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Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5Δ35"). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5Δ40"). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5-/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.
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Apolipoproteínas , Lipoproteína Lipasa , Ratones , Humanos , Animales , Proteínas Similares a la Angiopoyetina/genética , Proteínas Similares a la Angiopoyetina/metabolismo , Lipoproteína Lipasa/metabolismo , Proteína 3 Similar a la Angiopoyetina , Aminoácidos , Triglicéridos/metabolismo , Apolipoproteína A-V/genéticaRESUMEN
H2A variants are histones that carry out specialized nucleosome function during the eukaryote genome packaging. Most genes encoding H2A histone variants arose in the distant past, and have highly conserved domains and structures. Yet, novel H2A variants have continued to arise throughout the radiation of eukaryotes and disturbed the apparent tranquility of nucleosomes. These species-specific H2A variants contributed to the functional diversification of nucleosomes through changes in both their structure and expression patterns. In this short review, we discuss the evolutionary trajectories of these histone renegades in plants and animal genomes.
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Histonas , Nucleosomas , Animales , Histonas/genética , Histonas/metabolismo , Nucleosomas/genética , Plantas/genética , Plantas/metabolismo , Genoma , Evolución BiológicaRESUMEN
Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 â¥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 â¥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 â¥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .
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BACKGROUND: Severe first-degree atrioventricular (AV) block may produce symptoms similar to heart failure due to AV dyssynchrony, a syndrome termed AV dromotropathy. According to guidelines, it should be considered for permanent pacemaker implantation, yet evidence supporting this treatment is scarce. OBJECTIVES: This study aimed to determine the impact of AV-optimized conduction system pacing (CSP) in patients with symptomatic severe first-degree AV block and echocardiographic signs of AV dyssynchrony. METHODS: Patients with symptomatic first-degree AV block (PR > 250 ms), preserved left ventricular ejection fraction, narrow QRS, and AV dyssynchrony were included in the study. In a single-blind cross-over design, patients were randomized to AV sequential CSP or backup VVI pacing with a base rate of 40 bpm. We compared exercise capacity, echocardiographic parameters, and symptom occurrence at the end of 3 months of each period. RESULTS: Fourteen patients completed the study. During the AV-optimized CSP compared to the backup pacing period, patients achieved a higher workload on exercise test (147.2 ± 50.9 vs. 140.7 ± 55.8 W; p = .032), with a trend towards higher peak VO2 (23.3 ± 7.1 vs. 22.8 ± 7.1 mL/min/kg; p = .224), and higher left ventricular stroke volume (LVSV 74.5 ± 13.8 vs. 66.4 ± 12.5 mL; p < .001). Symptomatic improvement was recorded, with fewer patients reporting general tiredness and 71% of patients preferring the AV-optimized CSP (p = .008). CONCLUSIONS: AV-optimized CSP could improve symptoms, exercise capacity and LVSV in patients with severe first-degree AV block.
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Bloqueo Atrioventricular , Estimulación Cardíaca Artificial , Estudios Cruzados , Tolerancia al Ejercicio , Frecuencia Cardíaca , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Resultado del Tratamiento , Bloqueo Atrioventricular/terapia , Bloqueo Atrioventricular/fisiopatología , Bloqueo Atrioventricular/diagnóstico , Anciano , Método Simple Ciego , Persona de Mediana Edad , Factores de Tiempo , Potenciales de Acción , Recuperación de la Función , Volumen Sistólico , Nodo Atrioventricular/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Few studies have demonstrated a high degree of atrioventricular (AV) synchrony with a new leadless pacemaker called Micra AV. Our group previously reported a new and unique sensing method. We believe that this novel sensing method, "Simplified A3 method," might facilitate better AV synchrony than a conventional sensing method in almost all cases with Micra AV implantation. METHODS: We conducted a non-randomized retrospective study comparing the two pacing methods at two centers. From December 1, 2021 to October 31, 2022, Micra AV was implanted for 32 patients at the two centers. Twenty of the 32 patients with sinus rhythm and complete AV block were included in this study. In Group 1, the conventional setting was programmed as follows: auto A3 threshold, auto A3 window-end (WE), and auto A4 threshold turned on during hospitalization. In Group 2, the "Simplified A3 method" was programmed as follows: auto A3 threshold and auto A3WE turned off. Instead, an intentionally prolonged A3WE (850-1000 ms) and low A3 threshold (A3 signal amplitude + 0.5-1.0 m/s2) were programmed. RESULTS: Twenty patients were analyzed. In Group 2, AV synchrony (%AMVp) was significantly higher at the first outpatient clinic (63.0 ± 5.7% vs 81.0 ± 4.2%, p = .03). A3 threshold was significantly lower in Group 2 (5.9 ± 0.7 m/s2, p < .05 vs 2.3 ± 0.5 m/s2, p < .05). CONCLUSION: Our novel sensing method might be a more feasible sensing method for obtaining higher AV synchrony than the conventional algorithm.
