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The aim of this research is to evaluate the influence of the moisture content of wood on stress wave velocity, as a nondestructive technique for estimating the mechanical properties of gross cross-section Spanish Scots pine (Pinus sylvestris) lumber for structural use. 26 100 x 150 x 3000 mm pieces from Segovia, Spain, were tested with different moisture content values, from 35,5 to 9%. Measurements of longitudinal stress wave velocity were carried out during the natural drying process by using three commercial portable devices based on ultrasonic, acoustic and vibrational techniques. The results can be summarized as three percentage points of decreasing velocity per percentage point of increased wood moisture content in the range from 11,8 to 21,4%: 0,48% for ultrasonic, 0,50% for acoustic wave and 0,65% for longitudinal vibration. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to conduct a cost-utility analysis of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in real-world, comparing their use with standard care for managing cardiovascular disease. A multicenter prospective study was conducted across 12 Spanish hospitals from May 2020 to April 2022, involving 158 patients with hypercholesterolemia or atherosclerotic cardiovascular disease. This study assessed health-related quality of life (QoL) using the EQ-5D-3L questionnaire. The cost-utility analysis evaluated the economic impact of PCSK9 inhibitors when used with standard care compared to standard care alone, calculating the incremental cost-effectiveness ratio (ICER). This study included 158 patients with an average age of 61 years, male (66.5%). For patients initiating PCSK9 inhibitors, the treatment cost was EUR 13,633.39, while standard therapy cost EUR 3638.25 over two years. QoL for PCSK9 inhibitors stood at 1.6489 over two years, compared to 1.4548 for standard therapy. The results revealed favorable cost-utility outcomes, with an ICER of EUR 51,427.72. Significant improvements were observed in the domains of mobility, self-care, daily activities, pain/discomfort, and anxiety/depression ( p < 0.001). This study presents the first real-world cost-utility analysis of PCSK9 inhibitors, supporting their economic rationale and highlighting their benefits in clinical practice. Healthcare decision-makers can use these results to inform their decisions and reimbursement policies concerning PCSK9 inhibitors. Trial Registration clinicaltrials.gov Identifier: NCT04319081.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives., (© 2023. L’Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE).)

Introduction: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab., Methods: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA)., Results: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms., Conclusion: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab., Registration: ClinicalTtrials.gov Identifier number NCT04319081., (© 2023. The Author(s).)

Objectives: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety., Material and Methods: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time., Results: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1)., Conclusions: (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (<55mg/dL and/or reduction>50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P=.972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed., (Copyright © 2022 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

