Supramolecular gelation controlled by an iodine clock.

Programming supramolecular assembly in the time domain is a fundamental aspect of the design of biomimetic materials. We achieved the time-controlled sol-gel transition of a poly(vinyl alcohol)-iodine supramolecular complex by generating iodine in situ with a clock reaction. We demonstrate that both the gelation time and the mechanical properties of the resulting hydrogel can be tuned by properly selecting the clock parameters or through competitive iodine complexation.

Communication: Appearance of undershoots in start-up shear: Experimental findings captured by tumbling-snake dynamics.

Our experimental data unambiguously show (i) a damping behavior (the appearance of an undershoot following the overshoot) in the transient shear viscosity of a concentrated polymeric solution, and (ii) the absence of a corresponding behavior in the transient normal stress coefficients. Both trends are shown to be quantitatively captured by the bead-link chain kinetic theory for concentrated polymer solutions and entangled polymer melts proposed by Curtiss and Bird, supplemented by a non-constant link tension coefficient that we relate to the nematic order parameter. The observed phenomena are attributed to the tumbling behavior of the links, triggered by rotational fluctuations, on top of reptation. Using model parameters deduced from stationary data, we calculate the transient behavior of the stress tensor for this "tumbling-snake" model after startup of shear flow efficiently via simple Brownian dynamics. The unaltered method is capable of handling arbitrary homogeneous flows and has the promising capacity to improve our understanding of the transient behavior of concentrated polymer solutions.

Triggered release from liposomes through magnetic actuation of iron oxide nanoparticle containing membranes.

The ideal nanoscale drug delivery vehicle allows control over the released dose in space and time. We demonstrate that this can be achieved by stealth liposomes comprising self-assembled superparamagnetic iron oxide nanoparticles (NPs) individually stabilized with palmityl-nitroDOPA incorporated in the lipid membrane. Alternating magnetic fields were used to control timing and dose of repeatedly released cargo from such vesicles by locally heating the membrane, which changed its permeability without major effects on the environment.

[Abdominal pain in the general doctor's practice]. / Abdominalschmerzen in der Hausarztpraxis.

Abdominal pain is a frequent symptom and in the majority of cases the underlying disease is not life threatening. The general practitioner's first task is to differentiate between inflammatory and other diseases. The patient's history, the clinical examination and laboratory tests form the basis for the differential diagnosis. A sonography is the first additional examination in the vast majority of the cases. Accidentally found gallstones usually do not require surgical intervention. Surgery in asymptomatic patients should be limited to gallbladder polyps and patients with calcifications in their gallbladder wall.

Immobilization of Carbonic Anhydrase in Glass Micropipettes and Glass Fiber Filters for Flow-Through Reactor Applications.

There are various ways of immobilizing carbonic anhydrase (CA) on solid materials. One of the final aims is to apply immobilized CA for the catalytic hydration of carbon dioxide (CO2) as a first step in the conversion of gaseous CO2 into solid products. The immobilization method investigated allows a straightforward, stable, and quantifiable immobilization of bovine erythrocyte carbonic anhydrase (BCA) on silicate surfaces. The method is based on the use of a water-soluble, polycationic second-generation dendronized polymer with on average 1000 repeating units, abbreviated as de-PG21000. Several copies of BCA were first covalently linked to de-PG21000 through stable bisaryl hydrazone (BAH) bonds. Then, the de-PG21000-BAH-BCA conjugates obtained were adsorbed noncovalently either on microscopy glass coverslips, inside glass micropipettes, or in porous glass fiber filters. The apparent density of the immobilized BCA on the glass surfaces was about 8-10 pmol/cm2. In all three cases, the immobilized enzyme was highly active and stable when tested with p-nitrophenyl acetate as a model enzyme substrate at room temperature. The micropipettes and the glass fiber filters were applied as flow-through systems for continuous operation at room temperature. In the case of the glass fiber filters, the filters were placed inside a homemade flow-through filter holder which allows flow-through runs with more than one filter connected in series. This offers the opportunity of increasing the substrate conversion by increasing the number of BCA-containing filters.

The Young's modulus of fetal preterm and term amniotic membranes.

