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1.
Europace ; 23(5): 682-690, 2021 05 21.
Article in English | MEDLINE | ID: mdl-33319222

ABSTRACT

AIMS: Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden. METHODS AND RESULTS: Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1-1.14; P = 0.046). CONCLUSION: The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Fatty Acid-Binding Proteins/blood , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Female , Humans , Leptin , Male , Recurrence , Sex Characteristics , Treatment Outcome
2.
Am J Physiol Heart Circ Physiol ; 313(6): H1261-H1266, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29030340

ABSTRACT

Transcatheter aortic valve implantation (TAVI) is the method of choice in patients with high risk or contraindications for conventional aortic valve replacement. However, it is not well understood which parameters predict the overall cardiac function postprocedurally. miRNAs are small noncoding RNA molecules that repress gene expression by different mechanisms and can also be detected in the blood. Recent studies have shown that miRNAs detected in the blood may serve as sensitive and specific biomarkers in various diseases; therefore, we examined the levels of different microRNAs in the serum of patients undergoing TAVI. We thereby intended to find potential predictors for cardiac function after TAVI. Serum from patients with aortic valve disease was obtained at five different points: before the TAVI procedure, at days 1 and 3 after the TAVI procedure, and the day of dischargement and after a period of 3 mo. We next performed quantitative real-time PCRs to examine the samples for changes in the level of miRNAs previously described as cardiac enriched. Our results show that the level of miR-206 in the serum of patients after TAVI correlated negatively with the left ventricular ejection fraction of individual patients. We found left ventricular function to be better in patients with lower levels of miR-206 after implantation of the new valve. A decrease in the serum level of miR-206 may be linked to changes in cardiac function of patients after TAVI. Further studies are necessary to test the miRNA for its potential value as a prognostic marker. NEW & NOTEWORTHY This study is the first to investigate novel miRNA-based biomarkers within the context of transcatheter aortic valve implantation. miRNA-206 proved to correlate inversely with the postprocedural left ventricular ejection fraction of patients.


Subject(s)
Aortic Valve Stenosis/blood , MicroRNAs/blood , Ventricular Function, Left , Aged , Aged, 80 and over , Aortic Valve Stenosis/surgery , Biomarkers/blood , Female , Humans , Male , Transcatheter Aortic Valve Replacement
3.
Biochim Biophys Acta Mol Basis Dis ; 1863(6): 1500-1509, 2017 06.
Article in English | MEDLINE | ID: mdl-28245984

ABSTRACT

Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. Histopathological characterization is commonly used to detect the location, size and shape of MI sites. However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. In infarcted myocardium, the spectrum of these main absorptions was deeply altered. FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI.


Subject(s)
Muscle Proteins/metabolism , Myocardial Infarction/metabolism , Myocardium/metabolism , Ventricular Remodeling , Animals , Male , Mice , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/pathology , Protein Structure, Secondary , Spectroscopy, Fourier Transform Infrared/methods
4.
Eur Arch Otorhinolaryngol ; 273(9): 2335-42, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26404533

ABSTRACT

Knowledge of the vascularization of the malleus may help to better understand some unwanted effects occurred in those surgical techniques using the handle as an attachment site of ossicle-replacement prostheses. Our hypothesis is that vascular damage occurred in the long process of the malleus during tympanic membrane detachment before fastening a malleovestibulopexy (MVP) prosthesis promotes the lysis of this ossicle at the attachment site. To confirm this premise, we carried out an evolutive and descriptive study of ten MVP procedures as well as a morphological analysis of ten cadaveric mallei using both light and scanning electron microscopies. The arterial supply of the manubrium comes from two main sources: vascular branches that reach this ossicle from the site of insertion of the tensor tympani tendon and small perforating branches which penetrate the bone from arteries of the tympanic membrane that, following the periosteum/perichondrium, they arrange parallel to the bone. The detachment of the tympanic membrane to fasten a MVP prosthesis causes a damage in the periosteal/perichondral vascular supply of the handle as well as micro-trauma on it, which can promote bone resorption at the point of anchorage by osteoclast stimulation. Respect periosteal vascularization of the manubrium may be important to prevent damage in this ossicle caused by some middle ear reconstruction prostheses.


