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1.
Proc Natl Acad Sci U S A ; 120(8): e2209123120, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36780521

RESUMEN

Academic achievement in the first year of college is critical for setting students on a pathway toward long-term academic and life success, yet little is known about the factors that shape early college academic achievement. Given the important role sleep plays in learning and memory, here we extend this work to evaluate whether nightly sleep duration predicts change in end-of-semester grade point average (GPA). First-year college students from three independent universities provided sleep actigraphy for a month early in their winter/spring academic term across five studies. Findings showed that greater early-term total nightly sleep duration predicted higher end-of-term GPA, an effect that persisted even after controlling for previous-term GPA and daytime sleep. Specifically, every additional hour of average nightly sleep duration early in the semester was associated with an 0.07 increase in end-of-term GPA. Sensitivity analyses using sleep thresholds also indicated that sleeping less than 6 h each night was a period where sleep shifted from helpful to harmful for end-of-term GPA, relative to previous-term GPA. Notably, predictive relationships with GPA were specific to total nightly sleep duration, and not other markers of sleep, such as the midpoint of a student's nightly sleep window or bedtime timing variability. These findings across five studies establish nightly sleep duration as an important factor in academic success and highlight the potential value of testing early academic term total sleep time interventions during the formative first year of college.


Asunto(s)
Duración del Sueño , Sueño , Humanos , Universidades , Estudiantes , Escolaridad
2.
N Engl J Med ; 383(11): 1009-1017, 2020 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-32905673

RESUMEN

BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).


Asunto(s)
Remoción de Dispositivos , Terapia por Inhalación de Oxígeno , Succión , Traqueostomía , Enfermedad Crítica , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/métodos , Factores de Tiempo , Desconexión del Ventilador
3.
Perfusion ; : 2676591231178413, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37226290

RESUMEN

INTRODUCTION: High-risk procedures in interventional cardiology include a wide spectrum of clinical and anatomical scenarios related to a higher periprocedural morbidity and mortality. The prophylactic use of short-term mechanical circulatory support (ST-MCS) may improve both the safety and efficacy of the intervention by leading to more stable procedural hemodynamics. However, the significant costs may limit its use in resource constrained settings. To overcome this limitation, we ideated a modified, low-cost, veno-arterial extracorporeal membrane oxygenator (V-A ECMO) setup. METHODS: We conducted an observational prospective study including all patients undergoing a high-risk interventional cardiology procedure at our institution under prophylactic ST-MCS using a modified, low-cost version of V-A ECMO, where some components of the standard V-A ECMO circuit were replaced by supplies used for cardiac surgical cardiopulmonary bypass, achieving a cost reduction of 72%. We assessed in-hospital and mid-term outcomes, including procedural success, post-procedure complications and mortality. RESULTS: Between March 2016 and December 2021, ten patients underwent high-risk IC procedures with prophylactic use of V-A ECMO. Isolated percutaneous intervention (PCI) was performed in six patients, isolated transcatheter aortic valve replacement (TAVR) in two, and a combined procedure (PCI + TAVR) in two. Mean ejection fraction was 34% (range 20-64%). Mean STS PROM was 16.2% (range 9.5-35.8%) and mean EuroScore was 23.7% (range 1.5-60%). The planned intervention was successfully performed in all cases. There were no reports of V-A ECMO malfunction. In nine patients the VA-ECMO was withdrawn immediately after the procedure but one patient required extended - 24 h - support with no significant issues. One patient experienced a periprocedural myocardial infarction and another developed a femoral pseudoaneurysm. In-hospital and 30-day survival were 100%, and 1-year survival was 80%. CONCLUSIONS: High-risk procedures in interventional cardiology can be successfully performed under prophylactic ST-MCS using a modified, low-cost V-A ECMO, suitable for limited-resource settings.

4.
Clin Genet ; 102(1): 40-55, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35388452

RESUMEN

Glucose transporter 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder caused by haploinsufficiency of the GLUT1 glucose transporter (encoded by SLC2A1) leading to defective glucose transport across the blood-brain barrier. This work describes the genetic analysis of 56 patients with clinical or biochemical GLUT1DS hallmarks. 55.4% of these patients had a pathogenic variant of SLC2A1, and 23.2% had a variant in one of 13 different genes. No pathogenic variant was identified for the remaining patients. Expression analysis of SLC2A1 indicated a reduction in SLC2A1 mRNA in patients with pathogenic variants of this gene, as well as in one patient with a pathogenic variant in SLC9A6, and in three for whom no candidate variant was identified. Thus, the clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.


Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos , Errores Innatos del Metabolismo de los Carbohidratos/genética , Pruebas Genéticas , Transportador de Glucosa de Tipo 1/genética , Humanos , Proteínas de Transporte de Monosacáridos/deficiencia , Proteínas de Transporte de Monosacáridos/genética
5.
Rev Med Chil ; 150(11): 1422-1430, 2022 Nov.
Artículo en Español | MEDLINE | ID: mdl-37358167

RESUMEN

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) was introduced in 2002 and the first implants in our country were performed in 2010. AIM: To review the TAVI experience in our hospital, considering the technology improvements and gained experience throughout this period. MATERIAL AND METHODS: All patients undergoing TAVI in our center were included. Results and complications were adjudicated according to the Valve Academic Research Consortium-2 (VARC-2) criteria. Patients were divided in 3 groups, according to procedural year: Period 1: 2010-2015 (n = 35); Period 2: 2016-2018 (n = 35); Period 3: 2019-2021 (n = 41). Mortality up to one year after the procedure was recorded. RESULTS: Between 2010 and 2021, 111 TAVI procedures were performed. The mean age of patients was 82 years and 47% were women. Risk scores for in-hospital mortality were STS 6.7%, EUROSCORE II 8.0% and ACC/STS TAVR Score 4.9%. The trans-femoral route was used in 88% and a balloon-expandable valve was chosen in 82% of patients. A successful implant was achieved in 96%, with an in-hospital mortality of 1.8%. Mortality at 30 days and 1-year were 2.7 and 9.0%, respectively. During period 3, 100% of implants were successful, with no in-hospital mortality, less vascular complications (p < 0.01), less stroke (p = 0.04), less severe paravalvular leak (p = 0.01) and significantly lower rate of acute complications (p < 0.01). CONCLUSIONS: TAVI achieves excellent results. With greater experience and better available technologies, these results are even more favorable.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Femenino , Anciano de 80 o más Años , Masculino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estenosis de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Resultado del Tratamiento , Factores de Riesgo
6.
BMC Cancer ; 21(1): 1114, 2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34663256

RESUMEN

BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.


Asunto(s)
Cardiotoxicidad/diagnóstico por imagen , Ecocardiografía/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias/radioterapia , Traumatismos por Radiación/diagnóstico , Neoplasias de la Mama/radioterapia , Cardiotoxicidad/etiología , Protocolos Clínicos , Células Endoteliales , Neoplasias Esofágicas/radioterapia , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Contracción Miocárdica/fisiología , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Dosis de Radiación , Volumen Sistólico , Troponina T/análisis , Disfunción Ventricular Izquierda
7.
FASEB J ; 34(7): 9547-9562, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32501591

RESUMEN

Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail-/- versus Trail+/+ mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion. Gene enrichment analyses showed many of these genes were related to inflammation, cell-to-cell cytoskeletal interactions, and transcriptional modulation. We identified vascular protective and pathological gene clusters, with Ifi205 as the most significantly reduced vascular protective gene, whereas Glut1, the most significantly increased pathological gene with TRAIL deletion. We hypothesized that therapeutic targets could be devised from such integrated analysis and validated our findings from vascular tissues of diabetic mice. From the differentially expressed gene targets, enriched transcription factor (TF) and microRNA binding motifs were identified. The top two TFs were Elk1 and Sp1, with enrichment to eight gene targets common to both. miR-520d-3p and miR-377-3p were the top enriched microRNAs with TRAIL deletion; with four overlapping genes enriched for both microRNAs. Our findings offer an alternate in silico approach for therapeutic target identification and present a deeper understanding of gene signatures and pathways altered with TRAIL suppression in the vasculature.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Angiopatías Diabéticas/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Transcriptoma , Animales , Biología Computacional , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/patología , Humanos , Ratones , Ratones Noqueados , MicroARNs/genética
8.
Catheter Cardiovasc Interv ; 97(6): E748-E757, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33058429