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Potenciales de Acción , Bloqueo Atrioventricular , Estimulación Cardíaca Artificial , Estudios de Factibilidad , Frecuencia Cardíaca , Marcapaso Artificial , Humanos , Masculino , Femenino , Estimulación Cardíaca Artificial/métodos , Estudios Retrospectivos , Anciano , Bloqueo Atrioventricular/terapia , Bloqueo Atrioventricular/fisiopatología , Bloqueo Atrioventricular/diagnóstico , Resultado del Tratamiento , Diseño de Equipo , Anciano de 80 o más Años , Persona de Mediana Edad , Factores de Tiempo , Valor Predictivo de las Pruebas , Nodo Atrioventricular/fisiopatología , Procesamiento de Señales Asistido por ComputadorRESUMEN
INTRODUCTION: Pacemaker-mediated tachycardia is a known arrhythmia in patients with dual chamber pacemakers and defibrillators and intact ventriculoatrial (VA) conduction. We report a case of pacemaker-mediated reentrant arrhythmia (PMRA) in a patient with an atrioventricular (AV) synchronous leadless pacemaker. METHODS AND RESULTS: A 91-year-old female presented with 2:1 AV conduction and received an AV synchronous leadless pacemaker. She had atrial mechanical sense-ventricular paced beats between heart rates of 80-100 bpm more than 80% of the time. She was found to have a new cardiomyopathy and was referred for placement of biventricular pacemaker. At the time of device implantation, her electrocardiogram showed ventricular pacing with a short RP interval and superiorly directed P waves. Changes in the ventricular pacing rate resulted in changes in the atrial rate. Following device placement, her heart rate decreased to the lower rate limit of her pacemaker. The atrial mechanical sense impulse most likely was generated by a retrograde conducted P wave resulting in near incessant PMRA. CONCLUSION: PMRA may occur in patients who receive an AV synchronous leadless pacemaker with intact VA conduction and sinoatrial node dysfunction. Due to the lower rates of PMRA, this arrhythmia may be underrecognized. Interventions for and implications of PMRA need further investigation.
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Development of the heart is a very intricate and multiplex process as it involves not only the three spatial dimensions but also the fourth or time dimension. Over time, the heart of an embryo needs to adapt its function to serve the increasing complexity of differentiation and growth towards adulthood. It becomes even more perplexing by expanding time into millions of years, allocating related species in the tree of life. As the evolution of soft tissues can hardly be studied, we have to rely on comparative embryology, supported heavily by genetic and molecular approaches. These techniques provide insight into relationships, not only between species, but also between cell populations, signaling mechanisms, molecular interactions and physical factors such as hemodynamics. Heart development depends on differentiation of a mesodermal cell population that - in more derived taxa - continues in segmentation of the first and second heart field. These fields deliver not only the cardiomyocytes, forming the three-dimensionally looping cardiac tube as a basis for the chambered heart, but also the enveloping epicardium. The synchronized beating of the heart is then organized by the conduction system. In this Review, the epicardium is introduced as an important player in cardiac differentiation, including the conduction system.