Subject(s)
Malleus/blood supply , Ossicular Replacement/methods , Tympanoplasty/methods , Adult , Aged , Cadaver , Cholesteatoma, Middle Ear/surgery , Cohort Studies , Female , Humans , Male , Malleus/surgery , Middle Aged , Ossicular Prosthesis , Reoperation
5.
Histochem Cell Biol ; 141(5): 519-29, 2014 May.
Article in English | MEDLINE | ID: mdl-24310659

ABSTRACT

The Syrian hamster Harderian gland (HG) is an organ that undergoes physiological autophagy in response to oxidative stress induced by porphyrin production. Porphyrin production in the HG has marked sex differences and is closely linked to reproductive function. In the present study, we observed that the estrous cycle and associated estrogen variations may affect oxidative-stress-induced proteolytic processes. In particular, significant changes in autophagic activity were detected during the estrous cycle. Notably, increased activation of macroautophagy as well as chaperone-mediated autophagy in the estrus phase coincided with a minimal antioxidant capability and the highest protein damage levels. By contrast, autophagic machinery was found to be blocked in the diestrus phase, likely due to mammalian target of rapamycin activation, which could be corroborated by the subsequent pS6K activation. Analogous results were observed regarding proteasome activity, which also showed maximal activity in the estrus phase. Interestingly, all these mechanisms were associated with important morphological changes in the HG during the estrous cycle. We observed statistically significant increases in Type II cells, which may be related to extensive autophagy in the estrus phase. Physiologically, this would result in a significant release of porphyrins specifically when females are more receptive. These data support the role of porphyrins as pheromones, as other authors have previously suggested, thus making the HG a scent organ. In addition, these results suggest a porphyrin-based approach to the treatment of porphyria during pregnancy, a condition for which no treatment is currently known.


Subject(s)
Autophagy , Estrous Cycle/metabolism , Harderian Gland/metabolism , Porphyrins/metabolism , Proteolysis , Animals , Estrogens/metabolism , Female , Humans , Mesocricetus , Porphyrias/metabolism , Porphyrias/pathology , Pregnancy , Pregnancy Complications/metabolism , Pregnancy Complications/pathology
6.
Rev Neurol ; 79(3): 95-97, 2024 Aug 01.
Article in Spanish | MEDLINE | ID: mdl-39007861

ABSTRACT

INTRODUCTION: X-linked intellectual developmental disorder is clinically and genetically heterogeneous. The ubiquitin specific peptidase 27 X-linked gene (USP27X) has been associated with X-linked intellectual developmental disorder, and only 17 affected males have been described in the literature to date. CASE REPORT: A 6-year-old boy was assessed due to intellectual developmental disability, language delay, behavioural disorder, microcephaly and particular features. His mother had learning difficulties and a facial phenotypic overlap. A maternal uncle had an intellectual developmental disorder. Physical examination revealed an unusual phenotype (triangular facies, long palpebral fissures and eyelashes, medially eyebrow loss, prominent auricles), mild brachydactylia and hypoplasia in the distal phalanges. The clinical exome identified the probably pathogenic variant NM_001145073.3: c.692delT in the USP27X gene. The results of the family segregation analysis were positive: the mother and maternal uncle were harbourers, while healthy maternal aunt was not. CONCLUSIONS: We present two new cases of X-linked intellectual developmental disorder due to a previously unreported variant in the USP27X gene. Both patients presented neurological symptoms without any significant involvement at other levels, according to the literature. One of the cases presented microcephaly, particular features and digital anomalies, which broadens the phenotypic spectrum of this disease.