RESUMEN

OBJECTIVES: To describe the characteristics of patients who undergo balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and report the mid-term outcomes. BACKGROUND: BPA has been recently introduced in Latin America. Mid-term results have not been published. METHODS: Prospective Chilean Registry of inoperable CTEPH patients who underwent BPA. Clinical variables were analyzed at baseline, after each procedure and at follow-up. Hemodynamic variables were recorded before and after the last BPA. RESULTS: Between August 2016 and September 2019, 22 patients (17 women), 59 ± 12.7 years, underwent 81 BPA and were followed for as long as 33.1 months (mean 17.3 ± 7.5). Mean pulmonary artery pressure decreased by 17.4% (51.1 ± 12 vs. 42.2 ± 13 mmHg, p = .001), pulmonary vascular resistance by 23.9% (766.7 ± 351 vs. 583 ± 346 dynes/s/cm-5 , p = .001), cardiac index increased by 8% (2.3 ± 0.54 vs. 2.5 ± 0.54 L/min/m2 , p = .012), N-terminal pro-B-type natriuretic peptide decreased by 73.8% (1,685 ± 1,045 vs. 441.8 ± 276 pg/dl, p = .006), and 6-min walk distance improved by 135 m (316.7 ± 94 vs. 451.1 ± 113 m, p = .001). One patient (4.5%) developed lung reperfusion injury and four patients (18.2%) had minor bleeding (hemoptysis), after the procedure. There was no mortality associated with BPA. CONCLUSIONS: Our results confirm that BPA for inoperable CTEPH is a relatively safe procedure that improves clinical and hemodynamic parameters in the mid-term. This therapy should be considered as an alternative, mainly in places where access to PAH therapy or surgery is restricted.


Asunto(s)
Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Angioplastia de Balón/efectos adversos , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , América Latina , Pulmón , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagen , Resultado del Tratamiento
9.
Biol Res ; 54(1): 32, 2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34565477

RESUMEN

BACKGROUND: Deep breathing (DB) and handgrip (HG) exercise -with and without circulatory occlusion (OC) in muscle-, have been shown to have beneficial effects on cardiovascular function; however, the combination of these maneuvers on heart rate (HR) and cardiac sympathovagal balance have not been previously investigated. Therefore, the aim of the present study was to evaluate the effect of simultaneous DB, HG, and OC maneuvers on the sympathovagal balance in healthy women and men subjects. METHODS AND RESULTS: Electrocardiogram and ventilation were measured in 20 healthy subjects (Women: n = 10; age = 27 ± 4 years; weight = 67.1 ± 8.4 kg; and height = 1.6 ± 0.1 m. Men: n = 10; age = 27 ± 3 years; weight = 77.5 ± 10.1 kg; and height = 1.7 ± 0.1 m) at baseline and during DB, DB + HG, or DB + HG + OC protocols. Heart rate (HR) and respiratory rate were continuously recorded, and spectral analysis of heart rate variability (HRV) were calculated to indirectly estimate cardiac autonomic function. Men and women showed similar HR responses to DB, DB + HG and DB + HG + OC. Men exhibited a significant HR decrease following DB + HG + OC protocol which was accompanied by an improvement in cardiac autonomic control evidenced by spectral changes in HRV towards parasympathetic predominance (HRV High frequency: 83.95 ± 1.45 vs. 81.87 ± 1.50 n.u., DB + HG + OC vs. baseline; p < 0.05). In women, there was a marked decrease in HR after completion of both DB + HG and DB + HG + OC tests which was accompanied by a significant increase in cardiac vagal tone (HRV High frequency: 85.29 ± 1.19 vs. 77.93 ± 0.92 n.u., DB + HG vs. baseline; p < 0.05). No adverse effects or discomfort were reported by men or women during experimental procedures. Independent of sex, combination of DB, HG, and OC was tolerable and resulted in decreases in resting HR and elevations in cardiac parasympathetic tone. CONCLUSIONS: These data indicate that combined DB, HG and OC are effective in altering cardiac sympathovagal balance and reducing resting HR in healthy men and women.


Asunto(s)
Sistema Nervioso Autónomo , Fuerza de la Mano , Adulto , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Adulto Joven
10.
Traffic ; 18(8): 491-504, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28477369

RESUMEN

T Lymphocyte recognition of antigens leads to the formation of a highly organized structure termed immune synapse (IS) by analogy with the neuronals synapse. Sorting nexin 27 (SNX27) controls the endosomal traffic of PSD95, Dlg1, ZO-1 (PDZ) domain-interacting proteins, and its alteration is associated with impaired synaptic function and neurological diseases. In T-lymphocytes, SNX27-positive vesicles polarize to the IS, the identity of SNX27 interactors in these conditions nonetheless remains unknown. Here we used proteomics to analyze the SNX27 interactome purified from IS-forming T cells, and confirmed the conserved nature of the SNX27/WASH/retromer association in hematopoietic cells. Furthermore, our comparative interactome analysis of SNX27 wild-type and a mutant-deficient for PDZ cargo recognition identified the epithelial cell-cell junction protein zona occludens-2 (ZO-2) as an IS component. Biochemistry and microscopy approaches in T cells confirmed SNX27/ZO-2 PDZ-dependent interaction, and demonstrated its role controlling the dynamic localization of ZO-2 at the IS. This study broadens our knowledge of SNX27 function in T lymphocytes, and suggests that pathways that delimit polarized structures in nervous and epithelial systems also participate in IS regulation.


