Targeting Limb Muscle Dysfunction in COPD

Chronic obstructive pulmonary disease (COPD), is today one of the world’s most common chronic diseases, estimated by the World Health Organization to be the third leading cause of death worldwide by the year 2030. An often neglected aspect of COPD is that the course of the disease is linked to extrapulmonary manifestations that are currently not dealt with optimally, but that has a direct and substantial impact on the condition. Limb muscle dysfunction, at the functional level defined as the reduction of either strength or endurance (or both) properties of the muscle, is highly prevalent in COPD, closely linked to critical clinical and prognostic outcomes including functional status, quality of life, and even mortality. If the goal is to improve limb muscle function among people with COPD is exercise training recommended before other treatment modalities, highly prioritized in international guidelines. In this chapter, why and how to assess and manage limb muscle dysfunction among people with COPD will be targeted, highlighting the vital role of physical therapy and the physiotherapist

Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping.

Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples

Strain-level bacterial typing directly from patient samples using optical DNA mapping

For bacterial infections, it is important to rapidly and accurately identify and characterize the type of bacteria involved so that optimal antibiotic treatment can be given quickly to the patient. However, current diagnostic methods are sometimes slow and cannot be used for mixtures of bacteria. We have, therefore, developed a method to identify bacteria directly from patient samples. The method was tested on two common species of disease-causing bacteria - Escherichia coli and Klebsiella pneumoniae - and it could correctly identify the bacterial strain or subtype in both urine samples and mixtures. Hence, the method has the potential to provide fast diagnostic information for choosing the most suited antibiotic, thereby reducing the risk of death and suffering. Nyblom, Johnning et al. develop an optical DNA mapping approach for bacterial strain typing of patient samples. They demonstrate rapid identification of clinically relevant E. coli and K. pneumoniae strains, without the need for cultivation. BackgroundIdentification of pathogens is crucial to efficiently treat and prevent bacterial infections. However, existing diagnostic techniques are slow or have a too low resolution for well-informed clinical decisions.MethodsIn this study, we have developed an optical DNA mapping-based method for strain-level bacterial typing and simultaneous plasmid characterisation. For the typing, different taxonomical resolutions were examined and cultivated pure Escherichia coli and Klebsiella pneumoniae samples were used for parameter optimization. Finally, the method was applied to mixed bacterial samples and uncultured urine samples from patients with urinary tract infections.ResultsWe demonstrate that optical DNA mapping of single DNA molecules can identify Escherichia coli and Klebsiella pneumoniae at the strain level directly from patient samples. At a taxonomic resolution corresponding to E. coli sequence type 131 and K. pneumoniae clonal complex 258 forming distinct groups, the average true positive prediction rates are 94% and 89%, respectively. The single-molecule aspect of the method enables us to identify multiple E. coli strains in polymicrobial samples. Furthermore, by targeting plasmid-borne antibiotic resistance genes with Cas9 restriction, we simultaneously identify the strain or subtype and characterize the corresponding plasmids.ConclusionThe optical DNA mapping method is accurate and directly applicable to polymicrobial and clinical samples without cultivation. Hence, it has the potential to rapidly provide comprehensive diagnostics information, thereby optimizing early antibiotic treatment and opening up for future precision medicine management

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Relevans och bedömning av muskelfunktion hos personer med kroniskt obstruktiv lungsjukdom

Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD. Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2). Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49). Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity

Relevans och bedömning av muskelfunktion hos personer med kroniskt obstruktiv lungsjukdom

Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD. Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2). Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49). Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity

Kärlek kommer! : En undersökning av etnicitetsrepresentation i en svensk reklamföljetong

Den här uppsatsen undersöker om karaktärerna i Comviqs populära reklamföljetong om kioskägaren Karim utsatts för någon form av reduktion och/eller stereotypisering baserad på etnicitet. Med en teoretisk ansats från verk av erkända forskare som studerat stereotyper, representation, svensk film och media bland annat, har det empiriska materialet, reklamföljetongen, analyserats enligt den semiotiska traditionen. Materialet tolkas och diskuterats med stöd i den teoretiska ansatsen, med syfte att avslöja eventuell negativ missrepresentation av etniciteter. Uppsatsen avser också att diskutera vad framställningen av karaktärerna skulle kunna ha för effekt på diverse etniska grupper i samhället. Resultatet av undersökningen landade i att en viss grad av stereotyp framställning försiggår, men att det slutgiltiga budskapet som förs fram har en positiv och antirasistisk klang

Physiological responses to arm versus leg activity in patients with chronic obstructive pulmonary disease : a systematic review protocol

Compared with healthy older adults, people with chronic obstructive pulmonary disease (COPD) have reduced capacity and increased symptoms during leg and arm activities. While the mechanisms underlying limitations and symptoms during leg activities have been investigated in detail, limitations and symptoms during arm activities are not well understood, and the potential differences between physiological responses of leg and arm activities have not been systematically synthesised. Determining physiological responses and symptoms of arm activities compared with physiological responses and symptoms of leg activities will help us understand the mechanisms behind the difficulties that people with COPD experience when performing physical activities, and determine how exercise training should be prescribed. Thus, the aim of this systematic review is to compare the physiological responses and symptoms during activities involving the arms relative to activities involving the legs in people diagnosed with COPD

Physiological and Symptomatic Responses to Arm versus Leg Activities in People with Chronic Obstructive Pulmonary Disease : A Systematic Review and Meta-Analysis

While the mechanisms underlying exercise limitations and symptoms during leg activities have been investigated in detail, knowledge of potential differences between leg and arm activities are not well understood and results from individual studies are contradictory. Thus, the aim of the present study was to synthesize physiological and symptomatic responses during activities involving the arms relative to activities involving the legs in people with Chronic Obstructive Pulmonary Disease (COPD). Any study with a cross-sectional comparison of acute physiological (cardiorespiratory, metabolic) and symptomatic responses to activities performed with the arms versus the legs were included. Studies were sub-grouped based on the type of activity performed (cycle ergometer, resistance exercises, or functional test/activities). Eighteen studies with 423 individuals with COPD were included. Leg cycle ergometer resulted in greater tidal volume (137?mL), minute ventilation (4.8?L/min), and oxygen consumption (164?mL/min) than arm cycle ergometer, while symptomatic responses were similar. Resistance exercises resulted in similar physiological and symptomatic responses irrespective of whether the legs or the arms were involved while studies on functional activities report different results depending on the type and intensity of the activity performed. With the exception of cycle ergometer activities, physiological and symptomatic responses do not seem to depend on whether the arms or the legs are used, but rather seem to be task and intensity dependent. These novel findings suggest, for example, that strategies used to increase exercise tolerance should not be dependent on whether the arms or the legs are used, but rather the intensity of specific activity performed

Applicability of a supramaximal high-intensity interval training program for older adults previously not engaged in regular exercise : analyses of secondary outcomes from the Umeå HIT Study

This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults