Search

Volume changes of responsive microgels can probe interactions between polyelectrolytes and species of opposite charges such as peptides and proteins. We have investigated a microfluidics method to synthesize highly responsive, covalently crosslinked, hyaluronic acid microgels for such purposes. Sodium hyaluronate (HA), pre-modified with ethylacrylamide functionalities, was crosslinked in aqueous droplets created with a microfluidic technique. We varied the microgel properties by changing the degree of modification and concentration of HA in the reaction mixture. The degree of modification was determined by H-1 NMR. Light microscopy was used to investigate the responsiveness of the microgels to osmotic stress in aqueous saline solutions by simultaneously monitoring individual microgel species in hydrodynamic traps. The permeability of the microgels to FITC-dextrans of molecular weights between 4 and 250 kDa was investigated using confocal laser scanning microscopy. The results show that the microgels were spherical with diameters between 100 and 500 mu m and the responsivity tunable by changing the degree of modification and the HA concentration. Microgels were fully permeable to all investigated FITC-dextran probes. The partitioning to the microgel from an aqueous solution decreased with the increasing molecular weight of the probe, which is in qualitative agreement with theories of homogeneous gel networks.

Subcutaneous injection is one of the most common approaches for administering biopharmaceuticals unsuitable for oral delivery. However, there is a lack of methods to predict the behavior of biopharmaceuticals within the extracellular matrix of the subcutaneous tissue. In this work, we present a novel miniaturized microfluidic-based in vitro method able to investigate interactions between drug molecules and the polymers of the subcutaneous extracellular matrix. To validate the method, microgels consisting of, respectively, covalently cross-linked hy-aluronic acid, polyacrylic acid, and commercially available DC BeadTM, were exposed to three model substances: cytochrome C, protamine sulfate and amitriptyline hydrochloride. These components were chosen to include systems with widely different physiochemical properties (charge, size, self-assembly, etc.) The experimental results were compared with theoretical predictions from a gel model developed earlier. The results show that the method is suitable as a rapid screening method for automated, large-scale, probing of interactions between biopolymers and drug molecules, with small consumption of material.

Den praktiska ämnesdidaktik som projektet fokuserat på var en virtuell praktik, en lärarledd simuleringsundervisning med fem virtuella elever. Träningen på att undervisa de virtuella eleverna följdes av återkoppling som gavs av en ämnesdidaktiker i historia och en i samhällskunskap. Den virtuella praktiken bakades in som ett obligatoriskt moment i två campusförlagda kurser för blivande ämneslärare, i historia respektive samhällskunskap., Pedagogiskt utvecklingsprojekt för e-lärande 2020

Polyelectrolyte microgels may undergo volume phase transition upon loading and the release of amphiphilic molecules, a process important in drug delivery. The new phase is "born" in the outermost gel layers, whereby it grows inward as a shell with a sharp boundary to the "mother" phase (core). The swelling and collapse transitions have previously been studied with microgels in large solution volumes, where they go to completion. Our hypothesis is that the boundary between core and shell is stabilized by thermodynamic factors, and thus that collapsed and swollen phases should be able to also coexist at equilibrium. We investigated the interaction between sodium polyacrylate (PA) microgel networks (diameter: 400-850 mu m) and the amphiphilic drug amitriptyline hydrochloride (AMT) in the presence of NaCl/phosphate buffer of ionic strength (I) 10 and 155 mM. We used a specially constructed microscopy cell and micromanipulators to study the size and internal morphology of single microgels equilibrated in small liquid volumes of AMT solution. To probe the distribution of AMT micelles we used the fluorescent probe rhodamine B. The amount of AMT in the microgel was determined by a spectrophotometric technique. In separate experiments we studied the binding of AMT and the distribution between different microgels in a suspension. We found that collapsed, AMT-rich, and swollen AMT-lean phases coexisted in equilibrium or as long-lived metastable states at intermediate drug loading levels. In single microgels at I = 10 mM, the collapsed phase formed after loading deviated from the core-shell configuration by forming either discrete domains near the gel boundary or a calotte shaped domain. At I = 155 mM, single microgels, initially fully collapsed, displayed a swollen shell and a collapsed core after partial release of the AMT load. Suspensions displayed a bimodal distribution of swollen and collapsed microgels. The results support the hypothesis that the boundary between collaps

