COL4A3 is degraded in allergic asthma and degradation predicts response to anti-IgE therapy.

BACKGROUND: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). OBJECTIVE: To delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response. METHODS: The serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (paediatric cases/controls: n=134/n=35; adult cases/controls: n=149/n=31). Exacerbation of allergic airway disease in mice was induced by sensitising to ovalbumin (OVA), challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor; Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (n=14) and cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA; n=9) as well as patients with severe allergic uncontrolled asthma (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed using the Asthma Control Test. RESULTS: Serum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in cystic fibrosis plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic OR 31.5). CONCLUSION: C4Ma3 levels depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response

Defining components of early functional rehabilitation for acute achilles tendon rupture: A systematic review

Background: Early functional rehabilitation is frequently discussed in treating Achilles tendon rupture. A consistent definition of what constitutes early functional rehabilitation has not been established across the literature, despite studies supporting its efficacy. A standardized definition would be helpful to pool data across studies, allow for between-study comparisons, and ultimately work toward developing clinical guidelines. Purpose: To define early functional rehabilitation (including when it is initiated and what it entails) when used to treat Achilles tendon rupture and to identify outcome measures for evaluating the effect of treatment. Study Design: Systematic review; Level of evidence, 4. Methods: Ovid MEDLINE, EMBASE, PEDro, CINAHL, and Cochrane databases were searched for relevant studies. Eligibility criteria for selecting studies consisted of randomized controlled trials, cohort studies, and case series (≥10 participants) including weightbearing or exercise-based interventions within 8 weeks after Achilles tendon rupture. Results: A total of 174 studies published between 1979 and 2018 were included. Studies were rated a median (interquartile range [IQR]) of 17 (15-20) on the Downs & Black checklist and included 9098 participants. Early functional rehabilitation incorporated weightbearing (95%), range of motion (73%), and isometric/strengthening exercises (50%). Weightbearing was initiated within the first week, whereas exercise (eg, ankle range of motion, strengthening, whole-body conditioning) was initiated in the second week. Initiation of exercises varied based on whether treatment was nonsurgical (mean, 3.0 weeks; IQR, 2.0-4.0 weeks) or simple (mean, 2.0 weeks; IQR, 0.0-2.3 weeks) or augmented surgical repair (mean, 0.5 weeks; IQR, 0.0-2.8 weeks) ( Conclusion: Early functional rehabilitation includes weightbearing and a variety of exercise-based interventions initiated within the first 2 weeks after acute Achilles tendon rupture/repair. Because early functional rehabilitation has lacked a standardized definition, interventions and outcome measures are highly variable, and pooling data across studies should be done with attention paid to what was included in the intervention and how treatment was assessed

Feasibility of an early progressive resistance exercise program for acute Achilles tendon rupture

BACKGROUND: Long-term strength deficits are common after Achilles tendon ruptures. Early use of progressive resistance exercises may help reduce strength deficits, but the feasibility of this approach is unknown. The aim was to investigate the feasibility of early progressive resistance exercises regarding patient acceptability and compliance with the intervention.METHODS: We recruited patients with an acute Achilles tendon rupture treated non-surgically. During 9 weeks of immobilisation with a walking boot, participants attended weekly supervised physiotherapy sessions of progressive resistance exercises and performed home exercises, consisting of isometric ankle plantarflexion, seated heel-rise, and elastic band exercises. Acceptability was evaluated using a 7-point Likert scale (1 = very unacceptable and 7 = very acceptable) with feasibility threshold at 80% of the participants rating ≥ 4. Adherence to the exercises was defined as 80% of the participants performing at least 50% of the home exercises. During the intervention, tendon healing and adverse events were monitored.RESULTS: Sixteen participants (mean age 46 (range 28-61), male/female = 13/3) completed the intervention. Pre-injury Achilles tendon total rupture score was 98 (SD 8). All participants rated the acceptability of the exercises ≥ 5 (moderate acceptable to very acceptable) at 9- and 13-week follow-up and 9/16 rated 7 points (very acceptable). Participants performed 74% (range 4-117) of the total prescribed home exercises and 15/16 performed &gt; 50%. One participant was not compliant with the home exercises due to feeling uncomfortable performing these independently. There were no re-ruptures, but one case of deep venous thrombosis.CONCLUSIONS: The early progressive resistance exercise program for treatment of non-surgically treated Achilles tendon rupture was feasible. Future studies should investigate the efficacy of the progressive intervention.TRIAL REGISTRATION: The study was registered at Clinical Trials (NCT04121377) on 29 September 2019.CLINICALTRIALS: NCT04121377 .</p

The investigation of the permittivity of syntactic foam under varying humidity

The dielectric properties of syntactic foam samples, with emphasis on the complex permittivity, were studied via dielectric spectroscopy. The investigated syntactic foam samples consist of an epoxy matrix, filled with hollow glass spheres of 60 microns diameter on average with a high filler rate of 50% of volume. In order to see the influence of adsorbed water, the filler of one sample type was stored under 80% humidity to create wet samples, while the other samples were constantly kept dry. Previous measurements showed increased DC conductivity for syntactic foam - up to two orders of magnitude compared to conventional filled epoxy. This was suspected to be due to the relative high conductivity of the glass, as well as due to the sheer amount of glass spheres and therefore plenty of interfaces. Recent measurement at lower frequencies (below 10-2 Hz) showed quasi-dc-behavior and virtually no difference for both dry and wet samples at 70degC, while dry samples had generally higher values in permittivity for 40degC. It is shown that the glass spheres overshadow the influence of adsorbed water in the syntactic foam samples measured

