Validation of "CENTR(AR)" walking trails: Different field criteria do not lead to different physical activity intensities in people with COPD.

BACKGROUND: Validating walking trails is essential to promote physical activity (PA) safely and confidently in people with COPD. OBJECTIVES: We aimed to validate predetermined light, moderate, and vigorous intensities of walking trails in people with COPD. METHODS: This cross-sectional study included individuals with COPD walking in predetermined light, moderate and vigorous intensity trails. Activity intensity and volume outcomes were collected. Dyspnoea and fatigue (modified Borg scale), energy expenditure (EE, Sensewear), heart rate (HR, HR monitor), time spent in different PA intensities, and cadence (ActiGraph) were recorded and used to classify PA intensity. RESULTS: Twenty people with COPD [71(7) years, 80 % male, FEV1%predicted 65.6(11.6)] were included. Fatigue differed significantly between light and moderate [3.0(2.0;4.0) vs 3.4(2.5;4.5), p = 0.01], but not vigorous (3.5[2.5-4.0]) tracks. Dyspnoea [2.3(1.5) vs 2.7(1.6) vs 2.6(1.4)], EE [5.1(0.8) vs 4.9(0.5) vs 4.6(0.8) METs], HR [92.5(11.1) vs 93.7(18.6) vs 95.4(15.0) beats/min] and cadence [115.1(104.0;120.3) vs 104.7(99.6;117.6) vs 111.2(99.9;118.5) steps/min] were similar across trails (p > 0.05). Time spent in light and moderate PA, EE volume, walking time, and step count increased along with the proposed intensity levels (p < 0.01). Walking trails were categorised as moderate intensity in most participants. CONCLUSION: Walking trails were safe and valid for practising moderate-intensity PA in people with COPD. Participants adjusted their physiological responses and perceived symptoms to match a moderate intensity.

Effects of ActiGraph's filter, epoch length and non-wearing time algorithm on step counts in people with COPD.

The influence of the ActiGraph® processing criteria on estimating step counts in chronic obstructive pulmonary disease (COPD) remains uncertain. This study aimed to assess the influence of filters, epoch lengths and non-wearing time (NWT) algorithms on steps/day in people with COPD. ActiGraph GT3X+ was worn on the waist for seven days. Steps were detected using different filters (normal and low-frequency extension [LFE]), epoch lengths (15s and 60s), and NWT algorithms (Choi and Troiano). Linear mixed-effects model was applied to assess the effects of filter, epoch length, NWT algorithm on steps/day. Lin's concordance correlation and Bland-Altman were used to measure agreement. A total of 136 people with COPD (107 male; 69 ± 8 years; FEV1 51 ± 17% predicted) were included. Significant differences were found between filters (p < 0.001), but not between epoch lengths or NWT algorithms. The LFE increased, on average, approximately 7500 steps/day compared to the normal filter (p < 0.001). Agreement was poor (<0.3) and proportional bias was significant when comparing steps/day computed with different filters, regardless of the epoch length and NWT algorithm. Filter choice but not epoch lengths or NWT algorithms seem to impact measurement of steps/day. Future studies are needed to recommend the most accurate technique for measuring steps/day in people with COPD.

Analysis of atorvastatin in environmental waters: Validation of an electrochemical molecularly imprinted polymer sensor with application of life cycle assessment.

The widespread presence of pharmaceuticals in wastewater effluents after treatment stands as a significant challenge faced in the field of wastewater management and public health. Governments and the scientific community have worked to meet this urgent need for effective solutions. Nevertheless, the development of detection strategies for pharmaceutical monitorization capable of delivering rapid, on-site, and sensitive responses remains an ongoing necessity. In this work, the performance of a previously developed molecularly imprinted polymer (MIP) based electrochemical sensor for detecting atorvastatin (ATV) in wastewater effluents and surface waters is presented. A simple preconcentration method followed by electrochemical measurements by differential pulse voltammetry (DPV) in 0.1 M phosphate buffer (pH = 7), was implemented. The analytical results were validated with those obtained on a set of 16 water samples by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Additionally, a life cycle assessment (LCA) was conducted to compare the environmental impact of both methodologies. The results obtained demonstrated that ATV detection using MIP-sensor was reliable when compared to the results found by UHPLC-MS/MS presenting a robust linear correlation coefficient of 0.843. The LCA results show that the novel MIP-sensor technique has lower associated environmental impacts than UHPLC-MS/MS, when the current analytical protocol for pharmaceuticals detection is applied. These findings highlight the potential of the developed MIP-sensor as an eco-friendly analytical tool for routine analysis and point-of-care monitoring of ATV in WWTP wastewater and surface water samples.

