Correlating synthesis parameters with physicochemical properties of poly(glycerol sebacate)

[EN] Poly(glycerol sebacate), PGS, is an elastomeric biodegradable polyester increasingly proposed in a variety of biomedical applications. It is prepared by polycondensation of sebacic acid and glycerol in a first stage in which a prepolymer is obtained, followed by a curing to conveniently crosslink it. In this work, synthesis parameters such as the curing temperature and time, and the molar ratio between reactants, were systematically varied to correlate them with the physicochemical properties of the resulting polymer networks. The efficiency of each manufacturing process was quantified through, the relative mass effectively crosslinked and insoluble in tetrahydrofuran. Infrared spectra gave an estimation of the ratio of non-condensed polar terminal groups. These results were correlated with swelling results, which in turn provided the means to calculate the chains density through Flory-Rehner equilibrium swelling equation for lightly crosslinked polymers. The role of the synthesis parameters on the physical state of the resulting polymers, as well as their proneness to hydrolyze, were followed. The results obtained highlight the relevance of rinsing them following synthesis, to remove non-crosslinked chains that easily diffuse to the surrounding medium. Curing under mild conditions equimolar mixtures of sebacic acid and glycerol proved to lead to poorly crosslinked swellable networks, which hydrolyze easily in bulk mode. Alternative molar ratios yield sticky and difficult to handle materials at higher polyol fractions in the reactive mixture, whilst an excess of acid terminal groups leads to a faster mass loss by hydrolysis in aqueous media together with surface salts deposition, concomitant with a lesser cell viability in in vitro culture. PGS synthesized from an equimolar ratio between reactants and cured at 130 degrees C or higher, for 48 h or longer, show suitable features for their use in tissue engineering applications where hydrophobic surface-degradable rubbers are required, without significant differences among them.The authors acknowledge Spanish Ministerio de Economia y Competitividad through DPI2015-65401-C3-2-R project.Conejero-Garcia, Á.; Rivero-Gimeno, H.; Moreno-Sáez, Y.; Vilarino-Feltrer, G.; Ortuño-Lizarán, I.; Vallés Lluch, A. (2017). Correlating synthesis parameters with physicochemical properties of poly(glycerol sebacate). European Polymer Journal. 87:406-419. https://doi.org/10.1016/j.eurpolymj.2017.01.001S4064198

Dihydroartemisinin-Piperaquine vs. Artemether-Lumefantrine for First-Line Treatment of Uncomplicated Malaria in African Children: A Cost-Effectiveness Analysis.

Recent multi-centre trials showed that dihydroartemisinin-piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission. We developed a Markov model to assess the cost-effectiveness of DP versus AL for first-line treatment of uncomplicated malaria in young children from the provider perspective, taking into consideration the post-treatment prophylactic effects of the drugs as reported by a recent multi-centre trial in Africa and using the maximum manufacturer drug prices for artemisinin-based combination therapies set by the Global Fund in 2013. We estimated the price per course of treatment threshold above which DP would cease to be a cost-saving alternative to AL as a first-line antimalarial drug. First-line treatment with DP compared to AL averted 0.03 DALYs (95% CI: 0.006-0.07) and 0.001 deaths (95% CI: 0.00-0.002) and saved $0.96 (95$1.23 per course of treatment. DP is superior to AL from both the clinical and economic perspectives for treatment of uncomplicated P. falciparum malaria in young children. A paediatric dispersible formulation of DP is under development and should facilitate a targeted deployment of this antimalarial drug. The use of DP as first-line antimalarial drug in paediatric malaria patients in moderate to high transmission areas of Africa merits serious consideration by health policymakers

Evaluation of relationships between results of electrocardiography and echocardiography in 341 chimpanzees (Pan troglodytes)