Dielectric behavior of syntactic foams at low temperatures and frequencies

Syntactic foam is a lightweight composite consisting of hollow particles embedded in a polymer resin matrix. In this paper, results are presented of dielectric spectroscopy measurements on test specimens of syntactic foam with glass micro-spheres partially filled with SO2 . This type of syntactic foam is intended to be used as a high performance insulating material for lightweight high-voltage DC applications. The dielectric spectroscopy results showed an anomalous non-Debye behavior in a temperature range from roughly -140degC to +40degC. With increasing temperature the losses decrease at first, until they suddenly increase again at about +40degC. It has to be noted that the overall losses were quite high, compared to the base material. It appears that either the increased dc conductivity, the interfacial polarization at the interfaces between glass and epoxy, or both are the reason for these overall high losses. It is pointed out that the anomalous relaxation peak shifts to lower temperatures when the frequency is increased, contrary to normal behavior. In addition, a merge of two relaxation peaks is visible for higher frequencies at around 70degC, tentatively explained as being caused by the phase transition of SO2

Permittivity in epoxy based syntactic foam nanocomposites

Following previous work, this paper focuses on a new type of epoxy based syntactic foam, a lightweight material which is known to electrical engineering since the seventies, but so far couldn't live up to it's potential in high voltage applications. This is mainly because of the basic structure of syntactic foam, which provides closed cell porosity. The porosity, which gives syntactic foam its weight reduction, unfortunately leads to shortcomings in terms of dielectric strength and PD resistance. However: with recent advances in material science and the dawn of nanotechnology, there is a new take on this unique material, which can be used as insulating material for HV-applications, where weight is of vital importance. Four different types of epoxy based syntactic foam nanocomposites are presented, whose respective dielectric behavior were studied with help of dielectric spectroscopy. The measurement results, with emphasis on the complex permittivity, are presented in this work. Also the advantages and shortcomings of the various composites are discussed, as they are compared with both unmodified syntactic foam, as well as the unmodified base epoxy

More than just a barrier: The immune functions of the airway epithelium in asthma pathogenesis.

Allergic bronchial asthma is a chronic disease of the airways that is characterized by symptoms like respiratory distress, chest tightness, wheezing, productive cough, and acute episodes of broncho-obstruction. This symptom-complex arises on the basis of chronic allergic inflammation of the airway wall. Consequently, the airway epithelium is central to the pathogenesis of this disease, because its multiple abilities directly have an impact on the inflammatory response and thus the formation of the disease. In turn, its structure and functions are markedly impaired by the inflammation. Hence, the airway epithelium represents a sealed, self-cleaning barrier, that prohibits penetration of inhaled allergens, pathogens, and other noxious agents into the body. This barrier is covered with mucus that further contains antimicrobial peptides and antibodies that are either produced or specifically transported by the airway epithelium in order to trap these particles and to remove them from the body by a process called mucociliary clearance. Once this first line of defense of the lung is overcome, airway epithelial cells are the first cells to get in contact with pathogens, to be damaged or infected. Therefore, these cells release a plethora of chemokines and cytokines that not only induce an acute inflammatory reaction but also have an impact on the alignment of the following immune reaction. In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Recent studies indicate that the history of allergy- and pathogen-derived insults can leave some kind of memory in these cells that can be described as imprinting or trained immunity. Thus, the airway epithelium is in the center of processes that lead to formation, progression and acute exacerbation of asthma

Resistance Exercises in Early Functional Rehabilitation for Achilles Tendon Ruptures Are Poorly Described:A Scoping Review

OBJECTIVES: To (1) describe which resistance exercises are used in the first eight weeks of treatment for acute Achilles tendon rupture and (2) assess the completeness of reporting of the exercise descriptions. DESIGN: Scoping review LITERATURE SEARCH: We searched the Medline, Embase, Cinahl, Cochrane and PEDro databases. STUDY SELECTION CRITERIA: Randomized controlled trials, cohort studies and case series (n ≥ 10 participants) that reported using resistance exercise in the immobilization period in the first eight weeks of treatment for acute Achilles tendon rupture. DATA SYNTHESIS: Completeness of exercise description was assessed with the Consensus on Exercise Reporting Template (CERT) and Toigo and Boutellier’s exercise descriptor framework. RESULTS: 38 studies were included. Fifty-one resistance exercises were extracted and categorized as isometric exercises (n = 20), heel-rises (n = 6), strengthening with external resistance (n = 13) or unspecified (n = 12). The median CERT items reported was 8 (IQR 10;6) of a possible 19 items. The number of Toigo and Boutellier exercise descriptors described ranged from 0 to 11, of a possible 13. CONCLUSION: A variety of resistance exercises targeted at the ankle plantar flexors were used as part of early functional rehabilitation after Achilles tendon rupture. However, most studies provided inadequate description of resistance exercise interventions. REGISTRATION: PROSPERO: CRD4201706230