Effect of Data Reduction Techniques on Daily Moderate to Vigorous Physical Activity Collected with ActiGraph® in People with COPD.

ActiGraph® is a valid, frequently used, accelerometer to quantify moderate to vigorous physical activities (MVPA) in people with COPD. The impact of ActiGraph processing techniques on this population is unknown. This study aimed to explore the effect of data reduction techniques on MVPA in people with COPD. MVPA/day, through ActiGraph GT3X+, was estimated using: Troiano, Freedson 98 and FreedsonVM3 cutoffs, 15-s and 60-s epochs, and normal and low-frequency extension (LFE) filters. Cutoff, epoch, and filter effects were explored with Aligned Rank Transform-ANOVA. Lin's concordance correlation coefficients and Bland-Altman plots were used to evaluate agreement and bias between different techniques. The analysis included 136 people with COPD (79% male; 68 ± 8 years; FEV1 51 ± 17% predicted). MVPA/day differed according to cutoff, filter, and epoch selection (p-value < 0.001). FreedsonVM3 cutoff, 15-s epochs, and LFE yielded the highest MVPA (45 min/day, 68% of physically active participants). Troiano cutoff, 60-s epochs, and normal filter yielded the lowest MVPA (8 min/day, 20% of physically active participants). Only comparisons between Troiano and Freedson98 cutoffs presented an almost perfect agreement. ActiGraph data reduction techniques affected MVPA/day estimates and their interpretation at the individual and group level. Studies using different processing criteria should not be compared in people with COPD. Future studies with a gold standard are required to ascertain which processing technique produces the most accurate MVPA estimates in COPD. Meanwhile, future trials employing the ActiGraph GT3X+ may consider estimating MVPA based on Freedson VM3 cutofffs, 60-s epochs, and normal filter.

Computational Modelling and Sustainable Synthesis of a Highly Selective Electrochemical MIP-Based Sensor for Citalopram Detection.

A novel molecularly imprinted polymer (MIP) has been developed based on a simple and sustainable strategy for the selective determination of citalopram (CTL) using screen-printed carbon electrodes (SPCEs). The MIP layer was prepared by electrochemical in situ polymerization of the 3-amino-4 hydroxybenzoic acid (AHBA) functional monomer and CTL as a template molecule. To simulate the polymerization mixture and predict the most suitable ratio between the template and functional monomer, computational studies, namely molecular dynamics (MD) simulations, were carried out. During the experimental preparation process, essential parameters controlling the performance of the MIP sensor, including CTL:AHBA concentration, number of polymerization cycles, and square wave voltammetry (SWV) frequency were investigated and optimized. The electrochemical characteristics of the prepared MIP sensor were evaluated by both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Based on the optimal conditions, a linear electrochemical response of the sensor was obtained by SWV measurements from 0.1 to 1.25 µmol L-1 with a limit of detection (LOD) of 0.162 µmol L-1 (S/N = 3). Moreover, the MIP sensor revealed excellent CTL selectivity against very close analogues, as well as high imprinting factor of 22. Its applicability in spiked river water samples demonstrated its potential for adequate monitoring of CTL. This sensor offers a facile strategy to achieve portability while expressing a willingness to care for the environment.

Electropolymerized, Molecularly Imprinted Polymer on a Screen-Printed Electrode-A Simple, Fast, and Disposable Voltammetric Sensor for Trazodone.

In recent years, analytical chemistry has been facing new challenges, particularly in developing low-cost, green, and easy-to-reproduce methods. In this work, a simple, reproducible, and low-cost electrochemical (voltammetric) molecularly imprinted polymer (MIP) sensor was designed specifically for the detection of trazodone (TZD). Trazodone (TZD) is an antidepressant drug consumed worldwide since the 1970s. By combining electropolymerization (surface imprinting) with screen-printed electrodes (SPCEs), the sensor is easy to prepare, is environmentally friendly (uses small amounts of reagents), and can be used for in situ analysis through integration with small, portable devices. The MIP was obtained using cyclic voltammetry (CV), using 4-aminobenzoic acid (4-ABA) as the functional monomer in the presence of TZF molecules in 0.1 M HCl. Non-imprinted control was also constructed in the absence of TZD. Both polymers were characterized using CV, and TZD detection was performed with DPV using the oxidation of TZD. The polymerization conditions were studied and optimized. Comparing the TZD signal for MIP/SPCE and NIP/SPCE, an imprinting factor of 71 was estimated, indicating successful imprinting of the TZD molecules within the polymeric matrix. The analytical response was linear in the range of 5-80 µM, and an LOD of 1.6 µM was estimated. Selectivity was evaluated by testing the sensor for molecules with a similar structure to TZD, and the ability of MIP/SPCE to selectively bind to TZD was proven. The sensor was applied to spiked tap water samples and human serum with good recoveries and allowed for a fast analysis (around 30 min).

A simple electrochemical detection of atorvastatin based on disposable screen-printed carbon electrodes modified by molecularly imprinted polymer: Experiment and simulation.

Atorvastatin (ATV) is a statin member consumed in high quantities worldwide. In response to that, the occurrence of ATV in environmental waters has become a reality, highlighting the need of rapid and sensitive analytical devices for its monitoring. In this work, the first electrochemical molecularly imprinted polymer (MIP) sensor for the detection of ATV in water samples is presented. Computational studies were conducted based on quantum mechanical (QM) calculations and molecular dynamics (MD) simulations for rational selection of a suitable functional monomer and to study in detail the template-monomer interaction, respectively. The sensor was prepared by electropolymerisation of the selected 4-aminobenzoic acid (ABA) monomer with ATV, acting as template, on screen printed carbon electrode (SPCE). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques were applied to characterise the modified electrode surfaces. The quantitative measurements were carried out with differential pulse voltammetry (DPV) in 0.1 M phosphate buffer (pH = 7). After investigation and optimisation of important experimental parameters, a linear working range down to 0.05 µmol L-1 was determined with a correlation coefficient of 0.9996 and a limit of detection (LOD) as low as 0.049 µmol L-1 (S/N = 3). High sensitivity and selectivity of the prepared sensor were demonstrated with the ability to recognise ATV molecules over its closer structural analogues. Moreover, the sensor was quickly and successfully applied in spiked water samples, proving its potential for future on-site monitoring of ATV in environmental waters.

Measuring intensity during free-living physical activities in people with chronic obstructive pulmonary disease: A systematic literature review.

BACKGROUND: Measuring intensity of physical activity (PA) is important to ensure safety and the effectiveness of PA interventions in chronic obstructive pulmonary disease (COPD). OBJECTIVE: This systematic review identified which outcomes, outcome measures and instruments have been used to assess single free-living PA-related intensity in people with COPD and compared the intensity level (light, moderate, vigorous) obtained by different outcome measures. METHODS: PubMed, Scopus, Web of Science, Cochrane Library and EBSCO were searched for original studies of COPD and assessing single free-living PA-related intensity were included. Agreement was calculated as the number of agreements between 2 measures [same intensity level]/ number of comparisons using both measures*100. RESULTS: We included 43 studies (1282 people with COPD, mean age 66 years, 65% men, 49% FEV1%pred) and identified 13 outcomes, 46 outcome measures and 22 instruments. The most-reported outcomes, outcome measures and instruments were dyspnoea with the Borg scale 0-10; cardiac function, via heart rate (HR) using HR monitors; and pulmonary gas exchange, namely oxygen consumption (VO2), using portable gas analysers, respectively. The most frequently assessed PAs were walking and lifting, changing or moving weights/objects. Agreement between the outcome measures ranged from 0 (%VO2peak vs metabolic equivalent of task [MET];%HRpeak vs Fatigue Borg; MET vs walking speed) to 100% (%HRreserve vs dyspnoea Borg; fatigue and exertion Borg vs walking speed).%VO2peak/reserve elicited the highest intensity. Hence, Borg scores,%HRreserve and MET may underestimate PA-related intensity. CONCLUSIONS: Various methodologies are used to assess single free-living PA-related intensity and yield different intensity levels for the same PA. Future studies, further exploring the agreement between the different outcome measures of PA-related intensity and discussing their advantages, disadvantages and applicability in real-world settings, are urgent. These would guide future worldwide recommendations on how to assess single free-living PA-related intensity in COPD, which is essential to optimise PA interventions and ensure patient safety.

