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1.
Proc Natl Acad Sci U S A ; 119(33): e2209164119, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35878056

RESUMEN

Voltage-gated sodium (Nav) channel Nav1.7 has been targeted for the development of nonaddictive pain killers. Structures of Nav1.7 in distinct functional states will offer an advanced mechanistic understanding and aid drug discovery. Here we report the cryoelectron microscopy analysis of a human Nav1.7 variant that, with 11 rationally introduced point mutations, has a markedly right-shifted activation voltage curve with V1/2 reaching 69 mV. The voltage-sensing domain in the first repeat (VSDI) in a 2.7-Å resolution structure displays a completely down (deactivated) conformation. Compared to the structure of WT Nav1.7, three gating charge (GC) residues in VSDI are transferred to the cytosolic side through a combination of helix unwinding and spiral sliding of S4I and ∼20° domain rotation. A conserved WNФФD motif on the cytoplasmic end of S3I stabilizes the down conformation of VSDI. One GC residue is transferred in VSDII mainly through helix sliding. Accompanying GC transfer in VSDI and VSDII, rearrangement and contraction of the intracellular gate is achieved through concerted movements of adjacent segments, including S4-5I, S4-5II, S5II, and all S6 segments. Our studies provide important insight into the electromechanical coupling mechanism of the single-chain voltage-gated ion channels and afford molecular interpretations for a number of pain-associated mutations whose pathogenic mechanism cannot be revealed from previously reported Nav structures.


Asunto(s)
Canal de Sodio Activado por Voltaje NAV1.7 , Dolor , Secuencias de Aminoácidos , Microscopía por Crioelectrón , Humanos , Mutación , Canal de Sodio Activado por Voltaje NAV1.7/química , Canal de Sodio Activado por Voltaje NAV1.7/genética , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Dolor/genética , Dominios Proteicos , Rotación
2.
Adv Exp Med Biol ; 1441: 497-503, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884728

RESUMEN

Ventricular septal defects (VSDs) occur in 1.5-3.5 of 1000 live births and constitutes 20 % of congenital cardiac defects. There is no gender predominance.


Asunto(s)
Defectos del Tabique Interventricular , Humanos , Defectos del Tabique Interventricular/terapia , Defectos del Tabique Interventricular/diagnóstico por imagen , Femenino , Masculino , Recién Nacido
3.
Adv Exp Med Biol ; 1441: 535-549, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884730

RESUMEN

Ventricular septation is a complex process which involves the major genes of cardiac development, acting on myocardial cells from first and second heart fields, and on mesenchymal cells from endocardial cushions. These genes, coding for transcription factors, interact with each other, and their differential expression conditions the severity of the phenotype. In this chapter, we will describe the formation of the ventricular septum in the normal heart, as well as the molecular mechanisms leading to the four main anatomic types of ventricular septal defects: outlet, inlet, muscular, and central perimembranous, resulting from failure of development of the different parts of the ventricular septum. Experiments on animal models, particularly transgenic mouse lines, have helped us to decipher the molecular determinants of ventricular septation. However, a precise description of the anatomic phenotypes found in these models is mandatory to achieve a better comprehension of the complex mechanisms responsible for the various types of VSDs.


Asunto(s)
Modelos Animales de Enfermedad , Defectos del Tabique Interventricular , Animales , Humanos , Ratones , Regulación del Desarrollo de la Expresión Génica , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/patología , Defectos del Tabique Interventricular/metabolismo , Ratones Transgénicos , Transducción de Señal/genética , Tabique Interventricular/patología , Tabique Interventricular/metabolismo , Tabique Interventricular/embriología
4.
Adv Exp Med Biol ; 1441: 201-226, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884713

RESUMEN

A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases.


Asunto(s)
Corazón , Hemodinámica , Humanos , Animales , Hemodinámica/fisiología , Corazón/crecimiento & desarrollo , Corazón/fisiología , Cardiopatías Congénitas/fisiopatología
5.
Adv Exp Med Biol ; 1441: 875-884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884756

RESUMEN

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.


Asunto(s)
Atresia Tricúspide , Humanos , Aberraciones Cromosómicas , Fenotipo , Atresia Tricúspide/genética , Corazón Univentricular/genética
6.
Adv Exp Med Biol ; 1441: 505-534, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884729

RESUMEN

Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.


