Dietary supplementation of magnolol alleviates fatty liver hemorrhage syndrome in postpeak Xinhua laying hens via regulation of liver lipid metabolism.

As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has emerged as a major cause of noninfectious mortality in laying hens, resulting in substantial economic losses to the poultry industry. This study aimed to investigate the therapeutic effects of magnolol on FLHS in postpeak laying hen model, focusing on lipid metabolism, antioxidative capacity, and potential molecular mechanisms of action. We selected 150 Xinhua laying hens aged 50 wk and divided them into normal diet group (ND), high-fat diet group (HFD), 100 mg/kg magnolol group (MG100), 300 mg/kg magnolol group (MG300), 500 mg/kg magnolol group (MG500) on average. The experiment lasted for 6 wk, and liver samples were collected from the hens at the end of the experiment. The results demonstrated that the inclusion of magnolol in the diet had a significant impact on various factors. It led to a reduction in weight, an increase in egg production rate, a decrease in blood lipid levels, and an improvement in abnormal liver function, liver steatosis, and oxidative stress. These effects were particularly prominent in the MG500 group. The RNA-Seq analysis demonstrated that in the MG500 group, there was a down-regulation of genes associated with fatty acid synthesis (Acc, Fasn, Scd, Srebf1, Elovl6) compared to the HFD group. Moreover, genes related to fatty acid oxidation (CPT1A and PGC1α) were found to be up-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these differentially expressed genes indicated their enrichment in the PPAR signaling pathway. These findings demonstrate that magnolol can mitigate FLHS by inhibiting fatty acid synthesis and promoting fatty acid oxidation. This discovery offers a novel approach for treating FLHS in laying hens, reducing the economic losses associate with FLHS.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Dehydroepiandrosterone activates the GPER-mediated AMPK signaling pathway to alleviate the oxidative stress and inflammatory response in laying hens fed with high-energy and low-protein diets.

Fatty liver hemorrhagic syndrome (FLHS) seriously threatens the layer industry due to it can cause a sudden decline in egg production and acute death, and dietary supplement with bioactive substance is considered an effective way to prevent the FLHS occurrence. Dehydroepiandrosterone (DHEA) is a popular dietary supplement and it possesses anti-oxidative and anti-inflammatory functions; however, the effect and underlying mechanism about DHEA in protecting against the occurrence and development of FLHS remain elucidated. The current results showed that DHEA relieved HELP-induced decrease of egg productivity and liver injury in laying hens. Meanwhile, DHEA markedly enhanced the antioxidant capacity and then alleviated oxidative stress via activation of nuclear factor (erythroid-derived 2)-like 2 (NRF-2) signal in laying hens fed with HELP diets. In addition, DHEA significantly alleviated HELP-stimulated systemic inflammatory response by suppressing the overproduction of hepatic pro-inflammatory factors in laying hens, and further found this beneficial effect was achieved by blocking the activation of NF-κB pathway. Furthermore, we found that DHEA promoted the AMP-activated protein kinase α (AMPKα) activation and increased the G-protein-coupled estrogen receptor (GPER) expression level in laying hens fed with HELP diets. In summary, our data demonstrated that DHEA attenuates oxidative stress and inflammation through the activation of GPER-AMPK signal axis in laying hens fed with HELP diets. These results might facilitate an understanding of the benefits and mechanism of DHEA on the development of FLHS, and provide sufficient data to support it as a dietary supplement to control the FLHS-related metabolic diseases in chickens.

Dietary supplementation of salidroside alleviates liver lipid metabolism disorder and inflammatory response to promote hepatocyte regeneration via PI3K/AKT/Gsk3-ß pathway.

Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and inflammation, and promoting antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-ß, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced FLHS hens had heavier body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced FLHS hens had high levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1ß, IL-6, and IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-ß pathway in OA-induced fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.

Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study.

