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The discovery that certain diseases have specific miRNA signatures which correspond to disease progression opens a new biomarker category. The detection of these small non-coding RNAs is performed routinely using body fluids or tissues with real-time PCR, next-generation sequencing, or amplification-based miRNA assays. Antibody-based detection systems allow an easy onset handling compared to PCR or sequencing and can be considered as alternative methods to support miRNA diagnostic in the future. In this study, we describe the generation of a camelid heavy-chain-only antibody specifically recognizing miRNAs to establish an antibody-based detection method. The generation of nucleic acid-specific binders is a challenge. We selected camelid binders via phage display, expressed them as VHH as well as full-length antibodies, and characterized the binding to several miRNAs from a signature specific for dilated cardiomyopathy. The described workflow can be used to create miRNA-specific binders and establish antibody-based detection methods to provide an additional way to analyze disease-specific miRNA signatures.
Science education researchers have developed a refined understanding of the structure of science teachers’ pedagogical content knowledge (PCK), but how to develop applicable and situation-adequate PCK remains largely unclear. A potential problem lies in the diverse conceptualisations of the PCK used in PCK research. This study sought to systematize existing science education research on PCK through the lens of the recently proposed refined consensus model (RCM) of PCK. In this review, the studies’ approaches to investigating PCK and selected findings were characterised and synthesised as an overview comparing research before and after the publication of the RCM. We found that the studies largely employed a qualitative case-study methodology that included specific PCK models and tools. However, in recent years, the studies focused increasingly on quantitative aspects. Furthermore, results of the reviewed studies can mostly be integrated into the RCM. We argue that the RCM can function as a meaningful theoretical lens for conceptualizing links between teaching practice and PCK development by proposing pedagogical reasoning as a mechanism and/or explanation for PCK development in the context of teaching practice.
On Track to Success?
(2022)
Many countries consider expanding vocational curricula in secondary education to boost skills and labour market outcomes among non-university-bound students. However, critics fear this could divert other students from more profitable academic education. We study labour market returns to vocational education in England, where until recently students chose between a vocational track, an academic track and quitting education at age 16. Identification is challenging because self-selection is strong and because students’ next-best alternatives are unknown. Against this back- drop, we leverage multiple instrumental variables to estimate margin-specific treatment effects, i.e., causal returns to vocational education for students at the margin with academic education and, separately, for students at the margin with quitting education. Identification comes from variation in distance to the nearest vocational provider conditional on distance to the nearest academic provider (and vice-versa), while controlling for granular student, school and neighbourhood characteristics. The analysis is based on population-wide administrative education data linked to tax records. We find that the vast majority of marginal vocational students are indifferent be- tween vocational and academic education. For them, vocational enrolment substantially decreases earnings at age 30. This earnings penalty grows with age and is due to wages, not employment. However, consistent with comparative advantage, the penalty is smaller for students with higher revealed preferences for the vocational track. For the few students at the margin with no further education, we find merely tentative evidence of increased employment and earnings from vocational enrolment.
Objective
To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile).
Methods
A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the “Risk Profile” from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts.
Results
Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors.
Conclusion
An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.
Background
The aim of this study was to analyze the shoulder functional profile (rotation range of motion [ROM] and strength), upper and lower body performance, and throwing speed of U13 versus U15 male handball players, and to establish the relationship between these measures of physical fitness and throwing speed.
Methods
One-hundred and nineteen young male handball players (under (U)-13 (U13) [n = 85]) and U15 [n = 34]) volunteered to participate in this study. The participating athletes had a mean background of sytematic handball training of 5.5 ± 2.8 years and they exercised on average 540 ± 10.1 min per week including sport-specific team handball training and strength and conditioning programs. Players were tested for passive shoulder range-of-motion (ROM) for both internal (IR) and external rotation (ER) and isometric strength (i.e., IR and ER) of the dominant/non-dominant shoulders, overhead medicine ball throw (OMB), hip isometric abductor (ABD) and adductor (ADD) strength, hip ROM, jumps (countermovement jump [CMJ] and triple leg-hop [3H] for distance), linear sprint test, modified 505 change-of-direction (COD) test and handball throwing speed (7 m [HT7] and 9 m [HT9]).