Asunto(s)
Defectos del Tabique Interventricular , Humanos , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad/genética , Defectos del Tabique Interventricular/genética , Mutación , Factores de Transcripción/genética
7.
Cardiol Young ; 34(1): 189-191, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38031460

RESUMEN

Coronary cameral fistula is a rare congenital anomaly and clinical presentation depends on the location of the defect, degree of shunting, and associated complications. We present a case of coronary cameral fistula where segmental analysis by echocardiogram helped us to avoid misdiagnosis as a ventricular septal defect.


Asunto(s)
Enfermedad de la Arteria Coronaria , Fístula , Cardiopatías Congénitas , Defectos del Tabique Interventricular , Tabique Interventricular , Humanos , Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/diagnóstico por imagen
8.
Sensors (Basel) ; 24(5)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38475194

RESUMEN

This article presents an in-depth investigation of wearable microwave antenna sensors (MASs) used for vital sign detection (VSD) and lung water level (LWL) monitoring. The study looked at two different types of MASs, narrowband (NB) and ultra-wideband (UWB), to decide which one was better. Unlike recent wearable respiratory sensors, these antennas are simple in design, low-profile, and affordable. The narrowband sensor employs an offset-feed microstrip transmission line, which has a bandwidth of 240 MHz at -10 dB reflection coefficient for the textile substrate. The UWB microwave sensor uses a CPW-fed line to excite an unbalanced U-shaped radiator, offering an extended simulated operating bandwidth from 1.5 to 10 GHz with impedance matching ≤-10 dB. Both types of microwave sensors are designed on a flexible RO 3003 substrate and textile conductive fabric attached to a cotton substrate. The specific absorption rate (SAR) of the sensors is measured at different resonant frequencies on 1 g and 10 g of tissue, according to the IEEE C95.3 standard, and both sensors meet the standard limit of 1.6 W/kg and 2 W/kg, respectively. A simple peak-detection algorithm is used to demonstrate high accuracy in the detection of respiration, heartbeat, and lung water content. Based on the experimental results on a child and an adult volunteer, it can be concluded that UWB MASs offer superior performance when compared to NB sensors.


Asunto(s)
Microondas , Respiración , Humanos , Adulto , Niño , Frecuencia Cardíaca , Frecuencia Respiratoria , Pulmón
9.
Int Wound J ; 21(1): e14362, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37605359

RESUMEN

The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around foot and ankle with vaccum sealing drainage (VSD) or induction membrane (IM) of cement formation and attempt to provide an optimal strategy for elderly patients. A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from October of 2016 and October of 2020 was performed. Based on the different way, the patients were divided into two groups: VSD group (n = 26) and IM group (n = 27). Outcomes were assessed according to the size of the defect, frequency of debridement procedures, hospitalization time, duration of healing, the healing rate, major amputation rate, functional outcomes and complications. Immunohistochemistry (IHC) detection of vascular endothelial growth factor (VEGF) was also be completed. We found that there was no difference in demographic characteristics, size of the defect, debridement times and functional outcomes between the two groups (p > 0.05); however, a significant difference in the wound healing time, hospitalization time and complications were noted between them(p < 0.05). The fresh granulation tissue of both groups showed abundant positive expression of VEGF. Thus, the VSD and IM are both available for foot and ankle reconstruction in elderly patients. However, the IM group offers short hospitalization time, duration of healing and lower frequency of postoperative complications. Thus, we advocate the IM for reconstruction of defects of the foot and ankle region in the elderly patients.


Asunto(s)
Tobillo , Traumatismos de los Tejidos Blandos , Humanos , Anciano , Tobillo/cirugía , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular , Drenaje , Extremidad Inferior/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Resultado del Tratamiento , Trasplante de Piel/métodos
10.
J Med Virol ; 95(4): e28682, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36929732

