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1.
Mol Psychiatry ; 25(8): 1876-1900, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-29950682

RESUMEN

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.


Asunto(s)
Envejecimiento/metabolismo , Depresión Sináptica a Largo Plazo , Neuronas/metabolismo , Receptor de Adenosina A2A/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Adenosina/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Células Cultivadas , Hipocampo/metabolismo , Humanos , Ratones , Ratas , Ratas Sprague-Dawley , Memoria Espacial
2.
J Clin Monit Comput ; 35(5): 1229-1234, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33638061

RESUMEN

Strain echocardiography enables the automatic quantification of the global longitudinal strain (GLS), which is a direct measure of ventricular shortening during systole. In the current context of overwhelmed ICUs and clinician shortage, GLS has the advantage to be quick and easy to measure by non-experts. However, little is known regarding its value to assess bi-ventricular systolic function in critically ill COVID-19 patients. Therefore, we designed a study to compare right and left ventricular GLS with classic echo-Doppler indices of systolic function, namely the ejection fraction for the left ventricle (LVEF) and the fractional area change (FAC), the tricuspid annular plane systolic excursion (TAPSE), and the tissue Doppler velocity of the basal free lateral wall (S') for the right ventricle. Eighty transthoracic echocardiographic evaluations done in 30 ICU patients with COVID-19 were analyzed. We observed a fair relationship (r = 0.73, p < 0.01) between LVEF and left ventricular GLS. The GLS cut-off value of - 22% identified a LVEF < 50% with a sensitivity of 63% and a specificity of 80%. All patients with a GLS > - 17% had a LVEF < 50%. Although statistically significant, relationships between FAC (r = 0.41, p < 0.01), TAPSE (r = 0.26, p < 0.05) and right ventricular GLS were weak. S' was not correlated with right ventricular GLS. In conclusion, left ventricular GLS was useful to assess left ventricular systolic function. However, right ventricular GLS was poorly correlated with FAC, TAPSE and S'. Further studies are needed to clarify what is the best method to assess right ventricular systolic function in ICU patients with COVID-19.


Asunto(s)
COVID-19 , Disfunción Ventricular Derecha , Enfermedad Crítica , Ecocardiografía , Humanos , SARS-CoV-2 , Volumen Sistólico , Sístole , Disfunción Ventricular Derecha/diagnóstico por imagen
3.
Neurobiol Dis ; 145: 105043, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32798727

RESUMEN

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A2A/metabolismo , Síndrome de Rett/metabolismo , Transducción de Señal/fisiología , Animales , Hipocampo/metabolismo , Proteína 2 de Unión a Metil-CpG , Ratones , Ratones Noqueados , Receptor trkB/metabolismo , Síndrome de Rett/genética
4.
Nonlinear Dyn ; 101(1): 153-170, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32801477

RESUMEN

Representative models of the nonlinear behavior of floating platforms are essential for their successful design, especially in the emerging field of wave energy conversion where nonlinear dynamics can have substantially detrimental effects on the converter efficiency. The spar buoy, commonly used for deep-water drilling, oil and natural gas extraction and storage, as well as offshore wind and wave energy generation, is known to be prone to experience parametric resonance. In the vast majority of cases, parametric resonance is studied by means of simplified analytical models, considering only two degrees of freedom (DoFs) of archetypical geometries, while neglecting collateral complexity of ancillary systems. On the contrary, this paper implements a representative 7-DoF nonlinear hydrodynamic model of the full complexity of a realistic spar buoy wave energy converter, which is used to verify the likelihood of parametric instability, quantify the severity of the parametrically excited response and evaluate its consequences on power conversion efficiency. It is found that the numerical model agrees with expected conditions for parametric instability from simplified analytical models. The model is then used as a design tool to determine the best ballast configuration, limiting detrimental effects of parametric resonance while maximizing power conversion efficiency.

