Designing Bioactive Delivery Systems for Tissue Regeneration

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies

Goals, mood and performance duration on cognitive tasks during experimentally induced mechanical pressure pain

BACKGROUND: The present study tested the hypothesis that the affective and motivational context influences performance duration in the presence of pain. More specifically, the Mood-as-Input model (MAI) proposes that the interaction between goals and moods affects performance duration. When people adopt achievement goals, negative, as opposed to positive moods, signal that not enough progress has been made leading to task continuance. Negative as opposed to positive moods lead to task disengagement when adopting hedonic goals. METHODS: Participants completed three open-ended cognitive tasks while being exposed to mechanical pressure pain to a finger. Before each task, mood (positive versus negative) and goal pursuit (hedonic versus achievement) were manipulated, with mood as between-subjects and goal pursuit as within-subjects factor. Performance duration was the dependent variable and goal order and performance duration during a no-goal task were the covariates. RESULTS: In line with common theories on goals and mood, but in contrast to the MAI model, only main effects were found of mood and goal pursuit. Participants showed greater performance duration in an achievement than in a hedonic goal context. Moreover, they showed greater performance duration in relative positive than negative moods. LIMITATIONS: Pain may have decreased participants' mood below a certain threshold, which in turn may have obscured the MAI interaction effect. CONCLUSIONS: This study demonstrates that affective and motivational factors influence performance duration in a pain context.status: publishe

Synthesis and Characterization of Photocurable Elastomers from Poly(glycerol-co-sebacate)

Elastomeric networks are increasingly being investigated for a variety of biomedical applications including drug delivery and tissue engineering. However, in some cases, their preparation requires the use of harsh processing conditions (e.g., high temperature), which limits their biomedical application. Herein, we demonstrate the ability to form elastomeric networks from poly(glycerol-co-sebacate) acrylate (PGSA) under mild conditions while preserving a wide range of physical properties. These networks presented a Young's modulus between 0.05 and 1.38 MPa, an ultimate strength from 0.05 to 0.50 Mpa, and elongation at break between 42% and 189% strain, by varying the degree of acrylation (DA) of PGSA. The in vitro enzymatic and hydrolytic degradation of the polymer networks was dependent on the DA. The copolymerization of poly(ethylene glycol) diacrylate with PGSA allowed for an additional control of mechanical properties and swelling ratios in an aqueous environment, as well as enzymatic and hydrolytic degradation. Photocured PGSA networks demonstrated in vitro biocompatibility as judged by sufficient human primary cell adherence and subsequent proliferation into a confluent monolayer. These photocurable degradable elastomers could have potential application for the encapsulation of temperature-sensitive factors and cells for tissue engineering

Ambulatory haemodynamic‐guided management reduces heart failure hospitalizations in a multicentre European heart failure cohort

Aims To investigate the outcomes and associated costs of haemodynamic-guided heart failure (HF) management with a pulmonary artery pressure (PAP) sensor in a multicentre European cohort. Methods and results Data from all consecutive patients receiving a PAP sensor in Ziekenhuis Oost-Limburg, University Hospital Zurich and Sheffield Teaching Hospitals NHS Foundation Trust before January 2021 were collected. Medication changes, total number of HF hospitalizations and HF related health care costs (composed of HF hospitalizations, outpatient cardiology visits and monitoring costs) were compared between the pre-implantation and post-implantation period at 3, 6, and 12 months. PAP evolution post-implantation were grouped according to baseline mPAP ≥25 mmHg versus <25 mmHg and changes from baseline were analyzed via an area under the curve (AUC) analysis. A total of 48 patients received a PAP sensor (29 CardioMEMS and 19 Cordella devices) with a median follow-up of 19 (13–30) months. Mean age was 71 ± 10 years, 25.0% were female, 68.8% had a left ventricular ejection fraction < 50%, median NT-proBNP was 1801 (827–4503) pg/mL, and 89.6% were in NYHA class III. The number of diuretic therapy changes were non-significantly increased after 3 months (49 vs. 82; P = 0.284) and 6 months (82 vs. 127; P = 0.093) with a significant increase noted after 12 months (118 vs. 195; P = 0.005). The mPAP AUC decreased by −1418 mmHg-days for patients with a baseline mean PAP ≥ 25 mmHg. The number of HF hospitalizations was reduced for all patients after 6 (34 vs. 17; P = 0.014) and 12 months (48 vs. 29; P = 0.032). HF related health care costs were reduced from € 6286 to € 3761 at 6 months (P = 0.012) and from € 8960 to € 6167 at 12 months (P = 0.032). Conclusion Haemodynamic-guided HF management reduces HF hospitalizations and HF related health care costs in selected HF patients amongst different European health care systems

[Photograph 2012.201.B1308.0228]

Photograph used for a story in the Daily Oklahoman newspaper. Caption: "QB Phil Thompson.. . Central State Broncho football holdover from last season.

Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial

Aims: Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes. Methods: The ADVOR trial is set up as a multicentre, randomized, double-blind, placebo-controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high-dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (&lt; 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output &gt; 3.5 L during the first 30–48 h of decongestive treatment. Secondary endpoints include all-cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol-5 dimensions questionnaire. Conclusion: ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiolog