Functional, degradable polyester materials synthesized from poly(epsilon-caprolactone-co-2-oxepane-1,5-dione): An investigation into the derivatization, self assembly, and degradation behavior of poly(epsilon-caprolactone)-based materials

Biocompatible, degradable polymers possessing a high degree of complexity are an extremely desirable target for many applications. In order to further develop the range and utility of materials made from aliphatic polyesters, poly(epsilon-caprolactone-co-2-oxepane-1,5-dione) (P(CL-co-OPD)) was used as a polymeric precursor for the construction of a series of functional polyester-based materials. By taking advantage of the electrophilic ketone moieties characteristic of the OPD repeat unit, small molecule and polymer grafts were attached to the PCL backbone through the formation of both hydrazone and ketoxime ether linkages. This work has focused on both the synthesis and characterization of functional, degradable polyesters, including amphiphilic block graft copolymers, that possess significant potential for future use in diagnostic and therapeutic applications. A dansyl-functionalized poly(epsilon-caprolactone) was synthesized by reacting (P(CL-co-OPD) with dansyl hydrazine. The resulting dansylated-PCL displayed interesting fluorescence behavior and showed solvent polarity dependance as the fluorescence emission maxima shifted from 494 nm in toluene to 526 nm in dimethyl sulfoxide (DMSO). Analysis of the emission maximum of the dansyl-grafted polymer and a dansyl-functionalized small molecule analog with respect to three different solvent polarity parameters indicated that the fluorescence emission spectra of the dansylated polymer was influenced by solvent polarity, but that the dansyl fluorophore was overall less sensitive to the surrounding medium when grafted onto the polyester backbone. Degradable, amphiphilic graft copolymers of poly(epsilon-caprolactone)-graft-poly(ethylene oxide), PCL-g-PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical copolymer (PCL-co-OPD). Through the formation of stable ketoxime ether linkages, 3 kDa poly(ethylene oxide) (PEO) grafts and p-methoxybenzyl (pMeOBn) side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopy and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, Tm, in comparison to the parent PCL and PEO polymers. These amphiphilic block graft copolymers underwent self assembly in aqueous solution with the P(CL-co-OPD-co-(OPD-g-PEO)) polymer forming globular micelles and a P(CL-co-OPD-co-(OPD-g-PEO)-co-(OPD-g-pMeOBn)) forming cylindrical or rod-like micelles, as observed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). PCL-g-PEO copolymers synthesized from PCL-co-OPD that still contained free OPD units were found to undergo an early and rapid degradation upon being dispersed in aqueous solution. P(CL92-co-OPD5-co-(OPD-g-PEO)9) showed immediate signs of degradation upon being dispersed in aqueous solution based upon both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The solution state aggregates showed a minimal increase in aggregate size moving from a number-averaged hydrodynamic diameter (Dh) of 13 ± 3 nm at 0 h to 17 ± 3 nm at 24 h based upon analysis by dynamic light scattering (DLS). An increase in diameter upon degradation was corroborated by transmission electron microscopy (TEM) images showing circular particles that had a Dav of 15 ± 4 nm and 22 ± 5 nm at 0 and 24 h respectively. P(CL92-co-(OPD-g-PEO)8-co-(OPD-g-pMeOBn)6), a polyester having no free OPD units, showed no signs of rapid degradation over 24 h by 1H NMR or GPC analysis. Characterization of the solution state aggregates by DLS and TEM indicated that the circular particles formed by the PCL-g-PEO copolymer maintained both their size and morphology while being dispersed in aqueous solution for 24 h. P(CL327-co-OPD22-co-(OPD-g-PEO)15-co-(OPD-g-pMeOBn)8), a significantly larger PCL-PEO ketoxime ether conjugate possessing free OPD units, also showed signs of backbone degradation by 1H NMR and GPC upon being transitioned into aqueous solution. DLS analysis, of the solution state aggregates formed by this amphiphilic block graft copolymer showed no substantial changes in the hydrodynamic diameter over time. However, characterization by TEM showed a transition from circular to rod-like or cylindrical aggregates as hydrolysis occurred

Finite Element Analysis of Experimentally Tested Concrete Slabs Subjected to Airblast