5.
Cereb Cortex ; 27(1): 718-730, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-26534909

RESUMEN

Abnormal accumulation of aggregated α-synuclein (aSyn) is a hallmark of sporadic and familial Parkinson's disease (PD) and related synucleinopathies. Recent studies suggest a neuroprotective role of adenosine A2A receptor (A2AR) antagonists in PD. Nevertheless, the precise molecular mechanisms underlying this neuroprotection remain unclear. We assessed the impact of A2AR blockade or genetic deletion (A2AR KO) on synaptic plasticity and neuronal cell death induced by aSyn oligomers. We found that impairment of LTP associated with aSyn exposure was rescued in A2AR KO mice or upon A2AR blockade, through an NMDA receptor-dependent mechanism. The mechanisms underlying these effects were evaluated in SH-SY5Y cells overexpressing aSyn and rat primary neuronal cultures exposed to aSyn. Cell death in both conditions was prevented by selective A2AR antagonists. Interestingly, blockade of these receptors did not interfere with aSyn oligomerization but, instead, reduced the percentage of cells displaying aSyn inclusions. Altogether, our data raise the possibility that the well-documented effects of A2AR antagonists involve the control of the latter stages of aSyn aggregation, thereby preventing the associated neurotoxicity. These findings suggest that A2AR represent an important target for the development of effective drugs for the treatment of PD and related synucleinopathies.


Asunto(s)
Neuronas/metabolismo , Receptor de Adenosina A2A/metabolismo , alfa-Sinucleína/metabolismo , Antagonistas del Receptor de Adenosina A2/toxicidad , Animales , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Línea Celular Tumoral , Potenciales Postsinápticos Excitadores , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas Wistar , Receptor de Adenosina A2A/genética , Proteínas Recombinantes/metabolismo , Técnicas de Cultivo de Tejidos , alfa-Sinucleína/genética
6.
Psychol Health Med ; 23(3): 317-324, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28661187

RESUMEN

Burnout is a professional syndrome associated with stress caused by overwork. Our aim was to calculate the prevalence of burnout and stress on medical residents of Oncology, Haematology and Radiotherapy in Portugal, as well as to determine predictors of burnout and stress. An anonymous questionnaire was applied (n = 118). Statistical analysis consisted of a descriptive and inferential analysis. The prevalence of burnout and stress was calculated to be 45.2 and 50%, respectively. The dimensions that generated higher levels of stress were 'dealing with patients' and 'overwork'. Burnout was directly related with stress dimension 'overwork'. The prevalence of burnout in Portuguese oncological residents is high as in other European countries and in the U.S. Therefore, interventional strategies can be designed.


Asunto(s)
Agotamiento Profesional/psicología , Hematología/educación , Internado y Residencia , Oncología Médica/educación , Estrés Laboral/complicaciones , Radioterapia , Logro , Adulto , Agotamiento Profesional/epidemiología , Agotamiento Profesional/terapia , Estudios Transversales , Femenino , Humanos , Masculino , Estrés Laboral/epidemiología , Estrés Laboral/psicología , Relaciones Médico-Paciente , Portugal , Factores Sexuales , Encuestas y Cuestionarios
7.
Immunogenetics ; 65(10): 737-48, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23846851

RESUMEN

The coexistence of wild boars and domestic pigs across Eurasia makes it feasible to conduct comparative genetic or genomic analyses for addressing how genetically different a domestic species is from its wild ancestor. To test whether there are differences in patterns of genetic variability between wild and domestic pigs at immunity-related genes and to detect outlier loci putatively under selection that may underlie differences in immune responses, here we analyzed 54 single-nucleotide polymorphisms (SNPs) of 19 immunity-related candidate genes on 11 autosomes in three pairs of wild boar and domestic pig populations from China, Iberian Peninsula, and Hungary. Our results showed no statistically significant differences in allele frequency and heterozygosity across SNPs between three pairs of wild and domestic populations. This observation was more likely due to the widespread and long-lasting gene flow between wild boars and domestic pigs across Eurasia. In addition, we detected eight coding SNPs from six genes as outliers being under selection consistently by three outlier tests (BayeScan2.1, FDIST2, and Arlequin3.5). Among four non-synonymous outlier SNPs, one from TLR4 gene was identified as being subject to positive (diversifying) selection and three each from CD36, IFNW1, and IL1B genes were suggested as under balancing selection. All of these four non-synonymous variants were predicted as being benign by PolyPhen-2. Our results were supported by other independent lines of evidence for positive selection or balancing selection acting on these four immune genes (CD36, IFNW1, IL1B, and TLR4). Our study showed an example applying a candidate gene approach to identify functionally important mutations (i.e., outlier loci) in wild and domestic pigs for subsequent functional experiments.