TITLE: Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.Introducción. La discapacidad intelectual ligada al cromosoma X es un trastorno clínica y genéticamente heterogéneo. El gen de la proteasa 27 específica de la ubiquitina ligada al cromosoma X (USP27X) se ha asociado a discapacidad intelectual ligada al cromosoma X, y en la actualidad sólo se ha descrito a 17 varones afectos en la bibliografía. Caso clínico. Niño de 6 años valorado por discapacidad intelectual, retraso del lenguaje, trastorno de la conducta, microcefalia y rasgos particulares. Madre con dificultades de aprendizaje y fenotipo facial solapante. Un tío materno con discapacidad intelectual aislada. En la exploración física destaca un fenotipo peculiar (facies triangular, fisuras palpebrales y pestañas largas, cejas menos pobladas medialmente, pabellones auriculares prominentes), leve braquidactilia e hipoplasia de falanges distales. El exoma clínico identificó la variante probablemente patógena NM_001145073.3: c.692delT en el gen USP27X. El estudio de segregación familiar fue positivo: madre y tío materno portadores, tía materna sana no portadora. Conclusiones. Describimos dos nuevos casos con discapacidad intelectual ligada al cromosoma X por variante no descrita previamente en el gen USP27X. Ambos pacientes presentan clínica neurológica sin afectación significativa a otros niveles de acuerdo con la bibliografía. Uno de los casos asocia microcefalia, rasgos particulares y anomalías digitales, lo que permite ampliar el espectro fenotípico de esta enfermedad.


Subject(s)
Intellectual Disability , Humans , Male , Child , Intellectual Disability/genetics , Ubiquitin-Specific Proteases/genetics , Mental Retardation, X-Linked/genetics , Pedigree , Genetic Diseases, X-Linked/genetics
7.
Front Bioeng Biotechnol ; 12: 1310084, 2024.
Article in English | MEDLINE | ID: mdl-38464543

ABSTRACT

Introduction: Nanoporous alumina membranes present a honeycomb-like structure characterized by two main parameters involved in their performance in electrochemical immunosening: pore diameter and pore thickness. Although this first one has been deeply studied, the effect of pore thickness in electrochemical-based nanopore immunosensors has been less taken into consideration. Methods: In this work, the influence of the thickness of nanoporous membranes in the steric blockage is studied for the first time, through the formation of an immunocomplex in their inner walls. Finally, the optimal nanoporous membranes were applied to the detection of catalase, an enzyme related with chronic wound infection and healing. Results: Nanoporous alumina membranes with a fixed pore diameter (60 nm) and variable pore thicknesses (40, 60, 100 µm) have been constructed and evaluated as immunosensing platform for protein detection. Our results show that membranes with a thickness of 40 µm provide a higher sensitivity and lower limit-of-detection (LOD) compared to thicker membranes. This performance is even improved when compared to commercial membranes (with 20 nm pore diameter and 60 µm pore thickness), when applied for human IgG as model analyte. A label-free immunosensor using a monoclonal antibody against anti-catalase was also constructed, allowing the detection of catalase in the range of 50-500 ng/mL and with a LOD of 1.5 ng/mL. The viability of the constructed sensor in real samples was also tested by spiking artificial wound infection solutions, providing recovery values of 110% and 118%. Discussion: The results obtained in this work evidence the key relevance of the nanochannel thickness in the biosensing performance. Such findings will illuminate nanoporous membrane biosensing research, considering thickness as a relevant parameter in electrochemical-based nanoporous membrane sensors.

8.
Article in English, Spanish | MEDLINE | ID: mdl-38740262

ABSTRACT

INTRODUCTION: Pelvic organ prolapse is a condition with high prevalence in elderly women. With increasing life expectancy and a desire for improved quality of life, a rise in the frequency of surgical treatments for these women is anticipated. The aim is to compare complication, success, and satisfaction rates among elderly patients (aged >70 years) in comparison to younger women undergoing robotic sacrocolpopexy, thereby assessing the safety and efficacy of this surgery in this group of patients. METHOD: A prospective observational comparative study of 123 robotic sacrocolpopexies conducted between December 2016 and June 2022. Patients were stratified by age (cutoff point: 70 years). Baseline characteristics, type, and grade of prolapse, intra and postoperative data, complications, functional and anatomical outcomes, and satisfaction levels were collected. RESULTS: Among the 123 patients, 62.6% were under 70 years old, while 37.4% were 70 years or older, exhibiting similar baseline characteristics, prolapse grade, and type. The percentages of intraoperative (6.5%) and postoperative complications (4.4-9%) were comparable in both age groups. Furthermore, success and satisfaction rates exceeded 90%, with no significant differences between women under and over 70 years during a two-year follow-up. CONCLUSION: Robotic sacrocolpopexy is at least as effective and safe in women aged 70 years or older as in younger individuals, with no higher rates of intra and postoperative complications and similar rates of anatomical and subjective success.

