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Background: Asian representation in sport is increasing, yet there remains a lack of reference values for the Asian athlete's heart. Consequently, current guidelines for cardiovascular screening recommend using Caucasian athletes' norms to evaluate Asian athletes. This study aims to outline electrocardiographic and echocardiographic characteristics of the Asian athlete's heart using a Singaporean prospective registry of Southeast (SE) Asian athletes. Methods and Results: One hundred and fifty elite athletes, mean age of 26.1 ± 5.7 years (50% males, 88% Chinese), were evaluated using a questionnaire, 12-lead electrocardiogram (ECG) and transthoracic echocardiogram. All ECGs were analyzed using the 2017 International Recommendations. Echocardiographic data were presented by gender and sporting discipline. The prevalence of abnormal ECGs among SE Asian athletes was 6.7%-higher than reported figures for Caucasian athletes. The abnormal ECGs comprised mainly anterior T wave inversions (ATWI) beyond lead V2, predominantly in female athletes from mixed/endurance sport (9.3% prevalence amongst females). None had echocardiographic structural abnormalities. Male athletes had reduced global longitudinal strain compared to females (-18.7 ± 1.6 vs. -20.7 ± 2.1%, p < 0.001). Overall, SE Asian athletes had smaller left ventricular cavity sizes and wall thickness compared to non-Asian athletes. Conclusion: SE Asian athletes have higher abnormal ECG rates compared to Caucasian athletes, and also demonstrate structural differences that should be accounted for when interpreting their echocardiograms compared to athletes of other ethnicities.
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AIM: We aimed to assess the utility of four published risk-scoring methods in predicting intravenous immunoglobulins (IVIG) non-responsiveness in Kawasaki disease (KD) patients from Singapore and develop a new predictive model. METHODS: We reviewed the medical records of 215 KD children. The performance of existing scoring methods in identifying non-responsive cases based on sensitivities (SN) and specificities (SP) was evaluated in 122 Singaporean Chinese. From our dataset, a model involving six predictors was built. RESULTS: The following respective SN (%) and SP (%) were obtained: Egami: 26%, 68%; Kobayashi: 21%, 62%; Sano: 13%, 86% and Fukunishi: 46%, 71%. These results indicated that the existing scoring methods performed poorly compared to those reported in their respective original publications, which ranged between 68 and 87%. The new predictive model was derived with an improved SN (80%) and SP (80%). CONCLUSIONS: Currently available risk-scoring methods have less applicability in the Singaporean Chinese population. The proposed new risk-scoring predictive model derived based on data from Chinese cohort demonstrated much better SN and SP.
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Predicción , Inmunoglobulinas Intravenosas/farmacología , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Preescolar , Femenino , Humanos , Lactante , Masculino , Auditoría Médica , Modelos Estadísticos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Singapur , Resultado del TratamientoAsunto(s)
Cardiopatías Congénitas/cirugía , Complicaciones Posoperatorias/diagnóstico , ARN de Hongos/aislamiento & purificación , ARN Ribosómico 18S/aislamiento & purificación , Trichosporon/aislamiento & purificación , Tricosporonosis/diagnóstico , Procedimiento de Blalock-Taussing/efectos adversos , Niño , Cardiopatías Congénitas/complicaciones , Humanos , Síndrome de Klippel-Feil/complicaciones , Masculino , Complicaciones Posoperatorias/etiología , Tricosporonosis/etiologíaAsunto(s)
Cateterismo Cardíaco/métodos , Conducto Arterioso Permeable/cirugía , Costos de la Atención en Salud , Dispositivo Oclusor Septal , Adolescente , Cateterismo Cardíaco/economía , Niño , Preescolar , Femenino , Humanos , Lactante , Unidades de Cuidados Intensivos/economía , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Ligadura/economía , Ligadura/métodos , Masculino , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Dispositivo Oclusor Septal/economía , Singapur/epidemiología , Resultado del TratamientoRESUMEN
Transcatheter device closure of the secundum atrial septal defect (ASD) in children prevents atrial arrhythmias in older age. However, the benefits of favourable atrial electrocardiographic markers in these children remain elusive. We aimed to review the electrocardiographic markers of atrial activity in a longitudinal fashion. We retrospectively reviewed longitudinal data of all children who underwent transcatheter device closure at the National University Hospital between 2004 and 2013. The inclusion criteria included the presence of a secundum-type ASD with left to right shunt and evidence of increased right ventricular volume load (Q p/Q s ratio >1.5 and/or right ventricular dilatation). A total of 25 patients with a mean follow-up of 44.7 ± 33.47 (7.3-117.4) months were included. P maximum and P dispersion decreased at 2 months, P amplitude at 1 week and remained so until last follow-up. A positive trend was seen with a correlation coefficient of +0.12 for P maximum, +0.08 for P dispersion and 0.34 for P amplitude. There was a higher baseline P amplitude and P dispersion in patients who were older than 10 years and a non-significant trend to support an increase in both P maximum (71.0 ± 8.8 vs. 73.2 ± 12.7), P dispersion (17.0 ± 6.5 vs. 22.0 ± 11.3) and P amplitude (0.88 ± 0.25 vs. 1.02 ± 0.23) in patients with an ASD more than 15 mm compared with an ASD <15 mm. There is reduction in both P maximum and P dispersion as early as 2 months, which persisted on follow-up. Earlier closure may result in more favourable electrocardiographic results.
