Adeno-associated virus infection and its impact in human health: an overview.

Discovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35-80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.

Oxygen Desaturation in Daily Life and During a Laboratory-Based Protocol of Activities of Daily Living in COPD: Is There Relationship?

PURPOSE: To analyze the relationship between oxygen desaturation episodes during a laboratory-based ADL protocol and in real-life routine in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: Twenty patients with stable COPD (12 men, 70 ± 7 years, FEV1% 54 ± 15 predicted) with no indication for long-term oxygen therapy (LTOT) were submitted to assessments including ADL performance by the Londrina ADL Protocol (LAP) and level of physical activity in daily life, both while submitted to simultaneous activity and pulse oximeter monitoring. RESULTS: Episodes of desaturation ≥ 4% (ED ≥ 4%) during the LAP were correlated both with ED ≥ 4% in daily life (r = 0.45) and number of episodes of SpO2 under 88% (ED < 88%) in daily life (r = 0.59). ED < 88% during the LAP was also correlated with ED < 88% in daily life (r = 0.51), explaining 43% of its variance. CONCLUSION: In stable patients with COPD and no indication of LTOT, episodes of desaturation during a lab-based ADL protocol are moderately related to episodes of desaturation in daily (real) life, especially those episodes under 88%.

Physical Activity of Patients with COPD from Regions with Different Climatic Variations.

Seasonal changes in physical activity in daily life (PADL) of patients with Chronic Obstructive Pulmonary Disease (COPD) living in regions of the world with contrasting (i.e., mild or marked) weather variations have not been yet investigated. We aimed to quantify PADL and compare its variability caused by seasonality in patients with COPD who live in world regions with different summer-winter climatic variations (i.e. Londrina, Brazil and Leuven, Belgium). In a longitudinal, prospective and observational study, patients with COPD from Brazil and Belgium wore the SenseWear Armband for 7 days in summer and 7 days in winter. Active time (≥2METs) was the primary outcome. PADL data were matched day-by-day with weather information. Regarding the two assessment moments, median (min;max) temperatures were 11 (-5.5;27.2)°C in Leuven and 21 (7;27)°C in Londrina. Patients in Brazil (n = 19, 69 ± 7 years, FEV1 47 ± 15%pred) and Belgium (n = 18, 69 ± 6 years, FEV1 50 ± 15%pred) decreased their active time in winter compared to summer (p < 0.05), and this reduction was more pronounced in Brazil (p = 0.01, between group). Mean, minimum and maximum temperature, daylight duration and relative humidity were significantly related to active time. Patients with COPD decrease their PADL in winter even in a region with milder climatic variation.

Physical activity patterns and clusters in 1001 patients with COPD.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

GOLD B-C-D groups or GOLD II-III-IV grades: Which one better reflects the functionality of patients with chronic obstructive pulmonary disease?

The aim of this article is to investigate which global initiative for chronic obstructive lung disease (GOLD) classification (B-C-D or II-III-IV) better reflects the functionality of patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Ninety patients with COPD were classified according to the GOLD B-C-D and II-III-IV classifications. Functionality was assessed by different outcomes: 6-min walk test (6MWT), activities of daily living (ADL) (London Chest ADL Scale), and daily life activity/inactivity variables assessed by activity monitoring (SenseWear armband, Pittsburgh, Pennsylvania, USA). The 6MWT was the only outcome significantly associated with both the GOLD classifications. Good functionality as assessed by the 6MWT was observed in 80%, 69%, and 43.5% (GOLD B, C, and D, respectively) and 81%, 59%, and 29% (GOLD II, III, and IV, respectively) of the patients. Association (V Cramer's) and correlation (Spearman) coefficients of 6MWT with GOLD B-C-D and II-III-IV were V = 0.30, r = -0.35, and V = 0.37, r = -0.25, respectively. Neither GOLD classification showed V or r ≥ 0.30 with any other functionality outcome. Both the GOLD B-C-D and II-III-IV classifications do not reflect well COPD patients' functionality. Despite low association and correlation coefficients in general, both GOLD classifications were better associated with functional exercise capacity (6MWT) than with subjectively assessed ADL and objectively assessed outcomes of physical activity/inactivity.

