Energy Distribution in disordered elastic Networks

Disordered networks are found in many natural and artificial materials, from gels or cytoskeletal structures to metallic foams or bones. Here, the energy distribution in this type of networks is modeled, taking into account the orientation of the struts. A correlation between the orientation and the energy per unit volume is found and described as a function of the connectivity in the network and the relative bending stiffness of the struts. If one or both parameters have relatively large values, the struts aligned in the loading direction present the highest values of energy. On the contrary, if these have relatively small values, the highest values of energy can be reached in the struts oriented transversally. This result allows explaining in a simple way remodeling processes in biological materials, for example, the remodeling of trabecular bone and the reorganization in the cytoskeleton. Additionally, the correlation between the orientation, the affinity, and the bending-stretching ratio in the network is discussed

Facilitating implementation of medication reviews in the community pharmacy setting: an application of the implementation research logic model.

Previous research has identified both determinants and potential strategies to facilitate implementation of medication reviews (MR). A conceptual model which links determinants, strategies to support implementation and mechanisms of change to execute implementation, with projected outcomes is helpful to plan the approach and facilitate MR-implementation. The aim of this research was to apply the Implementation Research Logic Model (ILRM) for the implementation of medication reviews in the German community pharmacy setting, and thus illustrate the links between determinants, strategies, and implementation outcomes. The resulting map is meant to inform and facilitate MR-implementation. The IRLM was populated with determinants (barriers and facilitators structured using the Framework for Implementation of Services in Pharmacy, FISpH), proposed strategies (according to the Expert Recommendations for Implementing Change, ERIC) and mechanisms of change which were identified in an interview study with 21 German pharmacy owners. The research team linked these with 8 implementation outcomes derived from Proctor: acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, sustainability. Twenty strategies from the interview study were mapped against 32 determinants. All strategies were hypothesised to impact on one or several of the 8 implementation outcomes. Depending on pharmacies' implementation stage (exploration, preparation, implementation, and sustainment) the importance of strategies was expected to vary. Strategies such as educational meetings and learning collaboratives can increase perceived appropriateness and boost adoption of MRs which is particularly important for pharmacies in the early exploration stage. Strategies such as receiving support from external implementation advisors as well as recruiting and training internal implementation leaders were deemed particularly important for pharmacies at the preparation stage to strengthen feasibility and fidelity. In later stages (implementation and sustainment) pharmacies were thought to benefit from provision of clinical feedback, obtaining and using patient feedback and re-examining implementation to achieve high fidelity, penetration, and sustainability of MR-provision. Some strategies such as fixed payment and stable delivery contracts were deemed pre-requisites for implementation irrespective of the stage the pharmacy was at. The application of the Implementation Research Logic Model illustrated the relations between determinants, strategies, mechanisms, and implementation outcomes. Future research is needed to ascertain that strategies work as planned and achieve the projected implementation outcomes

Implementation of medication reviews in community pharmacy: reaching consensus on stakeholders' recommendations for mechanisms of change using the nominal group technique.

Since 2022, patients with five or more medicines are eligible for a medication review (MR) in a community pharmacy remunerated by the German health system. However, implementation has been slow, with few pharmacies providing MRs. Stakeholders' input is necessary to detail how implementation strategies can be executed effectively on a national level. Prior research identified "external facilitation" and "altering incentives" as crucial strategies to achieve implementation outcomes. To gather stakeholders’ recommendations for, and obtain consensus on, mechanisms of change that allow implementation strategies to work in practice. The consensus method used was the nominal group technique (NGT) with NGT-discussions held separately with pharmacy owners and pharmacy chambers employees. Votes were summed and the relative importance (rI) calculated, defined as (score achieved for a mechanism)/(maximum possible score) × 100. Content analysis provided context for the highest ranked mechanisms and allowed linking to implementation outcomes. Four NGT-discussions were held in 2023 (n = 2 owners; n = 2 chamber employees) with a total of 17 participants. The overall highest ranked mechanisms were fit-for-purpose software (rI = 154.7) detailed process support (rI = 104.9) and an expert support line (rI = 77.7). These together with financial viability (rI = 40.0) were prioritised by both participant groups. Three mechanisms were favoured for both implementation strategies, namely software, process support and materials (rI = 34.3). This study identified stakeholders' priorities for mechanisms of change to implement MRs in community pharmacies. Focusing efforts on the prioritised mechanisms is likely to significantly advance a national implementation plan for countries which are at an early implementation stage

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression

BACKGROUND: Low dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC. METHODS: Plaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 ± 7 years) was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan) was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA) of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min(-1 )with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes. RESULTS: Both inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI. CONCLUSION: Thus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process

Quantification of the Temporal Evolution of Collagen Orientation in Mechanically Conditioned Engineered Cardiovascular Tissues