Asunto(s)
Sinapsis Inmunológicas/metabolismo , Mapas de Interacción de Proteínas , Nexinas de Clasificación/metabolismo , Linfocitos T/metabolismo , Proteína de la Zonula Occludens-2/metabolismo , Línea Celular Tumoral , Humanos , Transporte de Proteínas
12.
J Environ Qual ; 47(5): 1293-1297, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30272789

RESUMEN

After rainfall or irrigation begins, surface-applied chemicals and manure-borne microorganisms typically enter the soil with infiltration until the soil saturates, after which time the chemicals and microbes are exported from the field in the overland flow. This process is viewed as a reason for the dependence of chemical export on the time between rainfall start and runoff initiation that has been documented for agricultural chemicals. The objective of this work was to observe and quantify such dependence for released from solid farmyard dairy manure in field conditions. Experiments were performed for 6 yr and consisted of manure application followed by an immediate simulated rainfall event and a second event 1 wk later. The nonlinearity of the release seen in laboratory and plot studies did not manifest itself in the field. The number of exported cells in runoff was proportional to rainfall depth after runoff initiation in each trial. The proportionality coefficient, termed export rate, demonstrated a strong dependence on the runoff delay time that could be approximated with the exponential decrease. The export rate decreased by one order of magnitude when the rainfall depth at runoff initiation increased from 18 to 42 mm. The same dependence could approximate data from the simulated rainfall event 1 wk after the manure application, assuming that the initial content in manure after 1 wk of weathering was 10% of the initial content. Overall, accounting for the dependence of manure-borne export on the runoff delay time should improve the accuracy of export predictions related to the assessment of agricultural practices on microbial water quality.


Asunto(s)
Monitoreo del Ambiente , Escherichia coli/crecimiento & desarrollo , Microbiología del Suelo , Microbiología del Agua , Agricultura , Fertilizantes , Estiércol , Lluvia , Movimientos del Agua
13.
Rev Med Chil ; 146(1): 68-77, 2018 Jan.
Artículo en Español | MEDLINE | ID: mdl-29806680

RESUMEN

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.


Asunto(s)
Antineoplásicos/efectos adversos , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Radioterapia/efectos adversos , Antineoplásicos/clasificación , Biomarcadores , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Desarrollo de Programa , Factores de Riesgo
14.
Mol Pharm ; 14(7): 2197-2208, 2017 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-28494157

RESUMEN

A1899 is a potent and selective inhibitor of the two-pore domain potassium (K2P) channel TASK-1. It was previously reported that A1899 acts as an open-channel blocker and binds to residues of the P1 and P2 regions, the M2 and M4 segments, and the halothane response element. The recently described crystal structures of K2P channels together with the newly identified side fenestrations indicate that residues relevant for TASK-1 inhibition are not purely facing the central cavity as initially proposed. Accordingly, the TASK-1 binding site and the mechanism of inhibition might need a re-evaluation. We have used TASK-1 homology models based on recently crystallized K2P channels and molecular dynamics simulation to demonstrate that the highly potent TASK-1 blocker A1899 requires binding to residues located in the side fenestrations. Unexpectedly, most of the previously described residues that interfere with TASK-1 blockade by A1899 project their side chains toward the fenestration lumina, underlining the relevance of these structures for drug binding in K2P channels. Despite its hydrophobicity, A1899 does not seem to use the fenestrations to gain access to the central cavity from the lipid bilayer. In contrast, binding of A1899 to residues of the side fenestrations might provide a physical "anchor", reflecting an energetically favorable binding mode that after pore occlusion stabilizes the closed state of the channels.