OBJECTIVES: It was the first time to examine the role of maternal polymorphisms of FOLR1 gene and FOLR2 gene, as well as their interactions with maternal folic acid supplementation (FAS), in the risk of ventricular septal defect (VSD). METHODS: A case-control study was conducted with 385 mothers of VSD infants and 652 controls. The exposures of interest were FAS and FOLR1 gene and FOLR2 gene polymorphisms. The logistic regression model was used for accessing the strength of association. RESULTS: After controlling for the potential confounders, women who did not utilize folic acid had a substantially higher risk of VSD (aOR = 2.25; 95% CI: 1.48 to 3.43), compared to those who did. We also observed genetic polymorphisms of FOLR1 gene at rs2071010 (GA vs. GG: aOR = 0.63, 95%CI: 0.45 to 0.88) and rs11235462 (AA vs. TT: aOR = 0.53, 95%CI: 0.33 to 0.84), as well as FOLR2 gene at rs651646 (AA vs. TT: aOR = 0.46, 95%CI: 0.30 to 0.70), rs2298444 (CC vs. TT: aOR = 0.58, 95%CI: 0.36 to 0.91) and rs514933 (TC vs. TT: aOR = 0.57, 95%CI: 0.41 to 0.78) were associated with a lower risk of VSD. Furthermore, there was a statistically significant interaction between maternal FAS and genetic polymorphisms at rs514933 on the risk of VSD (FDR_P = 0.015). CONCLUSIONS: The maternal genetic polymorphisms of the FOLR1 gene and FOLR2 gene, as well as FAS and their interactions, were shown to be significantly associated with the risk of VSD in offspring.

Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case-Control Study.

BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

The effect of music therapy on chronic pain, quality of life and quality of sleep in adolescents after transthoracic occlusion of ventricular septal defect.

OBJECTIVE: To investigate the effect of music therapy on chronic pain, quality of life, and quality of sleep in adolescent patients after transthoracic occlusion of ventricular septal defects. METHODS: Patients were divided into 2 groups based on whether they received music therapy: a control group and a music group. The music group received 30 minutes of music therapy every day for 6 months after surgery. Patients in the control group received standard treatment and had 30 minutes of quiet time every day for 6 months after surgery. The short-form McGill pain questionnaire (SF-MPQ), the SF-36 scale and the Karolinska Sleep Questionnaire (KSQ) was used as the evaluation tool for chronic pain, quality of life, and quality of sleep, respectively. RESULTS: In terms of the degree of postoperative chronic pain, the Pain Rating Index (PRI) emotion item score in the SF-MPQ evaluation of the music group was significantly lower than that of the control group (1.6 ± 1.1 versus 2.2 ± 0.9). The role emotional (RE) scores of the SF-36 in the music group were significantly higher than that in the control group (77.35 ± 18.55 versus 42.66 ± 22.63). KSQ scores were significantly higher in the music group than in the control group for sleep status (4.1 ± 1.0 versus 3.3 ± 0.9), falling asleep (3.9 ± 1.1 versus 3.1 ± 1.0), and not feeling refreshed by sleep (3.6 ± 1.3 versus 2.7 ± 0.9) (P < .05). CONCLUSION: This study preliminarily showed that music therapy could effectively reduce patients' chronic pain and improve quality of life and sleep after surgery. These results suggest that music therapy may be an essential therapy worth considering in managing patients' postoperative recovery after cardiovascular surgery.

Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.

Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

Successful Conservative Treatment of Mycotic Pulmonary Artery Aneurysms Caused by MRSA Bacteremia.