Results
U15 players outperformed U13 in upper (i.e., HT7 and HT9 speed, OMB, absolute IR and ER strength of the dominant and non-dominant sides; Cohen’s d: 0.76–2.13) and lower body (i.e., CMJ, 3H, 20-m sprint and COD, hip ABD and ADD; d: 0.70–2.33) performance measures. Regarding shoulder ROM outcomes, a lower IR ROM was found of the dominant side in the U15 group compared to the U13 and a higher ER ROM on both sides in U15 (d: 0.76–1.04). It seems that primarily anthropometric characteristics (i.e., body height, body mass) and upper body strength/power (OMB distance) are the most important factors that explain the throw speed variance in male handball players, particularly in U13.
Conclusions
Findings from this study imply that regular performance monitoring is important for performance development and for minimizing injury risk of the shoulder in both age categories of young male handball players. Besides measures of physical fitness, anthropometric data should be recorded because handball throwing performance is related to these measures.
Objective: A role for microRNAs is implicated in several biological and pathological processes. We investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on molecular markers of diabetic cardiomyopathy in rats.
Methods: Eighteen male Wistar rats (260 ± 10 g; aged 8 weeks) with streptozotocin (STZ)-induced type 1 diabetes mellitus (55 mg/kg, IP) were randomly allocated to three groups: control, MICT, and HIIT. The two different training protocols were performed 5 days each week for 5 weeks. Cardiac performance (end-systolic and end-diastolic dimensions, ejection fraction), the expression of miR-206, HSP60, and markers of apoptosis (cleaved PARP and cytochrome C) were determined at the end of the exercise interventions.
Results: Both exercise interventions (HIIT and MICT) decreased blood glucose levels and improved cardiac performance, with greater changes in the HIIT group (p < 0.001, η2: 0.909). While the expressions of miR-206 and apoptotic markers decreased in both training protocols (p < 0.001, η2: 0.967), HIIT caused greater reductions in apoptotic markers and produced a 20% greater reduction in miR-206 compared with the MICT protocol (p < 0.001). Furthermore, both training protocols enhanced the expression of HSP60 (p < 0.001, η2: 0.976), with a nearly 50% greater increase in the HIIT group compared with MICT.
Conclusions: Our results indicate that both exercise protocols, HIIT and MICT, have the potential to reduce diabetic cardiomyopathy by modifying the expression of miR-206 and its downstream targets of apoptosis. It seems however that HIIT is even more effective than MICT to modulate these molecular markers.
Background: As the number of cardiac diseases continuously increases within the last years in modern society, so does cardiac treatment, especially cardiac catheterization. The procedure of a cardiac catheterization is challenging for both patients and practitioners. Several potential stressors of psychological or physical nature can occur during the procedure. The objective of the study is to develop and implement a stress management intervention for both practitioners and patients that aims to reduce the psychological and physical strain of a cardiac catheterization.
Methods: The clinical study (DRKS00026624) includes two randomized controlled intervention trials with parallel groups, for patients with elective cardiac catheterization and practitioners at the catheterization lab, in two clinic sites of the Ernst-von-Bergmann clinic network in Brandenburg, Germany. Both groups received different interventions for stress management. The intervention for patients comprises a psychoeducational video with different stress management technics and additional a standardized medical information about the cardiac catheterization examination. The control condition includes the in hospitals practiced medical patient education before the examination (usual care). Primary and secondary outcomes are measured by physiological parameters and validated questionnaires, the day before (M1) and after (M2) the cardiac catheterization and at a postal follow-up 6 months later (M3). It is expected that people with standardized information and psychoeducation show reduced complications during cardiac catheterization procedures, better pre- and post-operative wellbeing, regeneration, mood and lower stress levels over time. The intervention for practitioners includes a Mindfulness-based stress reduction program (MBSR) over 8 weeks supervised by an experienced MBSR practitioner directly at the clinic site and an operative guideline. It is expected that practitioners with intervention show improved perceived and chronic stress, occupational health, physical and mental function, higher effort-reward balance, regeneration and quality of life. Primary and secondary outcomes are measured by physiological parameters (heart rate variability, saliva cortisol) and validated questionnaires and will be assessed before (M1) and after (M2) the MBSR intervention and at a postal follow-up 6 months later (M3). Physiological biomarkers in practitioners will be assessed before (M1) and after intervention (M2) on two work days and a two days off. Intervention effects in both groups (practitioners and patients) will be evaluated separately using multivariate variance analysis.