Asunto(s)
Inmunidad/genética , Polimorfismo de Nucleótido Simple , Sus scrofa/genética , Porcinos/genética , Animales , Antígenos CD36/genética , Frecuencia de los Genes , Variación Genética , Genotipo , Interferones/genética , Interleucina-1beta/genética , Modelos Genéticos , Selección Genética , Especificidad de la Especie , Receptor Toll-Like 4/genética
8.
BMJ Case Rep ; 16(8)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37558277

RESUMEN

Takotsubo syndrome is an acute reversible cardiomyopathy with left ventricular dysfunction and a clinical presentation similar to an acute coronary syndrome. Emotional or physical triggers can cause it, including neurological conditions such as seizures. We describe a case of a woman in her 50s with Takotsubo syndrome secondary to status epilepticus, presenting with cardiac arrest and cardiogenic shock. We excluded acute coronary syndrome with coronary angiography. Despite inotropic support, she remained haemodynamically unstable and a percutaneous left ventricular assistance with an Impella CP catheter was initiated. This resulted in a quick weaning of haemodynamic support and recovery of left ventricle systolic function in 2 weeks. This case illustrates the importance of a high index of suspicion to make this diagnosis and link it to neurological triggers, as well as to consider mechanical circulatory support in managing cardiogenic shock due to this cardiomyopathy.


Asunto(s)
Cardiomiopatías , Estado Epiléptico , Cardiomiopatía de Takotsubo , Femenino , Humanos , Choque Cardiogénico/terapia , Choque Cardiogénico/complicaciones , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/terapia , Cardiomiopatía de Takotsubo/diagnóstico , Ventrículos Cardíacos , Cardiomiopatías/complicaciones , Estado Epiléptico/complicaciones
9.
Ultrasound J ; 15(1): 2, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36633703

RESUMEN

INTRODUCTION: SARS-CoV-2 infection is associated with multiple cardiac manifestations. Left atrial strain (LA-S) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and diastolic dysfunction, which could lead to early recognition of cardiac injury in severe COVID-19 patients with possible implications on clinical management, organ dysfunction, and mortality. Cardiac injury may occur by direct viral cytopathic effects or virus-driven immune activation, resulting in heart infiltration by inflammatory cells, despite limited and conflicting data are available on myocardial histology. PURPOSE: We aimed to explore LA-S and immune profiles in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. METHODS: We enrolled 30 patients > 18 years with positive SARS-CoV-2 RT-PCR, admitted to ICU. Acute myocardial infarction and pulmonary embolism were exclusion criteria. On days D1, D3, and D7 after ICU admission, patients performed TTE, hemogram, cardiac (pro-BNP; troponin) and inflammatory biomarkers (ESR; ferritin; IL1ß; IL6; CRP; d-dimer; fibrinogen; PCT; adrenomedullin, ADM), and immunophenotyping by flow cytometry. RESULTS: Patient's mean age was 60.7 y, with 63% males. Hypertension was the most common risk factor (73%; with 50% of patients under ACEi or ARA), followed by obesity (40%, mean BMI = 31 kg/m2). Cardiac dysfunction was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. Mortality, hospitalization days, remdesivir use, organ dysfunction, cardiac and serum biomarkers were not different between patients with (DYS) and without cardiac dysfunction (nDYS), except for ADM (increased in nDYS group at D7). From the 77 TTE, there was a striking difference between diastolic dysfunction evaluation by classic criteria compared to STE (28.6% vs. 57.1%, p = 0.0006). Lower reservoir (Ɛ) and contraction (ƐCT) LA-S correlated with IL-6 (Ɛ, p = 0.009, r = - 0.47; ƐCT, p = 0.0002, r = - 0.63) and central memory CD4 T-cells (ƐCT, p = 0.049, r = - 0.24). Along all timepoints, DYS patients showed persistent low lymphocyte counts that recovered at D7 in nDYS patients. DYS patients had lower platelets at D3 and showed a slower recovery in platelet counts and CRP levels; the latter significantly decreased at D7 in nDYS patients (p = 0.009). Overall, patients recovered with an increasing P/F ratio, though to a lesser extent in DYS patients. DISCUSSION: Our study shows that LA-S may be a more sensitive marker for diastolic dysfunction in severe COVID-19, which could identify patients at risk for a protracted inflammatory state. A differential immune trait in DYS patients at ICU admission, with persistent lymphopenia, enriched CM T-cells, and higher IL-6 may suggest distinct inflammatory states or migration patterns in patients that develop cardiac injury.