OBJECTIVE: To examine the Young's modulus of the human amniotic membranes, as well as its relationship to gestational age. To determine whether cellular and material-related parameters affect this modulus. STUDY DESIGN: In a prospective study at the Obstetric outpatient clinic of the University Hospital Zurich Young's modulus, thickness and mesenchymal:epithelial cell ratio of amniotic membranes of preterm (N=23) and term (N=40) placentae were examined. Significance (P<0.05) was calculated with the Mann-Whitney two-sample rank sum test and Wilcoxon signed rank test, while correlations were made using the Spearman's correlation. RESULTS: The Young's modulus of preterm amniotic membranes was significantly higher than that of term membranes. It varied within the same amniotic membrane. The thickness of the amnion in both preterm and term membranes did not differ significantly. The thinner the preterm and term amniotic membranes, the higher the Young's modulus was. There was no relation to the mesenchymal:epithelial cell ratio in the amnion. CONCLUSIONS: Preterm amniotic membranes are stiffer than term amniotic membranes. Tentatively, we hypothesise that there may be a correlation between the extracellular matrix components and the elastic properties of the membrane.

Amyloid-hydroxyapatite bone biomimetic composites.

A "bottom up" strategy is proposed to synthesize high aspect ratio hydroxyapatite (and brushite) platelets, and combine them with amyloid fibrils into layered hybrid nanocomposites. Their hierarchical structure, despite the differences from natural bone, confers to the nanocomposites a density and elastic modulus matching those of cancellous bone. Evidence of good adhesion and spreading of human trabecular bone-derived pre-osteoblasts cells on these nanocomposites is provided.

Functionalizing a dentin bonding resin to become bioactive.

OBJECTIVES: To investigate chemo-mechanical effects of incorporating alkaline bioactive glass nanoparticles into a light-curable dental resin matrix. METHODS: An unfilled Bis-GMA/TEGDMA material was infiltrated with up to 20 wt% of ultrafine SiO2-Na2O-CaO-P2O5-Bi2O3 particles. The unfilled and filled resins were investigated regarding their viscosity before setting and compared to commercially available materials. Set specimens were immersed for 21 days in phosphate buffered saline at 37°C. Water uptake, pH, Knoop hardness, and degree of conversion of freshly polymerized and stored samples were investigated. Resin surfaces were viewed and mapped in a scanning electron microscope for the formation of calcium phosphate (Ca/P) precipitates. In addition, Raman spectroscopy was performed. Numeric values were statistically compared (p<0.01). RESULTS: Viscosity increased with particle loading, but remained below that of a flowable dental composite material. Water uptake into and pH induction from the polymerized samples also increased with particle loading (p<0.01). The addition of 20 wt% nanoparticles had no significant influence on microhardness, yet it slightly (p<0.01) increased the degree of conversion after 21 days. Ca/P precipitates formed on specimens filled with 20 wt% of the particles, while they were scarce on counterparts loaded with 10 wt%, and absent on unfilled resin surfaces. SIGNIFICANCE: The results of the current study show that a Bis-GMA-based resin can be functionalized using alkaline nanoparticles. A material with bioactive properties and similar hardness as the unfilled resin was obtained by incorporating 20wt% of ultrafine SiO2-Na2O-CaO-P2O5-Bi2O3 particles into the resin matrix.

Exercise-based injury prevention in child and adolescent sport: a systematic review and meta-analysis.

