Development and uniqueness test of highly selective atomic topological indices based on the number of attached hydrogen atoms.

On the basis of the atomic graph-theoretical index - aEAID (atomic Extended Adjacency matrix IDentification) and molecular adjacent topological index - ATID (Adjacent Topological IDentification) suggested by one of the authors (Zhang Q), a highly selective atomic topological index - aATID (atomic Adjacent Topological IDentification) index was suggested to identify the equivalent atoms in this study. The aATID index of an atom was derived from the number of the attached hydrogen atoms of the atom but omitting bond types. In this case, the suggested index can be used to identify equivalent atoms in chemistry but perhaps not equivalent in the molecular graph. To test the uniqueness of aATID indices, the virtual atomic data sets were derived from alkanes containing 15-20 carbon atoms and the isomers of Octogen, as well as a real data set was derived from the NCI database. Only four pairs of atoms from alkanes containing 20 carbons can't be discriminated by aATID, that is, four pairs of degenerates were found for this data set. To solve this problem, the aATID index was modified by introducing distance factors between atoms, and the 2-aATID index was suggested. Its uniqueness was examined by 5,939,902 atoms derived from alkanes containing 20 carbons and further 16,166,984 atoms from alkanes of 21 carbons, and no degenerates were found. In addition, another large real data set of 16,650,688 atoms derived from the PubChem database was also used to test the uniqueness of both aATID and 2-aATID. As a result, each atom was successfully discriminated by any of the two indices. Finally, the suggested aATID index was applied to the identification of duplicate atoms as data pretreatment for QSPR (Quantitative Structure-Property Relationships) studies.

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study.

Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients' responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer-Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 µmol/L vs. 332.7 ± 56 µmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974-0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 µmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer-Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit.   Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children. What is Known: • Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events. What is New: • A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

Congenital Anomalous Origin of Coronary Artery Disease in Children With Syncope: A Case Series.

Objective: This study is aimed to analyze the characteristics of congenital anomalous origin of coronary artery in pediatric patients with syncope. Methods: A total of eight patients were retrospectively analyzed from August 2018 to August 2020 who were admitted to the Peking University First Hospital with the complaint of syncope and were diagnosed with congenital coronary artery disease. Results: In total, eight patients were included in the study with a median age of 12.5 ± 2.7 (8-16) years. In total, four of them were males, and four were females. Six of the eight patients were diagnosed with right anomalous coronary artery from the opposite sinus (R-ACAOS), while two patients were diagnosed with left anomalous coronary artery from the opposite sinus (L-ACAOS). The most frequent inducement was exercise, and the commonest prodromes were dizziness and blurred vision. Serum cardiac markers and exercise electrocardiography test (EET) were normal in seven of the patients. The majority of cases had abnormal electrocardiograms (ECGs), but only two of them manifested elevated/depressed ST-T segments. In total, seven patients had positive head-up tilt test (HUT). Echocardiography and coronary artery computed tomography angiography (CTA) were performed to aid the diagnosis. Coronary unroofing procedures were conducted in four patients, and none of them reported syncope after the surgery. The other four patients received routine medical treatment for vasovagal-like syncope. In total, two patients out of them became asymptomatic, and in the other two patients, episodes of syncope were reduced, but they still required medical treatment. Conclusion: Congenital coronary artery anomalies in children with syncope need prompt attention. Though ECG and echocardiography are the common methods for investigating cardiac syncope, they have limited ability to find coronary artery anomalies. When coronary artery anomalies are suspected, coronary CTA should be considered.

Persulfidation of transcription factor FOXO1 at cysteine 457: A novel mechanism by which H2S inhibits vascular smooth muscle cell proliferation.

INTRODUCTION: The proliferation of vascular smooth muscle cells (VSMCs) is an important physiological and pathological basis for many cardiovascular diseases. Endogenous hydrogen sulfide (H2S), the third gasotransmitter, is found to preserve vascular structure by inhibiting VSMC proliferation. However, the mechanism by which H2S suppresses VSMC proliferation has not been fully clear. OBJECTIVES: This study aimed to explore whether H2S persulfidates the transcription factor FOXO1 to inhibit VSMC proliferation. METHODS: After the proliferation of VSMC A7r5 cells was induced by endothelin-1 (ET-1), FOXO1 phosphorylation and proliferating cell nuclear antigen (PCNA) expression were detected by Western blotting, the degree of FOXO1 nuclear exclusion and PCNA fluorescent signals in the nucleus were detected by immunofluorescence, and the persulfidation of FOXO1 was measured through a biotin switch assay. RESULTS: The results showed that ET-1 stimulation increased cell proliferation, FOXO1 phosphorylation and FOXO1 nuclear exclusion to the cytoplasm in the cells. However, pretreatment with NaHS, an H2S donor, successfully abolished the ET-1-induced increases in the VSMC proliferation, FOXO1 phosphorylation, and FOXO1 nuclear exclusion to the cytoplasm. Mechanistically, H2S persulfidated the FOXO1 protein in A7r5 and 293T cells, and the thiol reductant DTT reversed this effect. Furthermore, the C457S mutation of FOXO1 abolished the H2S-induced persulfidation of FOXO1 in the cells and the subsequent inhibitory effects on FOXO1 phosphorylation at Ser256, FOXO1 nuclear exclusion to the cytoplasm and cell proliferation. CONCLUSION: Thus, our findings demonstrated that H2S might inhibit VSMC proliferation by persulfidating FOXO1 at Cys457 and subsequently preventing FOXO1 phosphorylation at Ser256.

Estimation of Ionic Liquids Toxicity against Leukemia Rat Cell Line IPC-81 based on the Empirical-like Models using Intuitive and Explainable Fingerprint Descriptors.

Ionic liquids as green solvents have been paid extensive attention in recent years. However, mostly it is cost and time-consuming to measure their properties. Thus, theorical methods, especially ultrafast chemoinformatics methods were introduced into these studies. Instead of abstract and complex models in some QSPR studies, in this study, the 2D structural features related to the toxicity of ionic liquids were discussed at first, and then the corresponding intuitive and meaningful descriptors were suggested to construct quantitative chemoinformatics models, finally a multiple linear regression (MLR) based on the empirical-like models were applied to the estimation of toxicities of 304 ionic liquids. For the test sets, the relationship coefficients reached up to R=0.90. An external test set of 11 ionic liquids collected from other literatures was submitted to the achieved MLR equations, and the satisfactory result (R=0.94) was obtained.

Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells.

The regulatory mechanisms for proliferation and migration of vascular smooth muscle cells have not yet been clear. The present study was designed to investigate whether and how endothelin-1 (ET-1) impacted the generation of endogenous sulfur dioxide (SO2) in rat vascular smooth muscle cell (VSMC) proliferation and migration. Primary VSMCs and purified aspartate aminotransferase (AAT) protein were used in this study. We found that in the presence of ET-1, the expression of PCNA and Ki-67 was upregulated and the migration of VSMCs was promoted, while the AAT activity and SO2 levels in VSMCs were reduced without any changes in AAT1 and AAT2 expression. SO2 supplementation successfully prevented the ET-1-facilitated expression of PCNA and Ki-67 and the migration of VSMCs. Interestingly, ET-1 significantly increased reactive oxygen species (ROS) production in association with SO2/AAT pathway downregulation in VSMCs compared with controls, while the ROS scavenger N-acetyl-L-cysteine (NAC) and the antioxidant glutathione (GSH) significantly abolished the ET-1-stimulated downregulation of the SO2/AAT pathway. Moreover, the AAT activity was reduced in purified protein after the treatment for 2 h. However, NAC and GSH blocked the hydrogen peroxide-induced AAT activity reduction. In conclusion, our results suggest that ET-1 results in the downregulation of the endogenous SO2/AAT pathway via ROS generation to enhance the proliferation and migration of VSMCs.

Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy.

OBJECTIVE: Hydrogen sulfide (H2S), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that H2S regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that H2S targets cardiomyocyte autophagy to regulate cardiovascular function. DATA SOURCES: This review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases." STUDY SELECTION: Original articles and critical reviews on H2S and autophagy were selected for this review. RESULTS: When autophagy plays an adaptive role in the pathogenesis of diseases, H2S restores autophagy; otherwise, when autophagy plays a detrimental role, H2S downregulates autophagy to exert a cardioprotective function. For example, H2S has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. H2S postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy. CONCLUSIONS: H2S exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of H2S therapy for cardiovascular diseases.

Significance of red cell distribution width in the differential diagnosis between neurally mediated syncope and arrhythmic syncope in children.