The reduction of CO 2 emissions and its elimination from the atmosphere has become one of the major problems worldwide, since CO 2 is the main cause of the greenhouse effect and climate change. In recent years, a great number of carbonaceous materials that can be used as CO 2 adsorbents have been synthesized. The strategy is usually to synthesize the materials and determine their adsorption capacity without studying previously the factors that influence this capacity. In this work, different properties of the adsorbents are analyzed to study their influence on the CO 2 adsorption capacity. For this purpose, 10 adsorbents have been synthesized using different strategies and characterized with X-ray photoelectron spectroscopy, X-ray diffraction, and micro-Raman spectroscopy. The percentage of sp 2 carbons, the position of the D + D' peak of the second-order Raman spectrum, the micropore volume, and the grain size of the C sp 2 domains have been related to the amount of CO 2 adsorbed by the adsorbents. The results confirm a linear relationship between the volume of the micropores and the CO 2 uptake and it proves that CO 2 retention is favored in those materials that, in addition to having a high volume of micropores, also have low grain size of C., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objective: To describe the development of the Antidotos&#95;bot chatbot tool, which is used to facilitate the search for information in the Antidote Administration Guide and to perform useful calculations in the use of antidotes., Method: In January 2019, we proposed developing a freely accessible chatbot on Telegram® using Xenioo®. Software development  defined the way it interacts with users and incorporated calculation  functionalities. Internal validation was conducted and it was presented as  Antidotos&#95;bot in June 2019., Results: Antidotos&#95;bot included information in Spanish on 49 antidotes and 57 poisonings. Three types of calculations were provided  and two treatment algorithms could be consulted. Consultation was  possible through 332 questions. Internal validation needed five sets of  training over 2 months. By July 2020, it had 415 users. The most  frequently consulted antidotes were glucagon, penicillin G, protamine, n- acetylcysteine and flumazenyl. Regarding monthly activity, there was an  average of 29 calculations and an average of three new users and three  queries per user., Conclusions: Antidotos&#95;bot is a poisoning management decisionmaking tool that provides up-to-date information in a user-friendly manner. It could contribute to improving the quality and safety of care in  emergency situations., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Introduction: In Chile, Down syndrome has a prevalence of 2.5 in 1,000 live births. These patients present more congenital anomalies and comorbidities than the general population, increasing their hospitaliza tion rate., Objective: To describe congenital anomalies and comorbidities of neonates with Down syndrome born and/or hospitalized between 2008 and 2018., Patients and Method: We conducted a retrospective review of patient's medical records born and/or hospitalized during their first 28 days of life between January 1st, 2008, and December 31st, 2018. For each patient, we recorded maternal age, familiar cases of Down Syndrome, pre and perinatal history, genetic study result, as well as age at admission, reason for hospitalization, comorbidities, length of stay, and death. Two patients that had more than 50% of incomplete medical records were excluded. We studied the associations between comorbidities, congenital anomalies, and death., Results: 140 in 79,506 newborns (0.2%) were diagnosed at our center with Down Syndrome in their neonatal period. 24.7% were born preterm and 26.4% had low birth weight for gestational age. Morbidities and hospitalizations were present in 83.6% and 90%, of the study population, respectively. The main reason for hospitalization was polycythemia and the most frequent was hyperbilirubinemia. Four patients died (2.9%) and 70.7% presented at least one congenital anomaly, mainly heart disease. Median maternal age was 36 years and 57.1% of mothers were aged 35 or older., Conclusions: This cohort of patients with Down Syndrome provides important information for the optimization of their perinatal management and follow-up.

The antihypertensive activity of two α s1 -casein-derived peptides and casein hydrolysate containing these sequences was evaluated in the presence of naloxone. The activity was abolished by this opioid antagonist at 2, 4, and 6 h post-administration. Similarly, the antihypertensive effect of the α s1 -casein peptides 90 RYLGY 94 (-23.8 ± 2.5 mmHg) and 143 AYFYPEL 149 (-21.1 ± 3.2 mmHg) at 5 mg/kg of body weight was antagonized by the co-administration of naloxone. Because peptide 143 AYFYPEL 149 had recently shown opioid activity, a molecular dynamic simulation of this peptide with human μ-opioid receptor was performed to demonstrate its favorable structure and interaction energy, despite the presence of Ala at the N terminus. Altogether, these results revealed that the in vivo effect on systolic blood pressure of the studied α s1 -casein peptides is mediated by interaction with opioid receptors and the antihypertensive activity of casein hydrolysate can be very likely ascribed to them with the possible contribution of other mechanisms.

The use of multitarget drugs has evolved as an alternative to "magic bullets" for the treatment of complex diseases such as cancer, in order to affect simultaneously several targets relevant to the disease. We have designed and synthesized a series of dual agents as both Eg5 inhibitors and calcium channel blockers, bearing a 4-aryldihydropyrimidine core. Compound 2 (aryl: 3-nitrophenyl) was selected as potential dual agent due to displaying both activities: it is a vasorelaxant agent (>90% relaxation at 10 -5 M in KCl-precontracted aorta rings), it decreases the response to calcium and it is cytotoxic to MCF-7 (breast), HCT-116 (colon) and A-549 (lung) cancer cell lines. The dual mechanism of action was confirmed by blocking (-)-BAY K8644-induced vascular contraction and production of monopolar spindles, typical of Eg5 inhibition. Docking suggests that both ( R ) and ( S )-enantiomers could bind Eg5., (This journal is © The Royal Society of Chemistry 2019.)

Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3-/- mice. Vagal afferent inputs are also required for the development of additional pathophysiological conditions associated with deregulated rostral ventrolateral medulla activity. By contrast, they are dispensable for other peripheral sympathoexcitation-associated disorders sparing metabolic alterations in liver.

The bidirectional regulation of epithelial-mesenchymal transitions (EMT) is key in tumorigenesis. Rho GTPases regulate this process via canonical pathways that impinge on the stability of cell-to-cell contacts, cytoskeletal dynamics, and cell invasiveness. Here, we report that the Rho GTPase activators Vav2 and Vav3 utilize a new Rac1-dependent and miR-200c-dependent mechanism that maintains the epithelial state by limiting the abundance of the Zeb2 transcriptional repressor in breast cancer cells. In parallel, Vav proteins engage a mir-200c-independent expression prometastatic program that maintains epithelial cell traits only under 3D culture conditions. Consistent with this, the depletion of endogenous Vav proteins triggers mesenchymal features in epithelioid breast cancer cells. Conversely, the ectopic expression of an active version of Vav2 promotes mesenchymal-epithelial transitions using E-cadherin-dependent and independent mechanisms depending on the mesenchymal breast cancer cell line used. In silico analyses suggest that the negative Vav anti-EMT pathway is operative in luminal breast tumors. Gene signatures from the Vav-associated proepithelial and prometastatic programs have prognostic value in breast cancer patients.

Pediatric cataract surgery poses a significant challenge for the cataract surgeon, in part because an elastic anterior capsule can make capsulorhexis difficult. With the use of femtosecond laser-assisted cataract surgery (FLACS), however, the continuous curvilinear capsulorhexis can be made with predictable size, circular shape, centration, and accuracy. In addition, topical anesthesia can be used for the FLACS docking procedure in cooperative children above 6 years of age, using transparent adhesive polyurethane film segments., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Polo-like kinase 1 (PLK1), an essential regulator of cell division, is currently undergoing clinical evaluation as a target for cancer therapy. We report an unexpected function of Plk1 in sustaining cardiovascular homeostasis. Plk1 haploinsufficiency in mice did not induce obvious cell proliferation defects but did result in arterial structural alterations, which frequently led to aortic rupture and death. Specific ablation of Plk1 in vascular smooth muscle cells (VSMCs) led to reduced arterial elasticity, hypotension, and an impaired arterial response to angiotensin II in vivo. Mechanistically, we found that Plk1 regulated angiotensin II-dependent activation of RhoA and actomyosin dynamics in VSMCs in a mitosis-independent manner. This regulation depended on Plk1 kinase activity, and the administration of small-molecule Plk1 inhibitors to angiotensin II-treated mice led to reduced arterial fitness and an elevated risk of aneurysm and aortic rupture. We thus conclude that a partial reduction of Plk1 activity that does not block cell division can nevertheless impair aortic homeostasis. Our findings have potentially important implications for current approaches aimed at PLK1 inhibition for cancer therapy.

Objectives: Elevated levels of angiotensin II are implicated in the hypertensive pathophysiological process. Zofenopril has a sulphydryl group which gives it antioxidant properties. The aim of this study was to investigate its beneficial effects beyond angiotensin-converting enzyme (ACE) inhibition using angiotensin II-infused rats as hypertension model., Methods: Zofenopril was added in drinking water. Systolic blood pressure was assessed by the tail-cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. An estimate of the cardiac collagen was performed by measuring the content of hydroxyproline. Vascular reactivity was evaluated on aortic rings and isolated perfused kidney, and vascular structure in thoracic aorta was studied. Superoxide anion generation was quantified in aorta by lucigenin-enhanced chemiluminescence., Key Findings: Zofenopril partially prevented the increase in systolic blood pressure and cardiac hypertrophy induced by angiotensin II and avoided the increase in collagen deposition. The treatment improved vasorelaxing responses, reversed the vascular remodelling and abolished the effects of angiotensin II on the production of ·O2-. It is worth to mention that all these results are observed even with high levels of plasma angiotensin., Conclusion: Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II., (© 2016 Royal Pharmaceutical Society.)