BACKGROUND: The promotion of sport and physical activity (PA) for children is widely recommended to support a healthy lifestyle, but being engaged in sport bears the risk of sustaining injuries. Injuries, in turn, can lead to a reduction in current and future involvement in PA and, therefore, may negatively affect future health as well as quality of life. Thus, sports injury prevention is of particular importance in youth. OBJECTIVE: The aim of this systematic review was to quantify the effectiveness of exercise-based injury prevention programs in child and adolescent sport in general, and with respect to different characteristics of the target group, injury prevention program, and outcome variables. DATA SOURCES: An Internet-based literature search was conducted in six databases (CINAHL, Cochrane, EMBASE, ISI Web of Science, PubMed, SPORTDiscus) using the following search terms with Boolean conjunction: (sport injur* OR athletic injur* OR sport accident*) AND (prevent* OR prophylaxis OR avoidance) AND (child* OR adolescent OR youth). STUDY SELECTION: Randomized controlled trials and controlled intervention studies in organized sport, published in English in a peer-reviewed journal, analyzing the effects of an exercise-based injury prevention program in athletes younger than 19 years of age. DATA EXTRACTION: Two reviewers evaluated eligibility and methodological quality. Main outcome extracted was the rate ratio (RR). Statistical analyses were conducted using the inverse-variance random effects model. RESULTS: Twenty-one trials, conducted on a total of 27,561 athletes (median age 16.7 years [range 10.7-17.8]), were included. The overall RR was 0.54 (95% CI 0.45-0.67) [p < 0.001]. Girls profited more from injury prevention than boys (p = 0.05). Both prevention programs with a focus on specific injuries (RR 0.48 [95% CI 0.37-0.63]) and those aiming at all injuries (RR 0.62 [95% CI 0.48-0.81]) showed significant reduction effects. Pre-season and in-season interventions were similarly beneficial (p = 0.93). Studies on programs that include jumping/plyometric exercises showed a significant better (p = 0.002) injury preventive effect (RR 0.45 [95% CI 0.35-0.57], Z = 6.35, p < 0.001) than studies without such exercises (RR 0.74 [95% CI 0.61-0.90], Z = 3.03, p = 0.002). CONCLUSIONS: The results provide good evidence and clearly demonstrate beneficial effects of exercise-based injury prevention programs in youth sports as they can result in statistically significant and practically relevant injury reduction. In particular, multimodal programs including jumping/plyometric exercises can be recommended. However, there is a considerable lack of data for children (under 14 years of age) and for individual sports in general. Future research should include these groups and focus on the effect of specific exercises and compliance.

A toolbox of oligopeptide-modified polymers for tailored elastomers.

Biomaterials are constructed from limited sets of building blocks but exhibit extraordinary and versatile properties, because hierarchical structure formation lets them employ identical supramolecular motifs for different purposes. Here we exert a similar degree of structural control in synthetic supramolecular elastomers and thus tailor them for a broad range of thermomechanical properties. We show that oligopeptide-terminated polymers selectively self-assemble into small aggregates or nanofibrils, depending on the length of the oligopeptides. This process is self-sorting if differently long oligopeptides are combined so that different nanostructures coexist in bulk mixtures. Blends of polymers with oligopeptides matching in length furnish reinforced elastomers that exhibit shear moduli one order of magnitude higher than the parent polymers. By contrast, novel interpenetrating supramolecular networks that display excellent vibration damping properties are obtained from blends comprising non-matching oligopeptides or unmodified polymers. Hence, blends of oligopeptide-modified polymers constitute a toolbox for tailored elastomers with versatile properties.

A new telemonitoring system intended for chronic heart failure patients using mobile telephone technology--feasibility study.

BACKGROUND: Remote monitoring is one modality of structured care in chronic heart failure. The purpose of this study was to evaluate the feasibility of a new wireless telemonitoring system via a mobile phone network. METHODS: Portable home devices for electrocardiogram, blood pressure, body weight and self-assessment measurements were connected (via Bluetooth) to a personal digital assistant (PDA) that performs automated encrypted transmission via mobile phone. Two telemedical centres were set-up. RESULTS: 30 healthy volunteers were enrolled and followed for 26 days. A total of 4002 single measurements were taken, 133 ± 37 per person. No data was lost or incorrectly allocated. 880 of 937 (94%) of the ECG recordings had sufficient diagnostic quality for rhythm analysis and single beat measurements. 50 continuous ECG-streams (312 min) without disruption were performed. Total system availability was 96.6%, including that of the mobile phone network. CONCLUSIONS: Mobile phone technology is suitable for continuous and secure medical data transmission. To evaluate the clinical use in chronic heart failure patients, a large multicentre randomized controlled trial (ClinicalTrials.gov Identifier: NCT00543881) was started.

Telemedical Interventional Monitoring in Heart Failure (TIM-HF), a randomized, controlled intervention trial investigating the impact of telemedicine on mortality in ambulatory patients with heart failure: study design.