Pulmonary Rehabilitation Associated with Noninvasive Ventilation on Physical Capacity and Quality of Life in Post-COVID-19: A Randomized Controlled Double-Blinded Clinical Trial Protocol.

Background: The coronavirus disease-2019 (COVID-19) pulmonary rehabilitation (PR) seems to be a better choice to improve physical and functional capacity after acute infection. However, there is a lack of evidence regarding the effects of different strategies to optimize post-acute phase rehabilitation and reduce long COVID-19 physical deteriorations. Objective: To compare the use of a noninvasive ventilation (NIV) plus aerobic exercise strategy during PR program with to a standard PR (without NIV) on physical capacity and quality of life outcomes in post-COVID-19. Methods: Double-blinded randomized controlled clinical trial. A total of 100 individuals discharged from hospital in a post-acute phase of severe COVID-19 will be randomized into two groups: PR + NIV (Group 1) and PR (Group 2). Inclusion criteria include participants who present symptomatic dyspnea II and III by the modified Medical Research Council, aged 18 years or older. Both groups will receive aerobic and resistance exercise, and inspiratory muscle training. However, group 1 will perform aerobic training with bilevel NIV. Cardiopulmonary exercise test will assess the O2 peak uptake, 6-minute walk test will assess the walking distance and short-form 36 will assess the quality of life before and after 8 weeks (after 24 PR sessions). Moreover, patients will be contacted by telephone every 3 months for one year to record possible adverse events, hospitalizations, and death. All data will be registered in RedCap, and analyses will be performed in the STATA v13 software. Clinical Trial Registration: RBR-3t9pkzt.

Hepatitis B Virus Genotype D: An Overview of Molecular Epidemiology, Evolutionary History, and Clinical Characteristics.

The hepatitis B virus (HBV) genotype D (HBV/D) is the most extensively distributed genotype worldwide with distinct molecular and epidemiological features. This report provides an up-to-date review on the history of HBV/D subgenotyping and misclassifications, along with large-scale analysis of over 1000 HBV/D complete genome sequences, with the aim of gaining a thorough understanding of the global prevalence and geographic distribution of HBV/D subgenotypes. We have additionally explored recent paleogenomic findings, which facilitated the detection of HBV/D genomes dating back to the late Iron Age and provided new perspectives on the origins of modern HBV/D strains. Finally, reports on distinct disease outcomes and responses to antiviral therapy among HBV/D subgenotypes are discussed, further highlighting the complexity of this genotype and the importance of HBV subgenotyping in the management and treatment of hepatitis B.

Evaluation of a new motion sensor in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To assess the criterion validity and reproducibility of a new pedometer in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: Outpatient physiotherapy clinic from a university hospital. PARTICIPANTS: Patients with COPD (N=30; 17 men; forced expiratory volume in the first second, 44±17% predicted) were videotaped while performing 2 protocols: one including 2 slow and 2 fast 5-minute walks, and another including a circuit of activities of daily living (ADLs). Concomitantly, patients wore 2 motion sensors: the new pedometer and a multisensor accelerometer. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Step counting (SC), energy expenditure (EE), walking distance (WD), activity time (AT), and walking intensity (WI) registered by the pedometer were compared with video and the multisensor as criterion methods. RESULTS: Correlations between the pedometer and the criterion method were high for SC during slow and fast walking (r=.79 and r=.95) and for EE during fast walking (r=.83). Correlation was more modest for EE during slow walking (r=.65) and for WD and WI during both speeds (.47.79 for all). During the ADLs circuit, the pedometer underestimated AT by an average of 55% but provided an acceptable EE estimation in a group basis (average difference of 6% with the multisensor). CONCLUSIONS: In patients with COPD, the new pedometer analyzed in the present study is reproducible for most outcomes and highly valid for SC during slow and fast walking and EE during fast walking. The device's validity is more limited for EE during slow walking, and WD and WI at both speeds. Furthermore, during the performance of ADLs, it significantly underestimates activity time but provides an acceptable estimation of EE in a group basis.