Extended Cheese Whey Fermentation Produces a Novel Casein-Derived Antibacterial Polypeptide That Also Inhibits Gelatinases MMP-2 and MMP-9.

Our previous works produced a whey fermentation methodology that yielded antibacterial activity and potential inhibition of matrix metalloproteases (MMP)-2 and -9. Here, we evaluated if these activities were due to fermentation-produced peptides. Prolonged fermentation was carried out in the presence of our specific lactic acid bacteria (LAB) consortium. LAB fermentation yielded a total of 11 polypeptides, which were predominantly produced after 6 days of fermentation. One which was derived from beat casein presented a particularly high antibacterial activity against food pathogenic bacteria and was more effective than standard food disinfectants. This polypeptide was further studied and was also found to be active against several strains of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in a dose-dependent manner. It also inhibited MMP-2 and MMP-9 whilst reducing HT29 cancer cell migration in vitro. Overall, this novel whey-derived polypeptide presents dual antibacterial and anti-inflammatory activity, revealing a strong potential to be used in functional foods or as a nutraceutical. Its identification and further characterization can open novel perspectives in the field of preventive/curative diets related to gut microbiota, gut inflammation, and cancer prevention, particularly if used in in vivo studies.

Responsiveness and Minimal Clinically Important Difference of the Brief-BESTest in People With COPD After Pulmonary Rehabilitation.

OBJECTIVE: he Brief-Balance Evaluation Systems Test (Brief-BESTest) is a comprehensive, reliable, and valid balance test that provides valuable information to guide balance training in people with chronic obstructive pulmonary disease (COPD). Its clinical interpretability is, however, currently limited, because cutoff points to identify clinically relevant changes in people with COPD after pulmonary rehabilitation are still lacking. This study aimed to establish the responsiveness and minimal clinically important difference (MCID) for the Brief-BESTest in people with COPD after pulmonary rehabilitation (PR). METHODS: A secondary analysis of data from 2 previous studies was conducted. The modified British Medical Research Council (mMRC) dyspnea scale, the 6-Minute Walk Test (6-MWT), and the Brief-BESTest (0-24 points) were collected in people with COPD pre/post a 12-week PR program including balance training. The MCID was computed using anchor- and distribution-based methods. Changes in the 6-MWT and the mMRC were assessed and used as anchors. The pooled MCID was computed using the arithmetic weighted mean (2/3 anchor- and 1/3 distribution-based methods). RESULTS: Seventy-one people with COPD (69 years [SD = 8]; 76% male; FEV1 = 49.8%predicted [SD = 18%]) were included. There was a significant improvement in the Brief-BESTest after PR (mean difference = 3 points [SD = 3]). Significant correlations were found between the Brief-BESTest and the mMRC (r = -.31) and the 6-MWT (r = .37). The pooled MCID was 3.3 points. CONCLUSION: An improvement of at least 3 points in the Brief-BESTest in people with COPD will enhance the interpretability of PR effects on balance performance of this population and guide tailored interventions. IMPACT: The Brief-BESTest outcome measure is comprehensive, easily administered, and simple to interpret in clinical practice. This study represents a significant contribution toward the clinical interpretation of changes in balance in people with COPD following PR.

Minimal Clinically Important Difference for Quadriceps Muscle Strength in People with COPD following Pulmonary Rehabilitation.

Quadriceps strength training is a key component of pulmonary rehabilitation (PR). Clinical interpretability of changes in muscle strength following PR is however limited due to the lack of cut-off values to define clinical improvement. This study estimated the minimal clinically important difference (MCID) for the isotonic and isometric quadriceps muscle strength assessed with the one-repetition maximum (1RM) and hand-held dynamometry (HHD) in people with chronic obstructive pulmonary disease (COPD) following PR.A secondary analysis of a real life non-randomised controlled study was conducted in people with COPD enrolled in a 12-week community-based PR programme. Anchor and distribution-based methods were used to compute the MCIDs. The anchors explored were the St. George's respiratory questionnaire (SGRQ) and the six-minute walk test (6MWT) using Pearson's correlations. Pooled MCIDs were computed using the arithmetic weighted mean (2/3 anchor, 1/3 distribution-based methods) and reported as absolute and/or percentage of change values.Eighty-nine people with COPD (84% male, 69.9 ± 7.9 years, FEV1 49.9 ± 18.9% predicted) were included. No correlations were found between changes in 1RM and the SGRQ neither between changes in HHD and the SGRQ and 6MWT (p > 0.05). Thus, anchor-based methods were used only in the MCID of the 1RM with the 6MWT as the anchor. The pooled MCIDs were 5.7Kg and 26.9% of change for the isotonic quadriceps muscle strength with 1RM and 5.2KgF for isometric quadriceps muscle strength assessed with HHD.The MCIDs found are estimates to improve interpretability of community-based PR effects on quadriceps muscle strength and may contribute to guide interventions.

