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1.
Nature ; 631(8022): 796-800, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39048683

RESUMEN

Methane is an important greenhouse gas1, but the role of trees in the methane budget remains uncertain2. Although it has been shown that wetland and some upland trees can emit soil-derived methane at the stem base3,4, it has also been suggested that upland trees can serve as a net sink for atmospheric methane5,6. Here we examine in situ woody surface methane exchange of upland tropical, temperate and boreal forest trees. We find that methane uptake on woody surfaces, in particular at and above about 2 m above the forest floor, can dominate the net ecosystem contribution of trees, resulting in a net tree methane sink. Stable carbon isotope measurement of methane in woody surface chamber air and process-level investigations on extracted wood cores are consistent with methanotrophy, suggesting a microbially mediated drawdown of methane on and in tree woody surfaces and tissues. By applying terrestrial laser scanning-derived allometry to quantify global forest tree woody surface area, a preliminary first estimate suggests that trees may contribute 24.6-49.9 Tg of atmospheric methane uptake globally. Our findings indicate that the climate benefits of tropical and temperate forest protection and reforestation may be greater than previously assumed.


Asunto(s)
Atmósfera , Bosques , Metano , Árboles , Madera , Atmósfera/química , Metano/metabolismo , Metano/análisis , Taiga , Árboles/química , Árboles/metabolismo , Árboles/microbiología , Clima Tropical , Madera/química , Madera/metabolismo , Madera/microbiología , Gases de Efecto Invernadero/análisis , Gases de Efecto Invernadero/metabolismo , Isótopos de Carbono , Agricultura Forestal , Calentamiento Global/prevención & control , Calentamiento Global/estadística & datos numéricos , Efecto Invernadero/prevención & control , Efecto Invernadero/estadística & datos numéricos
2.
N Biotechnol ; 83: 110-120, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38960022

RESUMEN

The methylotrophic yeast Komagataella phaffii is a popular host system for the pharmaceutical and biotechnological production of recombinant proteins. CRISPR-Cas9 and its derivative CRISPR interference (CRISPRi) offer a promising avenue to further enhance and exploit the full capabilities of this host. MAD7 and its catalytically inactive variant "dead" MAD7 (dMAD7) represent an interesting alternative to established CRISPR-Cas9 systems and are free to use for industrial and academic research. CRISPRi utilizing dMAD7 does not introduce double-strand breaks but only binds to the DNA to regulate gene expression. Here, we report the first use of dMAD7 in K. phaffii to regulate the expression of the enhanced green fluorescent protein (eGFP). A reduction of eGFP fluorescence level (up to 88 %) was achieved in random integration experiments using dMAD7 plasmids. Integration loci/events of investigated strains were assessed through whole genome sequencing. Additionally, RNA-sequencing experiments corroborated the whole genome sequencing results and showed a significantly reduced expression of eGFP in strains containing a dMAD7 plasmid, among others. Our findings conclusively demonstrate the utility of dMAD7 in K. phaffii through successfully regulating eGFP expression.

3.
Rev Esp Patol ; 57(3): 182-189, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971618

RESUMEN

OBJECTIVE: To test the diagnostic concordance between microscopic (MI) and digital (DG) observation of cervico-vaginal (CV) cytology in a validation study of the technique. METHODS: Five cytotechnologists (CT) reviewed 888 routine CV cytology cases from the Cervical Pathology Unit of our center over a 2-week period of time. The cases were first observed by MI and at the end of the day the cases were observed by DG. STATISTICAL ANALYSIS USED: Agreement calculated using the Kappa index. RESULTS: Most of the diagnoses corresponded to benign (64%) or inflammatory conditions (14%) and 24% corresponded to the intraepithelial lesion or malignancy (ILM) category. The overall kappa coefficient of concordance was strong (0.87). Among the different CTs it was almost perfect in two, strong in two and moderate in one. In 18 cases (10%) there were discrepancies between techniques in the category of ILM. In 10 (56%) cases there was an overdiagnosis in DG and in 8 (44%) an overdiagnosis in MI. Only in two cases, the diagnostic discrepancy exceeded one degree of difference between lesions, and they were ASCUS or AGUS for DG and CIN 2 for MI. CONCLUSIONS: In this validation test in which routine cases during a two-week period have been used, observing the cases with both techniques on the same day, we have obtained a strong degree of concordance. The discordances obtained have not been considered relevant.