RESUMEN

The human virome, or the viral communities distributed on or in our body, is estimated to contain about 380 trillion of viruses (individuals), which has far reaching influences on our health and diseases. Obviously, the sheer numbers of viruses alone make the comparisons of two or multiple viromes extremely challenging. In fact, the theory of computation in computer science for so-termed NP-hard problems stipulates that the problem is unsolvable when the size of virome is sufficiently large even with fastest supercomputers. Practically, one has to develop heuristic and approximate algorithms to obtain practically satisfactory solutions for NP-hard problems. Here, we extend the species-specificity and specificity-diversity framework to develop a method for virome comparison (VC). The VC method consists of a pair of metrics: virus species specificity (VS) and virome specificity diversity (VSD) and corresponding pair of random search algorithms. Specifically, the VS and VS permutation (VSP) test can detect unique virus species (US) or enriched virus species (ES) in each virome (treatment), and the VSD and VSD permutation (VSDP) test can further determine holistic differences between two viromes or their subsets (assemblages of viruses). The test with four virome data sets demonstrated that the VC method is effective, efficient, and robust.


Asunto(s)
Viroma , Virus , Humanos , Viroma/genética , Especificidad de la Especie , Virus/genética , Metagenómica
11.
Ultrasound Obstet Gynecol ; 61(3): 346-355, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36565437

RESUMEN

OBJECTIVES: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls. METHODS: Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2 ) and an index of microvascular cerebral blood flow (CBFi ), along with peripheral arterial oxygen saturation (SpO2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. RESULTS: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA-VSD group. During the predischarge period, SO2 was higher in TGA-IVS than in TGA-VSD neonates, while CBFi was lower. CONCLUSIONS: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Conducto Arterial , Defectos del Tabique Interventricular , Transposición de los Grandes Vasos , Lactante , Recién Nacido , Femenino , Humanos , Embarazo , Defectos del Tabique Interventricular/cirugía , Hemodinámica/fisiología , Arteria Pulmonar , Oxígeno , Hemoglobinas
12.
BMC Cardiovasc Disord ; 23(1): 600, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38066421

RESUMEN

OBJECTIVE: To evaluate the accuracy of transthoracic echocardiography (TTE) and cardiac computed tomography angiography (CTA) in detecting the size and location of ventricular septal defects (VSD) in infants. METHODS: Data from 258 infants diagnosed with VSD between January 2020 and December 2022 were retrospectively analyzed. All infants underwent both TTE and cardiac CTA. The accuracy of these imaging modalities was assessed by comparing their findings with intraoperative observations of VSD size and location. RESULTS: Intraoperatively, the average VSD size was 6.1 ± 2.5 mm. The defects were classified as committed VSD (Type 1) in 45 patients, noncommitted VSD (Type 2) in 198 patients, inlet VSD (Type 3) in 12 patients, and muscular VSD (Type 4) in 3 patients. Echocardiography estimated the average VSD size at 5.6 ± 2.7 mm, with 42 patients identified as Type 1, 203 as Type 2, 10 as Type 3, and 3 as Type 4. Cardiac CTA estimated the average size at 5.9 ± 3.2 mm, with 48 patients identified as Type 1, 196 as Type 2, 11 as Type 3, and 3 as Type 4. The accuracy rates of TTE and cardiac CTA in diagnosing VSD location were 98.1% and 98.8%, respectively. A survey of surgeons indicated that 80% believe both TTE and cardiac CTA are essential preoperative evaluations. CONCLUSIONS: TTE accurately diagnoses the size and location of VSD, while cardiac CTA serves as a valuable complementary method to TTE. Most surgeons advocate for the combined use of these examinations for preoperative assessment.


Asunto(s)
Angiografía por Tomografía Computarizada , Defectos del Tabique Interventricular , Lactante , Humanos , Estudios Retrospectivos , Ecocardiografía/métodos , Corazón , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/cirugía
13.
Artículo en Inglés | MEDLINE | ID: mdl-37938799

RESUMEN

We report a 5-year-old girl with transient complete atrioventricular (AV) block following surgical closure of a symptomatic conoventricular ventricular septal defect (VSD) which recovered on post-operative day 9. She later presented with exertional dizziness and fatigue. While congenital cardiac defect repairs are occasionally complicated by complete heart block, this patient was found to have intra-Hisian Wenckebach which is rare in the pediatric population and can be very difficult to discern from surface electrocardiograms and by Holter monitoring. Mechanisms of post-surgical AV block, including intra-Hisian Wenckebach, are not well characterized in the pediatric population.