Construct validity of the brief physical activity assessment tool for clinical use in COPD.

INTRODUCTION: Low physical activity (PA) levels are associated with poor health-related outcomes in Chronic Obstructive Pulmonary Disease (COPD). Thus, PA should be routinely assessed in clinical practice. OBJECTIVES: This study assessed the construct validity of the Brief Physical Activity Assessment Tool (BPAAT) for clinical use in COPD and explored differences in age, sex and COPD grades. METHODS: After linguistic adaptation of the tool to Portuguese, 110 patients (66.4 ± 9.6yrs, 72.7% male, FEV1  = 59.3 ± 25.5%predicted) completed the BPAAT and received an accelerometer. The BPAAT includes two questions assessing the weekly frequency and duration of vigorous- and moderate-intensity PA/walking, classifying individuals as insufficiently or sufficiently active. The BPAAT was correlated with accelerometry (moderate PA, MPA = 1952-5724 counts-per-min [CPM]); vigorous PA, VPA = 5725-∞CPM; moderate-to-vigorous PA, MVPA = 1952-∞CPM; daily steps), through: Spearman's correlations (ρ) for continuous data; %agreement, Kappa, sensitivity and specificity, positive and negative predictive values (PPV, NPV) for categorical data. RESULTS: The BPAAT identified 73.6% patients as "insufficiently active" and 26.4% as "sufficiently active". The BPAAT was weakly to moderately correlated with accelerometry (0.394 ≤ ρ ≤ 0.435, P < 0.05), except for VPA (P = 0.440). This was also observed in age (<65/≥65yrs), COPD grades (GOLD 1-2/3-4) and in male patients (0.363 ≤ ρ ≤ 0.518, P < 0.05 except for VPA). No significant correlations were found in female patients (P > 0.05). Agreement was fair to moderate (0.36 ≤ κ ≤ 0.43; 73.6% ≤ %agreement ≤ 74.5%; 0.50 ≤ sensitivity ≤ 0.52; 0.84 ≤ specificity ≤ 0.91, 0.55 ≤ PPV ≤ 0.79, 0.72 ≤ NPV ≤ 0.82). CONCLUSION: The BPAAT may be useful to screen patients' PA, independently of age and COPD grade, and identify male patients who are insufficiently active. Care should be taken when using this tool to assess vigorous PA or female patients.

Molecularly imprinted polymer-based electrochemical sensors for environmental analysis.

The ever-increasing presence of contaminants in environmental waters is an alarming issue, not only because of their harmful effects in the environment but also because of their risk to human health. Pharmaceuticals and pesticides, among other compounds of daily use, such as personal care products or plasticisers, are being released into water bodies. This release mainly occurs through wastewater since the treatments applied in many wastewater treatment plants are not able to completely remove these substances. Therefore, the analysis of these contaminants is essential but this is difficult due to the great variety of contaminating substances. Facing this analytical challenge, electrochemical sensing based on molecularly imprinted polymers (MIPs) has become an interesting field for environmental monitoring. Benefiting from their superior chemical and physical stability, low-cost production, high selectivity and rapid response, MIPs combined with miniaturized electrochemical transducers offer the possibility to detect target analytes in-situ. In most reports, the construction of these sensors include nanomaterials to improve their analytical characteristics, especially their sensitivity. Moreover, these sensors have been successfully applied in real water samples without the need of laborious pre-treatment steps. This review provides a general overview of electrochemical MIP-based sensors that have been reported for the detection of pharmaceuticals, pesticides, heavy metals and other contaminants in water samples in the past decade. Special attention is given to the construction of the sensors, including different functional monomers, sensing platforms and materials employed to achieve the best sensitivity. Additionally, several parameters, such as the limit of detection, the linear concentration range and the type of water samples that were analysed are compiled.

Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts.

BACKGROUND: Aloe's reported bioactivities (anticancer, anti-inflammatory and wound healing) suggest they might inhibit a subgroup of matrix metalloproteinases (MMPs) called gelatinases (MMP-2 and MMP-9). The goal of the present study was to compare the MMP inhibitory potential of two Aloe species, A. vera and A. arborescens. METHODS: Different types of extraction were tested and specific bioactive compounds were quantified. Cancer cell invasion inhibitory activities were measured in vitro using the wound healing assay in human colon cancer cells (HT29). Effects on gelatinase activities were further assessed by dye-quenched gelatin and gelatin zymography. RESULTS: Different types of extraction yielded significantly different levels of bioactivities and of bioactive compounds, which might be due to a greater amount of extractable bioactive compounds such as anthraquinones. Both A. arborescens and A. vera have potential as inhibitory agents in cancer cell proliferation via MMP-9 and MMP-2 enzymatic activity inhibition, being able to reduce colon cancer cell proliferation and migration but A. arborescens showed to be a more effective inhibitor of cancer cell migration than A. vera. CONCLUSION: This work opens novel perspectives on the mode of action of Aloe species in cancer cell migration and may provide clues as to why there are so many conflicting results on Aloe's activities.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Fatigue in Patients With COPD Following Pulmonary Rehabilitation.

BACKGROUND: Fatigue is a burdensome and prevailing symptom in patients with COPD. Pulmonary rehabilitation (PR) improves fatigue; however, interpreting when such improvement is clinically relevant is challenging. Minimal clinically important differences (MCIDs) for instruments assessing fatigue are warranted to better tailor PR and guide clinical decisions. RESEARCH QUESTION: This study estimated MCIDs for the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-FS), the modified FACIT-FS, and the Checklist Individual Strength-Fatigue Subscale in patients with COPD following PR. STUDY DESIGN AND METHODS: Data from patients with COPD who completed a 12-week community-based PR program were used to compute the MCIDs. The pooled MCID was estimated by calculating the arithmetic weighted mean, resulting from the combination of anchor-based (weight, two-thirds) and distribution-based (weight, one-third) methods. Anchors were patients' and physiotherapists' Global Rating of Change Scale, COPD Assessment Test, St. George's Respiratory Questionnaire (SGRQ), and exacerbations. To estimate MCIDs, we used mean change, receiver-operating characteristic curves, and linear regression analysis for anchor-based approaches, and 0.5 × SD, SE of measurement, 1.96 × SE of measurement, and minimal detectable change for distribution-based approaches. RESULTS: Fifty-three patients with COPD (79% male, 68.4 ± 7.6 years of age, and FEV1 48.7 ± 17.4% predicted) were included in the analysis. Exacerbations and the SGRQ-impact and the SGRQ-total scores fulfilled the requirements to be used as anchors. Pooled MCIDs were 4.7 for FACIT-FS, 3.8 for the modified FACIT-FS, and 9.3 for the Checklist Individual Strength-Fatigue Subscale. INTRPRETATION: The MCIDs proposed in this study can be used by different stakeholders to interpret PR effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03799666; URL: www.clinicaltrials.gov.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Cough and Sputum in Patients with COPD.

Background: Cough and sputum are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) has shown to be effective in managing these symptoms. However, the interpretation of the magnitude of PR effects is hindered by the lack of minimal clinically important differences (MCIDs). Purpose: This study established MCIDs for the Leicester cough questionnaire (LCQ) and the cough and sputum assessment questionnaire (CASA-Q), in patients with COPD after PR. Patients and Methods: An observational prospective study was conducted in patients with COPD who participated in a 12-weeks community-based PR program. Anchor- (mean change, receiver operating characteristic curves and linear regression analysis) and distribution-based methods [0.5*standard deviation; standard error of measurement (SEM); 1.96*SEM; minimal detectable change and effect size] were used to compute the MCIDs. The anchors used were: i) patients and physiotherapists global rating of change scale, ii) COPD assessment test, iii) St. George's respiratory questionnaire and iv) occurrence of an exacerbation during PR. Pooled MCIDs were computed using the arithmetic weighted mean (2/3 for anchor- and 1/3 for distribution-based methods). Results: Forty-nine patients with COPD (81.6% male, 69.8±7.4years, FEV150.4±19.4%predicted) were used in the analysis. The pooled MCIDs were 1.3 for LCQ and for CASA-Q domains were: 10.6 - cough symptoms; 10.1 - cough impact; 9.5 - sputum symptoms and 7.8 - sputum impact. Conclusion: The MCIDs found in this study are potential estimates to interpret PR effects on cough and sputum, and may contribute to guide interventions.