Obesity and physical activity in the daily life of patients with COPD.

BACKGROUND: The aim of this study was to investigate the differences in body composition between physically active and inactive patients with chronic obstructive pulmonary disease (COPD) and the relationship of obesity [according to body mass index (BMI) and percentage of fat mass (%FM)] with physical activity in the daily life (PADL) in this population. METHODS: Body composition (bioelectrical impedance analysis) and level of PADL (activity monitors DynaPort and SenseWear) were evaluated in 74 patients with COPD (45 men, 65 ± 9 years old, FEV(1) = 40 ± 15%pred, BMI = 27 ± 6 kg m(-2)). Patients were divided in two groups: physically active (>30 min/day of physical activity of at least moderate intensity, or TPA > moderate) and inactive (did not achieve these recommendations). The sample was also classified according to BMI (underweight, normal weight, overweight, and obese) and their %FM (moderate obesity, high obesity, and morbid obesity). RESULTS: In the whole group, TPA > moderate correlated weakly with BMI (r = -0.28; p = 0.02) and FM (r = -0.30; p = 0.001) but not with fat-free mass (FFM) (r = -0.18; p = 0.13). Physically inactive patients had higher body weight (p = 0.002), FM (p = 0.0005), and lower FFM as % of body weight (p = 0.03) than active patients. Obese patients (according to BMI) had a worse PADL level than underweight and normal-weight patients (p < 0.0001). A poorer PADL level occurred in morbidly obese patients (p = 0.01) despite the weak correlation between FM and TPA > moderate in the whole group. CONCLUSION: Physically active patients with COPD have proportionally more FFM and less FM than inactive patients. More pronounced physical inactivity occurs in obese patients, although body composition does not qualify as an important correlate factor of the level of PADL in patients with COPD.

Step counting and energy expenditure estimation in patients with chronic obstructive pulmonary disease and healthy elderly: accuracy of 2 motion sensors.

OBJECTIVE: To compare the accuracy of 2 motion sensors (a pedometer and a multisensor) in terms of step counting and estimation of energy expenditure (EE) in patients with chronic obstructive pulmonary disease (COPD) and in healthy elderly. DESIGN: In this descriptive study, all participants wore both motion sensors while performing a treadmill walking protocol at 3 different speeds corresponding to 30%, 60%, and 100% of the average speed achieved during a six-minute walk test. As criterion methods, EE was estimated by indirect calorimetry, and steps were registered by videotape. SETTING: Research laboratory at a university hospital. PARTICIPANTS: Patients with COPD (n=30; 17 men; mean age +/- SD, 67+/-8 y; mean forced expiratory volume in the first second [FEV(1)] predicted +/- SD, 46%+/-17%; mean body mass index [BMI] +/- SD, 24+/-4 kg.m(2)) and matched healthy elderly (n=30; 15 men; mean age +/- SD, 68+/-7 y; mean FEV(1) predicted +/- SD, 104%+/-21%; mean BMI +/- SD, 25+/-3 kg.m(2)). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Step counting and EE estimation during a treadmill walking protocol. RESULTS: The pedometer was accurate for step counting and EE estimation in both patients with COPD and healthy elderly at the higher speed. However, it showed significant underestimation at the 2 slower speeds in both groups. The multisensor did not detect steps accurately at any speed, although it accurately estimated EE at all speeds in healthy elderly and at the intermediate and higher speeds in patients with COPD. CONCLUSIONS: In both patients with COPD and healthy elderly, the multisensor showed better EE estimates during most walking speeds than the pedometer. Conversely, for step counting, accuracy is observed only with the pedometer during the higher walking speed in both groups.

Relationship between pulmonary function and physical activity in daily life in patients with COPD.