OBJECTIVES: The aim of the present study was to explore the predictive value of red cell distribution width as a means to differentiate between neurally mediated syncope and arrhythmic syncope in children. METHOD: Patients were divided into a neurally mediated syncope group (n=72) and an arrhythmic syncope group (n=21) on the basis of clinical history, results of the head-up tilt test, electrocardiography, and 24-hour ambulatory electrocardiography. As controls, we recruited 55 healthy children. Red cell distribution width was determined for children in all groups. A receiver operating characteristic curve was drawn to study the predictive effect of red cell distribution width to differentiate between neurally mediated syncope and arrhythmic syncope. RESULTS: Red cell distribution width was significantly higher in children with neurally mediated syncope than in children with arrhythmic syncope and the control group. A receiver operating characteristic curve on the predictive value of red cell distribution width in differentiating neurally mediated syncope from arrhythmic syncope showed that the area under the curve was 0.841 (95% confidence interval: 0.737-0.945, p<0.05). A red cell distribution width value of 12.8% as the cut-off value yielded a sensitivity of 80.6% and a specificity of 76.2% in discriminating between patients with neurally mediated syncope and arrhythmic syncope. CONCLUSION: Red cell distribution width value of ⩾12.8% might be a useful adjunct for primary-care physicians to differentiate neurally mediated syncope from arrhythmic syncope in children.

[Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance].

OBJECTIVE: To explore possible mechanisms of postural tachycardia syndrome (POTS) by comparing plasma intermedin (IMD) during head-up tilt test (HUTT) in children with POTS. METHOD: The study subjects were divided into two groups: POTS group and control group. The POTS group consisted of twenty-nine children (male 14, female 15) with POTS, the mean age (12.4 ±3.1) years old, admitted into Peking University First Hospital from November 2013 to June 2014. The control group consisted of 32 healthy children (male 17, female 15). Their mean age was (11.6±2.2) years old, who were confirmed as healthy by physical examination and HUTT. Finapres Medical System was used to continuously monitor heart rate and blood pressure during HUTT, and electrocadiogram was performed. Supine systolic and diastolic blood pressure, mean arterial pressure (MAP), ΔMAP (standing mean arterial pressure-supine MAP), supine heart rate and ΔHR (standing HR-supine HR) were compared between POTS group and control group. Sandwich immunoluminescence assay was used to test plasma IMD. The plasma IMD level was compared in supine between POTS and control group. The plasma IMD level in supine was compared with HUTT in POTS group. RESULT: No significant differences were found in age, height, weight, supine systolic and diastolic blood pressure, MAP, ΔMAP and supine heart rate between POTS group and control group (P>0.05). ΔHR in POTS group was significantly higher than that of control group ((48±10) vs. (22±7) beats /min, t=9.797, P<0.05). The plasma IMD level in POTS group was lower than that of control group in supine position ((497±61)×10(-6) vs. (529±58)×10(-6) mg/L, t=2.117, P<0.05). But, it was higher during HUTT than supine IMD in POTS group ((537±57) ×10(-6) vs. (497±61)×10(-6) mg/L, t=-2.464, P<0.05). The plasma delta IMD level (HUTT vs. supine) was positively correlated with delta HR in POTS group (r=0.435, P<0.05). CONCLUSION: The excessively high heart rate during HUTT have a positive correlation with plasma IMD, which may play a role in the pathogenesis of POTS in children.

Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt.

BACKGROUND: The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods. RESULTS: High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt. CONCLUSION: H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.

Erythrocytic hydrogen sulfide production is increased in children with vasovagal syncope.

OBJECTIVES: To explore the differences in erythrocyte hydrogen sulfide (H2S) production in children with vasovagal syncope (VVS). STUDY DESIGN: A total of 54 children including 27 with VVS, aged 6-16 years (mean age 11.3 ± 3.3 years), and 27 healthy children, aged 3-17 years (mean age 10.4 ± 1.8 years) were included in the study. Children with VVS had symptoms of dizziness, pallor, blurred vision, nausea, and some had syncope. Erythrocyte H2S production was measured by a sulphur-sensitive electrode. Flow-mediated dilation (FMD) of brachial artery was measured for each patient by vascular ultrasound. RESULTS: H2S production from erythrocytes was significantly increased in the children with VVS compared with controls (P < .01). The erythrocytic H2S production in the VVS-vasoinhibitory subgroup was obviously higher than that in VVS-cardioinhibitory (P < .05) and VVS-mixed inhibitory subgroups (P < .05). FMD in the VVS-vasoinhibitory subgroup was greater than that in the VVS-cardioinhibitory (P < .05) and the VVS-mixed subgroups (P < .05). The erythrocytic H2S production had a positive linear correlation with FMD in children with VVS (P < .05). CONCLUSIONS: Increased erythrocyte H2S production may be involved in the pathogenesis of VVS in children.