9.
Analyst ; 138(12): 3512-21, 2013 Jun 21.
Article in English | MEDLINE | ID: mdl-23666341

ABSTRACT

A Differential Mobility Analyser (DMA) is a specific configuration of an Ion Mobility Spectrometer (IMS) where ions with different electrical mobilities are separated in space, instead of in time of drift, as in classical drift-time IMS. This work presents results obtained with a parallel plate DMA instrument, with crucial differences in the sheath flow and the detection system when compared to other instruments in the market. These differences improve the resolving powers and sensitivities of the instrument. Additionally, datasets from IMS or DMA instruments are typically processed with univariate techniques when only qualitative detection is of interest. However, good performance in quantitative measurements can be achieved using multivariate data processing. This work presents for the first time, measurements with a stand-alone DMA instrument and the multivariate data processing related to VOCs and environmentally interesting samples.

10.
Pulmonology ; 29(5): 362-374, 2023.
Article in English | MEDLINE | ID: mdl-36906462

ABSTRACT

INTRODUCTION AND OBJECTIVES: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. PATIENTS AND METHODS: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. RESULTS: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged ≥70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72-77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those ≥70 years; p<0.001). In-hospital mortality in the group ≥70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05-1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04-1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01-1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98-0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). CONCLUSIONS: Amongst critically-ill COVID-19 ventilated patients, those aged ≥70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patients.


Subject(s)
COVID-19 , Aged , Female , Humans , Male , Middle Aged , COVID-19/therapy , Critical Illness , Intensive Care Units , Risk Factors , Spain/epidemiology , Steroids
11.
Radiologia (Engl Ed) ; 65(3): 269-284, 2023.
Article in English | MEDLINE | ID: mdl-37268369

ABSTRACT

Magnetic resonance has become a first-line imaging modality in various clinical scenarios. The number of patients with different cardiovascular devices, including cardiac implantable electronic devices, has increased exponentially. Although there have been reports of risks associated with exposure to magnetic resonance in these patients, the clinical evidence now supports the safety of performing these studies under specific conditions and following recommendations to minimize possible risks. This document was written by the Working Group on Cardiac Magnetic Resonance Imaging and Cardiac Computed Tomography of the Spanish Society of Cardiology (SEC-GT CRMTC), the Heart Rhythm Association of the Spanish Society of Cardiology (SEC-Heart Rhythm Association), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Cardiothoracic Imaging (SEICAT). The document reviews the clinical evidence available in this field and establishes a series of recommendations so that patients with cardiovascular devices can safely access this diagnostic tool.


Subject(s)
Cardiology , Heart Diseases , Humans , Consensus , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy
12.
Phys Rev Lett ; 108(4): 042501, 2012 Jan 27.
Article in English | MEDLINE | ID: mdl-22400828

ABSTRACT

Evidence for the neutron-rich hypernucleus (Λ)(6)H is presented from the FINUDA experiment at DAΦNE, Frascati, studying (π+,π-) pairs in coincidence from the K(stop)(-) + (6)Li →(Λ)(6)H + π+ production reaction followed by (Λ)(6)H → (6)He + π- weak decay. The production rate of (Λ)(6) undergoing this two-body π- decay is determined to be (2.9 ± 2.0) × 10(-6)/K(stop)(-). Its binding energy, evaluated jointly from production and decay, is BΛ((Λ)(6)H) = (4.0 ± 1.1) MeV with respect to (5)H+Λ. A systematic difference of (0.98 ± 0.74) MeV between BΛ values derived separately from decay and from production is tentatively assigned to the (Λ)(6)H 0(g.s.)(+) → 1+ excitation.