14.
BMC Pediatr ; 23(1): 67, 2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-36759823

RESUMEN

BACKGROUND: With prevalence up to 4%, Ventricular Septal Defect (VSD) is one of the leading causes of neonatal deaths. VSD is a common complex genetic disorder that has been associated with many genetic determinants. Variants from genes for the transcription factors including T-Box TBX5 and NFATc1 (nuclear factor of activated T cells, cytoplasmic 1), Vascular endothelial growth factor (VEGF), ISLET1 (encoded by the ISL1 gene) and enzyme MTHFR, a methylene tetrahydrofolate reductase were selected. Genetic risk score (GRS) is a widely accepted approach used to convert the genetic data into prediction and assessment tool for disease susceptibility. METHODS: A total of 200 participants were recruited for the current study, 100 VSD patients and 100 controls. Genotyping of the ISL1: rs1017, NFATc1: rs7240256, VEGF: rs36208048, TBX5: rs11067075, and MTHFR: rs1801133 variants was performed using tetra primer ARMS PCR and PCR-RFLP. For the statistical analysis, the software SPSS version 23 was used. Genotypic frequencies of cases and controls were calculated using chi-square (χ²) whereas allelic frequencies were calculated by using the SNPStats tool. The association of GRS quartiles with VSD was examined using binary logistic regression. Adjusted p-value 0.01 was used as significance threshold for all analyses. RESULTS: The ISL1 (OD: 0.242, CI: 0.158-0.37, p-value: 2.15 × 10- 4 :), NFATc1 (OD: 2.53, CI: 1.64-3.89, p-value: 2.11 × 10- 5), TBX5 (OD: 2.24, CI: 1.47-3.41, p-value:1.6 × 10- 4) and MTHFR (OD: 10.46, CI: 5.68-19.26, p-value: 2.09 × 10- 9:) variants were found to be in association with VSD. In contrast, the VEGF (OD: 0.952, CI: 0.56-1.62, p-value: 0.8921) variant did not show significance association with the VSD. For cases, the mean GRS score was 3.78 ± 1.285 while in controls it was 2.95 ± 1.290 (p-value: 0.479, CI: 0.474-1.190). Comparison of GRS between cases and control showed that mean GRS of cases was 1.90 ± 0.480 while in controls it was 1.68 ± 0.490 (p-value: 0.001, CI: 0.086-0.354). Higher quartiles were more prevalent in cases whereas lower quartiles were more prevalent in controls. CONCLUSION: GRS of these five loci was strongly associated with VSD. Moreover, genetic risk score can provide better information for the association between variants and disease as compared to a single SNP. We also illustrated that the cumulative power of GRS is greater over the single SNP effect. This is a pilot scale study with a relatively small sample size whose findings should be replicated in a larger sample size for the unique local Pakistani population.


Asunto(s)
Defectos del Tabique Interventricular , Factor A de Crecimiento Endotelial Vascular , Recién Nacido , Femenino , Humanos , Factor A de Crecimiento Endotelial Vascular/genética , Pakistán , Proyectos Piloto , Defectos del Tabique Interventricular/genética , Genotipo , Factores de Transcripción/genética , Estudios de Casos y Controles
15.
Proc Natl Acad Sci U S A ; 117(43): 27016-27021, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33051293

RESUMEN

The opening and closing of voltage-gated ion channels are regulated by voltage sensors coupled to a gate that controls the ion flux across the cellular membrane. Modulation of any part of gating constitutes an entry point for pharmacologically regulating channel function. Here, we report on the discovery of a large family of warfarin-like compounds that open the two voltage-gated type 1 potassium (KV1) channels KV1.5 and Shaker, but not the related KV2-, KV4-, or KV7-type channels. These negatively charged compounds bind in the open state to positively charged arginines and lysines between the intracellular ends of the voltage-sensor domains and the pore domain. This mechanism of action resembles that of endogenous channel-opening lipids and opens up an avenue for the development of ion-channel modulators.