Asunto(s)
Benzamidas/farmacología , Bencenoacetamidas/farmacología , Simulación de Dinámica Molecular , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Canales de Potasio de Dominio Poro en Tándem/antagonistas & inhibidores , Animales , Benzamidas/química , Bencenoacetamidas/química , Sitios de Unión , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Canales de Potasio de Dominio Poro en Tándem/química , Canales de Potasio de Dominio Poro en Tándem/metabolismo
15.
Acta Odontol Scand ; 75(1): 30-35, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27796162

RESUMEN

OBJECTIVE: This study was conducted to establish associations among the Candida carriage rate, the diversity of Candida species carried and the different caries status of preschool children. MATERIALS AND METHODS: Sixty-one children between 2 and 5 years of age were examined by a single expert examiner and were divided into three groups, the caries-free, moderate caries and severe caries groups, according to the criteria of the International Caries Detection and Assessment System II (ICDAS). Saliva samples were obtained from the members of each group and were plated on Sabouraud agar plates to assess the Candida carriage rates. CHROMagar Candida medium was used for the preliminary screening. Biochemical testing or PCR/sequencing was conducted to identify the different Candida species in the samples. The differences observed were considered significant if the p value was <0.05. RESULTS: The Candida carriage rate and the number of species of this fungus carried were higher in the group with the highest level of caries severity (p < 0.05). Whereas Candida albicans was the most predominant Candida species in the saliva of all of the children, C. dubliniensis was identified only in the most caries-affected group in addition to other rare species of Candida non-albicans. CONCLUSIONS: A high salivary Candida carriage rate and the presence of specific species of this fungus (such as C. albicans and C. dubliniensis) appear to be related to the severity of caries experienced by preschool children.


Asunto(s)
Candida albicans/aislamiento & purificación , Candida/aislamiento & purificación , Índice CPO , Saliva/microbiología , Candida/clasificación , Candida tropicalis/aislamiento & purificación , Preescolar , Recuento de Colonia Microbiana , Medios de Cultivo , Caries Dental/microbiología , Femenino , Humanos , Masculino , Micología/métodos
16.
Clin Sci (Lond) ; 130(14): 1237-46, 2016 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-27129183

RESUMEN

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1ß secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1ß compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1ß.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Caspasa 1/metabolismo , Colchicina/uso terapéutico , Monocitos/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Síndrome Coronario Agudo/inmunología , Síndrome Coronario Agudo/metabolismo , Anciano , Anciano de 80 o más Años , Células Cultivadas , Colchicina/farmacología , Femenino , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/fisiología
17.
Pflugers Arch ; 467(5): 1091-104, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25369776

RESUMEN

Two-pore domain potassium (K2P) channels are membrane proteins widely identified in mammals, plants, and other organisms. A functional channel is a dimer with each subunit comprising two pore-forming loops and four transmembrane domains. The genome of the model plant Arabidopsis thaliana harbors five genes coding for K2P channels. Homologs of Arabidopsis K2P channels have been found in all higher plants sequenced so far. As with the K2P channels in mammals, plant K2P channels are targets of external and internal stimuli, which fine-tune the electrical properties of the membrane for specialized transport and/or signaling tasks. Plant K2P channels are modulated by signaling molecules such as intracellular H(+) and calcium and physical factors like temperature and pressure. In this review, we ask the following: What are the similarities and differences between K2P channels in plants and animals in terms of their physiology? What is the nature of the last common ancestor (LCA) of these two groups of proteins? To answer these questions, we present physiological, structural, and phylogenetic evidence that discards the hypothesis proposing that the duplication and fusion that gave rise to the K2P channels occurred in a prokaryote LCA. Conversely, we argue that the K2P LCA was most likely a eukaryote organism. Consideration of plant and animal K2P channels in the same study is novel and likely to stimulate further exchange of ideas between students of these fields.


Asunto(s)
Concentración de Iones de Hidrógeno , Filogenia , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Potasio/metabolismo , Transducción de Señal/fisiología , Animales , Humanos , Plantas
18.
Heart Lung Circ ; 23(5): 462-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24315653

