Cardiac Rehabilitation Increases Plasma Klotho Levels Pello Lázaro, Ana María; Villelabeitia Jaureguizar, Koldo; Franco Peláez, Juan Antonio ...
Journal of clinical medicine,
03/2024, Volume:
13, Issue:
6
Journal Article
Peer reviewed
Open access
: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV ...events, although its potential relationship with changes in MM is unknown.
: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups.
: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL;
< 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL;
< 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% +44 to +205;
= 0.003).
: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.
We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID‐19) in Spain until 13 ...July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range IQR: 52‐70), and 66% were male. The incidence of COVID‐19 in SOT recipients was two‐fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18‐131). Infection was hospital‐acquired in 13% of cases. No donor‐derived COVID‐19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon‐β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow‐up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio OR: 2.5; 95% CI: 1.4‐4.6), age >60 years (OR: 3.7; 95% CI: 2.5‐5.5), and hospital‐acquired COVID‐19 (OR: 3.0; 95% CI: 1.9‐4.9).
The authors report the Spanish nationwide experience with solid organ and hematopoietic stem cell transplant recipients diagnosed with COVID‐19, revealing a higher incidence and more aggressive course of infection than in the general population.
Phenolic compounds are responsible of the nutritional and sensory quality of extra-virgin olive oil (EVOO). The composition of phenolic compounds in EVOO is related to the initial content of phenolic ...compounds in the olive-fruit tissues and the activity of enzymes acting on these compounds during the industrial process to produce the oil. In this work, the phenolic composition was studied in six major cultivars grown in the same orchard under the same agronomical and environmental conditions in an effort to test the effects of cultivars on phenolic composition in fruits and oils as well as on transfer between matrices. The phenolic fractions were identified and quantified using high-performance liquid chromatography-diode array detector-time-of-flight-mass spectrometry. A total of 33 phenolic compounds were determined in the fruit samples and a total of 20 compounds in their corresponding oils. Qualitative and quantitative differences in phenolic composition were found among cultivars in both matrices, as well as regarding the transfer rate of phenolic compounds from fruits to oil. The results also varied according to the different phenolic groups evaluated, with secoiridoids registering the highest transfer rates from fruits to oils. Moreover, wide-ranging differences have been noticed between cultivars for the transfer rates of secoiridoids (4.36%-65.63% of total transfer rate) and for flavonoids (0.18%-0.67% of total transfer rate). 'Picual' was the cultivar that transferred secoiridoids to oil at the highest rate, whereas 'Changlot Real' was the cultivar that transferred flavonoids at the highest rates instead. Principal-component analysis confirmed a strong genetic effect on the basis of the phenolic profile both in the olive fruits and in the oils.
State‐of‐the‐art chiroptical spectroscopies are valuable tools for structural elucidation. However, the potential of these spectroscopies for everyday applications has not been exploited to date ...partially due to the lack of sufficiently stable and efficient chiroptical systems. To this end, the development of suitable chiroptical structures is essential. Herein, we present the synthesis of spiro‐compounds (P2)‐1 and (P4)‐2 as well as (M2)‐1 and (M4)‐2 exhibiting remarkable chiroptical responses. Theoretical simulations show that (P2)‐1, constituted by two (P)‐configured spiranic chiral axes, presents an all‐carbon double helix structure with (M)‐helicity. On the other hand, molecular dynamic simulations reveal (P4)‐2 to have a single path for geometry‐modification along its flat conformational space, certifying it as a chiral flexible shape‐persistent macrocycle. Geometric quantification of chirality has been used to compare the spiranic derivatives presented herein.
Revealing chirality′s secrets: Diethynylspiranes have been employed for the construction of all‐carbon double helices as well as chiral flexible shape‐persistent macrocycles. The uncovering of these very diverse chiral scaffolds opens new opportunities for chiroptical applications (see scheme).
Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease ...contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.
Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association ...of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.
Abstract The aim of this study is to establish the existing relationship among variables referred to the person, specifically age and gender, and the functional dependence in basic ADL and in IADL, ...as well as the possible relationship it has with the increase of morbidity and mortality in a random sample of 598 individuals older than 65 years. Of these individuals, 34.6% were categorized as dependent for at least one ADL, and 53.5% if we refer to IADL. Regarding the ADL, the risk of dependence increases (odds ratio = OR = 1.089) per year of age, (OR = 2.48) in women's case; while there is an IADL correlation between age and the score ( r = −0.527; p < 0.001). A relationship exists between dependence and the days of hospitalization (for ADL: r = −0.12, p = 0.018 and IADL: r = −0.97, p = 0.003), the number of visits to the doctor (ADL: r = −0.27, p < 0.001; IADL: r = −0.25, p < 0.001) or the presence of concomitant pathologies such as dementia (ADL: p < 0.001; IADL: p < 0.001). There is a significant association between age, gender and dependence, as well as between dependence and morbidity and mortality, so that dependence could be used as a predictor of both.
The growing use of antidepressants in recent years has led to their increasing presence in forensic analyses. In this work, microextraction by packed sorbent followed by ultra‐performance liquid ...chromatography with photodiode array detection provided a fast method for determining the antidepressants mirtazapine, venlafaxine, escitalopram, fluoxetine, fluvoxamine, and sertraline in human urine. The microextraction conditions (viz., type of sorbent, number of draw–eject extraction cycles or strokes, sample volume and pH, and type and volume of washing solution and eluent) were optimized by using an experimental design. The ensuing analytical method was validated in terms of linearity (25–1000 ng/mL urine), limit of detection (lower than 7.1 ng/mL), limit of quantification (25 ng/mL), precision (4.7–15.1% as relative standard deviation), and accuracy (80.4–126.1% as mean recovery for four replicate determinations). The proposed method allowed the six target antidepressants to be determined at concentrations from therapeutic to toxic levels. The application to small volumes (300 μL) of urine afforded fast extraction of the analytes and provided results on a par with those of existing clinical and forensic alternatives.
Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for ...both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case–control association study performed on 391 Spanish sporadic cases and 1,170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27,000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28y) than sporadic cases (33y), using a Mann–Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) versus controls (almost 1,170), and three of them PLEC (OR = 6.28, p = 6.42 × 10−23) (p.Arg2016Trp), EXO5 (OR = 3.37, p = 4.82 × 10−09) (p.Arg344AlafsTer10) and DNAH7 (OR = 1.64, p = 0.048) were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT.
What's new?
Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low‐susceptibility risk loci have been identified for both sporadic and familial cases. In this first TGCT genetic study performed in the Spanish population, the authors studied both the monogenic and polygenic models of inheritance by using Next Generation Sequencing. Three new susceptibility variant alleles were identified, providing additional evidence in favor of a polygenic model of inheritance for familial testicular cancer, and contributing to improving the genetic counselling of families with TGCT cases and stratification of people at risk.
C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with ...corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.
We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (
=81) or dense deposit disease (
=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).
The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.
The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.
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