Mycotic pulmonary artery aneurysms (MPAAs) are rare and life-threatening with currently no recommended treatment strategies. In this report, we describe a successfully treated case of ventricular septal defect in an 11-month-old girl who developed bacteremia, infective endocarditis, and MPAA caused by methicillin-resistant Staphylococcus aureus (MRSA). We first started vancomycin, gentamycin, and panipenem-betamipron for infective endocarditis but switched to teicoplanin and arbekacin on day 3 after initiating treatment because bacteremia persisted, and vancomycin minimum inhibitory concentration was relatively high at 2 mg/L. Although we added clindamycin on day 5 and fosfomycin on day 7, MRSA bacteremia persisted, and we finally added daptomycin at 10 mg/kg per day on day 8, whereupon the bacteremia subsided within a day. Although the bacteremia subsided, the patient developed septic pulmonary embolisms and septic arthritis on her left knee. We continued daptomycin but switched the concomitant drug to linezolid, trimethoprim-sulfamethoxazole, and rifampicin on day 11. After several repeats of puncture and lavage of her knee joint, she became afebrile on day 16. Computed tomography scans taken on day 32 revealed right pulmonary artery MPAAs. She was treated with long-term multidrug therapy, and MPAAs were absent on subsequent computed tomography scans on day 184. Multidrug therapy mainly based on daptomycin could be a possible salvage therapy for refractory MRSA bacteremia with high vancomycin minimum inhibitory concentration. Conservative treatment should be selectively considered as a treatment option for clinically stable MPAA instead of surgical and endovascular treatment.

Caracterización de las enfermedades valvulares congénitas en la edad pediátrica / Characterization the pediatric patients with diagnostic of illnesses congenital valvulares

Introducción: Las valvulopatías congénitas son un grupo de entidades en las cuales la principal alteración anatomofuncional está en las válvulas cardiacas. Objetivo: Caracterizar los pacientes pediátricos nacidos vivos con diagnósticos de valvulopatías congénitas. Métodos: Se realizó una investigación descriptiva retrospectiva a partir de los registros de valvulopatías congénitas del Servicio de Cardiología del Hospital Pediátrico Universitario José Luis Miranda en Santa Clara, Cuba, en el periodo de 2005 a 2016. La población estuvo conformada por los 147 niños nacidos vivos con diagnóstico de valvulopatías congénitas. Se empleó un muestreo no probabilístico intencional por criterios y la muestra quedó conformada por 143. La recogida de la información se realizó a través de la revisión documental de las historias clínicas. Resultados: La tasa de incidencia de la valvulopatías congénitas fue de 1,5 x 1 000 nacidos vivos, predominó la estenosis pulmonar que agrupó el 70,6 por ciento de los diagnosticados. Se encontró predominio del sexo masculino con 50,3 por ciento, se determinó que 45,5 por ciento de los casos se diagnosticaron antes de los 29 días de nacido, período que incluye un diagnóstico prenatal. Conclusiones: El desarrollo del diagnóstico prenatal de las cardiopatías congénitas ha posibilitado la disminución de la incidencia de las malformaciones más complejas. El conocimiento de las enfermedades congénitas del corazón contribuye a operar de forma segura y con resolución anatómica completa a muchos de estos niños en el período prenatal o cuando son lactantes pequeños, para evitar el deterioro global de estos cuando la cardiopatía no está resuelta(AU)

Introduction: The congenital valvulopatías is a group of entities in which the main alteration anatomofuncional is in the heart valves. Objective: To characterize the pediatric patients with diagnostic of born congenital valvulopatías. Methods: He/she was carried out a retrospective descriptive investigation starting from the registrations of congenital valvulopatías of the service of Cardiology of the Hospital Pediatric University student José Luis Miranda in the period of 2005 at the 2016. The population was conformed by the 147 alive born children with diagnostic of congenital valvulopatías, a sampling was not used intentional probabilístico by approaches, being conformed the sample by 143. The collection of the information was carried out through the documental revision of the clinical histories. Results: The rate of incidence of the congenital valvulopatías was of 1,5 x 1000 born alive, the lung estenosis prevailed containing to 70,6 percent of those diagnosed he/she was prevalence of the masculine sex in 50,3 percent, it was determined that 45,5 percent of the cases was diagnosed before the 29 days where a prenatal diagnosis is included. Conclusions: The development of the prenatal diagnosis of the congenital cardiopatías has facilitated the decrease of the incidence of the most complex malformations. The knowledge of the congenital illnesses of the heart contributes to operate in a sure way and with complete anatomical resolution to many of these children in the prenatal period or when they are small nurslings, to avoid the global deterioration of these when the cardiopatía is not resolved(AU)

Prevalence of congenital heart diseases in children with Down syndrome in Mansoura, Egypt: a retrospective descriptive study.