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Evolución Biológica , Sistema de Conducción Cardíaco , Hemodinámica , Pericardio , Vertebrados , Animales , Pericardio/fisiología , Pericardio/embriología , Vertebrados/fisiología , Sistema de Conducción Cardíaco/fisiología , Corazón/fisiología , Corazón/embriologíaRESUMEN
The second generation of transcatheter pacing systems, called Micra AV, can provide atrioventricular (AV) synchronous pacing via a new pacing algorithm relying on sensing mechanical atrial contraction. Several novel programming parameters were introduced to enable AV synchronous pacing, including an A3 window and A4 window as well as a conduction mode switch and an activity mode switch. In addition to several automated features, manual programming optimization of some of the novel parameters is key to improving AV synchrony. A solid knowledge of the features and their programming is essential for electrophysiologists implanting or following patients with Micra AV devices. Differences in programming optimization might partially explain the high variability of AV synchrony published in real-world data reports. This article reviews the key programming parameters of Micra AV. Subsequently, optimal programming recommendations for defined patient profiles are presented. Those were established by consensus within an expert panel comprised of 11 European electrophysiologists from high-volume Micra AV centres. The patient profiles were (1) high degree AV block and slow sinus rhythm; (2) high degree AV block and fast sinus rhythm; and (3) intermittent AV block. The panel recommended to evaluate the mechanical atrial activity on transthoracic echocardiography prior to implant. It was also agreed that Auto A3 Threshold and Tracking Check should be turned off in all patients, AV conduction mode switch should be turned off in all patients with high degree AV block, and the lower rate should be programmed to 50â bpm with exceptions based on individual clinical assessment. Future studies will be useful to evaluate the strength of those recommendations to improve the AV synchrony.
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Bloqueo Atrioventricular , Marcapaso Artificial , Humanos , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/terapia , Estimulación Cardíaca Artificial/efectos adversos , Arritmias Cardíacas/terapia , Frecuencia Cardíaca/fisiologíaRESUMEN
A 16-year-old female with dual-chamber pacemaker (Medtronic Azure XT DR), due to symptomatic third-degree congenital atrioventricular (AV) block, presented to our ambulatory with dizziness and presyncopal episodes preceded by prodromes, occurring over the last few months. The device was programmed in DDD mode with an upper rate of 150 bpm. A head-up Tilt Test (HUTT) revealed the unexpected emergence of 2:1 electronic AV block at a sinus rate of 130 bpm.
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INTRODUCTION: Micra AV Transcatheter Pacing System (TPS) represents an innovative second-generation leadless pacemaker which represents an effective alternative to conventional devices in selected cases. Intrinsic malfunctions of these devices are rare, requiring sometimes their retrieval. When performed in experienced centers, this procedure is safe. CASE PRESENTATION: We describe a case of sudden battery malfunction of a Micra AV TPS, which required the extraction and the placement of a new pacing system in the right ventricle. DISCUSSION: This case, which has never been reported, highlights the need to a careful fluoroscopic evaluation and the usefulness of remote monitoring.
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Arritmias Cardíacas , Marcapaso Artificial , Humanos , Resultado del Tratamiento , Diseño de Equipo , Marcapaso Artificial/efectos adversos , Estimulación Cardíaca ArtificialRESUMEN
In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent improvements in the engineering, delivery, and safety of viral vectors have set the stage for their application as RNA interference (RNAi) delivery tools. Viral vector-based delivery of RNAi has made remarkable breakthroughs in the treatment of several debilitating diseases and disorders (e.g., neurological diseases); however, their novelty has yet to be fully applied and utilized for the treatment of cancer. This review highlights the most promising and emerging viral vector delivery tools for RNAi therapeutics while discussing the variables limiting their success and suitability for cancer therapy. Specifically, we outline different integrating and non-integrating viral platforms used for gene delivery, currently employed RNAi targets for anti-cancer effect, and various strategies used to optimize the safety and efficacy of these RNAi therapeutics. Most importantly, we provide great insight into what challenges exist in their application as cancer therapeutics and how these challenges can be effectively navigated to advance the field.
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Vectores Genéticos , Neoplasias , Interferencia de ARN , Vectores Genéticos/genética , Terapia Genética , Técnicas de Transferencia de Gen , Neoplasias/genética , Neoplasias/terapiaRESUMEN
BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.
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Hipertrigliceridemia , Pancreatitis , Humanos , Apolipoproteína A-V/genética , Apolipoproteínas A/genética , Apolipoproteínas A/metabolismo , Enfermedad Aguda , Pancreatitis/genética , Lipoproteína Lipasa/genética , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/genética , MutaciónRESUMEN
Severe hypertriglyceridemia is a pathological condition caused by genetic factors alone or in combination with environmental factors, sometimes leading to acute pancreatitis (AP). In this study, exome sequencing and biochemical analyses were performed in 4 patients with hypertriglyceridemia complicated by obesity or diabetes with a history of AP or decreased post-heparin LPL mass. In a patient with a history of AP, SNP rs199953320 resulting in LMF1 nonsense mutation and APOE rs7412 causing apolipoprotein E2 were both found in heterozygous form. Three patients were homozygous for APOA5 rs2075291, and one was heterozygous. ELISA and Western blot analysis of the serum revealed the existence of apolipoprotein A-V in the lipoprotein-free fraction regardless of the presence or absence of rs2075291; furthermore, the molecular weight of apolipoprotein A-V was different depending on the class of lipoprotein or lipoprotein-free fraction. Lipidomics analysis showed increased serum levels of sphingomyelin and many classes of glycerophospholipid; however, when individual patients were compared, the degree of increase in each class of phospholipid among cases did not coincide with the increases seen in total cholesterol and triglycerides. Moreover, phosphatidylcholine, lysophosphatidylinositol, and sphingomyelin levels tended to be higher in patients who experienced AP than those who did not, suggesting that these phospholipids may contribute to the onset of AP. In summary, this study revealed a new disease-causing gene mutation in LMF1, confirmed an association between overlapping of multiple gene mutations and severe hypertriglyceridemia, and suggested that some classes of phospholipid may be involved in the pathogenesis of AP.
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Apolipoproteína A-V , Hipertrigliceridemia , Lipoproteína Lipasa , Pancreatitis , Humanos , Pancreatitis/genética , Pancreatitis/sangre , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/sangre , Hipertrigliceridemia/genética , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Apolipoproteína A-V/genética , Apolipoproteínas E/genética , Polimorfismo de Nucleótido Simple , Secuenciación del Exoma , Obesidad/complicaciones , Obesidad/genética , Obesidad/sangre , Enfermedad Aguda , Triglicéridos/sangre , Proteínas de la MembranaRESUMEN
BACKGROUND: Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. METHODS: We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. RESULTS: We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). CONCLUSION: There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.
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Fístula Arteriovenosa , Malformaciones Vasculares del Sistema Nervioso Central , Embolización Terapéutica , Radiocirugia , Masculino , Humanos , Niño , Lactante , Preescolar , Resultado del Tratamiento , Embolización Terapéutica/métodos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/etiologíaRESUMEN
INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.
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Fístula Arteriovenosa , Piamadre , Humanos , Niño , Fístula Arteriovenosa/cirugía , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/terapia , Piamadre/irrigación sanguínea , Preescolar , Adolescente , Lactante , Femenino , Recién Nacido , Resultado del Tratamiento , Masculino , Malformaciones Arteriovenosas Intracraneales/terapia , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/cirugíaRESUMEN
Ebstein's anomaly is a congenital malformation of the tricuspid valve characterized by abnormal attachment of the valve leaflets, resulting in varying degrees of valve dysfunction. The anatomic hallmarks of this entity are the downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Additional intracardiac malformations are common. From an embryological point of view, the cavity of the future right atrium does not have a direct orifice connected to the developing right ventricle. This chapter provides an overview of current insight into how this connection is formed and how malformations of the tricuspid valve arise from dysregulation of molecular and morphological events involved in this process. Furthermore, mouse models that show features of Ebstein's anomaly and the naturally occurring model of canine tricuspid valve malformation are described and compared to the human model. Although Ebstein's anomaly remains one of the least understood cardiac malformations to date, the studies summarized here provide, in aggregate, evidence for monogenic and oligogenic factors driving pathogenesis.
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Modelos Animales de Enfermedad , Anomalía de Ebstein , Válvula Tricúspide , Anomalía de Ebstein/genética , Anomalía de Ebstein/patología , Anomalía de Ebstein/fisiopatología , Animales , Humanos , Perros , Ratones , Válvula Tricúspide/anomalías , Válvula Tricúspide/patologíaRESUMEN
The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.
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Modelos Animales de Enfermedad , Transducción de Señal , Atresia Tricúspide , Animales , Atresia Tricúspide/genética , Atresia Tricúspide/metabolismo , Atresia Tricúspide/patología , Humanos , Ratones , Corazón Univentricular/genética , Corazón Univentricular/metabolismo , Corazón Univentricular/fisiopatología , Corazón Univentricular/patología , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Receptores Notch/metabolismo , Receptores Notch/genéticaRESUMEN
The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of two separate atrial chambers, the formation of an atrial/atrioventricular (AV) septal complex, the incorporation of the caval veins and coronary sinus into the right atrium, and the remodeling events that result in pulmonary venous return draining into the left atrium. In these processes, the atrioventricular mesenchymal complex, consisting of the major atrioventricular (AV) cushions, the mesenchymal cap on the primary atrial septum (pAS), and the dorsal mesenchymal protrusion (DMP), plays a crucial role.