10.
Bioelectrochemistry ; 152: 108461, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37192590

RESUMEN

STEAP1 is a cell surface protein of the STEAP family whose main function focuses on intercellular communication and cell growth. STEAP1 is considered a promising putative biomarker and a candidate target for prostate cancer treatment. For specific and selective detection of STEAP1, a molecularly imprinted polymers (MIP) was developed on a screen-printed electrode (C-SPE) whose surface was modified with a nanocomposite based on carbon nanotubes decorated with dendritic platinum nanoparticles (CNTs- PAH /Pt). Then, the MIPs were produced on the modified C-SPE by electropolymerization of a mixture of STEAP1 and a monomer (pyrrole-2-carboxylic acid). Then, the protein was removed from the polymeric network by enzymatic treatment with trypsin, which created the specific template cavities for further STEAP1 detection. Electrochemical techniques such as EIS and CV were used to follow the chemical modification steps of C-SPE. The analytical performance of the biosensor was evaluated by SWV in PBS buffer and in lysates of neoplastic prostate cancer cells (LNCaP) extracts. The MIP material showing a linear range from 130 pg/ml to 13 µg/ml. Overall, the biosensor exhibits essential properties such as selectivity, sensitivity and reproducibility for its application in medical and clinical research diagnosis and/or prognosis of prostate cancer.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Impresión Molecular , Nanotubos de Carbono , Neoplasias de la Próstata , Masculino , Humanos , Plásticos , Nanotubos de Carbono/química , Reproducibilidad de los Resultados , Platino (Metal) , Biomarcadores , Anticuerpos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Neoplasias de la Próstata/diagnóstico , Impresión Molecular/métodos , Electrodos , Antígenos de Neoplasias , Oxidorreductasas
11.
J Neurochem ; 123(6): 1030-40, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23057965

RESUMEN

In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored. We now evaluated the interaction between A(2A) and CRF receptors (CRFR) function, upon glutamate insult. Primary rat cortical neuronal cultures (9 days in vitro) expressing both CRF(1)R and CRF(2)R were challenged with glutamate (20-1000 µM, 24 h). CRF(1)R was found to co-localize with neuronal markers and CRF(2)R to be present in both neuronal and glial cells. The effects of the CRF and A(2A) receptors ligands on cell viability were measured using propidium iodide and Syto-13 fluorescence staining. Glutamate decreased cell viability in a concentration-dependent manner. Urocortin (10 pM), an agonist of CRF receptors, increased cell survival in the presence of glutamate. This neuroprotective effect was abolished by blocking either CRF(1)R or CRF(2)R with antalarmin (10 nM) or anti-Sauvagine-30 (10 nM), respectively. The blockade of A(2A) receptors with a selective antagonist SCH 58261 (50 nM) improved cell viability against the glutamate insult. This effect was dependent on CRF(2)R, but not on CRF(1)R activation. Overall, these data show a protective role of CRF in cortical neurons, against glutamate-induced death. The neuroprotection achieved by A(2A) receptors blockade requires CRF(2)R activation. This interaction between the adenosine and CRF receptors can explain the beneficial effects of using A(2A) receptor antagonists against stress-induced noxious effects.


Asunto(s)
Antagonistas del Receptor de Adenosina A2/farmacología , Hormona Liberadora de Corticotropina/fisiología , Ácido Glutámico/toxicidad , Inhibición Neural/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Receptor de Adenosina A2A/metabolismo , Animales , Corteza Cerebral/patología , Ácido Glutámico/metabolismo , Inhibición Neural/fisiología , Neuronas/metabolismo , Neuronas/patología , Cultivo Primario de Células , Pirimidinas/farmacología , Pirroles/farmacología , Ratas , Ratas Sprague-Dawley , Triazoles/farmacología
12.
Nephrol Dial Transplant ; 27 Suppl 3: iii135-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22498917