Asunto(s)
Activación del Canal Iónico , Canal de Potasio Kv1.5/agonistas , Canales de Potasio de la Superfamilia Shaker/agonistas , Animales , Ensayos Analíticos de Alto Rendimiento , Canal de Potasio Kv1.5/metabolismo , Simulación del Acoplamiento Molecular , Técnicas de Placa-Clamp , Canales de Potasio de la Superfamilia Shaker/metabolismo , Xenopus laevis
16.
Pediatr Cardiol ; 44(3): 587-598, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35852568

RESUMEN

We sought to characterize the clinical course and outcomes of intervention for Tetralogy of Fallot (TOF) with associated conal septal hypoplasia (CSH) compared to those with identifiable conal septum on initial newborn echocardiogram. We performed a retrospective, 1:2 case-control study of children with TOF anatomy, 33 with CSH and 66 with typical TOF, who underwent surgical repair from 1991-2019 at Children's Wisconsin. Data on echocardiographic anatomic features, systemic oxygen saturations, medical therapies, admissions, palliative interventions, operative strategies, and long-term follow-up were compared. The CSH group had fewer hypercyanotic spells (6% vs 42%, p < 0.001), beta-blockers prescribed (12% vs 41%, p = 0.005), and hospital admissions for cyanosis (12% vs 44%; p = 0.001) prior to any intervention. Of 14 who required palliative intervention, 8 had balloon pulmonary valvuloplasty (BPV) (7 from the CSH group and 1 from the control group), and 6 had systemic-to-pulmonary artery shunts (all from the control group). Definitive repair was performed at a significantly older age in the CSH group (10.2 ± 10 vs 5.6 ± 5.9 months, p = 0.011), with less subpulmonary muscle resection (57.6% in vs 92.4%, p < 0.001) and higher use of a transannular patch (84.8% vs 65.2%, p = 0.040). The average time to surgical reintervention was similar in both groups (9.7 ± 5.9 vs 8.6 ± 6.4 years in controls). We conclude that infants with TOF and CSH have a milder preoperative clinical course with fewer hypercyanotic spells or need for medical therapy. They also respond well to palliative BPV and can safely undergo later definitive repair compared to typical TOF with a well-developed conal septum.


Asunto(s)
Caracol Conus , Tetralogía de Fallot , Lactante , Recién Nacido , Niño , Animales , Humanos , Tetralogía de Fallot/cirugía , Estudios Retrospectivos , Estudios de Casos y Controles , Progresión de la Enfermedad , Resultado del Tratamiento
17.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37511161

RESUMEN

This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. This investigation reveals a relatively new and underexplored phenomenon: protein-mediated electroporation. Our research focused on the voltage-sensing domain (VSD) of the NaV1.5 sodium cardiac channel in response to nsPEF stimulation. We scrutinized the VSD structures that form pores and thereby contribute to the physical chemistry that governs the defibrillation effect of nsPEF. To do so, we conducted a comprehensive analysis involving the clustering of 142 replicas simulated for 50 ns under nsPEF stimuli. We subsequently pinpointed the representative structures of each cluster and computed the free energy between them. We find that the selected VSD of NaV1.5 forms pores under nsPEF stimulation, but in a way that significant differs from the traditional VSD opening. This study not only extends our understanding of nsPEF and its interaction with protein channels but also adds a new effect to further study.


Asunto(s)
Electricidad , Electroporación , Electroporación/métodos , Terapia de Electroporación , Corazón
18.
Int Wound J ; 20(3): 768-773, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36382601

RESUMEN

To investigate the clinical application of vacuum sealing drainage (VSD) in chronic osteomyelitis of the extremities combined with soft tissue defects in adults. This study retrospectively included 32 adult patients with clearly diagnosed chronic osteomyelitis of the extremities combined with local soft tissue defects, and the trauma was covered by VSD after debridement, osteotomy, and vancomycin-laden bone cement filling of the occupancy, and the trauma was covered by selecting a suitable flap transfer repair according to the site and extent of the soft tissue defect after the trauma condition was suitable, and the secondary trauma was taken from the abdominal full-thickness skin free skin slice graft, according to whether the skin graft area was performed. The skin flap hematoma and infection rate, as well as the skin flap survival rate and implant fixation time were compared and analysed between the two groups. The primary outcome is the implant fixation time, and the secondary outcome is the skin fragment survival rate. In 32 patients, VSD was performed on the bone cement surface to cover the trauma, and 33.2 to 39.8 kPa continuous vacuum sealing drainage was set. The average VSD time duration before soft tissue coverage was 47.87 ± 23.14 days, and the average number of VSD use was 7.18 ± 3.23. The use of VSD before soft tissue coverage did not cause complications such as negative pressure could not be maintained, vacuum sealing drainage was not smooth, skin blistering, trauma. Among the 32 patients, 12 cases of soft tissue coverage were followed by trauma free skin grafting with packing + VSD, and 20 cases were fixed with packing alone, and the duration of continuous packing and fixation of free skin pieces in the VSD group was significantly less than that in the control group (P = .006). The survival rate was significantly higher than that of the control group (P = .019). VSD in adult patients with chronic osteomyelitis of the extremities combined with soft tissue defects can effectively improve the trauma condition, provide the possibility of second-stage soft tissue coverage, and significantly shorten the preparation time for soft tissue coverage. In addition, when soft tissue coverage trauma is performed, VSD combined with skin graft packing technique can significantly improve the survival rate of skin pieces, shorten the time of skin graft fixation.