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Atrios Cardíacos , Animales , Humanos , Seno Coronario/embriología , Seno Coronario/anomalías , Corazón/embriología , Mesodermo/embriología , Venas Pulmonares/anomalíasRESUMEN
Tricuspid atresia (TA) is a rare congenital heart condition that presents with a complete absence of the right atrioventricular valve. Because of the rarity of familial and/or isolated cases of TA, little is known about the potential genetic abnormalities contributing to this condition. Potential responsible chromosomal abnormalities were identified in exploratory studies and include deletions in 22q11, 4q31, 8p23, and 3p as well as trisomies 13 and 18. In parallel, potential culprit genes include the ZFPM2, HEY2, NFATC1, NKX2-5, MYH6, and KLF13 genes. The aim of this chapter is to expose the genetic components that are potentially involved in the pathogenesis of TA in humans. The large variability in phenotypes and genotypes among cases of TA suggests a genetic network that involves many components yet to be unraveled.
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Atresia Tricúspide , Humanos , Aberraciones Cromosómicas , Fenotipo , Atresia Tricúspide/genética , Corazón Univentricular/genéticaRESUMEN
BACKGROUND: In China, mitral valve regurgitation (MR) is the most common cardiovascular valve disease. However, patients in China typically experience a high incidence of this condition, coupled with a low level of health knowledge and a relatively low rate of surgical treatment. TikTok hosts a vast amount of content related to diseases and health knowledge, providing viewers with access to relevant information. However, there has been no investigation or evaluation of the quality of videos specifically addressing MR. OBJECTIVE: This study aims to assess the quality of videos about MR on TikTok in China. METHODS: A cross-sectional study was conducted on the Chinese version of TikTok on September 9, 2023. The top 100 videos on MR were included and evaluated using quantitative scoring tools such as the modified DISCERN (mDISCERN), the Journal of the American Medical Association (JAMA) benchmark criteria, the Global Quality Score (GQS), and the Patient Education Materials Assessment Tool for Audio-Visual Content (PEMAT-A/V). Correlation and stepwise regression analyses were performed to examine the relationships between video quality and various characteristics. RESULTS: We obtained 88 valid video files, of which most (n=81, 92%) were uploaded by certified physicians, primarily cardiac surgeons, and cardiologists. News agencies/organizations and physicians had higher GQS scores compared with individuals (news agencies/organizations vs individuals, P=.001; physicians vs individuals, P=.03). Additionally, news agencies/organizations had higher PEMAT understandability scores than individuals (P=.01). Videos focused on disease knowledge scored higher in GQS (P<.001), PEMAT understandability (P<.001), and PEMAT actionability (P<.001) compared with videos covering surgical cases. PEMAT actionability scores were higher for outpatient cases compared with surgical cases (P<.001). Additionally, videos focused on surgical techniques had lower PEMAT actionability scores than those about disease knowledge (P=.04). The strongest correlations observed were between thumbs up and comments (r=0.92, P<.001), thumbs up and favorites (r=0.89, P<.001), thumbs up and shares (r=0.87, P<.001), comments and favorites (r=0.81, P<.001), comments and shares (r=0.87, P<.001), and favorites and shares (r=0.83, P<.001). Stepwise regression analysis identified "length (P<.001)," "content (P<.001)," and "physicians (P=.004)" as significant predictors of GQS. The final model (model 3) explained 50.1% of the variance in GQSs. The predictive equation for GQS is as follows: GQS = 3.230 - 0.294 × content - 0.274 × physicians + 0.005 × length. This model was statistically significant (P=.004) and showed no issues with multicollinearity or autocorrelation. CONCLUSIONS: Our study reveals that while most MR-related videos on TikTok were uploaded by certified physicians, ensuring professional and scientific content, the overall quality scores were suboptimal. Despite the educational value of these videos, the guidance provided was often insufficient. The predictive equation for GQS developed from our analysis offers valuable insights but should be applied with caution beyond the study context. It suggests that creators should focus on improving both the content and presentation of their videos to enhance the quality of health information shared on social media.