This study aimed to determine whether the serotonergic modulation, through selective 5-HT 2 receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT 2 receptor was blocked by sarpogrelate (30 mg/kg.day; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O 2 • - ) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O 2 • - production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O 2 • - production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT 2 receptors has beneficial effects on impaired cardiovascular parameters in diabetes.

Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39(+) regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The self-diffusion coefficient of a granular gas in the homogeneous cooling state is analyzed near the shearing instability. Using mode-coupling theory, it is shown that the coefficient diverges logarithmically as the instability is approached, due to the coupling of the diffusion process with the shear modes. The divergent behavior, which is peculiar in granular gases and disappears in the elastic limit, does not depend on any other transport coefficient. The theoretical prediction is confirmed by molecular dynamics simulation results for two-dimensional systems.

The hydrodynamic part of the velocity autocorrelation function of a granular fluid in the homogeneous cooling state has been calculated by using mode-coupling theory for a finite system with periodic boundary conditions. The existence of the shearing instability, leading to a divergent behavior of the velocity flow fluctuations, is taken into account. A time region in which the velocity autocorrelation function exhibits a power-law decay, when time is measured by the number of collisions per particle, has been been identified. Also the explicit form of the exponential asymptotic long time decay has been obtained. The theoretical prediction for the power-law decay is compared with molecular dynamics simulation results, and a good agreement is found, after taking into account finite size corrections. The effects of approaching the shearing instability are also explored.

Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically engineered mice to manipulate the signaling output of Rac1 in these cells at will using inducible, Cre-loxP-mediated DNA recombination techniques. Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic loss of wild-type Vav2. Conversely, the specific depletion of Rac1 in vSMCs causes defective nitric oxide vasodilation responses and hypertension. Rac1, but not Vav2, also is important for neointima formation but not for hypertension-driven vascular remodeling. These animals also have allowed us to dismiss etiological connections between hypertension and metabolic disease and, most importantly, identify pathophysiological programs that cooperate in the development and consolidation of hypertensive states caused by local vascular tone dysfunctions. Finally, our results suggest that the therapeutic inhibition of Rac1 will be associated with extensive cardiovascular system-related side effects and identify pharmacological avenues to circumvent them., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner., Methods: Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls)., Results: Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors., Conclusions: Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

The scarce data concerning the gasification of carbonaceous solids with supercritical water (SCW) suggest the great potential of this method to produce a valuable green fuel such as H2. However, the extraordinary properties of SCW have not been properly applied to H2 production because the mechanism that governs gasification under these conditions remains unclear. Here, we present a study in which this reaction is explored within the largest pressure range ever assayed in this field, from 1 to 1000 bar. The amplitude of the experimental conditions investigated highlights the various pathways that govern gasification with steam and SCW. Under supercritical conditions, the clusters formed around the superficial groups of the solid reduce the energetic requirements for gasification and generate CO2 as a primary product of the reaction. Consequently, gasification with SCW is significantly faster than that using steam, and the produced gases are richer and more appropriate to obtain pure H2.

We construct a novel class of exact solutions to the Boltzmann equation, in both its classical and quantum formulation, for arbitrary collision laws. When the system is subjected to a specific external forcing, the precise form of which is worked out, nonequilibrium dampingless solutions are admissible. They do not contradict the H theorem, but are constructed from its requirements. Interestingly, these solutions hold for time-dependent confinement. We exploit them, in a reverse-engineering perspective, to work out a protocol that shortcuts any adiabatic transformation between two equilibrium states in an arbitrarily short time span, for an interacting system. Particle simulations of the direct Monte Carlo type fully corroborate the analytical predictions.