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Cateterismo Cardíaco/métodos , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Defectos del Tabique Interatrial/terapia , Dispositivo Oclusor Septal , Adolescente , Cateterismo Cardíaco/instrumentación , Niño , Preescolar , Femenino , Estudios de Seguimiento , Defectos del Tabique Interatrial/fisiopatología , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The trimeric protein AMP-activated protein kinase (AMPK) is an important sensor of energetic status and cellular stress, and mutations in genes encoding two of the regulatory γ subunits cause inherited disorders of either cardiac or skeletal muscle. AMPKγ2 mutations cause hypertrophic cardiomyopathy with glycogen deposition and conduction abnormalities; mutations in AMPKγ3 result in increased skeletal muscle glycogen. In order to gain further insight into the roles of the different γ subunits in muscle and into possible disease mechanisms, we localised the γ2 and γ3 subunits, along with the more abundant γ1 subunit, by immunofluorescence in cardiomyocytes and skeletal muscle fibres. The predominant cardiac γ2 variant, γ2-3B, gave a striated pattern in cardiomyocytes, aligning with the Z-disk but with punctate staining similar to T-tubule (L-type Ca(2+) channel) and sarcoplasmic reticulum (SERCA2) markers. In skeletal muscle fibres AMPKγ3 localises to the I band, presenting a uniform staining that flanks the Z-disk, also coinciding with the position of Ca(2+) influx in these muscles. The localisation of γ2-3B- and γ3-containing AMPK suggests that these trimers may have similar functions in the different muscles. AMPK containing γ2-3B was detected in oxidative skeletal muscles which had low expression of γ3, confirming that these two regulatory subunits may be co-ordinately regulated in response to metabolic requirements. Compartmentalisation of AMPK complexes is most likely dependent on the regulatory γ subunit and this differential localisation may direct substrate selection and specify particular functional roles.
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Proteínas Quinasas Activadas por AMP/metabolismo , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Animales , Cardiomiopatías/enzimología , Humanos , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Músculo Esquelético/citología , Músculo Esquelético/enzimología , Miocardio/citología , Miocardio/enzimología , Subunidades de ProteínaRESUMEN
AMP-activated protein kinase (AMPK), the key sensor and regulator of cellular energy status, is a heterotrimeric enzyme with multiple isoforms for each subunit (α1/α 2; ß1/ß2; γ1/γ2/γ3). Mutations in PRKAG2, which encodes the γ2 regulatory subunit, cause a cardiomyopathy characterized by hypertrophy and conduction abnormalities. The two reported PRKAG2 transcript variants, γ2-short and γ2-long (encoding 328 and 569 amino acids respectively), are both widely expressed in adult tissues. We show that both γ2 variants are also expressed during cardiogenesis in mouse embryos; expression of the γ3 isoform was also detected unexpectedly at this stage. As neither γ2 transcript is cardiac specific nor differentially expressed during embryogenesis, it is paradoxical that the disease is largely restricted to the heart. However, a recently annotated γ2 transcript, termed γ2-3B as transcription starts at an alternative exon 3b, has been identified; it is spliced in-frame to exon 4 thus generating a protein of 443 residues in mouse with the first 32 residues being unique. It is increasingly expressed in the developing mouse heart and quantitative PCR analysis established that γ2-3B is the major PRKAG2 transcript (~60%) in human heart. Antibody against the novel N-terminal sequence showed that γ2-3B is predominantly expressed in the heart where it is the most abundant γ2 protein. The abundance of γ2-3B and its tissue specificity indicate that γ2-3B may have non-redundant role in the heart and hence mediate the predominantly cardiac phenotype caused by PRKAG2 mutations.