Since the last century, concrete has been used to protect structures against intentional or accidental detonation of explosives. Recently, as concerns about terrorist activities and accidents in plants using explosives increase worldwide, the study of the behaviour of this type of material and any civil or military structure under the influence of explosions has increased. Among the lethal effects of explosive devices, which cause greater loads in structural elements is the airblast effect. For this reason, this paper presents a series of airblast finite element (FEM) simulations developed in Abaqus/Explicit®. To validate the computational method, such simulations are geometrically and structurally kept similar to full-scale tests conducted in a blast test area of the Science and Technology Aerospace Department (Brazilian Air Force). Both simulations and tests consisted of seven reinforced concrete slabs with compressive strengths of about 40 to 60 MPa, variable steel reinforcement areas, slab dimensions measuring 1×1 m, and subjected to 2.7 kg of non-confined plastic bonded explosive. The results demonstrated that FEM simulations can predict the rupture of the tested slabs and how the effect occurs, showing a valid method to investigating the response of RC slabs when compared to expensive field tests. Differences in displacements were observed between the results of FEM simulations and blast field tests, mainly caused by the sensitivity of the case studied, limits of computational capacity, and intrinsic variations in the materials and sensors used in the field tests. However, these differences showed an order of magnitude compatible with the safety coefficients used with RC, demonstrating that the method can be used for the design of RC slabs under the effect of airblast

Comparison of Predicted and Experimental Behaviour of RC Slabs Subjected to Blast using SDOF Analysis

Explosions emanating from terrorist attacks or military weapons cause damage to civilian and military facilities. Understanding the mechanical behaviour of reinforced concrete structures subjected to blast is of paramount importance for minimizing the possible blast damage. A full-scale experimental program consisting of six reinforced concrete slabs with compressive strengths of 60 MPa, 50 MPa and 40 MPa, measuring 1.0 m × 1.0 m × 0.08 m, and subjected to 2.7 kg of non-confined plastic bonded explosive, was conducted in blast test area of Science and Technology Aerospace Department (Brazilian Air Force). This paper compares experimentally measured peak displacement values with theoretical values. Theoretical analysis was carried out using single degree of freedom (SDOF) models. The comparison showed that SDOF analysis worked very well in predicting the reinforced concrete slab peak displacement against blast effects. Qualitative analysis after the experiments showed that the blast wave shape generated by the cylindrical explosive was not uniformly distributed on the slabs for the standoff distance of 0.927 m∕kg1/3

Different Predictors of Right and Left Ventricular Metabolism in Healthy Middle-Aged Men

Dysfunction of the right ventricle (RV) plays a crucial role in the outcome of various cardiovascular diseases. Previous studies on RV metabolism are sparse although evidence implies it may differ from left ventricular (LV) metabolism. Therefore, the aims of this study were (1) to determine predictors of RV glucose uptake (GU) and free fatty acid uptake (FFAU) and (2) to compare them to predictors of LV metabolism in healthy middle-aged men. Altogether 28 healthy, sedentary, middle-aged (40-55 years) men were studied. Insulin-stimulated GU and fasting FFAU were measured by positron emission tomography and RV and LV structural and functional parameters by cardiac magnetic resonance. Several parameters related to whole-body health were also measured. Predictors of RV and LV metabolism were determined by pairwise correlation analysis, lasso regression models, and variable clustering using heatmap. RVGU was most strongly predicted by age and moderately by RV ejection fraction (EF). The strongest determinants of RVFFAU were exercise capacity (peak oxygen uptake), resting heart rate, LVEF, and whole body insulin stimulated glucose uptake rate. When considering LV metabolism, age and RVEF were associated also with LVGU. In addition, LVGU was strongly, and negatively, influenced by whole-body insulin-stimulated glucose uptake rate. LVFFAU was predicted only by LVEF. This study shows that while RV and LV metabolism have shared characteristics, they also have unique properties. Age of the subject should be taken into account when measuring myocardial glucose utilization. Ejection fraction is related to myocardial metabolism, and even so that RVEF may be more closely related to GU of both ventricles and LVEF to FFAU of both ventricles, a finding supporting the ventricular interdependence. However, only RV fatty acid utilization associates with exercise capacity so that better physical fitness in a relatively sedentary population is related with decreased RV fat metabolism. To conclude, this study highlights the need for further study designed specifically on less known RV as the results on LV metabolism and physiology may not be directly applicable to the RV.</p

Effects of alcohol preload on attentional bias towards cocaine-related cues

Background Drug and alcohol users have an ‘attentional bias’ for substance-related cues, which is likely to reflect the incentive-motivational properties of those cues. Furthermore, administration of an alcohol preload increases attentional bias for alcohol and tobacco-related cues in heavy drinkers and tobacco smokers, respectively. The present study investigated attentional bias for cocaine cues in cocaine users and non-users following administration of either alcohol or placebo. Method Thirty-two regular cocaine users and 40 non-users took part. Participants were administered alcohol or placebo, and administration was double blind. After drink administration, a Visual Probe task and Modified Stroop task were used to assess attentional bias. Subjective craving and alcohol outcome expectancies were also measured. Results There was a significant interaction between group and drink type on the visual probe task indicating that cocaine users who had received alcohol had increased attentional bias for cocaine pictures compared to non-users and cocaine users who received placebo. The cocaine Stroop revealed no differences between cocaine users and non-users, and no effects of alcohol in either group. Conclusions Alcohol preload in regular cocaine users increases attentional bias for cocaine cues. However, cocaine users who received placebo did not show attentional bias for cocaine stimuli. Future research should investigate the effects of alcohol preload on attentional bias in cocaine-dependent individuals