RESUMEN

BACKGROUND: It is known that chronic kidney disease (CKD) is continuously increasing all over the world, but the available numbers of affected subjects are mostly collected from renal replacement therapy services and they correspond to individuals with end-stage renal disease. The aim of the present study was to diagnose CKD in its earliest stages in the general population based on detection of proteinuria. METHODS: In public prevention campaigns, from 2005 to 2010, 38 721 inhabitants were evaluated in the state of Sao Paulo (Brazil). Screening procedures included a dipstick test, blood pressure measurement and application of a medical questionnaire. RESULTS: In the whole population, urine samples of 37 771 individuals (mean age: 44.59 + 21.70, 55.74% females) were evaluated, 7.3% presented proteinuria (1+ or more) in the screening test and 85.5% of them had no previous knowledge of this urinary abnormality. Those individuals were referred for further clinical evaluation in order to confirm the detected alterations. Considering being diabetic and/or hypertensive as important risk factors for CKD, it was observed that they corresponded to 9.7 and 28.4% of the population screened for proteinuria, respectively. Newly detected cases of possible CKD, diabetes and hypertension corresponded to 6.2, 0.3 and 6.5%, respectively. CONCLUSIONS: This initiative provided information on proteinuria and possible cases of CKD based on a large sampling of the Brazilian population. Proteinuria was detected in 7.3% of these individuals, and such prevalence is similar to that previously described in developed countries.


Asunto(s)
Encuestas Epidemiológicas , Tamizaje Masivo , Proteinuria/diagnóstico , Insuficiencia Renal Crónica/diagnóstico , Adulto , Brasil/epidemiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Proteinuria/epidemiología , Proteinuria/etiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios
13.
J Clin Med ; 11(7)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35407485

RESUMEN

Background: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE). Peripheral blood immunophenotyping, cardiac (pro-BNP; troponin) and inflammatory biomarkers were simultaneously evaluated. Results: Cardiac dysfunction (DYS) was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. High-sensitivity cardiac troponin (hs-cTn) was detectable in 43.3% of the patients with a median value of 13.00 ng/L. There were no significant differences between DYS and nDYS patients regarding mortality, organ dysfunction, cardiac (including hs-cTn) or inflammatory biomarkers. Patients with DYS showed persistently lower lymphocyte counts (median 896 [661−1837] cells/µL vs. 2141 [924−3306] cells/µL, p = 0.058), activated CD3 (median 85 [66−170] cells/µL vs. 186 [142−259] cells/µL, p = 0.047) and CD4 T cells (median 33 [28−40] cells/µL vs. 63 [48−79] cells/µL, p = 0.005), and higher effector memory T cells (TEM) at baseline (CD4%: 10.9 [6.4−19.2] vs. 5.9 [4.2−12.8], p = 0.025; CD8%: 15.7 [7.9−22.8] vs. 8.1 [7.7−13.7], p = 0.035; CD8 counts: 40 cells/µL [17−61] vs. 10 cells/µL [7−17], p = 0.011) than patients without cardiac dysfunction. Conclusion: Our study suggests an association between the immunological trait and cardiac dysfunction in severe COVID-19 patients.

14.
Biosensors (Basel) ; 11(6)2021 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-34072661

RESUMEN

This work reports the design of a novel plastic antibody for cystatin C (Cys-C), an acute kidney injury biomarker, and its application in point-of-care (PoC) testing. The synthetic antibody was obtained by tailoring a molecularly imprinted polymer (MIP) on a carbon screen-printed electrode (SPE). The MIP was obtained by electropolymerizing pyrrole (Py) with carboxylated Py (Py-COOH) in the presence of Cys-C and multiwall carbon nanotubes (MWCNTs). Cys-C was removed from the molecularly imprinted poly(Py) matrix (MPPy) by urea treatment. As a control, a non-imprinted poly(Py) matrix (NPPy) was obtained by the same procedure, but without Cys-C. The assembly of the MIP material was evaluated in situ by Raman spectroscopy and the binding ability of Cys-C was evaluated by the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) electrochemical techniques. The MIP sensor responses were measured by the DPV anodic peaks obtained in the presence of ferro/ferricyanide. The peak currents decreased linearly from 0.5 to 20.0 ng/mL of Cys-C at each 20 min successive incubation and a limit of detection below 0.5 ng/mL was obtained at pH 6.0. The MPPy/SPE was used to analyze Cys-C in spiked serum samples, showing recoveries <3%. This device showed promising features in terms of simplicity, cost and sensitivity for acute kidney injury diagnosis at the point of care.