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Proteínas Quinasas Activadas por AMP/genética , Regulación del Desarrollo de la Expresión Génica , Corazón/embriología , Miocardio/metabolismo , Subunidades de Proteína/genética , Isoformas de ARN/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Empalme Alternativo , Animales , Exones , Orden Génico , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación , Subunidades de Proteína/metabolismo , Transcripción GenéticaRESUMEN
OBJECTIVE: To assess whether genetic variation in cMET is associated with refractive error or change in refractive error over time. DESIGN: Cohort study. PARTICIPANTS AND CONTROLS: Discovery set (Set 1: N = 579 children; 403 cases, 176 controls). Confirmatory set (Set 2: N = 547 children; 338 cases, 209 controls). METHODS: Children in the discovery set were genotyped for a panel of genetic markers within cMET. Markers that were found to be significantly associated with the presence of refractive error or more rapid change in refractive error were then genotyped in the confirmatory set. MAIN OUTCOME MEASURES: Presence or absence of myopia and the rate of change in refractive error over a 3-year follow-up period. RESULTS: Carriage of the variant cMET +110703 A allele was found to associate with increased susceptibility to myopia. The variant was also found to associate with a faster rate of change in refractive error in both the discovery set and the confirmatory cohort regardless of the initial refractory ability (School 1; chi(2) for trend P = 0.014) (Schools 2 and 3; chi(2) for trend = 5.42, P = 0.020) (combined N = 1126, overall chi(2) for trend = 10.90, P = 9.6 x 10(-4)). Carriage of the variant allele was also found to be significantly overrepresented in children within the fastest changing quartile (Q4: mean change of -3.01 D over 3 years) compared with the slowest (Q1: mean change of -0.28 D over 3 years) (P(Set1) = 0.004, P(Set2) = 0.02, Combined N = 559, P = 3.0 x 10(-4)). CONCLUSIONS: Our data implicate the involvement of cMET in the pathogenesis of myopia in general, as well as more rapid progression in refractive error regardless of the initial refractory ability. These results underline the importance of eye growth genes in the development of common myopia.
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Proteínas Proto-Oncogénicas c-met/genética , Errores de Refracción/genética , Errores de Refracción/fisiopatología , Niño , Progresión de la Enfermedad , Femenino , Marcadores Genéticos , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple , Refracción Ocular , Factores de RiesgoRESUMEN
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.
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Bacteriemia/genética , Malaria/genética , Proteínas de Transporte de Membrana/genética , Proteínas de la Mielina/genética , Infecciones Neumocócicas/genética , Polimorfismo de Nucleótido Simple , Proteolípidos/genética , Tuberculosis/genética , África , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/fisiología , Modelos Moleculares , Proteínas de la Mielina/fisiología , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito , Polimorfismo de Nucleótido Simple/fisiología , Proteolípidos/fisiología , Receptores de Interleucina-1/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Reino Unido , VietnamRESUMEN
BACKGROUND: To evaluate the impact of the genetic polymorphisms affecting aspirin response using platelet aggregation and the response to different aspirin doses after cardiopulmonary bypass, we performed a subanalysis of the results from a randomized trial evaluating low- and medium-dose aspirin and clopidogrel. METHODS: Blood was collected from consenting patients and DNA extracted. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to detect Pl(A2), C807T, and A842/C50T polymorphisms. Aspirin efficacy was assessed using light transmission platelet aggregometry, and reported as percentage aggregation and EC50 concentrations using the technique of Born. RESULTS: Of 90 patients, 80 consented to further genetic testing, of whom 63 patients were randomly assigned to medium- (325 mg) or low-dose (100 mg) aspirin. The Pl(A2), C807T, and A842/C50T gene frequencies were 30%, 66%, and 21%, respectively, with no identifiable differences in the baseline platelet aggregation. Postoperatively, after 5 days of aspirin, platelet aggregation was consistently but not significantly impaired with Pl(A2) and A842/C50T carriers and consistently but not significantly improved with C50T carriers. An interaction term was identified on percentage aggregation and EC50 using epinephrine. The interaction coefficient describes a higher aggregation of 19% (95% confidence interval: 2 to 36; p = 0.03) and less inhibition with an EC50 of -2.07 (-4.19 to 0.04; p = 0.06) in patients who were both Pl(A2) positive and receiving low-dose aspirin. CONCLUSIONS: Genetic polymorphisms that affect the response to aspirin are common. The impaired response of persons with the Pl(A2) polymorphism to aspirin may be dose related, with significant improvement observed in patients using medium- rather than low-dose aspirin.
