Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds ...presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.
For the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.
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The body temperature of lizards is strongly influenced by the thermal quality of microhabitats, exploiting the favourable environmental temperatures, and avoiding exposure to extreme thermal ...conditions. For these reasons, reptile populations are considered to be especially vulnerable to changes in environmental temperatures produced by climate change. Here, we study the thermal physiology of the critically endangered Añelo Sand Dunes Lizard (Liolaemus cuyumhue Avila, Morando, Perez and Sites, 2009). We hypothesise that (i) there is a thermal coadaptation between optimal temperature for locomotor performance of L. cuyumhue and its thermal preference; (ii) L. cuyumhue lives in an environment with low thermal quality; and (iii) a rise in environmental temperatures due to global warming will impose a decrement in locomotor speed represented by lower warming tolerance and narrower thermal safety margins, increasing their already high vulnerability. We recorded field body temperatures (T
b
), preferred body temperatures (T
pref
), the operative temperature (T
e
), and the thermal sensitivity of locomotion at different body temperatures. Our results indicate that this lizard is not currently under environmental stress or exceeding its thermal limits, but that it is thermoregulating below T
pref
to avoid overheating, and that an increase in environmental temperature higher than 3.5 °C will strongly affect the use of microhabitats with direct sun exposure.
To describe the prevalence of Peripheral Artery Disease (PAD) in a random population sample and to evaluate its relationship with Mediterranean diet and with other potential cardiovascular risk ...factors such as serum uric acid and pulse pressure in individuals ranged 45 to 74 years.
Cross-sectional analysis of 1568 subjects (mean age 6.5 years, 43% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and HbA1C levels. An oral glucose tolerance test was performed in non-diabetic subjects. PAD was evaluated by ankle-brachial index and/or having a prior diagnosis.
PAD prevalence was 3.81% (95% CI, 2.97-4.87) for all participants. In men, PAD prevalence was significantly higher than in women 5.17% (95% CI, 3.74-7.11) vs. 2.78% (95% CI, 1.89-4.07); p = 0.014. Serum uric acid in the upper quartile was associated with the highest odds ratio (OR) of PAD (for uric acid > 6.1 mg/dl, OR = 4.31; 95% CI, 1.49-12.44). The remaining variables more strongly associated with PAD were: Heart rate >90 bpm (OR = 4.16; 95%CI, 1.62-10.65), pulse pressure in the upper quartile (≥ 54 mmHg) (OR = 3.82; 95%CI, 1.50-9.71), adherence to Mediterranean diet (OR = 2.73; 95% CI, 1.48-5.04), and former smoker status (OR = 2.04; 95%CI, 1.00-4.16).
Our results show the existence of a low prevalence of peripheral artery disease in a population aged 45-74 years. Serum uric acid, pulse pressure and heart rate >90 bpm were strongly associated with peripheral artery disease. The direct association between Mediterranean diet and peripheral artery disease that we have found should be evaluated through a follow-up study under clinical practice conditions.
The osteogenic capability of mesoporous bioactive nanoparticles (MBNPs) in the SiO2CaO system has been assessed in vivo using an osteoporotic rabbit model. MBNPs have been prepared using a double ...template method, resulting in spherical nanoparticles with a porous core-shell structure that has a high surface area and the ability to incorporate the anti-osteoporotic drug ipriflavone. In vitro expression of the pro-inflammatory genes NF-κB1, IL-6, TNF-α, P38 and NOS2 in RAW-264.7 macrophages, indicates that these nanoparticles do not show adverse inflammatory effects. An injectable system has been prepared by suspending MBNPs in a hyaluronic acid-based hydrogel, which has been injected intraosseously into cavitary bone defects in osteoporotic rabbits. The histological analyses evidenced that MBNPs promote bone regeneration with a moderate inflammatory response. The incorporation of ipriflavone into these nanoparticles resulted in a higher presence of osteoblasts and enhanced angiogenesis at the defect site, but without showing significant differences in terms of new bone formation.
Mesoporous bioactive glass nanoparticles have emerged as one of the most interesting materials in the field of bone regeneration therapies. For the first time, injectable mesoporous bioactive nanoparticles have been tested in vivo using an osteoporotic animal model. Our findings evidence that MBG nanoparticles can be loaded with an antiosteoporotic drug, ipriflavone, and incorporated in hyaluronic acid to make up an injectable hydrogel. The incorporation of MBG nanoparticles promotes bone regeneration even under osteoporotic conditions, whereas the presence of IP enhances angiogenesis as well as the presence of osteoblast cells lining in the newly formed bone. The injectable device presented in this work opens new possibilities for the intraosseous treatment of osteoporotic bone using minimally invasive surgery.