Asunto(s)
Técnicas Biosensibles , Cistatina C/análisis , Nanotubos de Carbono/química , Polímeros/química , Pirroles/química , Espectroscopía Dieléctrica , Técnicas Electroquímicas , Electrodos , Humanos , Límite de Detección , Impresión Molecular , Plásticos
15.
Cell Rep ; 36(9): 109574, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34469732

RESUMEN

Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Conducta Animal , Encéfalo/metabolismo , Cognición , Mediadores de Inflamación/metabolismo , Interleucina-17/metabolismo , Linfocitos Intraepiteliales/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Sinapsis/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/psicología , Animales , Antiinflamatorios/farmacología , Anticuerpos Monoclonales/farmacología , Anticuerpos Neutralizantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Cognición/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Mediadores de Inflamación/antagonistas & inhibidores , Interleucina-17/antagonistas & inhibidores , Linfocitos Intraepiteliales/efectos de los fármacos , Masculino , Memoria a Corto Plazo , Ratones de la Cepa 129 , Ratones Transgénicos , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/prevención & control , Enfermedades Neuroinflamatorias/psicología , Plasticidad Neuronal , Sinapsis/efectos de los fármacos , Sinapsis/patología
16.
Neurobiol Aging ; 94: 281-286, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32711258

RESUMEN

Aging is associated with the progressive decay of cognitive function. Hippocampus-dependent processes, such as the formation of spatial memory, are particularly vulnerable to aging. Currently, the molecular mechanisms responsible for age-dependent cognitive decline are largely unknown. Here, we investigated the expression and function of the growth arrest DNA damage gamma (Gadd45γ) during aging and cognition. We report that Gadd45γ expression is increased in the hippocampus of aged humans and that Gadd45γ overexpression in the young adult mouse hippocampus compromises cognition. Moreover, Gadd45γ overexpression in hippocampal neurons disrupted cAMP response element-binding protein signaling and the expression of well-established activity-regulated genes. This work shows that Gadd45γ expression is tightly controlled in the hippocampus and its disruption may be a mechanism contributing to age-related cognitive impairments observed in humans.


Asunto(s)
Envejecimiento/genética , Envejecimiento/psicología , Cognición/fisiología , Envejecimiento Cognitivo/psicología , Expresión Génica , Hipocampo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Trastornos de la Memoria/genética , Trastornos de la Memoria/psicología , Memoria Espacial/fisiología , Adulto , Anciano , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Hipocampo/fisiología , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Proteinas GADD45
17.
Stud Health Technol Inform ; 150: 76-80, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19745270

RESUMEN

This paper addresses the role of IT Governance in a Hospital Information System (HIS) management. ITIL is introduced as a best practice for supporting HIS development. Since IT Governance is extensive, we focused our study on an ITIL Assessment. The assessment was centred on IT Service Management, and which, according to our findings, is being carried inefficiently in Hospital São Sebastião. Although the literature quotes the many benefits brought by ITIL to the organizations, they all depend on how good the planning and implementing processes are. The implementation process itself is very complex and we focused our study on the assessment step. The ITIL assessment was crucial to identify IT Governance weakness; and it is a way for the organization to become consciousness about IT improvement priorities. The results were used to rethink HIS strategy in order to properly address the next challenges.


Asunto(s)
Sistemas de Computación , Estudios de Evaluación como Asunto , Sistemas de Información en Hospital/organización & administración , Estudios de Casos Organizacionales , Portugal
18.
Cuad. psicol. deporte ; 24(1): 182-199, Ene 2, 2024. tab, graf
Artículo en Inglés | IBECS (España) | ID: ibc-229626

RESUMEN

Este estudo analisou as diferenças na perceção dos atletas acerca dos comportamentos parentais, considerando também a importância do escalão desportivo dos atletas. Além disso, foi analisado se diferentes perfis de envolvimento parental, segundo a avaliação dos atletas aos seus pais, correspondiam a diferenças na orientação motivacional e na perceção de rendimento dos jovens atletas. Participaram no estudo 292 atletas do sexo masculino com idades compreendidas entre os 12 e 19 anos (M = 15.0; DP = 1.5), praticantes de futebol no campeonato nacional. Foram aplicados três instrumentos, (1) Questionário de Comportamentos Parentais no Desporto; (2) Escala de Objetivos de Realização no Desporto Juvenil; (3) Questionário de Perceção de Rendimento Desportivo. Os resultados indicaram (a) diferenças na perceção de comportamentos do pai e da mãe separadamente, sendo que, a perceção dos atletas variou em função do seu escalão desportivo; e (b) a orientação motivacional e a perceção de rendimento variaram em função do perfil de envolvimento parental percebido. Em suma, os resultados demonstram a importância do envolvimento parental no desporto juvenil, devendo este fator ser considerado pelos profissionais que intervêmjunto dos jovens atletas.(AU)