Internal mammary artery (IMA) and radial artery (RA) are the 2 main arterial conduits used in coronary artery bypass grafting (CABG). The aim of this study was to analyze in vitro the vasoreactive properties in both vessels and to investigate the effects of pravastatin incubation on vascular function. IMA and RA rings obtained from patients undergoing CABG were studied in organ baths. We examined the contractile responses to phenylephrine and U46619 and the relaxation to acetylcholine (ACh) and sodium nitroprusside. In another series of experiments, the vascular reactivity and the superoxide anion production were studied after incubation with pravastatin. The effect of mevalonic acid on such responses was also assessed. Our results show that RA significantly evoked greater tension in response to vasoconstrictor agents and higher relaxation to ACh than IMA. In contrast, relaxation induced by sodium nitroprusside was not significantly different. Incubation with pravastatin reduced the contractile response to U46619 and improved the endothelium-dependent relaxation to ACh in both arteries. Whereas the effect of pravastatin on response to U46619 was completely abolished by coincubation with mevalonic acid, only a partial inhibition on ACh relaxation was observed. In conclusion, in vitro incubation with pravastatin enhanced endothelial function in IMA and RA. This suggests that postoperative (may include intraoperative) administration of statins could improve the endothelial function of arterial grafts in patients undergoing CABG.

The shearing instability of a dilute granular mixture composed of smooth inelastic hard spheres or disks is investigated. By using the Navier-Stokes hydrodynamic equations, it is shown that the scaled transversal velocity mode exhibits a divergent behavior, similarly to what happens in one-component systems. The theoretical prediction for the critical size is compared with direct Monte Carlo simulations of the Boltzmann equations describing the system, and a good agreement is found. The total energy fluctuations in the vicinity of the transition are shown to scale with the second moment of the distribution. The scaling distribution function is the same as found in other equilibrium and nonequilibrium phase transitions, suggesting the existence of some kind of universality.

Scope: The aim of this study was to investigate the antihypertensive effect of a peptide fraction (PepC) obtained from a whey protein concentrate following hydrolysis by Cynara cardunculus, as well as of its fraction with MW below 3 kDa (PepCF). Both these concentrates encompassed peptides that exhibited potent in vitro inhibition of angiotensin-converting enzyme (ACE): two were released from α-lactalbumin--KGYGGVSLPEW and DKVGINYW, and one from β-lactoglobulin--DAQSAPLRVY., Methods and Results: Upon oral administration, by gastric intubation, of 400 mg/kg body weight (bw) of those peptide concentrates, or 5 mg/kg bw of the corresponding synthetic peptides, to 12 wk-old spontaneously hypertensive rats (SHR), the systolic and diastolic blood pressures were monitored by the tail-cuff method--before, and 2, 4, 6, 8 and 24 h afterwards. Water and zofenopril (5 mg/kg bw)--a known ACE-inhibitor, were used as negative and positive controls, respectively. Acute administration of PepC, PepCF, KGYGGVSLPEW, DKVGINYW and DAQSAPLRVY caused antihypertensive effects in SHR; the maximum effect occurred by 4 h and 6 h after administration of the peptide concentrates and the synthetic peptides, respectively. PepC and KGYGGVSLPEW also showed ACE-inhibitory activity in vivo: the pressor effect of angiotensin I was significantly lower, and the response to bradykinin increased when the rats were pre-treated with either product., Conclusion: Our results strongly suggest that PepC will be effective as nutraceutical ingredient for the formulation of functional foods aimed at hypertension control., (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The local cooling rates of the components of a vibrated binary granular mixture in a steady state are investigated. The accuracy of the expression obtained by assuming a local homogeneous cooling state distribution of the gas is analyzed by comparing it with molecular dynamics simulation results. A good agreement is observed. Also, the profiles of the partial temperatures are compared with the theoretical prediction following from the application of the Chapman-Enskog method to solve the kinetic Enskog equations of the mixture. In this case, the agreement is satisfactory if the boundary layers near the walls are excluded. The implications of the results are discussed.

Essential hypertension is considered a serious health problem and diet can play an important role in its prevention and treatment. The aim of this study was to evaluate the effect of the long-term intake of a product based on milk casein hydrolysate on the development of hypertension in spontaneously hypertensive rats (SHR). A daily dose of 800 mg/kg body weight of the casein hydrolysate product was administered dissolved in drinking water during 6 weeks. Systolic and diastolic blood pressures were measured weekly by the tail-cuff method. Endothelial function in aorta and mesenteric segments, left ventricular hypertrophy, endothelial nitric oxide synthase (eNOS) expression in aorta and plasmatic angiotensin conversion enzyme (ACE) activity were also evaluated at the end of treatment. The development of hypertension was attenuated in the group treated with the casein hydrolysate product; in this sense the systolic blood pressure increased 33±3 mmHg in control group and only 18±5 mmHg in the treated group during the experimental period. In addition, the treatment improved aorta and mesenteric acetylcholine relaxations and increased the eNOS expression in aorta. Left ventricular hypertrophy decreased in treated SHR accompanied by a significant decrease in interstitial fibrosis. These results warrant evaluation in humans to determine if the product based on a casein hydrolysate could be used as a functional food ingredient to prevent blood pressure increased with additional cardiovascular benefits., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The influence of texture and surface chemistry on the phenol adsorption capacity of activated carbon fibres (ACFs) was studied. ACFs were prepared by carbonization of a phenolic textile fibre under nitrogen flow, followed by activation with H(2)O and CO(2) (under atmospheric pressure and supercritical state). The materials were characterised by N(2) and CO(2) adsorption, and by temperature programmed desorption studies. A strong correlation between the amount of adsorbed phenol and the micropore volume has been observed. The relationship between surface oxygen concentration and amount of physisorbed and chemisorbed phenol was assessed, and it was shown that higher amounts of surface oxygen groups decreased the phenol chemisorption capacity of ACFs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aryl hydrocarbon receptor (Ahr) is a transcriptional factor involved in detoxification responses to pollutants and in intrinsic biological processes of multicellular organisms. We recently described that Vav3, an activator of Rho/Rac GTPases, is an Ahr transcriptional target in embryonic fibroblasts. These results prompted us to compare the Ahr(-/-) and Vav3(-/-) mouse phenotypes to investigate the implications of this functional interaction in vivo. Here, we show that Ahr is important for Vav3 expression in kidney, lung, heart, liver, and brainstem regions. This process is not affected by the administration of potent Ahr ligands such as benzo[a]pyrene. We also report that Ahr- and Vav3-deficient mice display hypertension, tachypnea, and sympathoexcitation. The Ahr gene deficiency also induces the GABAergic transmission defects present in the Vav3(-/-) ventrolateral medulla, a main cardiorespiratory brainstem center. However, Ahr(-/-) mice, unlike Vav3-deficient animals, display additional defects in fertility, perinatal growth, liver size and function, closure, spleen size, and peripheral lymphocytes. These results demonstrate that Vav3 is a bona fide Ahr target that is in charge of a limited subset of the developmental and physiological functions controlled by this transcriptional factor. Our data also reveal the presence of sympathoexcitation and new cardiorespiratory defects in Ahr(-/-) mice.