Asunto(s)
Terapia de Presión Negativa para Heridas , Osteomielitis , Traumatismos de los Tejidos Blandos , Humanos , Adulto , Cicatrización de Heridas , Cementos para Huesos , Estudios Retrospectivos , Terapia de Presión Negativa para Heridas/métodos , Resultado del Tratamiento , Trasplante de Piel/métodos , Extremidades/cirugía , Osteomielitis/cirugía , Osteomielitis/complicaciones , Traumatismos de los Tejidos Blandos/cirugía , Traumatismos de los Tejidos Blandos/etiología
19.
Int Wound J ; 20(10): 4253-4261, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37574848

RESUMEN

The present study aimed to investigate the effect of local oxygen therapy combined with vacuum sealing drainage (VSD) on the healing of stage IV pressure ulcers sacrococcygeal. In this prospective study, we included a total of 98 patients with stage IV sacrococcygeal pressure ulcers in our hospital between February 2021 and June 2022. The patients enrolled were randomly and equally divided into two groups: the study group (undergoing local oxygen therapy combined with VSD treatment) and the control group (receiving conventional treatment). The wound healing time and hospital stay were compared between the two groups. Additionally, the wound area, tissue type, wound exudation and pain intensity were assessed before treatment, 10, 20, 30 and 40 days after treatment. The incidence of complications was also calculated. The study group demonstrated significantly shorter wound healing time and hospital stays compared to the control group (p < 0.05). Before treatment, there were no significant differences in terms of wound area, tissue type and wound exudation between the two groups (p > 0.05); after 10, 20, 30 and 40 days of treatment, however, evidently smaller wound areas, improved tissue types and reduced wound exudation were observed in the study group compared to the control group (p < 0.05). Furthermore, the study group exhibited increased microvascular count compared to the control group (p < 0.05). Before treatment, there was no significant difference in pain intensity between the two groups (p > 0.05), whereas markedly lower pain intensity was seen in the study group than in the control group after 10, 20, 30 and 40 days of treatment (p < 0.05). The incidence of complications did not significantly differ between the two groups after 40 days of treatment (p > 0.05). Local oxygen therapy combined with VSD was found to effectively accelerate the healing process of stage IV sacrococcygeal pressure ulcers, leading to shorter hospital stays and improved patient prognosis. This combined therapy shows promise for widespread application in clinical practice.


Asunto(s)
Terapia de Presión Negativa para Heridas , Úlcera por Presión , Humanos , Úlcera por Presión/terapia , Oxígeno/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Cicatrización de Heridas , Drenaje
20.
Catheter Cardiovasc Interv ; 99(5): 1679-1682, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35253339

RESUMEN

Significant hemolysis is a recognized complication of transcatheter high-velocity shunt occlusion using some Amplatzer devices. We describe a case of severe hemolysis following occlusion of an iatrogenic Gerbode defect with an Amplatzer muscular ventricular septal defect occluder successfully managed by transcatheter device removal and reocclusion with a Gore Cardioform Atrial Septal Defect Occluder.


Asunto(s)
Defectos del Tabique Interatrial , Defectos del Tabique Interventricular , Dispositivo Oclusor Septal , Cateterismo Cardíaco/efectos adversos , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/terapia , Hemólisis , Humanos , Dispositivo Oclusor Septal/efectos adversos , Resultado del Tratamiento
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