Improving access to community-based pulmonary rehabilitation: 3R protocol for real-world settings with cost-benefit analysis.

BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated patients' physiological and psychosocial improvements, symptoms reduction and health-economic benefits whilst enhances the ability of the whole family to adjust to illness. However, PR remains highly inaccessible due to lack of awareness of its benefits, poor referral and availability mostly in hospitals. Novel models of PR delivery are needed to enhance its implementation while maintaining cost-efficiency. We aim to implement an innovative community-based PR programme and assess its cost-benefit. METHODS: A 12-week community-based PR will be implemented in primary healthcare centres where programmes are not available. Healthcare professionals will be trained. 73 patients with CRD and their caregivers (dyads patient-caregivers) will compose the experimental group. The control group will include dyads age- and disease-matched willing to collaborate in data collection but not in PR. Patients/family-centred outcomes will be dyspnoea (modified Medical Research Council Questionnaire), fatigue (Checklist of individual strength and Functional assessment of chronic illness therapy - fatigue), cough and sputum (Leicester cough questionnaire and Cough and sputum assessment questionnaire), impact of the disease (COPD Assessment Test), emotional state (The Hospital Anxiety and Depression Scale), number of exacerbations, healthcare utilisation, health-related quality of life and family adaptability/cohesion (Family Adaptation and Cohesion Scale). Other clinical outcomes will be peripheral (biceps and quadriceps-hand held dynamometer, 1 or 10 repetition-maximum) and respiratory (maximal inspiratory and expiratory pressures) muscle strength, muscle thickness and cross sectional area (biceps brachialis, rectus femoris and diaphragm-ultrasound imaging), exercise capacity (six-minute walk test and one-minute sit to stand test), balance (brief-balance evaluation systems test) and physical activity (accelerometer). Data will be collected at baseline, at 12 weeks, at 3- and 6-months post-PR. Changes in the outcome measures will be compared between groups, after multivariate adjustment for possible confounders, and effect sizes will be calculated. A cost-benefit analysis will be conducted. DISCUSSION: This study will enhance patients access to PR, by training healthcare professionals in the local primary healthcare centres to conduct such programmes and actively involving caregivers. The cost-benefit analysis of this intervention will provide an evidence-based insight into the economic benefit of community-based PR in chronic respiratory diseases. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov U.S. National Library of Medicine, on 10th January, 2019 (registration number: NCT03799666 ).

Electrochemical sensing of the thyroid hormone thyronamine (T0AM) via molecular imprinted polymers (MIPs).

Recent studies have shown that besides the well-known T3 (triiodothyronine) and T4 (thyroxine) there might be other important thyroid hormones, in particular T0AM (thyronamine) and T1AM (3-iodothyronamine). The absence of a large number of studies showing their precise importance might be explained by the limited number of analytical methodologies available. This work aims to show an electroanalytical alternative making use of electropolymerized molecularly imprinted polymer (MIPs). The MIPs' polymerization is performed on the surface of screen-printed carbon electrodes (SPCEs), using 4-aminobenzoic acid (4-ABA) as the building and functional monomer and the analyte T0AM as the template. The step-by-step construction of the SPCE-MIP sensor was studied by cyclic voltammetry (CV) and by electrochemical impedance spectroscopy (EIS). After optimization, by means of square-wave voltammetry, the SPCE-MIP showed suitable selectivity (in comparison with other thyroid hormones and catechol amines), repeatability (intra-day of 3.9%), a linear range up to 10 µmol L-1 (0.23 × 103 µg dL-1) with an r2 of 0.998 and a limit of detection (LOD) and quantification (LOQ) of 0.081 and 0.27 µmol L-1 (1.9 and 6.2 µg dL-1), respectively.

PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer.

BACKGROUND: Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. METHODS: We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test. DISCUSSION: Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice. TRIAL REGISTRATION: ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD.