Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary ...prevention of cardiovascular disease.
The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937.
From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 95% CI 27·9–28·3 in the Mediterranean diet group vs 37·7 37·5–37·9 in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541–0·957) to 0·753 (0·568–0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 95% CI 0·489–0·915, log-rank p=0·013), than in 175 women for whom no difference was found between groups.
In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention.
Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.
This study reveals the existence of oxidative stress (reactive oxygen species (ROS)) in non-nervous organs and tissues in multiple sclerosis (MS) by means of a model of experimental autoimmune ...encephalomyelitis (EAE) in rats. This model reproduces a similar situation to MS, as well as its relationship with intestinal microbiota starting from the changes in bacterial lipopolysaccharide levels (LPS) in the outer wall of the gram-negative bacteria. Finally, the administration of extra-virgin olive oil (EVOO), hydroxytirosol (HT), and oleic acid (OA) exert beneficial effects. Twenty-five Dark Agouti two-month-old male rats, weighing around 190 g, were distributed into the following groups: Control, EAE (experimental autoimmune encephalomyelitis group), EAE + EVOO, EAE + HT, and EAE + OA. The glutathione redox system with the EAE was measured in heart, kidney, liver, and small and large intestines. The LPS and the correlation with oxidative stress in the small and large intestines were also investigated. The results showed that (1) the oxidative damage in the EAE model affects non-nervous organs and tissues; (2) The LPS is related to inflammatory phenomena and oxidative stress in the intestinal tissue and in other organs; (3) The administration of EVOO, HT, and OA reduces the LPS levels at the same time as minimizing the oxidative damage; (4) EVOO, HT, and OA improve the disease's clinical score; and (5) on balance, EVOO offers a better neuroprotective effect.
Trapping Charge Mechanism in Hv1 Channels ( Ci Hv1) Fernández, Miguel; Alvear-Arias, Juan J; Carmona, Emerson M ...
International journal of molecular sciences,
12/2023, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The majority of voltage-gated ion channels contain a defined voltage-sensing domain and a pore domain composed of highly conserved amino acid residues that confer electrical excitability via ...electromechanical coupling. In this sense, the voltage-gated proton channel (Hv1) is a unique protein in that voltage-sensing, proton permeation and pH-dependent modulation involve the same structural region. In fact, these processes synergistically work in concert, and it is difficult to separate them. To investigate the process of Hv1 voltage sensor trapping, we follow voltage-sensor movements directly by leveraging mutations that enable the measurement of Hv1 channel gating currents. We uncover that the process of voltage sensor displacement is due to two driving forces. The first reveals that mutations in the selectivity filter (D160) located in the S1 transmembrane interact with the voltage sensor. More hydrophobic amino acids increase the energy barrier for voltage sensor activation. On the other hand, the effect of positive charges near position 264 promotes the formation of salt bridges between the arginines of the voltage sensor domain, achieving a stable conformation over time. Our results suggest that the activation of the Hv1 voltage sensor is governed by electrostatic-hydrophobic interactions, and S4 arginines, N264 and selectivity filter (D160) are essential in the
-Hv1 to understand the trapping of the voltage sensor.
About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic ...biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.
Seed is the dissemination unit of plants initiating an important stage in the life cycle of plants. Seed development, comprising two phases: embryogenesis and seed maturation, may define the quality ...of sown seed, especially under abiotic stress. In this review we have focused on the recent advances in the molecular mechanisms underlying these complex processes and how they are controlled by distinct environmental factors regulating ion homeostasis into the seed tissues. The role of transporters affecting seed embryogenesis and first stages of germination as imbibition and subsequent radicle protrusion and extension were revised from a molecular point of view. Seed formation depends on the loading of nutrients from the maternal seed coat to the filial endosperm, a process of which the efflux is not clear and where different ions and transporters are involved. The clear interrelation between soil nutrients, presence of heavy metals and the ion capacity of penetration through the seed are discussed in terms of ion effect during different germination stages. Results concerning seed priming techniques used in the improvement of seed vigor and radicle emergence are shown, where the use of nutrients as a novel way of osmopriming to alleviate abiotic stress effects and improve seedlings yield is discussed. Novel approaches to know the re-translocation from source leaves to developing seeds are considered, as an essential mechanism to understand the biofortification process of certain grains in order to cope with nutrient deficiencies, especially in arid and semiarid areas. Finally, the role of new genes involved in hormone-dependent processes, oxidative response and water uptake into the seeds during their development or germination, have been described as plant mechanisms to deal with abiotic stresses.
Voltage-gated proton channels (Hv1) are important regulators of the immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice and have been proposed as a potential therapeutic ...target to alleviate dysregulated immunosuppression in tumors. However, till date, there is a lack of evidence regarding the functioning of the Hvcn1 and reports on mHv1 isoform diversity in mice and MDSCs. A computational prediction has suggested that the Hvcn1 gene may express up to six transcript variants, three of which are translated into distinct N-terminal isoforms of mHv1: mHv1.1 (269 aa), mHv1.2 (269 + 42 aa), and mHv1.3 (269 + 4 aa). To validate this prediction, we used RT-PCR on total RNA extracted from MDSCs, and the presence of all six predicted mRNA variances was confirmed. Subsequently, the open-reading frames (ORFs) encoding for mHv1 isoforms were cloned and expressed in
oocytes for proton current recording using a macro-patch voltage clamp. Our findings reveal that all three isoforms are mammalian mHv1 channels, with distinct differences in their activation properties. Specifically, the longest isoform, mHv1.2, displays a right-shifted conductance-voltage (GV) curve and slower opening kinetics, compared to the mid-length isoform, mHv1.3, and the shortest canonical isoform, mHv1.1. While mHv1.3 exhibits a V
similar to that of mHv1.1, mHv1.3 demonstrates significantly slower activation kinetics than mHv1.1. These results suggest that isoform gating efficiency is inversely related to the length of the N-terminal end. To further explore this, we created the truncated mHv1.2 ΔN20 construct by removing the first 20 amino acids from the N-terminus of mHv1.2. This construct displayed intermediate activation properties, with a V
value lying intermediate of mHv1.1 and mHv1.2, and activation kinetics that were faster than that of mHv1.2 but slower than that of mHv1.1. Overall, these findings indicate that alternative splicing of the N-terminal exon in mRNA transcripts encoding mHv1 isoforms is a regulatory mechanism for mHv1 function within MDSCs. While MDSCs have the capability to translate multiple Hv1 isoforms with varying gating properties, the
gene promotes the dominant expression of mHv1.1, which exhibits the most efficient gating among all mHv1 isoforms.
The influence of the orthorhombic to tetragonal phase transition near room temperature in the poling process of KNN‐modified piezoceramics was studied. Poling temperatures of 25° and 120°C were used. ...The percentage of 90° domains reorientation induced by poling was evaluated trough X‐ray diffraction analysis. The improvement of the piezoelectric properties when the poling temperature was 25°C could not be explained by the reorientation of 90° domains alone. Raman spectroscopy evidenced that the polarization process was assisted by the stabilization of orthorhombic phase, which promotes a stress reduction in the material.
The purpose of this study was to explore the trigonometric principles of the spherical osteotomy, establish guidelines for its application and test the guidelines on bone models using a new blade ...design. We propose a new rule of osteotomies incorporating the outlined geometric principles, and applicable to the use of spherical cuts in veterinary orthopaedic surgery.
The trigonometric principles for the execution of neutral, closing and opening spherical osteotomies were explored in silico. A modification of the existing commercially available dome blade was designed and manufactured such that it facilitated the performance of spherical osteotomy with a minimized blade radius. A pilot study was performed whereby the modified dome blade was used to create spherical osteotomy in canine radial bone models. The surfaces of the osteotomy models were laser-scanned using a three-dimensional (3D) scanner; the resultant scans were imported into and analysed using a commercial 3D analysis software. The accuracy of osteotomy execution was measured as the distance between the targeted centre of osteotomy and the actual centre of osteotomy as found on the 3D scans.
By utilizing the geometric principles of spherical osteotomy, an accurate osteotomy position was achieved. The centre of the spherical cut performed on bone models was confirmed to be within 5% tolerance of the location as planned in silico demonstrating the accurate and relevant clinical application of geometric principles.
The trigonometric guidelines for the execution of spherical osteotomy can be applied in a pre-clinical environment with accuracy. The new guidelines combined with the proposed new rule for spherical osteotomy utilizing the new blade design are translatable into clinical application, permitting the surgeon to accurately plan osteotomy application while mitigating the significant loss of bone-to-bone contact during correction of torsional deformities inherent in the principles of dome osteotomy use.
Soil micromorphology in thin section and near infrared reflectance spectroscopy (NIRS) are useful techniques for assessing the participation of soil macrofauna in the formation of aggregates and soil ...structure. The purpose of this study was to use micromorphological analysis and NIRS techniques to assess the role of soil fauna in the recovery of soil aggregates and in the modification of soil microstructure in a chronosequence of rehabilitated areas at Cerrejon coal mine (La Guajira, Colombia). 64 soil samples were taken from rehabilitated areas (from 1 to 20years ago) and from natural dry tropical forests Soil macroaggregates were subdivided into three categories: biogenic (BA), physical (PA), and non-aggregated soil (NAS). 32 samples were used for NIRS analysis, while ten thin sections of resin-impregnated soil blocks were micromorphologically analyzed. Principal component analysis of NIRS spectra showed a clear separation between BA, PA, and NAS. Likewise, an increase in BA was observed in the intermediate and advanced stages of rehabilitation. Respect to the micromorphological features, there was a clear change from a matrix of silt-sized quartz, unaccomodated peds, and unstructured materials with non-existent biogenic activity at the 2-year site to the formation of consolidated aggregates, more homogenized soil and increased biological activity at the 20-year site. Soil biological activity, principally the footprint of macrofauna, was recognized using the two techniques as well as at both the micro- and macro-morphology scales. These results reveal how the rehabilitation program being undertaken at Cerrejón mine is promoting the soil macrofauna population and associated bioturbation.
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•Translocation of topsoil and revegetation promotes soil supporting ecosystem services restoration.•To six years old of rehabilitation, soil structure is reorganized quickly due to the high participation of soil fauna.•Micromorphology and NIRS analyses reveal accumulated soil organic matter.
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