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The monitoring of ecosystems and forests is an urgent requirement in the current framework of global change. It is particularly necessary on oceanic islands where their rich biodiversity is highly ...vulnerable, with many narrow-ranged endemic species. Quantifying and mapping forest health through key ecological variables are essential steps for management, but it will also be challenging and may require a lot of resources. Remote sensing has the potential to be a very useful tool to assess the development and conservation status of forests. We assessed the applicability of the light detection and ranging (LiDAR) on the laurel forests of La Gomera, making allometric equations for various measurements of the forest structure, linking field inventory from 2019 and 2017 LiDAR data through standard linear regressions. Decision trees and logistic regressions were also used to assess the performance of LiDAR in the recognition of young-growth and old-growth laurel forests. The obtained allometric models were a good fit in general and their predictions were in line with already known data. Likewise, decision tree and logistic regression to distinguish young-growth and old-growth forests had a similar performance in both cases, with a high to medium-high degree of accuracy. Therefore, LiDAR was revealed to be a useful tool for the monitoring of the laurel forest by the managers.
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•Glucosamine (GlcN) is a weak direct antioxidant.•GlcN induces ROS production in a concentration-dependent manner in HMEC-1.•GlcN is an indirect antioxidant, it induces Nrf2 ...expression in HMEC-1.•O-GlcNAc plays a key role in ROS production and Nrf2 expression in HMEC-1.
Glucosamine (GlcN) is the most used supplement for osteoarthritis treatment. In vitro studies have related GlcN to beneficial and detrimental effects on health. The aim of this study was to evaluate the effects of O-linked-N-acetylglucosaminylation (O-GlcNAc) on GlcN-induced ROS production and Nrf2 expression in human dermal microvascular endothelial cells-1 (HMEC-1) and to evaluate the antioxidant capacity of GlcN compared to well-known antioxidants. For this, we evaluate the antioxidant capacity by in vitro assays. Besides, the GlcN (5–20 mM) effects on cell viability, reactive oxygen species (ROS) production, O-GlcNAc, and nuclear factor erythroid-2-related factor 2 (Nrf2) expression with and without the O-GlcNAc inhibitor OSMI-1 (10 μM) in HMEC-1 were evaluated. GlcN showed high inhibitory concentration (low scavenging activity) against superoxide (O2•─, IC20 = 47.67 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH•, IC50 = 21.32 mM), and hydroxyl (HO•, IC50 = 14.04 mM) radicals without scavenging activity against hydrogen peroxide (H2O2) and low antioxidant capacity determined by oxygen radical absorbance capacity (ORAC, 0.001 mM Trolox equivalent) and ferric reducing antioxidant power (FRAP, 0.046 mM Trolox equivalent). In cell culture, GlcN (20 mM) reduced cell viability up to 26 % and induced an increase in ROS production (up to 70 %), O-GlcNAc (4-fold-higher vs. control), and Nrf2 expression (56 %), which were prevented by OSMI-1. These data suggest an association between O-GlcNAc, ROS production, and Nrf2 expression in HMEC-1 cells stimulated with GlcN.
Antioxidant response was used to assess the effects of the main pollutants in wild mussels (
Mytilus galloprovincialis) along the Mediterranean coast of Spain. Antioxidant enzyme activities – those ...of catalase, superoxide dismutase, glutathione peroxidases, glutathione reductase, glutathione S-transferase and DT-diaphorase – as well as lipid peroxidation and metallothionein concentrations were measured in gills of mussels from 16 selected sites. Furthermore, concentrations of the main contaminants (Hg, Pb, Cd, Cu, Zn, As, PAH, PCB, and DDT) were quantified in mussel tissue, and environmental parameters were measured in water samples collected at each site. Results showed that the glutathione-dependent antioxidant enzymes offered an increased and coordinated response against metal (Hg, Pb and Cd) contamination. These enzymatic activities correlated positively to temperature, suggesting the influence of this environmental parameter on antioxidant responses in gill tissues. Furthermore, although temperature did not reach stressful levels in the study area, it seemed to add a synergistic effect to that produced by metals to induce antioxidant enzymes in the most metal-polluted sites. Catalase activity appeared to be involved in a different antioxidant pathway, more related to organic pollutant bioaccumulation, offering an efficient protection mechanism against reactive oxygen species generation due both to organic exposure and high physiological activity, reflected by high condition indices. In general terms, increased levels of antioxidant enzymes at some sites suffering from metal and organic pollution indicated a situation of oxidative stress that nevertheless did not appear to be harmful, since lipid peroxidation levels showed no peroxidative damage in gill tissues of mussels collected from even the most heavily polluted sites. On the other hand, metallothionein and DT-diaphorase did not reflect pollutant exposure and seemed to be more influenced by environmental variables than by the pollutants.
Abstract Background and Aim To investigate whether rosuvastatin can improve insulin sensitivity in overweight rats having a high fat diet (HFD). The potential mechanisms involved in this action were ...evaluated, including SIRT-1, other factors involved in glucose metabolism and stress signaling pathways. Methods and Results Male Wistar rats ( n = 30) were divided into three groups: (i) rats fed a standard diet (3.5% fat); (ii) rats fed a HFD (33.5% fat); and (iii) rats fed a HFD and treated with rosuvastatin (15 mg/kg/day). Evolution: 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Plasma levels of cholesterol, triglycerides, VLDL, glucose and insulin and leptin/adiponectin ratio were higher in HFD rats, and rosuvastatin treatment reduced them. SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 protein levels in white adipose tissue (WAT) were lower, and JNK was higher in HFD rats compared to controls. Rosuvastatin treatment normalized expression of these mediators. Endothelium-dependent relaxation was reduced in mesenteric rings from HFD rats compared to controls and rosuvastatin enhanced it in HFD rats. Conclusion Rosuvastatin treatment reduced insulin resistance without affecting body weight or WAT loss in HFD rats. Reduction of leptin and JNK, and enhancement of SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 expression in WAT could contribute to insulin sensitization. Normalization of SIRT-1 expression in WAT could be considered a key novel mechanism that aids in explaining the beneficial effects of rosuvastatin on the amelioration of glucose metabolism and the arrangement of multiple signaling pathways participating in insulin resistance in overweight HFD rats.
HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective ...was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry.
We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively).
We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001).
The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.
HeartLogic es un algoritmo multiparamétrico incorporado a desfibriladores automáticos implantables (DAI). La alerta asociada predice descompensaciones de insuficiencia cardiaca (IC). Nuestro objetivo es analizar la asociación entre alertas y eventos clínicos bajo un protocolo de seguimiento común en un registro multicéntrico.
Se evaluaron la fase 1 (investigadores ciegos al estado de la alerta) y las fases 2 y 3 (tras la activación de HeartLogic, según práctica local y un protocolo común respectivamente).
Se incluyó a 288 pacientes en 15 centros. En fase 1, tras una media de observación de 10 meses, hubo 73 alertas (0,72 alertas/paciente-año), con 8 hospitalizaciones y 2 visitas a urgencias por IC (0,10 eventos/año-paciente). No hubo hospitalizaciones fuera del periodo de alerta. Las fases activas tuvieron una media de seguimiento de 16 (IC95%, 15-22) meses, con 277 alertas (0,89 alertas/año-paciente); 33 se asociaron con hospitalizaciones o muerte por IC, 46 con descompensaciones menores y 78 con otros eventos. La tasa de alertas inexplicables fue 0,39/año-paciente. Fuera del estado de alerta solo hubo una hospitalización y una descompensación menor. La mayoría de las alertas (el 82% en fase 2 y el 81% en fase 3; p=0,861) se gestionaron a distancia. La mediana de NT-proBNP fue superior en estado de alerta que fuera de él (7.378 frente a 1.210 pg/ml; p <0,001).
El índice HeartLogic se asoció con descompensaciones de IC y otros eventos relevantes, con baja tasa de alertas inexplicables. Un protocolo estandarizado permitió detectar y actuar a distancia con seguridad sobre las alertas.
Neutron beams, both pulsed and continuous, are a powerful tool in a wide variety of research fields and applications. Nowadays, pulsed neutron beams are produced in conventional accelerator ...facilities in which the time-of-fight technique is used to determine the kinetic energy of the neutrons inducing the reactions of interest.
In the last decades, the development of ultra-short (femtosecond) and ultra-high power (> 10
18
W/
cm
2
) lasers has opened the door to a vast number of new applications, including the production and acceleration of pulsed ion beams. These have been recently used to produce pulsed neutron beams, reaching fluxes per pulse similar and even higher than those of conventional neutron beams, hence becoming an alternative for the pulsed neutron beam users community. Nevertheless, these laser-driven neutrons have not been exploited in nuclear physics experiments so far.
Our main goal is to produce and characterize laser-driven neutrons but optimizing the analysis, diagnostic and detection techniques currently used in conventional neutron sources to implement them in this new environment. As a result, we would lay down the viability of carrying out nuclear physics experiments using this kind of sources by identifying the advantages and limitations of this production method.
To achieve this purpose, we plan to perform experiments in both medium (50TW@L2A2, in Santiago de Com-postela) and high (1PW@APOLLON, in Paris) power laser facilities.