BACKGROUND: The pattern and risk factors for congenital heart diseases (CHD) in children with Down syndrome (DS) vary over time. OBJECTIVES: To update knowledge of the prevalence, types, trends and associated factors for CHD in children with DS in the Egyptian Delta. DESIGN: A retrospective hospital record-based descriptive study. SETTING: A tertiary care center in Mansoura, Egypt during a period of 14 years from 2003 up to 2016. PATIENTS AND METHODS: We studied children with genetically proven DS. Relevant sociodemographic factors, medical history, clinical examination, karyotype and echocardiographic data were statistically analyzed. MAIN OUTCOME MEASURES: Prevalence, types and risk factors of CHD in DS. RESULTS: The prevalence of overall, isolated and multiple CHD in 1720 children with DS were 36.9%, 29% and 8%, respectively. Isolated defects accounted for 78.4% of all CHD. Ventricular septal defect, atrioventricular septal defect and atrial septal defect were the most frequent isolated defects. There was a downward trend in the prevalence of overall CHD (from 56.2% to 25.0%) and isolated CHD (from 56.2% to 19.8%). The logistic regression model predicted 65.7% of CHD and revealed that passive maternal smoking, lack of folic acid/multivitamin supplementation and parental consanguinity were the independent predictors of CHD in children with DS with adjusted odds ratios of 1.9, 1.8 and 1.9, respectively. CONCLUSION: More than one-third of children with DS have CHD with ventricular septal defect, which is the most common. Avoidance of passive maternal smoking and consanguineous marriage together with maternal folic acid supplementation could contribute to further reduction of CHD in children with DS. LIMITATIONS: Single-center study and retrospective.

Altered Carnitine Homeostasis in Children With Increased Pulmonary Blood Flow Due to Ventricular Septal Defects.

OBJECTIVES: Congenital heart disease with increased pulmonary blood flow results in progressive pulmonary vascular endothelial dysfunction and associated increased perioperative morbidity. Using our ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated progressive endothelial dysfunction associated with disruption in carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide signaling, and enhanced reactive oxygen species generation. However, potential alterations in these parameters in patients with congenital heart disease have not been investigated. The objective of this study was to test the hypothesis that children with increased pulmonary blood flow will have evidence of altered carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide levels, and increased reactive oxygen species generation. DESIGN: A prospective single-center cohort study. SETTING: A tertiary care cardiac ICU/PICU. PATIENTS: Arterial blood samples from 18 patients with congenital heart disease associated with increased pulmonary blood flow (ventricular septal defect), 20 with congenital heart disease without increased pulmonary blood flow (tetralogy of Fallot), and 10 without heart disease (controls) were obtained. INTERVENTIONS: Plasma levels of total carnitine, free carnitine, acylcarnitine, and lactate-to-pyruvate ratios, an indicator of mitochondrial function, were determined and compared. In addition, levels of superoxide and hydrogen peroxide were determined and compared in patients with ventricular septal defect and controls. Statistical analysis was performed using an unpaired t test and analysis of variance. MEASUREMENTS AND MAIN RESULTS: Baseline acylcarnitine levels (25.7 ± 13 vs 12.7 ± 8.3; p < 0.05), the acylcarnitine-to-free carnitine ratio (0.8 ± 0.1 vs 0.3 ± 0.05; p < 0.05), and the lactate-to-pyruvate ratio were higher in ventricular septal defect (27.5 ± 3.8 vs 11.1 ± 4.1, p < 0.05) than tetralogy of Fallot; there were no differences between tetralogy of Fallot and control. Superoxide and H2O2 levels were also higher in ventricular septal defect compared with controls, and NOx levels were lower in ventricular septal defect patients compared with tetralogy of Fallot and controls (p < 0.05). CONCLUSIONS: These data suggest that increased pulmonary blood flow from ventricular septal defect results in altered carnitine and mitochondrial homeostasis, decreased nitric oxide signaling, and increased reactive oxygen species production. These data are consistent with our animal data demonstrating that altered carnitine homeostasis results in mitochondrial dysfunction, increased reactive oxygen species production, and decreased bioavailable nitric oxide. Since disruption of carnitine metabolism may contribute to endothelial dysfunction, carnitine supplementation may attenuate endothelial dysfunction associated with increased pulmonary blood flow and warrants further investigation.

Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case-control study.

OBJECTIVE: Previous Hungarian intervention trials have shown an association between periconceptional folic-acid-containing multivitamin supplementation and significantly reduced risk of congenital heart defects (CHDs). These findings were confirmed in observational multivitamin studies in the USA, and studies in the Netherlands and China regarding folic acid. The objective of this observational population-based study was to estimate the possible preventive effect of folic acid supplementation for different CHDs during their critical period of development. STUDY DESIGN: Evaluation of medically recorded use of folic acid (calculated daily average 5.6mg) during the critical period of development of eight types of CHD (verified through autopsy reports or after catheter examination and/or surgical correction) in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996, containing 22,843 cases with congenital abnormalities and 38,151 population controls without any CHDs, including 5395 matched controls of 3567 live-born cases with various CHDs. A conditional logistic regression model was used to estimate the relative risk/protection [odds ratio (OR) with 95% confidence intervals (CI)] of folic acid in the mothers of cases with various types of CHD and their matched controls. RESULTS: There was a significant decrease in the prevalence of cases with ventricular septal defect (OR 0.57, 95% CI 0.45-0.73), tetralogy of Fallot (OR 0.53, 95% CI 0.17-0.94), d-transposition of great arteries (OR 0.47, 95% CI 0.26-0.86) and atrial septal defect secundum (OR 0.63, 95% CI 0.40-0.98) in infants born to mothers who had taken high doses of folic acid during the critical period of CHD development. CONCLUSIONS: The risk of development of certain types of CHD was significantly reduced in pregnant women who were supplemented with folic acid. Thus, CHDs should be included as a secondary assessment in neural-tube-defect preventive programs.

Acupuncture regulates the heart rate variability.

Acupuncture is widely used in clinical practice. According to traditional acupuncture theory, the Neiguan acupoint (PC6) is one of the most commonly used acupoints and is indicated for treating cardiovascular-related disorders. We present the case of a 27-year-old female who had been diagnosed with ventricular septal defect and had undergone surgery to repair the defect at the age of 11 years. The patient had no obvious symptoms, such as palpitations and difficulty breathing. However, while performing electrocardiography (ECG), we found that she suffered from arrhythmia, and therefore, we treated her by acupuncture at the left PC6. An ECG monitor was used to record data during the entire acupuncture procedure, which was divided into the following three segments: prior to, during, and after acupuncture. Various indices of heart rate variability (HRV) were then determined and analyzed. The results indicate that acupuncture can regulate the HRV effectively; however, more studies are needed to confirm this finding.

Effect of complex cardiac rehabilitation on physical activity and quality of life during long-term follow-up after surgical correction of congenital heart disease.