Asunto(s)
Frotis Vaginal , Femenino , Humanos , Cuello del Útero/patología , Microscopía , Reproducibilidad de los Resultados , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Vagina/patología
4.
Hypertens Res ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38942814

RESUMEN

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.

5.
Arch Dis Child ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811054

RESUMEN

OBJECTIVE: It is known that exposure to air pollution is associated with an increased risk for cardiovascular and respiratory diseases. This review aimed to summarise observational studies on the impact of short and long-term exposure to ambient air pollution on prevalence of hospitalisations and/or emergency department visits caused by respiratory diseases in children and adolescents. SOURCES: Pubmed, Scopus, Embase and Cochrane Library databases were searched for the years 2018 to December 2022, including studies in any language. SUMMARY OF THE FINDINGS: A total of 15 studies published between 2018 and 15 January 2022 were included in this review. PM2.5 was the most type of particulate matter studied. Short-term exposure to PM2,5, PM10, NO2, SO2 and O3, even at concentrations less than the current health-based guidelines, was significantly correlated with increased risk of outpatient/hospital visits and hospitalisations for respiratory diseases by children. CONCLUSIONS: Our findings emphasise the importance and urgency of long-term control of air pollution and pollution-related diseases, especially among children and adolescents. There is a need for further research employing more homogeneous methodologies for assessing exposure and outcome measurements, in order to enable systematic reviews with meta-analysis.

6.
J Neurointerv Surg ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637151

RESUMEN

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

7.
Eur Stroke J ; 9(1): 251-258, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37873938

RESUMEN

INTRODUCTION: Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). PATIENTS AND METHODS: We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. RESULTS: Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. CONCLUSIONS: cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Hipercolesterolemia , Rigidez Vascular , Masculino , Humanos , Anciano , Adulto Joven , Adulto , Femenino , Estudios Longitudinales , Análisis de la Onda del Pulso , Hipercolesterolemia/complicaciones , Monitoreo Ambulatorio de la Presión Arterial , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Estudios de Cohortes , Hemorragia Cerebral/diagnóstico por imagen
9.
Nat Commun ; 14(1): 2916, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37225741

RESUMEN

The association between long-term exposure to ambient air pollutants and severe COVID-19 is uncertain. We followed 4,660,502 adults from the general population in 2020 in Catalonia, Spain. Cox proportional models were fit to evaluate the association between annual averages of PM2.5, NO2, BC, and O3 at each participant's residential address and severe COVID-19. Higher exposure to PM2.5, NO2, and BC was associated with an increased risk of COVID-19 hospitalization, ICU admission, death, and hospital length of stay. An increase of 3.2 µg/m3 of PM2.5 was associated with a 19% (95% CI, 16-21) increase in hospitalizations. An increase of 16.1 µg/m3 of NO2 was associated with a 42% (95% CI, 30-55) increase in ICU admissions. An increase of 0.7 µg/m3 of BC was associated with a 6% (95% CI, 0-13) increase in deaths. O3 was positively associated with severe outcomes when adjusted by NO2. Our study contributes robust evidence that long-term exposure to air pollutants is associated with severe COVID-19.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Adulto , Humanos , España/epidemiología , Estudios de Cohortes , Dióxido de Nitrógeno/toxicidad , COVID-19/epidemiología , Contaminación del Aire/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Material Particulado/efectos adversos
10.
Rev. argent. salud publica ; 15: 1-8, 16 Febrero 2023.
Artículo en Español | LILACS, ARGMSAL, BINACIS | ID: biblio-1524240