BACKGROUND: It remains unclear how closely the physical inactivity observed in patients with Chronic Obstructive Pulmonary Disease (COPD) relates to the severity of their airflow limitation. Furthermore, it is unknown whether spirometric variables such as maximal voluntary ventilation (MVV) and inspiratory capacity (IC) reflect the level of physical activity in daily life better than the forced expiratory volume in the first second (FEV(1)), the main spirometric variable used to determine the severity of COPD. The objective of the present study was to investigate the relationship between physical activity in daily life and the severity of COPD assessed by different spirometric variables: MVV, IC and FEV(1). METHODS: Forty patients with COPD (21 men; 68+/-7 years; FEV(1) 41+/-14% predicted) were performed spirometry and assessment of the physical activity level in daily life using an accelerometer (SenseWear Armband). RESULTS: MVV was significantly correlated to total energy expenditure per day, energy expenditure per day in activities demanding more than 3 metabolic equivalents (METs), number of steps per day and time spent per day in moderate and vigorous activities (0.42

Londrina Activities of Daily Living Protocol: Reproducibility, Validity, and Reference Values in Physically Independent Adults Age 50 Years and Older.

BACKGROUND: It is important to assess activities of daily living (ADL) in older adults due to impairment of independence and quality of life. However, there is no objective and standardized protocol available to assess this outcome. Thus, the aim of this study was to verify the reproducibility and validity of a new protocol for ADL assessment applied in physically independent adults age ≥50 y, the Londrina ADL protocol, and to establish an equation to predict reference values of the Londrina ADL protocol. METHODS: Ninety-three physically independent adults age ≥50 y had their performance in ADL evaluated by registering the time spent to conclude the protocol. The protocol was performed twice. The 6-min walk test, which assesses functional exercise capacity, was used as a validation criterion. A multiple linear regression model was applied, including anthropometric and demographic variables that correlated with the protocol, to establish an equation to predict the protocol's reference values. RESULTS: In general, the protocol was reproducible (intraclass correlation coefficient 0.91). The average difference between the first and second protocol was 5.3%. The new protocol was valid to assess ADL performance in the studied subjects, presenting a moderate correlation with the 6-min walk test (r = -0.53). The time spent to perform the protocol correlated significantly with age (r = 0.45) but neither with weight (r = -0.17) nor with height (r = -0.17). A model of stepwise multiple regression including sex and age showed that age was the only determinant factor to the Londrina ADL protocol, explaining 21% (P < .001) of its variability. The derived reference equation was: Londrina ADL protocolpred (s) = 135.618 + (3.102 × age [y]). CONCLUSIONS: The Londrina ADL protocol was reproducible and valid in physically independent adults age ≥50 y. A reference equation for the protocol was established including only age as an independent variable (r2 = 0.21), allowing a better interpretation of the protocol's results in clinical practice.

Development, Validity and Reliability of the Londrina Activities of Daily Living Protocol for Subjects With COPD.

BACKGROUND: To avoid symptoms, patients with COPD may reduce the amount of activities of daily living (ADL). Therefore, the aim of the present study was to develop a standardized protocol to evaluate ADL performance in subjects with COPD (Londrina ADL protocol) and to assess the validity and reliability of the protocol in this population. METHODS: The Londrina ADL protocol was created based on activities included in previous studies aimed at investigating outcomes from ADL. Activities were included in the protocol because they could represent other activities of similar patterns and because they could be actually performed, not simulated. Twenty subjects with COPD (12 men, 70 ± 7 y old, FEV1 = 54 ± 15% predicted) wore 2 motion sensors while performing the protocol 4 times, 2 of them wearing a portable gas analyzer. Subjects were also submitted to assessments of lung function, functional exercise capacity, functional status, impact on health status, and physical activity in daily life. RESULTS: The Londrina ADL protocol comprised of 5 activities representing ADL, involving upper limbs, lower limbs, and trunk movements. Londrina ADL protocol duration presented high values of intraclass correlation coefficient, even using a mask for gas analysis (intraclass correlation coefficient >0.90, P < .001). Intensity of movement during the protocol performance was highly correlated to intensity of movement in daily life (r = 0.71). The protocol duration was correlated with functional status and impact on health status variables from questionnaires (0.36 ≤ r ≤ 0.59). There was also correlation between functional exercise capacity and the protocol duration (r = -0.64). CONCLUSIONS: The Londrina ADL protocol was a valid and reliable protocol to evaluate ADL performance in subjects with COPD. It is a protocol that can be used in clinical practice and in future studies to investigate ADL outcomes, including those studies that require gas analysis and the wearing of a mask.

Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life.

Objective: To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method: Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age ≥65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results: In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion: In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients.

Comparison of daily physical activity between COPD patients from Central Europe and South America.

BACKGROUND: In healthy elderly and adults, lower physical activity level in daily life has been associated with lower socio-economic level and non-Caucasian race. The objective of this study was to determine if this is also applicable in chronic obstructive pulmonary disease (COPD) by comparing physical activity levels in daily life in stable patients from two countries (Austria and Brazil) with different socio-economic and ethnic characteristics. METHODS: Physical activity in daily life was objectively assessed in 40 Austrian and 40 Brazilian COPD patients. Groups were matched for age, gender, body mass index, disease severity, smoking history, presence of concomitant heart disease, lung function, dyspnea and functional exercise capacity. In addition, climatic conditions were similar during the period of data collection in the two groups. RESULTS: In comparison to Brazilian patients, Austrian patients had a significantly lower walking time (p=0.04), higher sitting time (p=0.02) and lower movement intensity (p=0.0001). The proportion of patients who did not reach an average of 30min of walking per day was 48% in the Austrian group and 23% in the Brazilian group. CONCLUSIONS: Austrian patients with COPD showed a significantly lower daily physical activity level in comparison to matched Brazilian patients. Socio-economic and ethnic factors appear to influence stable COPD patients differently than described in previous studies including healthy subjects.

Uma visão fisioterapêutica sobre as estratégias ventilatórias utilizadas no manejo do paciente com síndrome do desconforto respiratório agudo (PAP)

A Síndrome do Desconforto Respiratório Agudo foi descrita pela primeira vez em 1967, por Ashbaugh et al. Seu diagnóstico requer a presença de opacidade radiográfica bilateral na ausência de insuficiência cardíaca esquerda ou com pressão da artéria pulmonar menor ou igual a 18 mmHg, com uma relação entre apressão parcial de oxigênio no sangue arterial e a fração inspirada de oxigênio (PaO2/FiO2) menor que 200 mmHg. As tensões mecânicas próprias desta síndrome podem ser pioradas com o uso inadequado da ventilação mecânica, podendo ocorrer a hiperdistensão de alvéolos normais e abertura e fechamento cíclico de alvéolos comprometidos. Há alguns anos, o propósito da assistência ventilatória consistia em ajustar os ventiladores com parâmetros o mais próximos do fisiológico. Já o conceito atual, busca promover suporte ventilatório protetor, ou seja, ventilar evitando os efeitos adversos da ventilação mecânica. Portanto, o presente estudo tem como objetivo mostrar as diversas formas citadas por vários autores sobre a melhor maneira de ventilar um pulmão acometido pela SDRA, assim como a importância da estratégia protetora e a manobra de recrutamento alveolar como uma tentativa de abrir alvéolos colapsados, para obter uma melhor troca gasosa e permitir redução do suporte ventilatório. Para isso, foi realizada uma revisão bibliográfica através de consulta a artigos experimentais e clínicos, nacionais e internacionais, que abordavam a clínica e o tratamento da SDRA com enfoque na ventilação mecânica. Os artigos foram encontrados na base de dados Bireme, MedLine, SciElo, LILACS, CAPES, além de livros e sites de busca, de 1967 a 2008. Após extensa revisão da bibliografia, pode-se sugerir que a assistência ventilatória é primordial para o sucesso do tratamento de indivíduos acometidos pela SDRA, sendo indispensável a utilização de critérios para a escolha da melhor estratégiaventilatória, com o objetivo de minimizar a ocorrência de LPIV, colaborando com...