AIMS: Remote patient management (telemonitoring) may help to detect early signs of cardiac decompensation, allowing optimization of and adherence to treatments in chronic heart failure (CHF). Two meta-analyses have suggested that telemedicine in CHF can reduce mortality by 30-35%. The aim of the TIM-HF study was to investigate the impact of telemedical management on mortality in ambulatory CHF patients. Methods CHF patients [New York Heart Association (NYHA) II/III, left ventricular ejection fraction (LVEF)≤35%] with a history of cardiac decompensation with hospitalization in the past or therapy with intravenous diuretics in the prior 24 months (no decompensation required if LVEF≤25%) were randomized 1:1 to an intervention group of daily remote device monitoring (electrocardiogram, blood pressure, body weight) coupled with medical telephone support or to usual care led by the patients' local physician. In the intervention group, 24/7 physician-led medical support was provided by two central telemedical centres. A clinical event committee blinded to treatment allocation assessed cause of death and reason for hospitalization. The primary endpoint was total mortality. The first secondary endpoint was a composite of cardiovascular mortality or hospitalization due to heart failure. Other secondary endpoints included cardiovascular mortality, all-cause and cause-specific hospitalizations (all time to first event) as well as days lost due to heart failure hospitalization or cardiovascular death (in % of follow-up time), and changes in quality of life and NYHA class. Overall, 710 CHF patients were recruited. The mean follow-up was 21.5±7.2 months, with a minimum of 12 months. Perspective The study will provide important prospective outcome data on the impact of telemedical management in patients with CHF.

Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathways.

Hemoglobin (Hb) released into the circulation during hemolysis and chemically modified Hb proposed for use as oxygen therapeutics exert toxic effects that are partially attributable to heme's oxidant activity. Native extracellular Hb is scavenged by haptoglobin (Hp) after alphabeta-subunit dimerization. In the absence of Hp, monocyte/macrophage cell-surface CD163 binds and clears Hb. We evaluated several chemically modified Hbs to establish the role of chemical cross-linking patterns and molecular sizes on binding and clearance by each pathway. We found that Hbs possessing beta-globin cross-linking, irrespective of polymerization, demonstrate increased Hp affinity compared with alpha-globin-stabilized Hbs. These data suggest that Hb alpha-subunit accessibility is critical for Hp binding in the absence of dimerization. beta-Globin chain cross-linked tetramers/polymers displayed strong polyvalent Hp binding with increased viscosity and formation of visible gel matrices. Modified Hb interaction with CD163 and cellular uptake demonstrated an inverse relation with molecular size, irrespective of alpha and beta cross-linking. These findings were confirmed by HO-1 induction and intracellular ferritin accumulation in CD163-expressing HEK293 cells. Based on these results, a rational and systematic approach to HBOC design may be used to optimize interaction with endogenous Hb clearance and detoxification pathways.

Carbohydrate polymers in amorphous states: an integrated thermodynamic and nanostructural investigation.

The effect of water on the structure and physical properties of amorphous polysaccharide matrices is investigated by combining a thermodynamic approach including pressure- and temperature-dependent dilatometry with a nanoscale analysis of the size of intermolecular voids using positron annihilation lifetime spectroscopy. Amorphous polysaccharides are of interest because of a number of unusual properties which are likely to be related to the extensive hydrogen bonding between the carbohydrate chains. Uptake of water by the carbohydrate matrices leads to a strong increase in the size of the holes between the polymer chains in both the glassy and rubbery states while at the same time leading to an increase in matrix free volume. Thermodynamic clustering theory indicates that, in low-moisture carbohydrate matrices, water molecules are closely associated with the carbohydrate chains. Based on these observations, we propose a novel model of plasticization of carbohydrate polymers by water in which the water dynamically disrupts chains the hydrogen bonding between the carbohydrates, leading to an expansion of the matrix originating at the nanolevel and increasing the number of degrees of freedom of the carbohydrate chains. Consequently, even in the glassy state, the uptake of water leads to increased rates of matrix relaxation and mobility of small permeants. In contrast, low-molecular weight sugars plasticize the carbohydrate matrix without appreciably changing the structure and density of the rubbery state, and their role as plasticizer is most likely related to a reduction of the number of molecular entanglements. The improved molecular packing in glassy matrices containing low molecular weight sugars leads to a higher matrix density, explaining, despite the lower glass transition temperature, the reduced mobility of small permeants in such matrices.