BACKGROUND: Comprehensive cardiac rehabilitation (CCR) is an important element of the comprehensive management of grown-up congenital heart disease (GUCH) patients after surgical correction of congenital heart disease (CHD) but access to this treatment is still limited. We still lack Polish guidelines on CCR, including controlled training in young adults several years after surgical correction of CHD. AIM: To assess the effect of a CCR program on physical capacity, exercise tolerance, quality of life, and severity of depressive symptoms in GUCH patients long-term after surgical correction of CHD. METHODS: We studied 57 CHD patients (30 females, 27 males, mean age 23 ± 3.4 years) at least 12 months after surgical correction of a ventricular septal defect (VSD) or ostium secundum atrial septal defect (ASD II). All patients were offered a CCR program, and 31 of them participated (rehabilitation group [Reh]) and 26 refused (non-rehabilitated group [NReh]). All patients underwent baseline cardiopulmonary exercise testing (CPET) using a cycloergometer and a ramp protocol with an initial load of 20 W followed by 10 W load increments per minute. Psychological evaluation included the Beck Depression Inventory (BDI) and the Euro QoL 5D questionnaire to evaluate quality of life. Patients were reassessed 30 days after the initial evaluation using the same investigations. RESULTS: During CPET, all patients reached peak exercise intensity at the level of 15-17 in the Borg scale without complications. Resting HR was lower in the Reh group (74 ± 8 bpm) compared to the NReh group (81 ± 14 bpm). During CPET, patients in the Reh group reached significantly higher peak HR and percent maximum HR. Workload increased nonsignificantly (144 W vs. 124 W, p = 0.121), while duration of exercise and peak oxygen consumption was significantly longer in the Reh group compared to the NReh group (14 min vs. 11 min, p = 0.001; and 27.5 mL/kg/min vs. 23 mL/kg/min, p = 0.003, respectively). Patients in the NReh group showed non significantly higher severity of depressive symptoms compared to the Reh group, as evaluated using BDI at 30 days (mean score 4.8 vs. 2.2, respectively, p = 0.59). In contrast, subjectively and objectively rated quality of life was significantly higher in the Reh group compared to the NReh (score 89 vs. 74.4, p < 0.01; and 94 vs. 83, p < 0.01, respectively). CONCLUSIONS: Implementation of a CCR program improves physical capacity, exercise tolerance, and quality of life and reduces depressive symptoms in patients late after surgical correction of CHD. Introduction of such programs seems reasonable as a supplement to the holistic care for GUCH patients.

Moderately high intake of folic acid has a negative impact on mouse embryonic development.

BACKGROUND: The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20-fold higher FA than the recommended intake for rodents had adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10-fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR). METHODS: Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA-supplemented diet (FASD; 10-fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness. RESULTS: Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet. CONCLUSIONS: Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.

Landiolol for junctional ectopic tachycardia refractory to amiodarone after pediatric cardiac surgery.

Postoperative junctional ectopic tachycardia (JET) in children undergoing cardiac surgery is a serious arrhythmia that is associated with considerable morbidity and mortality. We present here a case of successful landiolol therapy for postoperative JET in a 3-month-old infant who underwent ventricular septal defect closure and right pulmonary artery plasty. His left ventricular function was poor postoperatively. The JET was refractory to amiodarone and caused severe hypotension, which was required cardiac massage. Continuous intravenous infusion of low-dose landiolol reduced the persistent JET rate immediately, and restored to sinus rhythm with stable hemodynamics.

Cryoablation of ventricular tachycardia arising from the left-coronary sinus cusp.

Ventricular tachycardia (VT) arising from the coronary sinus cusps and mimicking right-ventricular morphology is a rare entity. In this report, we report the successful cryoablation of left-coronary sinus cusp VT.

Association of maternal diseases during pregnancy with the risk of single ventricular septal defects in the offspring--a population-based case-control study.

OBJECTIVE: In general, the analytical epidemiological studies evaluated cases with congenital heart defects (CHDs) together. However, different CHD entities have different etiology, and in the vast majority of patients the underlying causes are unclear. Thus the objective of the study was to evaluate the possible etiological factors in the origin of single ventricular septal defect (VSD) after surgical intervention or lethal outcome, i.e. as homogeneous as possible. METHOD: In the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities acute and chronic maternal diseases with related drug treatments and pregnancy supplements in early pregnancy were evaluated in the mothers of 1661 cases with isolated/single VSD and their 2534 matched and 38,151 all controls without defect, and 19,833 malformed controls with other isolated non-cardiac defect. RESULTS: There was a higher risk of VSD in the children of mothers with high fever related influenza during the critical period of VSD and this risk was limited by antifever therapy. In addition paroxysmal supraventricular tachycardia and epilepsy treated with anticonvulsant drugs associated with higher risk of VSD. Finally, the high doses of folic acid alone in early pregnancy. CONCLUSIONS: High-fever-related maternal diseases may have a role in the origin of VSD which is preventable with antifever drug therapy, and the high doses of folic acid in early pregnancy reduced the risk of VSD.