RESUMEN

INTRODUCCIÓN: El Código Internacional de Comercialización de Sucedáneos de la Leche Materna de la Organización Mundial de la Salud (OMS) contribuye a proteger y promover la lactancia humana, para evitar que la comercialización aliente la utilización de sucedáneos. El objetivo fue evaluar el cumplimiento de las disposiciones del Código de la OMS respecto del etiquetado de fórmulas de inicio, fórmulas especiales, fórmulas de seguimiento y leches de crecimiento en la ciudad de Buenos Aires durante julio, agosto y septiembre de 2019. MÉTODOS: Se realizó un estudio observacional de tipo descriptivo, corte transversal y enfoque cualitativo en 93 etiquetas. Se aplicó la metodología propuesta por el Fondo de las Naciones Unidas para la Infancia (UNICEF), la International Baby Food Action Network (IBFAN) y el International Code Documentation Centre (ICDC) en el documento Herramienta Monitoreo del Código (2015). RESULTADOS: El 90,32% incumple al menos un requisito definido en el Art. 9 del Código de la OMS. El 88,17% de las etiquetas analizadas incumple por la presencia de textos e imágenes que desalientan la lactancia materna. DISCUSIÓN: Las etiquetas cumplen parcialmente los lineamientos del Código de la OMS según la herramienta de investigación utilizada. Por lo tanto, se sugiere garantizar la protección del derecho a la alimentación adecuada durante la primera infancia mediante el monitoreo, control y fiscalización del Código por parte de las autoridades sanitarias


Asunto(s)
Lactancia Materna , Sustitutos de la Leche Humana , Etiquetado de Alimentos , Abastecimiento de Alimentos , Política de Salud
11.
Cerebrovasc Dis ; 50(4): 435-442, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33831860

RESUMEN

BACKGROUND AND PURPOSE: The minor stroke concept has not been analyzed in intracerebral hemorrhage (ICH) patients. Our purpose was to determine the optimal cut point on the NIH Stroke Scale (NIHSS) for defining a minor ICH (mICH) in patients with primary ICH. METHODS: An ICH was considered minor if associated with a favorable 3-month outcome (modified Rankin Scale score ≤2). For supratentorial ICH, the discovery cohort consisted of 478 patients prospectively admitted at University Hospital del Mar. Association between NIHSS at admission and 3-month outcome was evaluated with area under the curve-receiver operating characteristics (AUC-ROC) and Youden's index to identify the optimal NIHSS cutoff point to define mICH. External validation was performed in a cohort of 242 supratentorial ICH patients from University Hospital Sant Pau. For infratentorial location, patients from both hospitals (n = 85) were analyzed together. RESULTS: The best -NIHSS cutoff point defining supratentorial-mICH was 6 (AUC-ROC = 0.815 [0.774-0.857] in the discovery cohort and AUC-ROC = 0.819 [0.756-0.882] in the external validation cohort). For infratentorial ICH, the best cutoff point was 4 (AUC-ROC = 0.771 [0.664-0.877]). Using these cutoff points, 40.5% of all primary ICH cases were mICH. Of these, 70.2% were living independently at 3-month follow-up (72% for supratentorial ICH and 56.1% for infratentorial ICH) and 6.5% had died (5.3% for supratentorial ICH, and 14.6% for infratentorial ICH). For patients identified as non-mICH, good 3-month outcome was observed in 11.3% of cases; mortality was 51%. CONCLUSIONS: The definition of mICH using the NIHSS cutoff point of 6 for supratentorial ICH and 4 for infratentorial ICH is useful to identify good outcome in ICH patients.


Asunto(s)
Hemorragia Cerebral/diagnóstico , Evaluación de la Discapacidad , Accidente Cerebrovascular Hemorrágico/diagnóstico , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/terapia , Femenino , Estado Funcional , Accidente Cerebrovascular Hemorrágico/mortalidad , Accidente Cerebrovascular Hemorrágico/fisiopatología , Accidente Cerebrovascular Hemorrágico/terapia , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , España , Factores de Tiempo
12.
J Neurol ; 268(1): 285-292, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32789606