13.
Rev Esp Quimioter ; 34(4): 315-319, 2021 Aug.
Article in Spanish | MEDLINE | ID: mdl-34032111

ABSTRACT

OBJECTIVE: Among the new antiretroviral treatment (ART) regimens, bictegravir (BIC) stands out, a recently incorporated integrase inhibitor. BIC conjugated with emtricitabine (FTC) and tenofovir alafenamide (TAF) has been shown to be non-inferior in efficacy as initiation therapy in a single daily dose regimen compared to other initiation ART. The objective of our study is to evaluate the impact of the inclusion of this new ART scheme in real clinical practice. METHODS: Observational, retrospective and descriptive study that included all adult HIV patients (age ≥18 years) who had been treated with BIC/FTC/TAF for at least 24 consecutive weeks for 1.5 year to evaluate effectiveness, safety and economic impact. RESULTS: A total of 115 patients were included. There were 28 patients without previous treatment, naive, (24.3%). The pretreated patients had a mean of 42±9 months of prior ART. The percentage of patients at week 24 after switching to BIC/FTC/TAF with suppressed plasma viral load was 88% in the naive group and 94.1% in the pretreated group. Adverse events were reported in 8 (7%) patients. The economic impact of the change to BIC/FTC/TAF for these patients was €1,202.63/patient/year, representing an increase of 9.3%. CONCLUSIONS: Our results correlate with the results of two phase 3 non-inferiority clinical trials in naive patients (88% and 84%) and those of a phase 3 non-inferiority clinical trial in pretreated patients (86%). However, we found a large difference between the high percentages of patients reporting an adverse event in three phase 3 clinical trials and our results.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adolescent , Adult , Alanine , Amides , Anti-HIV Agents/adverse effects , Emtricitabine/adverse effects , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring , Humans , Piperazines , Pyridones , Retrospective Studies , Tenofovir/analogs & derivatives
14.
J Insect Sci ; 10: 177, 2010.
Article in English | MEDLINE | ID: mdl-21062148

ABSTRACT

Implications for adults' fitness through the foliage effects of five different host plants on larval survival and performance of the lappet moth, Streblote panda Hübner (Lepidoptera: Lasiocampidae), as well as their effect on species fitness were assayed. Larvae were reared under controlled laboratory conditions on excised foliage. Long-term developmental experiments were done using first instar larvae to adult emergence, and performance experiments were done using fifth instar larvae. Survival, development rates, and food use were measured. Foliar traits analysis indicated that leaves of different host plants varied, significantly affecting larvae performance and adult fitness. Pistacia lentiscus L. (Sapindales: Anacardiaceae), Arbutus unedo L. (Ericales: Ericaceae), and Retama sphaerocarpa (L.) Boiss. (Fabales: Fabaceae) were the most suitable hosts. Larvae fed on Tamarix gallica L. (Caryophyllales: Tamaricaceae) and Spartium junceum L. (Fabales: Fabaceae) showed the lowest survival, rates of development and pupal and adult weight. In general, S. panda showed a relatively high capacity to buffer low food quality, by reducing developmental rates and larvae development thereby reaching the minimum pupal weight that ensures adult survival. Less suitable plants seem to have indirect effects on adult fitness, producing smaller adults that could disperse to other habitats.


Subject(s)
Adaptation, Biological/physiology , Ecosystem , Genetic Fitness/physiology , Moths/physiology , Plant Leaves/chemistry , Analysis of Variance , Animals , Larva/growth & development , Moths/genetics
15.
Mol Neurobiol ; 57(11): 4363-4372, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32720075

ABSTRACT

The diagnosis of obstructive sleep apnea (OSA) in Alzheimer's disease (AD) by polysomnography (PSG) is challenging due to the required collaboration of the patients. In addition, screening questionnaires have demonstrated limited usefulness with this subpopulation. Considering this, we investigated the circulating microRNA (miRNA) profile associated with OSA in AD patients. This study included a carefully selected cohort of females with mild-moderate AD confirmed by biological evaluation (n = 29). The individuals were submitted to one-night PSG to diagnose OSA (apnea-hypopnea index ≥ 15/h) and the blood was collected in the following morning. The plasma miRNA profile was evaluated using RT-qPCR. The patients had a mean (SD) age of 75.8 (5.99) years old with a body mass index of 28.6 (3.83) kg m-2. We observed a subset of 15 miRNAs differentially expressed between OSA and non-OSA patients, of which 10 were significantly correlated with the severity of OSA. Based on this, we built a prediction model that generated an AUC (95% CI) of 0.95 (0.88-1.00) including 5 of the differentially expressed miRNAs that correlated with OSA severity: miR-26a-5p, miR-30a-3p, miR-374a-5p, miR-377-3p, and miR-545-3p. Our preliminary results suggest a plasma miRNA signature associated with the presence of OSA in AD patients. Further studies will be necessary to validate these findings.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/genetics , Circulating MicroRNA/blood , Circulating MicroRNA/genetics , Gene Expression Profiling , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/genetics , Aged , Alzheimer Disease/complications , Cohort Studies , Female , Gene Expression Regulation , Humans , Male , ROC Curve , Signal Transduction/genetics , Sleep Apnea, Obstructive/complications
16.
Alzheimers Res Ther ; 12(1): 163, 2020 12 05.
Article in English | MEDLINE | ID: mdl-33278902