Este estudio analizó las diferencias en la percepción de los atletas sobre los comportamientos de sus padres, considerando también la importancia del nivel deportivo de los atletas. Además, se analizó si los diferentes perfiles de participación de los padres, según la evaluación de los deportistas sobre sus padres, se correspondían con diferencias en la orientación motivacional y en la percepción del rendimiento de los jóvenes deportistas. Participaron del estudio 292 atletas masculinos con edades entre 12 y 19 años (M = 15,0; SD = 1,5), futbolistas del campeonato nacional. Se aplicaron tres instrumentos, (1) Cuestionario de Conductas Parentales en el Deporte; (2) Escala de Metas de Logro en Deportes Juveniles; (3) Cuestionario de Percepción del Rendimiento Deportivo. Los resultados indicaron: (a)diferencias en la percepción de los comportamientos del padre y de la madre por separado, y la percepción de los deportistas varió según su nivel deportivo; e (b)la orientación motivacional y la percepción de rendimiento varió según el perfil de participación parental percibida. En resumen, los resultados demuestran la importancia de la participación de los padres en el deporte juvenil, y este factor debe ser considerado por los profesionales que trabajan con jóvenes deportistas.(AU)


This study analysed the differences in athletes’ perception of parental behaviours, considering the importance of athletes’ age category. It was also verified if different parental involvement profiles, according to athletes’ evaluation of their parents’ behaviours, corresponded to differences in motivational orientation and in performance perception of the young athletes. The study included 292 male athletes, aged between 12 and 19 years old (M = 15.0; DP = 1.5), playing football in the national championship. Three instruments were used: (1) Parental Behaviours in Sports Questionnaire; (2) Achievement goal scale for youth sport; (3) Sport Performance Perception Questionnaire. The results indicated: (a)differences in the perception of father’s and mother’s behaviours, separately, and these differences changed according to athletes’ age category; and (b)motivational orientation and performance perception varied according to the perceived parental involvement profile. In sum, the results demonstrate the importance of parental behaviours in youth sports and this aspect should be considered by professionals who work with young athletes.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Fútbol/psicología , Atletas/psicología , Relaciones Padres-Hijo , Percepción , Rendimiento Atlético , Motivación , Deportes/psicología , Psicología del Deporte , Medicina Deportiva , Responsabilidad Parental
19.
Cell Rep ; 29(2): 317-331.e5, 2019 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-31597094

RESUMEN

There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenesis, and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothesize that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological, and behavioral techniques, we show that pathological AICD levels weaken CA1 neuron firing activity through a gene-transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the γ-frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal aging to AD.


Asunto(s)
Potenciales de Acción/fisiología , Precursor de Proteína beta-Amiloide/química , Precursor de Proteína beta-Amiloide/metabolismo , Región CA1 Hipocampal/fisiología , Neuronas/fisiología , Memoria Espacial/fisiología , Animales , Canales de Calcio/metabolismo , Ritmo Gamma/fisiología , Humanos , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Canales de Potasio/metabolismo , Dominios Proteicos , Ratas Sprague-Dawley , Relación Estructura-Actividad , Transcripción Genética
20.
Stud Health Technol Inform ; 136: 765-70, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18487824

RESUMEN

Security is a vital part of daily life to Hospitals that need to ensure that the information is adequately secured. In Portugal, more CIOs are seeking that their hospital IS departments are properly protecting information assets from security threats. It is imperative to take necessary measures to ensure risk management and business continuity. Security management certification provides just such a guarantee, increasing patient and partner confidence. This paper introduces one best practice for implementing four security controls in a hospital datacenter infrastructure (ISO27002), and describes the security assessment for implementing such controls.


Asunto(s)
Redes de Comunicación de Computadores/normas , Seguridad Computacional/normas , Sistemas de Información en Hospital/normas , Gestión de la Información/normas , Computación en Informática Médica/normas , Sistemas de Computación , Confidencialidad/legislación & jurisprudencia , Humanos , Sistemas de Registros Médicos Computarizados/normas , Portugal , Programas Informáticos , Integración de Sistemas
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