RESUMEN

BACKGROUND: The aim of this study was to report our initial experience with the transapical approach to transcatheter aortic valve implantation (TAVI) at an Australian institution. METHODS: All patients with severe, symptomatic aortic stenosis were assessed by our multidisciplinary team. A total of 32 patients received a transapical TAVI using an Edwards SAPIEN prosthesis. Data were prospectively collected and analysed according to the Valve Academic Research Consortium version 2 guidelines. RESULTS: Intraoperative outcomes included: 100% device success with no conversion to surgical valve replacement, extracorporeal membrane oxygenation was used electively in 15.6% and emergently in 6.3%, and no valve migration or malpositioning requiring prosthesis retrieval and re-implantation. Outcomes at 30 days post-TAVI included: No mortality, 3.1% myocardial infarction, no disabling stroke, 3.1% non-disabling stroke, no transient ischaemic attacks, 6.3% life-threatening bleeding, 15.6% major bleeding, 3.1% major vascular complications, and 12.5% postoperative acute kidney injury requiring renal replacement therapy. Mild paravalvular regurgitation was present in 29%, and there was no moderate or severe regurgitation. Mean follow-up time was 28.8±12.9 months. Cumulative results included: 9.4% mortality, 6.3% stroke, 6.3% myocardial infarction, and no repeat procedures. At one year postoperation, echocardiography demonstrated that the mean pressure across the prosthesis was 10.1±1.7mmHg, and the mean aortic valve area was 1.4±0.2cm(2). CONCLUSION: Good short-term outcomes and low or zero mortality are achievable with transapical TAVI at an Australian institution.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Anciano , Anciano de 80 o más Años , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/patología , Australia/epidemiología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Tasa de Supervivencia
19.
Heart Lung Circ ; 23(10): 957-62, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24954708

RESUMEN

BACKGROUND: Transcatheter aortic valve implantation (TAVI) can cause profound haemodynamic perturbation in the peri-operative period. Veno-arterial extracorporeal membrane oxygenation (ECMO) can be used to provide cardiorespiratory support during this time, either prophylactically or emergently. METHOD: 100 TAVI procedures were performed between 2009 and 2013 in our institution. ECMO was used in 11 patients, including eight prophylactic and three rescue cases. Rescue ECMO was required for ventricular fibrillation after valvuloplasty, and aortic annulus rupture. The criteria for prophylactic ECMO included heart failure requiring stabilisation pre-TAVI, haemodynamic instability with balloon aortic valvuloplasty performed to improve heart function pre-TAVI, moderate or severe left and/or right ventricular failure, or borderline haemodynamics at procedure. Differences in preoperative characteristics and postoperative outcomes between ECMO and non-ECMO TAVI patients were compared, and significant results were further assessed controlling for EuroSCORE. RESULTS: Compared to TAVI patients who did not require ECMO, ECMO patients had significantly higher mean EuroSCORE (51 vs. 30%, p<.05). Postoperative outcomes, however, were largely comparable between the two groups. All-cause mortality occurred in nil prophylactic ECMO patients, one rescue ECMO patient, and two non-ECMO patients. The difference in mortality between ECMO and non-ECMO patients was not significantly different (9 vs. 2%; p>.05). ECMO patients were more likely to develop acute renal failure than non-ECMO patients (36 vs. 8%, p<.05), which was most likely due to haemodynamic collapse and end-organ dysfunction in patients that required ECMO rescue. CONCLUSIONS: Instituting prophylactic ECMO in selected very high-risk patients may help avoid consequences of intra-operative complications and the need for emergent rescue ECMO.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Oxigenación por Membrana Extracorpórea , Reemplazo de la Válvula Aórtica Transcatéter , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Urgencias Médicas , Oxigenación por Membrana Extracorpórea/efectos adversos , Femenino , Insuficiencia Cardíaca/complicaciones , Hemodinámica , Humanos , Masculino , Procedimientos Quirúrgicos Profilácticos , Medición de Riesgo , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Fibrilación Ventricular/etiología , Fibrilación Ventricular/terapia
20.
Front Cardiovasc Med ; 11: 1356023, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993522

RESUMEN

Acute Coronary Syndrome (ACS) significantly contributes to cardiovascular death worldwide. ACS may arise from the disruption of an atherosclerotic plaque, ultimately leading to acute ischemia and myocardial infarction. In the pathogenesis of atherosclerosis, inflammation assumes a pivotal role, not solely in the initiation and complications of atherosclerotic plaque formation, but also in the myocardial response to ischemic insult. Acute inflammatory processes, coupled with time to reperfusion, orchestrate ischemic and reperfusion injuries, dictating infarct magnitude and acute left ventricular (LV) remodeling. Conversely, chronic inflammation, alongside neurohumoral activation, governs persistent LV remodeling. The interplay between chronic LV remodeling and recurrent ischemic episodes delineates the progression of the disease toward heart failure and cardiovascular death. Colchicine exerts anti-inflammatory properties affecting both the myocardium and atherosclerotic plaque by modulating the activity of monocyte/macrophages, neutrophils, and platelets. This modulation can potentially result in a more favorable LV remodeling and forestalls the recurrence of ACS. This narrative review aims to delineate the role of inflammation across the different phases of ACS pathophysiology and describe the mechanistic underpinnings of colchicine, exploring its purported role in modulating each of these stages.

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