Discussion: This study evaluates the effectiveness of two stress management intervention programs for patients and practitioners within cardiac catheter laboratory. Study will disclose strains during a cardiac catheterization affecting both patients and practitioners. For practitioners it may contribute to improved working conditions and occupational safety, preservation of earning capacity, avoidance of participation restrictions and loss of performance. In both groups less anxiety, stress and complications before and during the procedures can be expected. The study may add knowledge how to eliminate stressful exposures and to contribute to more (psychological) security, less output losses and exhaustion during work. The evolved stress management guidelines, training manuals and the standardized patient education should be transferred into clinical routines
Cutting-edge hyperscanning methods led to a paradigm shift in social neuroscience. It allowed researchers to measure dynamic mutual alignment of neural processes between two or more individuals in naturalistic contexts. The ever-growing interest in hyperscanning research calls for the development of transparent and validated data analysis methods to further advance the field. We have developed and tested a dual electroencephalography (EEG) analysis pipeline, namely DEEP. Following the preprocessing of the data, DEEP allows users to calculate Phase Locking Values (PLVs) and cross-frequency PLVs as indices of inter-brain phase alignment of dyads as well as time-frequency responses and EEG power for each participant. The pipeline also includes scripts to control for spurious correlations. Our goal is to contribute to open and reproducible science practices by making DEEP publicly available together with an example mother-infant EEG hyperscanning dataset.
Cardiovascular diseases are the main cause of death worldwide, and their prevalence is expected to rise in the coming years. Polymer-based artificial replacements have been widely used for the treatment of cardiovascular diseases. Coagulation and thrombus formation on the interfaces between the materials and the human physiological environment are key issues leading to the failure of the medical device in clinical implantation. The surface properties of the materials have a strong influence on the protein adsorption and can direct the blood cell adhesion behavior on the interfaces. Furthermore, implant-associated infections will be induced by bacterial adhesion and subsequent biofilm formation at the implantation site. Thus, it is important to improve the hemocompatibility of an implant by altering the surface properties. One of the effective strategies is surface passivation to achieve protein/cell repelling ability to reduce the risk of thrombosis.
This thesis consists of synthesis, functionalization, sterilization, and biological evaluation of bulk poly(glycerol glycidyl ether) (polyGGE), which is a highly crosslinked polyether-based polymer synthesized by cationic ring-opening polymerization. PolyGGE is hypothesized to be able to resist plasma protein adsorption and bacterial adhesion due to analogous chemical structure as polyethylene glycol and hyperbranched polyglycerol. Hydroxyl end groups of polyGGE provide possibilities to be functionalized with sulfates to mimic the anti-thrombogenic function of the endothelial glycocalyx.
PolyGGE was synthesized by polymerization of the commercially available monomer glycerol glycidyl ether, which was characterized as a mixture of mono-, di- and tri-glycidyl ether. Cationic ring opening-polymerization of this monomer was carried out by ultraviolet (UV) initiation of the photo-initiator diphenyliodonium hexafluorophosphate. With the increased UV curing time, more epoxides in the side chains of the monomers participated in chemical crosslinking, resulting in an increase of Young’s modulus, while the value of elongation at break of polyGGE first increased due to the propagation of the polymer chains then decreased with the increase of crosslinking density. Eventually, the chain propagation can be effectively terminated by potassium hydroxide aqueous solution. PolyGGE exhibited different tensile properties in hydrated conditions at body temperature compared to the values in the dry state at room temperature. Both Young’s modulus and values of elongation at break were remarkably reduced when tested in water at 37 °C, which was above the glass transition temperature of polyGGE. At physiological conditions, entanglements of the ployGGE networks unfolded and the free volume of networks were replaced by water molecules as softener, which increased the mobility of the polymer chains, resulting in a lower Young’s modulus.
Protein adsorption analysis was performed on polyGGE films with 30 min UV curing using an enzyme-linked immunosorbent assay. PolyGGE could effectively prevent the adsorption of human plasma fibrinogen, albumin, and fibronectin at the interface of human plasma and polyGGE films. The protein resistance of polyGGE was comparable to the negative controls: the hemocompatible polydimethylsiloxane (PDMS), showing its potential as a coating material for cardiovascular implants. Moreover, antimicrobial tests of bacterial activity using isothermal microcalorimetry and the microscopic image of direct bacteria culturing demonstrated that polyGGE could directly interfere biofilm formation and growth of both Gram-negative and antibiotic-resistant Gram-positive bacteria, indicating the potential application of polyGGE for combating the risk of hospital-acquired infections and preventing drug-resistant superbug spreading.