Load-bearing soft tissues predominantly consist of collagen and exhibit anisotropic, non-linear visco-elastic behavior, coupled to the organization of the collagen fibers. Mimicking native mechanical behavior forms a major goal in cardiovascular tissue engineering. Engineered tissues often lack properly organized collagen and consequently do not meet in vivo mechanical demands. To improve collagen architecture and mechanical properties, mechanical stimulation of the tissue during in vitro tissue growth is crucial. This study describes the evolution of collagen fiber orientation with culture time in engineered tissue constructs in response to mechanical loading. To achieve this, a novel technique for the quantification of collagen fiber orientation is used, based on 3D vital imaging using multiphoton microscopy combined with image analysis. The engineered tissue constructs consisted of cell-seeded biodegradable rectangular scaffolds, which were either constrained or intermittently strained in longitudinal direction. Collagen fiber orientation analyses revealed that mechanical loading induced collagen alignment. The alignment shifted from oblique at the surface of the construct towards parallel to the straining direction in deeper tissue layers. Most importantly, intermittent straining improved and accelerated the alignment of the collagen fibers, as compared to constraining the constructs. Both the method and the results are relevant to create and monitor load-bearing tissues with an organized anisotropic collagen network

Effect of Strain Magnitude on the Tissue Properties of Engineered Cardiovascular Constructs

Mechanical loading is a powerful regulator of tissue properties in engineered cardiovascular tissues. To ultimately regulate the biochemical processes, it is essential to quantify the effect of mechanical loading on the properties of engineered cardiovascular constructs. In this study the Flexercell FX-4000T (Flexcell Int. Corp., USA) straining system was modified to simultaneously apply various strain magnitudes to individual samples during one experiment. In addition, porous polyglycolic acid (PGA) scaffolds, coated with poly-4-hydroxybutyrate (P4HB), were partially embedded in a silicone layer to allow long-term uniaxial cyclic mechanical straining of cardiovascular engineered constructs. The constructs were subjected to two different strain magnitudes and showed differences in biochemical properties, mechanical properties and organization of the microstructure compared to the unstrained constructs. The results suggest that when the tissues are exposed to prolonged mechanical stimulation, the production of collagen with a higher fraction of crosslinks is induced. However, straining with a large strain magnitude resulted in a negative effect on the mechanical properties of the tissue. In addition, dynamic straining induced a different alignment of cells and collagen in the superficial layers compared to the deeper layers of the construct. The presented model system can be used to systematically optimize culture protocols for engineered cardiovascular tissues

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K(2)Cr(2)O(7)-induced nephrotoxicity

BACKGROUND: Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative and nitrosative stress. In this study we investigated the relation between the time course of the oxidative and nitrosative stress with kidney damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT). METHODS: Nephrotoxicity was induced in rats by a single injection of K(2)Cr(2)O(7). Groups of animals were sacrificed on days 1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and total protein. Oxidative and nitrosative stress were measured by immunohistochemical localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD, Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content of chromium and urinary excretion of NO(2 )(-)/NO(3)(-). Data were compared by two-way analysis of variance followed by a post hoc test. RESULTS: Serum and kidney chromium content increased reaching the highest value on day 1. Nephrotoxicity was made evident by the decrease in creatinine clearance (days 1–4) and by the increase in serum creatinine (days 1–4), BUN (days 1–6), urinary excretion of NAG (days 1–4), and total protein (day 1–6) and by the structural damage to the proximal tubules (days 1–6). Oxidative and nitrosative stress were clearly evident on days 1–8. Urinary excretion of NO(2)(-)/NO(3)(- )decreased on days 2–6. Mn-SOD and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity remained unchanged. Activity of GPx decreased on days 3–12 and those of GR and CAT on days 2–10. Similar findings were observed by immunohistochemistry of CAT. CONCLUSION: These data show the association between oxidative and nitrosative stress with functional and structural renal damage induced by K(2)Cr(2)O(7). Renal antioxidant enzymes were regulated differentially and were not closely associated with oxidative or nitrosative stress or with kidney damage. In addition, the decrease in the urinary excretion of NO(2)(-)/NO(3)(- )was associated with the renal nitrosative stress suggesting that nitric oxide was derived to the formation of reactive nitrogen species involved in protein nitration

Low Drift Thrust Balance with High Resolution

In this paper we present a small thrust balance for thrusters up to 2 kg developed by AST Advanced Space Technologies GmbH in cooperation with Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR). The measurement range is optimized for 0.1mN to 250mN while the full range is up to 1 N. In high dynamic mode the balance is able to resolve a pulsed force of 100mN with a duration of 100ms at a repetition rate of 1 Hz. By design the thrust balance is very insensitive to external disturbances. This leads to a very low long term drift which could be demonstrated to be smaller than 250 µN over 27 hours within a non-vacuum laboratory environment with only rudimentary decoupling from external influences