Objective: To examine potential relationships between ECG characteristics and echocardiographic measures of cardiac structure in chimpanzees (Pan troglodytes). Animals: 341 chimpanzees (175 males and 166 females) from 5 sanctuaries and 2 zoological collections. PROCEDURES Chimpanzees were anesthetized for routine health examinations between May 2011 and July 2017 as part of the International Primate Heart Project and, during the same anesthetic events, underwent 12-lead ECG and transthoracic echocardiographic assessments. Relationships between results for ECG and those for echocardiographic measures of atrial areas, left ventricular internal diameter in diastole (LVIDd), and mean left ventricular wall thicknesses (MLVWT) were assessed with correlational analysis, then multiple linear regression analyses were used to create hierarchical models to predict cardiac structure from ECG findings. Results: Findings indicated correlations (r = –0.231 to 0.310) between results for ECG variables and echocardiographic measures. The duration and amplitude of P waves in lead II had the strongest correlations with atrial areas. The Sokolow-Lyon criteria, QRS-complex duration, and R-wave amplitude in leads V6 and II had the strongest correlations with MLVWT, whereas the Sokolow-Lyon criteria, QRS-complex duration, and S-wave amplitude in leads V2 and V1 had the strongest correlations with LVIDd. However, the ECG predictive models that were generated only accounted for 17%, 7%, 11%, and 8% of the variance in the right atrial end-systolic area, left atrial end-systolic area, MLVWT, and LVIDd, respectively. Conclusions and Clinical Reelvance: Results indicated that relationships existed between ECG findings and cardiac morphology in the chimpanzees of the present study; however, further research is required to examine whether the predictive models generated can be modified to improve their clinical utility. (Am J Vet Res 2020;81:488–498

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

[EN] Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.The authors acknowledge financing through projects MAT2011-28791-C03-02 and 03, and ERA-NET NEURON project PRI-PIMNEU-2011-1372. We thank the Cytomics Core Facility at Principe Felipe Research Center (CIPF, Valencia, Spain) for their support and advice in flow cytometry experiments, and the Electron Microscopy Service at the UPV, where the SEM images were obtained. The authors thankfully acknowledge the reviewers' comments, which have helped to improve the clarity of the paper's presentation.Vilariño Feltrer, G.; Martínez Ramos, C.; Monleon De La Fuente, A.; Vallés Lluch, A.; Moratal Pérez, D.; Barcia Albacar, JA.; Monleón Pradas, M. (2016). Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity. Acta Biomaterialia. 30:199-211. https://doi.org/10.1016/j.actbio.2015.10.040S1992113

Comparison of isoflurane and sevoflurane for short-term anesthesia in meerkats (suricata suricatta)-are there benefits that outweigh costs?

Meerkats (Suricata suricatta) are routinely anesthetized with isoflurane in zoo and field settings. Twenty healthy adult meerkats of mixed age and sex held in the Zoological Society of London's collection were anesthetized with 4% isoflurane by face mask for routine health examinations. The procedure was repeated 5 mo later in the same group of animals utilizing sevoflurane at 5% for induction, and again 3 mo later with sevoflurane at 6.5% for induction to approximate equipotency with isoflurane. The speed and quality of induction and recovery were compared between the two volatile anesthetic agents. There was no statistically significant difference in the speed of induction across any of the anesthetic regimes. There was a significant difference in recovery times between isoflurane and 6.5% sevoflurane (427 ± 218 and 253 ± 65 sec, respectively [mean ± SD]). Under the conditions of this study, sevoflurane at 6.5% induction dose resulted in better quality induction and recovery than sevoflurane at 5% induction or isoflurane. The mean heart and respiratory rates during anesthesia were higher using 5% sevoflurane for induction but there was no significant difference in either rate between isoflurane and sevoflurane used at a 6.5% induction dose. This study suggests that sevoflurane at a dose of 6.5% for induction and 4% for maintenance is a safe and effective anesthetic agent in healthy adult meerkats. Rapid return to normal behavior after anesthesia is important in all zoo species but particularly so in animals with a complex social and hierarchical structure such as meerkats. For this species, the advantage afforded by the speed of recovery with sevoflurane may offset the cost in certain circumstances