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Aspirina/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/genética , Polimorfismo Genético , Anciano , Puente Cardiopulmonar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacosRESUMEN
AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a key role in the regulation of energy metabolism. In humans, mutations in the gamma2-subunit of AMPK cause cardiac hypertrophy associated with Wolff-Parkinson-White syndrome, characterized by ventricular preexcitation. The effect of these mutations on AMPK activity and in development of the disease is enigmatic. Here we report that transgenic mice with cardiac-specific expression of gamma2 harboring a mutation of arginine residue 531 to glycine (RG-TG) develop a striking cardiac phenotype by 4 wk of age, including hypertrophy, impaired contractile function, electrical conduction abnormalities, and marked glycogen accumulation. At this stage, AMPK activity isolated from hearts of RG-TG mice was almost completely abolished but could be restored after phosphorylation by an upstream AMPK kinase. At 1 wk of age, there was no detectable evidence of a cardiac phenotype, and AMPK activity in RG-TG hearts was similar to that in nontransgenic, control mice. We propose that mutations in gamma2 lead to suppression of total cardiac AMPK activity secondary to increased glycogen accumulation. The subsequent decrease in AMPK activity provides a mechanism that may explain the development of cardiac hypertrophy in this model.
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Cardiomegalia/enzimología , Cardiomegalia/genética , Modelos Animales de Enfermedad , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Síndrome de Wolff-Parkinson-White/enzimología , Síndrome de Wolff-Parkinson-White/genética , Proteínas Quinasas Activadas por AMP , Animales , Femenino , Humanos , Ratones , Ratones Transgénicos , Mutagénesis Sitio-Dirigida , Mutación , Relación Estructura-ActividadAsunto(s)
Puente de Arteria Coronaria , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Pericardio/cirugía , Enfisema Pulmonar/etiología , Enfisema Pulmonar/prevención & control , Presión Sanguínea/fisiología , Puente Cardiopulmonar , Circulación Coronaria/fisiología , Humanos , Contrapulsador Intraaórtico , Complicaciones Intraoperatorias/fisiopatología , Masculino , Persona de Mediana Edad , Contracción Miocárdica/fisiología , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Pericardio/fisiopatología , Enfisema Pulmonar/fisiopatología , Esternón/cirugíaRESUMEN
We compared the anatomy of human and porcine aortic valves. Porcine hearts were collected from the abattoir. Human hearts from patients who had died of non-cardiac causes were examined in the mortuary; only undamaged and anatomically normal hearts were used. Silicon casts were prepared by injecting engineering silicon at 80 mm Hg into the aortic arch. Various features of the aortic valve were measured: circumference, length between the commissural end point and central point of coaptation, surface diameter, and surface area. In total, 12 porcine and 12 human aortic valves were studied. The average circumferences of the human and porcine aortic valves were 8.00 +/- 0.2 (SD) cm and 7.90 +/- 1.0 cm, respectively. The central point of coaptation in human valves was skewed toward the left coronary cusp, whereas in porcine valves it was skewed toward the non-coronary cusp. In human aortic valves, the non-coronary cusp had the largest surface diameter and surface area with mean measurements of 3.6 +/- 0.2 cm and 1.230 +/- 0.228 cm(2), respectively; the left coronary cusp was smallest for the same variables with measurements of 3.1 +/- 0.3 cm and 0.898 +/- 0.357 cm(2). In porcine valves, the right coronary cusp had the largest surface diameter and surface area with mean measurements of 3.9 +/- 0.7 cm and 1.716 +/- 0.81 cm(2), respectively; the non-coronary cusp was the smallest for the same variables with measurements of 2.9 +/- 0.5 cm and 1.023 +/- 0.659 cm(2). These differences suggest that when using porcine valves as transplant material (e.g., stentless valves), geometric considerations, such as commissural length, may be important.