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer's disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. METHODS: We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aß42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI -), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. RESULTS: Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. CONCLUSIONS: We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , MicroRNAs , Alzheimer Disease/genetics , Biomarkers , Cognitive Dysfunction/genetics , Female , Humans , Reference Standards
17.
BJS Open ; 4(3): 524-534, 2020 06.
Article in English | MEDLINE | ID: mdl-32073224

ABSTRACT

BACKGROUND: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. METHODS: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. RESULTS: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). CONCLUSION: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.


ANTECEDENTES: La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. MÉTODOS: Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. RESULTADOS: Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan-1, trombomodulina, angiopoyetina-2, endocan-1, molécula de adhesión endotelial 1 y E-selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15-32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80-0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa-3 y lipocalina-2) (OR 8,09, i.c. del 9% 1,34-48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47-17,77, P = 0,002), pero la lipocalina-2 presentó la mejor AUC (0,81, i.c. del 95% 0,73-0,90, P < 0,001). CONCLUSIÓN: la proadrenomedulina y la lipocalina-2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección.


Subject(s)
Adrenomedullin/blood , Lipocalin-2/blood , Neutrophils/pathology , Protein Precursors/blood , Sepsis/blood , Shock, Septic/blood , Adult , Aged , Angiopoietin-2/blood , Area Under Curve , Biomarkers/blood , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Multivariate Analysis , Organ Dysfunction Scores , Prognosis , ROC Curve , Sepsis/diagnosis , Shock, Septic/diagnosis , Spain , Thrombomodulin/blood , Vascular Cell Adhesion Molecule-1/blood
18.
Rev Neurol ; 67(4): 115-120, 2018 Aug 16.
Article in Spanish | MEDLINE | ID: mdl-30039838

ABSTRACT

INTRODUCTION: Data from clinical experience highlight the high prevalence of traumatic experiences in subjects with schizophrenia spectrum disorder. However, much is left to examine about the effect of traumatic experiences in the development and severity of psychosis. The Stroop Test assess the verbal response inhibition, an executive function which allows to stop an automatic response and makes possible the inhibition of new behaviours, depending on the situation. AIM: To examine the relationship between subjective experience of trauma, verbal response inhibition in the Stroop Test, and severity of the diagnosis at six months from the onset of the disease, in patients with first episode psychosis. PATIENTS AND METHODS: Data were obtained from a longitudinal intervention program of first-episode of psychosis (PAFIP) conducted at the University Hospital Marques de Valdecilla, Spain. The variables of interest in the present study were the Stroop Test and the Childhood Trauma Questionnaire as part of the neuropsychological assessment of PAFIP. RESULTS: Statistically significant differences were obtained in verbal response inhibition, being more subjects with high response inhibition when the said trauma was of low intensity. CONCLUSIONS: These data support the relationship between intensity of the traumatic experience in childhood and response inhibition dysfunction in people with first episode psychosis, although we cannot conclude a more severe diagnosis at six months from the onset of psychosis in people with traumatic experiences more intense.