To investigate its cell compatibility, polyGGE films were extracted by different solvents (ethanol, chloroform, acetone) and cell culture medium. Indirect cytotoxicity tests showed extracted polyGGE films still had toxic effects on L929 fibroblast cells. High-performance liquid chromatography/electrospray ionization mass spectrometry revealed the occurrence of organochlorine-containing compounds released during the polymer-cell culture medium interaction. A constant level of those organochlorine-containing compounds was confirmed from GGE monomer by a specific peak of C-Cl stretching in infrared spectra of GGE. This is assumed to be the main reason causing the increased cell membrane permeability and decreased metabolic activity, leading to cell death. Attempts as changing solvents were made to remove toxic substances, however, the release of these small molecules seems to be sluggish. The densely crosslinked polyGGE networks can possibly contribute to the trapping of organochlorine-containing compounds. These results provide valuable information for exploring the potentially toxic substances, leaching from polyGGE networks, and propose a feasible strategy for minimizing the cytotoxicity via reducing their crosslinking density.
Sulfamic acid/ N-Methyl-2-pyrrolidone (NMP) were selected as the reagents for the sulfation of polyGGE surfaces. Fourier transform attenuated total reflection infrared spectroscopy (ATR-FT-IR) was used to monitor the functionalization kinetics and the results confirmed the successful sulfate grafting on the surface of polyGGE with the covalent bond -C-O-S-. X-ray photoelectron spectroscopy was used to determine the element composition on the surface and the cross-section of the functionalized polyGGE and sulfation within 15 min guarantees the sulfation only takes place on the surface while not occurring in the bulk of the polymer. The concentration of grafted sulfates increased with the increasing reaction time. The hydrophilicity of the surface of polyGGE was highly increased due to the increase of negatively charged end groups. Three sterilization techniques including autoclaving, gamma irradiation, and ethylene oxide (EtO) sterilization were used for polyGGE sulfates. Results from ATR-FT-IR and Toluidine Blue O quantitative assay demonstrated the total loss of the sulfates after autoclave sterilization, which was also confirmed by the increased water contact angle. Little influence on the concentration of sulfates was found for gamma-irradiated and autoclaving sterilized polyGGE sulfates. To investigate the thermal influence on polyGGE sulfates, one strategy was to use poly(hydroxyethyl acrylate) sulfates (PHEAS) for modeling. The thermogravimetric analysis profile of PHEAS demonstrated that sulfates are not thermally stable independent of the substrate materials and decomposition of sulfates occurs at around 100 °C. Although gamma irradiation also showed little negative effect on the sulfate content, the color change in the polyGGE sulfates indicates chemical or physical change might occur in the polymer. EtO sterilization was validated as the most suitable sterilization technique to maintain the chemical structure of polyGGE sulfates.
In conclusion, the conducted work proved that bulk polyGGE can be used as an antifouling coating material and shows its antimicrobial potential. Sulfates functionalization can be effectively realized using sulfamic acid/NMP. EtO sterilization is the most suitable sterilization technique for grafted sulfates. Besides, this thesis also offers a good strategy for the analysis of toxic leachable substances using suitable physicochemical characterization techniques. Future work will focus on minimizing/eliminating the release of toxic substances via reducing the crosslinking density. Another interesting aspect is to study whether grafted sulfates can meet the need for anti-thrombogenicity.
Background
Wearables, as small portable computer systems worn on the body, can track user fitness and health data, which can be used to customize health insurance contributions individually. In particular, insured individuals with a healthy lifestyle can receive a reduction of their contributions to be paid. However, this potential is hardly used in practice.
Objective
This study aims to identify which barrier factors impede the usage of wearables for assessing individual risk scores for health insurances, despite its technological feasibility, and to rank these barriers according to their relevance.
Methods
To reach these goals, we conduct a ranking-type Delphi study with the following three stages. First, we collected possible barrier factors from a panel of 16 experts and consolidated them to a list of 11 barrier categories. Second, the panel was asked to rank them regarding their relevance. Third, to enhance the panel consensus, the ranking was revealed to the experts, who were then asked to re-rank the barriers.
Results
The results suggest that regulation is the most important barrier. Other relevant barriers are false or inaccurate measurements and application errors caused by the users. Additionally, insurers could lack the required technological competence to use the wearable data appropriately.
Conclusion
A wider use of wearables and health apps could be achieved through regulatory modifications, especially regarding privacy issues. Even after assuring stricter regulations, users’ privacy concerns could partly remain, if the data exchange between wearables manufacturers, health app providers, and health insurers does not become more transparent.