The aim of this study was to investigate the effects of astaxanthin-enriched diet on blood pressure, cardiac hypertrophy, both vascular structure and function and superoxide ((*)O(2-)) production in spontaneously hypertensive rats (SHR). Twelve-week-old SHR were treated for 8 weeks with an astaxanthin-enriched diet (75 or 200mg/kg body weight per day). Systolic blood pressure was monitorized periodically during the study by the tail cuff method. At the end of the study animals were sacrificed and heart, kidneys and aorta were removed. Left ventricular weight/body weight ratio was used as left ventricular hypertrophy index (LVH). Vascular function and structure were studied in conductance (aortic rings) and resistance (renal vascular bed) arteries. Also (*)O(2-) production was evaluated by lucigenin-enhanced chemiluminescence. Systolic blood pressure was lower in astaxanthin-treated groups than the control group from the first week of treatment, and LVH was significantly reduced. Astaxanthin improved endothelial function on resistance arteries, but had no effect on aorta. These effects were accompanied by a decrease in oxidative stress and improvements in NO bioavailability. Taken together, these results show that diet supplemented with astaxanthin has beneficial effects on hypertension, by decreasing blood pressure values, improving cardiovascular remodeling and oxidative stress., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Vav3 is a phosphorylation-dependent activator of Rho/Rac GTPases that has been implicated in hematopoietic, bone, cerebellar, and cardiovascular roles. Consistent with the latter function, Vav3-deficient mice develop hypertension, tachycardia, and renocardiovascular dysfunctions. The cause of those defects remains unknown as yet. Here, we show that Vav3 is expressed in GABAegic neurons of the ventrolateral medulla (VLM), a brainstem area that modulates respiratory rates and, via sympathetic efferents, a large number of physiological circuits controlling blood pressure. On Vav3 loss, GABAergic cells of the caudal VLM cannot innervate properly their postsynaptic targets in the rostral VLM, leading to reduced GABAergic transmission between these two areas. This results in an abnormal regulation of catecholamine blood levels and in improper control of blood pressure and respiration rates to GABAergic signals. By contrast, the reaction of the rostral VLM to excitatory signals is not impaired. Consistent with those observations, we also demonstrate that Vav3 plays important roles in axon branching and growth cone morphology in primary GABAergic cells. Our study discloses an essential and nonredundant role for this Vav family member in axon guidance events in brainstem neurons that control blood pressure and respiratory rates.

The production of reactive oxygen species plays roles during the development of endothelial dysfunction and it represents a significant prognostic factor for evaluating the risk of cardiovascular disease. Although statins target cholesterol biosynthesis, the beneficial effects on cardiovascular disease remain to be fully elucidated. In this work, we explored the in vitro effects of pravastatin on vascular functionality. We studied the effect of the incubation with this statin on acetylcholine relaxation using aorta from spontaneously hypertensive rats (SHR). Consistent with a cholesterol-independent mechanism of action, we show that pravastatin induces a significant improvement of endothelium-dependent relaxation that is not completely reversed by mevalonic acid. Assays with 250microM of lucigenin were carried out to verify whether such action could be mediated by the scavenger properties of pravastatin. Treatment of aortic rings derived from Wistar rats with lucigenin promotes superoxide generation (O(2)(-)) and the subsequent loss of both endothelium-dependent and independent relaxations. The addition of pravastatin reduced the lucigenin-triggered O(2)(-) levels as well as its inhibitory effects on acetylcholine- and sodium nitroprusside-dependent responses. These effects were not counteracted by mevalonic acid, further supporting the idea that the effects of pravastatin do not entail alterations in cholesterol biosynthesis. In conclusion, this study can contribute to elucidate the mechanism responsible for the antioxidant activity of pravastatin, and describes relationship between a scavenger effect of pravastatin and the improvement of vascular reactivity.

The volume fluctuations in the steady state reached by a vibrated granular gas of hard particles confined by a movable piston on the top are investigated by means of event-driven simulations. Also, a compressibility factor, measuring the response in volume of the system to a change in the mass of the piston, is introduced and measured. From the second moment of the volume fluctuations and the compressibility factor, an effective temperature is defined by using the same relation as obeyed by equilibrium molecular systems. The interpretation of this effective temperature and its relationship with the granular temperature of the gas, and also with the velocity fluctuations of the movable piston, is discussed. It is found that the ratio of the temperature based on the volume fluctuations to the temperature based on the piston kinetic energy obeys simple dependencies on the inelasticity and on the piston-particle mass ratio.