TITLE: Evaluacion del control inhibitorio verbal con el test de Stroop en primeros episodios de psicosis con experiencia de trauma en la infancia.Introduccion. Los datos aportados por la experiencia clinica evidencian la elevada prevalencia de experiencias traumaticas en sujetos que desarrollan psicosis. No obstante, queda mucho por examinar sobre el efecto de las experiencias traumaticas en su desarrollo y gravedad. El test de Stroop mide la inhibicion cognitiva verbal, una funcion ejecutiva que permite frenar una respuesta automatizada y posibilita la inhibicion de comportamientos alternativos a los ya aprendidos, en funcion de las demandas. Objetivo. Examinar la relacion entre la experiencia subjetiva de trauma, el control inhibitorio verbal medido con el test de Stroop y la gravedad del diagnostico a los seis meses desde el inicio de la enfermedad en sujetos con un primer episodio psicotico. Pacientes y metodos. La muestra estuvo formada por 119 pacientes del «Programa Asistencial para Fases Iniciales de Psicosis¼ del Hospital Universitario Marques de Valdecilla. Las variables de interes fueron el test de Stroop y el Childhood Trauma Questionnaire como parte del protocolo de evaluacion neuropsicologica de dicho programa. Resultados. Se obtuvieron diferencias estadisticamente significativas en control inhibitorio verbal y se encontro un mayor numero de sujetos con alto control inhibitorio cuando el trauma referido fue de baja intensidad. Conclusiones. Estos datos confirman la relacion entre intensidad de la experiencia traumatica en la infancia y alteracion del control inhibitorio verbal en personas con primer episodio psicotico, aunque no permiten concluir una mayor gravedad del diagnostico a los seis meses del inicio de la psicosis en personas con experiencias traumaticas de mayor intensidad.


Subject(s)
Executive Function/physiology , Inhibition, Psychological , Psychotic Disorders/psychology , Stress Disorders, Traumatic/psychology , Stroop Test , Verbal Behavior/physiology , Adolescent , Age Factors , Aripiprazole/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Male , Prefrontal Cortex/physiopathology , Psychotic Disorders/drug therapy , Psychotic Disorders/etiology , Risperidone/therapeutic use , Stress Disorders, Traumatic/physiopathology , Surveys and Questionnaires
19.
Actas Urol Esp (Engl Ed) ; 42(5): 344-349, 2018 Jun.
Article in English, Spanish | MEDLINE | ID: mdl-29526251

ABSTRACT

INTRODUCTION: Pudendal nerve entrapment syndrome (PNE) is characterised by the presence of neuropathic pain in the pudendal nerve (PN) territory, associated or not with urinary, defecatory and sexual disorders. Surgical PN decompression is an effective and safe alternative for cases when conservative treatment fails. The aim of this study is to describe the first robot-assisted pudendal neurolysis procedure performed in our country. MATERIAL AND METHODS: We describe step by step the technique of robot-assisted laparoscopic neurolysis of the left PN performed with intraoperative neurophysiological monitoring on a 60-year-old patient diagnosed with left PNE. RESULTS: The procedure was performed satisfactorily without complications. After 24h, the patient was discharged from the hospital. We observed a 50% reduction in pain measured using the visual analogue scale 2 weeks after the procedure, which remained after 10 weeks of the neurolysis. CONCLUSIONS: Robot-assisted neurolysis of the PN constitutes a feasible and safe approach, enabling better visualisation and accuracy in the dissection of the PN. Intraoperative neurophysiological monitoring is useful for locating the PN and for detecting intraoperative changes after the release of the nerve.


Subject(s)
Decompression, Surgical/methods , Pudendal Nerve/surgery , Pudendal Neuralgia/surgery , Robotic Surgical Procedures , Female , Humans , Middle Aged
20.
Int J Cardiol ; 228: 870-880, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27889554

ABSTRACT

Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited cardiomyopathies over the past decades. Genetic screening of first-degree relatives has revealed that 30-50% of the cases have a familial origin. Similar to other heart diseases, familial dilated cardiomyopathy is characterized by a high genetic heterogeneity that complicates family studies. Cli'nical screening, 12-lead electrocardiogram and transthoracic echocardiogram are recommended for patients and first-degree family members. Magnetic resonance also needs to be considered. Genetic technologies have become fundamental for the clinical management of this disease. New generation sequencing methods have made genetic testing feasible for extensive panels of genes related to the disease. Recently, new imaging modalities such as speckle-tracking, strain and strain rate or magnetic resonance, and circulating biomarkers such as non-coding RNAs, have emerged as potential strategies to help cardiologists in their clinical practice. Imaging, genetic and blood-based techniques should be considered together in the evaluation and testing of familial dilated cardiomyopathy. Here, we discuss the current procedures and novel approaches for the clinical management of familial dilated cardiomyopathy.


Subject(s)
Cardiomyopathy, Dilated/diagnosis , Biomarkers/blood , Cardiomyopathy, Dilated/blood , Cardiomyopathy, Dilated/genetics , Diagnostic Imaging , Genetic Testing , Humans
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