Background Previous studies have shown that rapid treatment for stroke, especially ischemic stroke, reduces mortality and disability. The focus has mainly been on reducing time from arrival at hospital to start of treatment. However, the main reason for delay is often time from symptom onset to arrival at hospital. This study therefore aimed to explore decision‐making processes after the onset of stroke symptoms in patients experiencing a first‐time stroke. Methods We included 36 patients aged 18 and older, all of whom were hospitalized with a first‐time stroke between October 2018 and April 2020. All patients were interviewed once within 4 weeks of symptom onset and before hospital discharge. Eligible patients were identified retrospectively through a targeted review of medical records. The data were collected and analyzed according to the grounded theory methodology. Results In total, 43 potential patients were identified and asked to participate. Overall, 36 patients were included in the study: 17 women (median age 77.0 years, interquartile range 17.5) and 19 men (median age 65.7 years, interquartile range 17.2). All interviewees felt fear, and this affected their decision to seek emergency care. The decision‐making processes were described by the core category of “Acting on fear.” The reason for feeling frightened determined the actions taken. The reasons were sorted into 3 main categories: (1) “seeking care”–recognized stroke symptoms and acted immediately; (2) “pending and reluctance”–suspected stroke but awaited to seek care; and (3) “seeking an explanation”–confused by symptoms. Conclusion We found that decision‐making when experiencing stroke symptoms was complex. All patients felt fear, which determined their actions. Some patients knew about stroke symptoms and acted immediately. Others suspected stroke but still chose to wait, whereas others were confused and tried to find answers. These results could contribute to form future awareness campaigns.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive a

Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventiv

Strong interest from researchers and industry is accelerating development of flexible energy storage technologies for future flexible devices. It is critical to consider the environmental perspective in early development of new emerging technologies. In this study, cradle-to-factory gate prospective life cycle assessment (LCA) was per-formed on production of an all-organic battery with conductive redox polymers as electrode material. To gain a better understanding of the environmental performance of the all-organic battery, a flexible lithium-ion (Li-ion) battery with lithium titanate oxide and lithium cobalt oxide as electrode active materials was modeled as reference. Main environmental impacts of the all-organic battery were attributable to anode and cathode pro-duction, with electrode backbones being the main contributors. Solvents, catalysts, waste treatment, energy, and bromine were key individual contributors. Comparison with the flexible Li-ion battery indicated inferior envi-ronmental performance of the all-organic battery due to its relatively low specific energy (Wh/kg) and large amount of materials needed for production of its electrode backbones. Sensitivity analysis showed that changing scaling-up parameters and the production route of 3,4-ethylenedioxythiophene (a precursor of electrode back-bones) strongly influenced the results. In order to lower the environmental impacts of the all-organic battery, future research should focus on designing a short production chain with lower material inputs of electrode backbones, increasing battery cycle life, and improving the specific energy of the battery. In addition, relevant recommendations were provided for prospective LCAs of upscaled systems.

In recent decades, pre-corona, we have seen unprecedented progress towards achieving the United Nations Sustainable Development Goals (SDG) concerning access to water, sanitation, education, and poverty reduction and increased life expectancy. However, human rights are not a similar success story. During the pandemic we have experienced in many countries police brutality and violation of rights. Post-corona education therefore has an essential role in promoting human rights, gender equality and democracy and thus supporting, strengthening and rebuilding quality education for all. Research has shown that effective education programmes can reduce misinformation, increase knowledge, strengthen positive values and attitudes, increase skills to make informed decisions and act upon them, and improve perceptions of social norms (UNESCO, 2009).