculated using Chi-square and Pearson test statistics. Results: Compared to alcohol, tobacco use was more prevalent, more intense and showed more health-, social-, legal- and financial-related damage. Tobacco smoking presented a positive significant (p<0.0001) correlation with respiratory diseases. According to the questionnaire's criteria, few alcohol users would be referred to clinical interventions in comparison to smokers. Conclusion: Respiratory diseases and tobacco use were well correlated based on the ASSIST questionnaire. The preventive value of the questionnaire was more evident in relation to tobacco than alcohol consumption.

RESUMO Objetivo: Descrever um modelo murino de enfisema induzido por exposição a fumaça de cigarro (FC) e instilação de elastase pancreática porcina (EPP). Métodos: Trinta e oito camundongos C57BL/6 foram aleatoriamente divididos em quatro grupos: controle (uma instilação intranasal de solução salina a 0,9%); EPP (duas instilações intranasais de EPP); FC (exposição a FC durante 60 dias) e FC + EPP (duas instilações intranasais de EPP + exposição a FC durante 60 dias). No fim do protocolo experimental, todos os animais foram anestesiados e traqueostomizados para o cálculo de parâmetros de mecânica respiratória. Em seguida, todos os animais foram sacrificados e seus pulmões foram removidos para a medição da intercepção linear média (Lm) e a determinação do número de células imunorreativas a antígeno macrofágico (MAC)-2, metaloproteinase da matriz (MMP)-12 e glicoproteína glicosilada de 91 kDa (gp91phox) no parênquima pulmonar distal e na região peribrônquica. Resultados: Embora não tenha havido diferenças entre os quatro grupos quanto aos parâmetros de mecânica respiratória avaliados, houve aumento da Lm no grupo FC + EPP. O número de células positivas para MAC-2 na região peribrônquica e no parênquima pulmonar distal foi maior no grupo FC + EPP do que nos outros grupos, assim como o foi o número de células positivas para MMP-12 e gp91phox, porém somente no parênquima pulmonar distal. Conclusões: Nosso modelo de enfisema induzido por instilação de EPP e exposição a FC resulta em um grau significativo de destruição parenquimatosa em um período de tempo menor que o empregado em outros modelos de enfisema induzido por FC, o que reforça a importância do desequilíbrio entre proteases e antiproteases e entre oxidantes e antioxidantes na patogênese do enfisema.

ABSTRACT Objective: To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE). Methods: A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days). At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region. Results: Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma. Conclusions: Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema.

RESUMO Objetivo Desenvolver um novo modelo experimental de doença pulmonar alérgica crônica por ácaro, com proeminente produção de imunoglobulina E (IgE) específica, infiltrado inflamatório eosinofílico nas vias aéreas e remodelamento, comparando duas vias diferentes de sensibilização. Métodos O protocolo teve duração de 30 dias. Camundongos BALB/c foram divididos em seis grupos submetidos à sensibilização por via subcutânea ou intraperitoneal com solução salina (controles negativos),Dermatophagoides pteronyssinus (Der p) 50 ou 500mcg, em três aplicações. Posteriormente, foram submetidos à provocação intranasal com Der p ou salina por 7 dias e sacrificados 24 horas após o último desafio. Avaliamos a titulação de IgE específica anti-Der p, densidade eosinofílica no espaço peribroncovascular e remodelamento das vias aéreas. Resultados Tanto os animais sensibilizados por via subcutânea como intraperitoneal produziram IgE específica anti-Der p. Ocorreu aumento da eosinofilia peribroncovascular apenas nos animais que receberam menor dose de Der p. Porém apenas o grupo sensibilizado com Der p 50mcg subcutânea apresentou remodelamento significativo das vias aéreas. Conclusão Neste modelo murino de asma, as duas vias de sensibilização levaram à produção de IgE específica e eosinofilia nas vias aéreas. No entanto, apenas a via subcutânea foi capaz de induzir ao remodelamento. Além disso, doses menores de Der p utilizadas foram superiores às mais elevadas, sugerindo tolerância. Mais estudos são necessários para avaliar a eficácia deste modelo no desenvolvimento da hiperresponsividade brônquica, mas ele pode ser replicado em experimentos para criação de novas estratégias terapêuticas medicamentosas ou imunoterápicas.

ABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

OBJECTIVES:This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma.METHODS:This was a randomized, controlled, crossover trial conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A total of 74 patients with mild/moderate, persistent asthma were randomized into two therapeutic groups: Group A - 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short- and long-acting β-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (α=0.05).RESULTS:In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation.CONCLUSION:Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma.

PURPOSE:To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats.METHODS: Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded.RESULTS: Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871). Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups.CONCLUSIONS:Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day. Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group. BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.

RESUMO OBJETIVO: A investigação de intensidades padrão de exercício físico é importante para melhor compreender e desenvolver programas de reabilitação para enfisema. Nosso objetivo foi avaliar os efeitos de diferentes intensidades (moderada e alta) de exercício físico sobre o desenvolvimento de enfisema induzido por protease (instilação endotraqueal de papaína) em ratos. MÉTODOS: Ratos Wistar machos foram divididos aleatoriamente em cinco grupos que receberam instilação intra-traqueal de solução de papaína ou veículo: (i) papaína, exercício de alta intensidade, (ii) papaína, exercício moderado, (iii) soro fisiológico, exercício de alta intensidade, (iv) soro fisiológico, sedentário e (v) papaína, sedentário. Quarenta dias após a instilação intra-traqueal os grupos de exercício foram submetidos a um protocolo de treinamento físico em esteira durante 10 semanas, 5 dias/ semana, a 0.9 km/h (papaína e solucão salina exercício de alta intensidade), ou em 0.6km/h (papaína exercício moderado). Medimos elastância do sistema respiratório e resistência, as fibras de colágeno no parênquima pulmonar, e a intercepção linear média pulmonar. RESULTADOS: Todos os grupos de animais que receberam instilação de papaína apresentaram maior destruição da parede alveolar em comparação com animais que receberam apenas solução salina. O grupo papaína exercício de alta intensidade apresentou maiores valores de intercepto linear médio em comparação com grupos de enfisema que foram treinados em uma intensidade moderada ou não submetidos ao exercício. CONCLUSÃO: A alta intensidade de treinamento físico produziu mais destruição alveolar em um modelo experimental de enfisema em ratos quando comparada ao exercício de intensidade moderada, ou a nenhum exercício.

OBJECTIVE: Investigation of standard intensities of physical exercise is important to better comprehend and develop rehabilitation programs for emphysema. We aimed to evaluate the effects of different intensities (moderate and high-intensity) of physical exercise on the development of a protease-induced (papain intratracheal instillation) emphysema in rats. METHODS: Male Wistar rats were randomly separated into five groups that received intratracheal instillation of papain solution or vehicle: (i) papain high intensity exercise, (ii) papain moderate exercise, (iii) saline high intensity exercise, (iv) saline sedentary and (v) papain sedentary. Forty days after intratracheal instillation, the exercise groups were submitted to an exercise-training protocol on a treadmill during 10 weeks, 5 days/week, at 0.9 km/h (Papain and saline high exercise), or at 0.6 km/h (papain moderate exercise).We measured respiratory system elastance and resistance, the collagen fiber lung parenchyma, and the pulmonary mean linear intercept. RESULTS: All animal groups that received papain instillation presented higher alveolar wall destruction compared to animals that received only saline solution. The papain high intensity exercise group presented higher values of mean linear intercept compared to emphysema groups that were trained at a moderate intensity or not submitted to exercise. CONCLUSION: High intensity exercise training worsened alveolar destruction in an experimental model of emphysema in rats when compared to moderate intensity exercise, or to no exercise.

OBJECTIVES: Cognitive impairment in the elderly is frequently overlooked by general practitioners. The use of subjective memory complaints as a sign of cognitive impairment by the general practice is controversial. METHODS: Elderly individuals (N = 248) were asked whether they had memory complaints and underwent a cognitive impairment screening. Subjects classified as exhibiting “probable cognitive impairment” underwent a complete cognitive evaluation, and the final diagnoses were established by expert consensus. RESULTS: A total of 147 patients presented with subjective memory complaints, and 43 were further classified as demented or “cognitively impaired not demented”. Subjective memory complaints presented a sensitivity of 100% and a negative predictive value of 100%. CONCLUSION: Subjective memory complaints are an indicator for cognitive impairment screening.