Attentional Processing of Food Cues in Overweight and Obese Individuals

The incentive sensitization model of obesity hypothesizes that obese individuals in the western world have acquired an enhanced attention bias to food cues, because of the overwhelming exposure to food. This article gives an overview of recent studies regarding attention to food and obesity. In general, an interesting approach-avoidance pattern in food-related attention has been found in overweight/obese individuals in a number of studies. However, it should be noted that study results are contradictory. This might be due to methodological issues, such as the choice of attention measurements, possibly tapping different underlying components of information processing. Although attention research is challenging, researchers are encouraged to further explore important issues, such as the exact circumstances in which obese persons demonstrate enhanced attention to food, the directional relationship between food-related attention bias, overeating and weight gain, and the underlying involvement of the reward system. Knowledge on these issues could help improve treatment programs

Evaluation of arterial anatomy in congenital clubfoot with color doppler ultrasound

OBJECTIVE: This investigation intended to evaluate anterior and posterior tibial arteries at the ankle joint level in congenital clubfoot, by using color Doppler ultrasound (CDU). MATERIAL AND METHOD: Twenty patients with idiopathic clubfoot were selected, from which 18 had unilateral involvement and two had bilateral involvement. Of the 18 patients with unilateral clubfoot, 16 went through surgical treatment and the other two were submitted to conservative treatment with serial casting. Of the bilateral cases, one patient was treated surgically and the other was treated with serial casting. All patients were clinically and radiographically assessed. We used the functional rating as described by Lehman. Then, CDU was applied bilaterally at the ankle joint level, trying to identify both posterior and anterior tibial arteries. RESULTS: In our present series of 20 cases with idiopathic clubfoot, in just one patient we could not identify the anterior tibial artery at the ankle joint level. In 12 patients who have had their arterial flow speeds and diameters measured by UDC, a positive correlation was found between functional level and anterior tibial artery diameter. No statistically significant differences were found between both flow speed and diameter of anterior tibial artery of the normal side, when compared to the affected side (in patients with unilateral disease). CONCLUSION: In our sample, we could not find any significant differences in arterial morphology and flow speed between the normal and the affected side. Furthermore, we noticed that the better the clinical result of clubfoot correction, the larger the diameter of anterior tibial artery in affected feet.OBJETIVO: Avaliação ultrassonográfica das artérias tibial anterior e posterior no pé torto congênito (PTC). MATERIAL E MÉTODO: Foram incluídos 20 pacientes portadores de PTC idiopático compreendendo 18 casos unilaterais e dois bilaterais, sendo que 17 pacientes foram submetidos a tratamento cirúrgico e três a tratamento conservador. Todos os pacientes apresentavam pés plantígrados e foram submetidos à avaliação clínica e radiográfica, seguido pelo exame de ultrassom Doppler colorido (UDC), visando a identificação das artérias tibiais anterior e posterior na altura do tornozelo. O nível funcional foi classificado pelos critérios de Lehman. RESULTADOS: Nesta série de 20 pacientes, somente em um não foi identificada a artéria tibial anterior. Nos 12 pacientes submetidos à mensuração de fluxo e calibre pelo UDC, foi encontrada uma correlação positiva entre o grau funcional do PTC e o calibre da artéria tibial anterior. Não houve redução estatisticamente significante entre o fluxo e calibre da artéria tibial anterior do lado normal em comparação com o lado alterado (nos casos de doença unilateral). CONCLUSÕES: Não houve alteração significativa da morfologia e fluxo arterial quando comparamos os lados afetado e normal. Além disso, quanto melhor o resultado clínico da correção do PTC, maior foi o calibre da artéria tibial anterior.UNIFESP Departamento de Ortopedia e TraumatologiaUNIFESP, Depto. de Ortopedia e TraumatologiaSciEL

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Dental Fear: One Single Clinical Question for Measurement

A new dental fear measurement instrument, the Short Dental Fear Question (SDFQ), was developed and tested for clinical practice purposes. The correlations of the SDFQ with the Dental Anxiety Scale (DAS) and the Dental Fear Survey (DFS) were tested in 15-16-year-old adolescents. The Spearman correlations (rs) between the dental fear measurement instruments were: SDFQ – DFS: rs = 0.79, n = 26; DFS – DAS: rs = 0.72, n = 26; SDFQ– DAS: rs = 0.69, n = 27. DAS and DFS mean scores were clearly higher in the SDFQ fear group than SDFQ in the relaxed group. The SDFQ is a short and compact instrument which might be convenient for the measurement of dental fear in clinical practice