The regulation of arterial contractility is essential for blood pressure control. The GTPase RhoA promotes vasoconstriction by modulating the cytoskeleton of vascular smooth muscle cells. Whether other Rho/Rac pathways contribute to blood pressure regulation remains unknown. By studying a hypertensive knockout mouse lacking the Rho/Rac activator Vav2, we have discovered a new signaling pathway involving Vav2, the GTPase Rac1, and the serine/threonine kinase Pak that contributes to nitric oxide-triggered blood vessel relaxation and normotensia. This pathway mediated the Pak-dependent inhibition of phosphodiesterase type 5, a process that favored RhoA inactivation and the subsequent depolymerization of the F-actin cytoskeleton in vascular smooth muscle cells. The inhibition of phosphodiesterase type 5 required its physical interaction with autophosphorylated Pak1 but, unexpectedly, occurred without detectable transphosphorylation events between those 2 proteins. The administration of phosphodiesterase type 5 inhibitors prevented the development of hypertension and cardiovascular disease in Vav2-deficient animals, demonstrating the involvement of this new pathway in blood pressure regulation. Taken together, these results unveil one cause of the cardiovascular phenotype of Vav2-knockout mice, identify a new Rac1/Pak1 signaling pathway, and provide a mechanistic framework for better understanding blood pressure control in physiological and pathological states.

The influence of the heating mechanism on the kinetic energy densities of the components of a vibrated granular mixture is investigated. Collisions of the particles with the vibrating wall are inelastic and characterized by two coefficients of normal restitution, one for each of the two species. By means of molecular-dynamics simulations, it is shown that the nonequipartition of kinetic energy is not affected by the differential mechanism of energy injection aside the usual boundary layer around the wall. The macroscopic state of the mixture in the bulk is defined by intensive variables that do not include the partial granular temperatures of the components.

The steady state of a vibrated granular gas confined by a movable piston on top is discussed. Particular attention is given to the hydrodynamic boundary conditions to be used when solving the inelastic Navier-Stokes equations. The relevance of an exact general condition relating the grain fluxes approaching and moving away from each of the walls is emphasized. It is shown how it can be used to get a consistent hydrodynamic description of the boundaries. The obtained expressions for the fields do not contain any undetermined parameter. Comparison of the theoretical predictions with molecular-dynamics simulation results is carried out, and a good agreement is observed for low density and not too large inelasticity. A practical way of introducing small finite density corrections to the dilute limit theory is proposed to improve the accuracy of the theory.

Hydrodynamic equations are used to identify the final state reached by a freely evolving granular gas above but close to its shear instability. The theory predicts the formation of a two bands shear state with a steady density profile. There is a modulation between temperature and density profiles as a consequence of the energy balance, the density fluctuations remaining small, without producing clustering. Moreover, the time dependence of the velocity field can be scaled out with the squared root of the average temperature of the system. The latter follows the Haff law, but with an effective cooling rate that is smaller than that of the free homogeneous state. The theoretical predictions are compared with numerical results for inelastic hard disks obtained by using the direct Monte Carlo simulation method, and a good agreement is obtained for low inelasticity.

Although much is known about environmental factors that predispose individuals to hypertension and cardiovascular disease, little information is available regarding the genetic and signaling events involved. Indeed, few genes associated with the progression of these pathologies have been discovered despite intensive research in animal models and human populations. Here we identify Vav3, a GDP-GTP exchange factor that stimulates Rho and Rac GTPases, as an essential factor regulating the homeostasis of the cardiovascular system. Vav3-deficient mice exhibited tachycardia, systemic arterial hypertension and extensive cardiovascular remodeling. These mice also showed hyperactivity of sympathetic neurons from the time of birth. The high catecholamine levels associated with this condition led to the activation of the renin-angiotensin system, increased levels of kidney-related hormones and the progressive loss of cardiovascular and renal homeostasis. Pharmacological studies with drugs targeting sympathetic and renin-angiotensin responses confirmed the causative role and hierarchy of these events in the development of the Vav3-null mouse phenotype. These observations uncover the crucial role of Vav3 in the regulation of the sympathetic nervous system (SNS) and cardiovascular physiology, and reveal a signaling pathway that could be involved in the pathophysiology of human disease states involving tachycardia and sympathetic hyperactivity with unknown etiologies.