RESUMEN

BACKGROUND: Stroke recurrence (SR) after an ischemic stroke is an important cause of death and disability. We conducted a hospital-based study to evaluate the role of biological age (b-Age: age-related DNA-methylation changes) as a risk factor for SR. METHODS: We included 587 patients in the acute phase of stroke, assessed at one tertiary stroke center (Hospital del Mar: Barcelona, Spain). B-Age was estimated with 5 different methods based on DNA methylation, and Hannum's method was the one that better performed. We analyzed the relationships between b-Age, chronological age, sex, vascular risk factors, coronary and peripheral arterial disease, atrial fibrillation, initial neurological severity assessed by National Institutes of Health Stroke Scale (NIHSS), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and symptomatic atherosclerosis. Stroke recurrence definition include: new symptoms that suggest a new ischemic event had occurred within 3 months after stroke onset and worsening by four points in the initial neurological severity (measured by National Institutes of Health Stroke Scale (NIHSS) score). RESULTS: Logistic regression analysis associated b-Age with SR [p = 0.003; OR = 1.06 (95% CI: 1.02-1.09)], independently of chronological age [p = 0.022; OR = 0.96 (95% CI 0.94-1.00)], symptomatic atherosclerosis (stenosis > 50% in the symptomatic territory), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and initial NIHSS. The b-Age of patients with SR was 2.7 years older than patients without SR. CONCLUSIONS: Patients with SR were biologically older than those without SR. B-Age was independently associated with high risk of developing SR.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular , Envejecimiento , Biomarcadores , Preescolar , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Recurrencia , Factores de Riesgo , España/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Factores de Tiempo
13.
Neurology ; 95(13): e1819-e1829, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32796129

RESUMEN

OBJECTIVE: To describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment. METHODS: In this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3-6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed. RESULTS: Of 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54-0.84]). CONCLUSIONS: Patients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.


Asunto(s)
Aneurisma Roto/cirugía , Aneurisma Intracraneal/cirugía , Hemorragia Subaracnoidea/cirugía , Aneurisma Roto/mortalidad , Femenino , Humanos , Aneurisma Intracraneal/mortalidad , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , España/epidemiología , Hemorragia Subaracnoidea/mortalidad , Factores de Tiempo , Resultado del Tratamiento
14.
Methods Mol Biol ; 2141: 37-72, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32696352

RESUMEN

Short linear motifs (SLiMs) are important mediators of interactions between intrinsically disordered regions of proteins and their interaction partners. Here, we detail instructions for the computational prediction of SLiMs in disordered protein regions, using the main tools of the SLiMSuite package: (1) SLiMProb identifies and calculates enrichment of predefined motifs in a set of proteins; (2) SLiMFinder predicts SLiMs de novo in a set of proteins, accounting for evolutionary relationships; (3) QSLiMFinder increases SLiMFinder sensitivity by focusing SLiM prediction on a specific query protein/region; (4) CompariMotif compares predicted SLiMs to known SLiMs or other SLiM predictions to identify common patterns. For each tool, command-line and online server examples are provided. Detailed notes provide additional advice on different applications of SLiMSuite, including batch running of multiple datasets and conservation masking using alignments of predicted orthologues.


Asunto(s)
Biología Computacional/métodos , Proteínas Intrínsecamente Desordenadas/química , Programas Informáticos , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Motor de Búsqueda , Alineación de Secuencia
15.
Epigenetics ; 15(9): 988-997, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32202197

RESUMEN

DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1-2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes. A two-stage case-control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways. We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.


Asunto(s)
Metilación de ADN , Epigenoma , Sitios Genéticos , Accidente Cerebrovascular Isquémico/genética , Anciano , Islas de CpG , Femenino , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Masculino , Persona de Mediana Edad
16.
Clin Drug Investig ; 40(2): 105-117, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31721070

RESUMEN

BACKGROUND: Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO3-) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO3- leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO3 inhalation may be a low-cost, easily accessible therapy for CF. OBJECTIVE: To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO3 solutions (4.2% and 8.4%). METHODS: An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18 years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels. RESULTS: Sputum pH increased immediately after inhalation of NaHCO3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G' (elasticity of the mucus) = - 0.241; G″ (viscosity of the mucus) = - 0.287; G* (viscoelasticity of the mucus) = - 0.275]. G* and G' were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed. CONCLUSION: Nebulized NaHCO3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.


Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Bicarbonato de Sodio/administración & dosificación , Administración por Inhalación , Adolescente , Adulto , Fibrosis Quística/fisiopatología , Fibrosis Quística/psicología , Elasticidad , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Calidad de Vida , Bicarbonato de Sodio/efectos adversos , Esputo/metabolismo , Viscosidad
17.
Environ Res ; 179(Pt A): 108725, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31539843

RESUMEN

BACKGROUND AND PURPOSE: A number of environmental risk factors of acute ischemic stroke have been identified, but few studies have evaluated the influence of the outdoor environment on stroke severity. We assessed the association of residential ambient fine particulate matter air pollution (PM2.5), noise, and surrounding greenspace with initial stroke severity. METHODS: We obtained data on patients hospitalized with acute ischemic stroke from a hospital-based prospective stroke register (2005-2014) in Barcelona. We estimated residential PM2.5 based on an established land use regression model, greenspace as the average satellite-based Normalized Difference Vegetation Index (NDVI) within a 300 m buffer of the residence, and daily (Lday), evening (Levening), night (Lnight) and average noise (Lden) level at the street nearest to the residential address using municipal noise models. Stroke severity was assessed at the time of hospital presentation using the National Institute of Health Stroke Scale (NIHSS).We used logistic regression and binomial models to evaluate the associations of PM2.5, greenspace, and noise with initial stroke severity adjusting for potential confounders. RESULTS: Among 2761 patients, higher residential surrounding greenspace was associated with lower risk of severe stroke (OR for NIHSS>5, 0.75; 95% CI: 0.60-0.95), while, living in areas with higher Lden was associated with a higher risk of severe stroke (OR, 1.30; 95% CI: 1.02-1.65). PM2.5 was not associated with initial stroke severity. CONCLUSIONS: In an urban setting, surrounding greenspace and traffic noise at home are associated with initial stroke severity, suggesting an important influence of the built environment on the global burden of ischemic stroke.


Asunto(s)
Contaminación del Aire/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Ruido , Accidente Cerebrovascular/epidemiología , Contaminantes Atmosféricos , Isquemia Encefálica/epidemiología , Humanos , Material Particulado , Estudios Prospectivos
20.
BMC Pulm Med ; 18(1): 153, 2018 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-30217179

RESUMEN

BACKGROUND: The sweat test (ST) is the gold standard for the diagnosis of cystic fibrosis (CF). However, little is known about sweat induction using different types of currents and waves. In this context, our objective was to develop a device to induce sweat and compare the use of continuous constant current (CCC) and continuous pulsed current (CPC) in individuals with CF and healthy controls. METHODS: A prospective cross-sectional study with experimental intervention. The variables of gender, ethnicity, age, and body mass index (BMI) were considered. The method of Gibson and Cooke was used, and the following markers were evaluated: sweat weight, electrical impedance, sufficient sweat amount, and CF diagnosis. Triangular (TPC) or sinusoidal (SPC) pulsed current was applied to the right arm, and CCC was applied to the left arm. RESULTS: The study analyzed 260 individuals, 141/213 (54.2%) were female participants, 135/260 (51.9%) were Caucasians. The distribution of individuals by concentration of chloride at the ST was: (CF) 26/260 (10%); (borderlines) 109/260 (41.9%); (healthy) 97/260 (37.3%); (insufficient weight in sweat) 28/260 (10.8%). No association was observed between the sufficient sweat amount to perform the ST when we compared the currents. However, the SPC showed a higher amount of sweat weight. Using Bland and Altman plot considering the agreement between the sweat chloride values achieved from CPC [SPC and TPC] and CCC, there was no proportional bias and mean values are unrelated and only explain less than 8% of the variation. Moreover, TPC presented higher electrical impedance when compared with SPC and CCC. SPC presented lower electrical impedance and higher sweat weight than CCC. Male participants presented lower electrical impedance and higher sweat weight with CCC and TPC, and higher sweat weight with SPC. CONCLUSIONS: The evaluated currents are safe and able to induce and produce sweat in sufficient quantities for the ST. SPC presented lower electrical impedance when compared with other currents. The use of SPC is recommended to induce sweat in patients with sweat problems. Finally, ethnicity, gender, age and BMI did not influence sweat induction at the ST, and no side effect was observed in our study.


Asunto(s)
Cloruros/análisis , Fibrosis Quística/diagnóstico , Sudor/química , Adolescente , Adulto , Anciano , Biomarcadores , Niño , Preescolar , Estudios Transversales , Impedancia Eléctrica , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Sodio/análisis , Manejo de Especímenes , Adulto Joven
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