[Significance of serum iron in the differential diagnosis between vasovagal syncope and postural orthostatic tachycardia syndrome in children].

OBJECTIVE: To explore the predictive value of serum iron in differentiating between vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children. METHODS: Totally 57 children (aged 4-17 years, POTS 40 cases, and VVS 17 cases) who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2009 to September 2012 were included in the study. The diagnoses were analyzed by the value of serum iron and receiver operating characteristic (ROC) curves used to explore the predictive value of different serum iron in differential diagnosis between VVS and POTS. RESULTS: There were significant differences in the median value of POTS [17.4 (interquartile range 13.5 -21.8) µmol/L] and VVS [8.9 (interquartile range 7.5-17.6) µmol/L] (P<0.01). When the value of serum iron was 11.8 µmol/L, the sensitivity and specificity of the differential diagnosis between VVS and POTS were 92.5% and 64.7%, respectively. CONCLUSION: The serum iron might be used as an initial diagnostic method in differential diagnosis between VVS and POTS, based on the history of the patients.

Value of history taking in children and adolescents with cardiac syncope.

AIM: This study was designed to investigate the value of history taking in identifying children with cardiac syncope, and to improve diagnostic efficiency and accuracy in children with cardiac syncope. METHODS AND RESULTS: We compared the characteristics of a group of children and adolescents with cardiac syncope at the Pediatric Syncope Unit of five hospitals in China with those with typical vasovagal syncope. We included a cohort of 275 patients in Pediatric Syncope Unit. A cardiac cause of syncope was established in 31 patients, autonomic-mediated reflex syncope in 214, non-syncopal attacks in 15, and in the remaining 15 the cause of syncope remained unexplained. Cardiac syncope was triggered by exercise, whereas vasovagal syncope by prolonged standing, warm-crowded place, and fear or pain emotion. Syncopal spells occurred at various positions in cardiac syncope. Children who had prodromal symptoms with cardiac syncope were significantly fewer than those with vasovagal syncope. Most children with cardiac syncope had history of abnormal electrocardiogram findings when compared with children suffering from vasovagal syncope. On multivariable analysis, history of abnormal electrocardiogram findings and exercise-triggered syncope were independent predictors of cardiac syncope. CONCLUSION: Children and adolescents with a history of abnormal electrocardiogram findings and exercise-related syncope spells were at high risk for cardiac syncope.

[A modified Calgary syncope syndrome score in the differential diagnosis between cardiac syncope and vasovagal syncope].

OBJECTIVE: This study aimed at analyzing the usefulness of a modified Calgary Syncope Syndrome Score in the differential diagnosis between cardiac syncope (CS) and vasovagal syncope (VVS) in children through a large sample clinical study. METHOD: Totally 189 children [112 males, 77 females, aged 2 - 18 yrs, mean age (12.4 ± 3.1) yrs] with CS and VVS who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2002 to April 2011 were included in the study. The diagnosis was analyzed by a modified Calgary Syncope Syndrome Score and receiver operating characteristic (ROC) curve was used to explore the predictive value of different Calgary Syncope Syndrome Scores in differential diagnosis between CS and VVS. RESULT: There were significant differences in the score between CS [-5.00(-7, 1)] and VVS [1(-4, 6)] (P < 0.01). When the score was ≤ -2.5, the sensitivity and specificity of the differential diagnosis between CS and VVS were 95.4% and 67.7%, respectively. Since the modified Calgary Syncope Syndrome Score was integer number, CS should be considered when the score was less than -3. CONCLUSION: The modified Calgary Syncope Syndrome Score might be used as an initial diagnostic method in differential diagnosis between CS and VVS, based on the history of the patients.

[Diagnosis of unexplained syncope in children: a multi-center study].

OBJECTIVE: To examine the diagnostic value of head-up tilt test in children with unexplained syncope (UPS). METHODS: A total of 379 children (171 males, 208 females) aged 3-18 years, mean age (12 +/- 3) years with unexplained syncope from Beijing, Hunan, Hubei and Shanghai and undergoing baseline head-up tilt tests (BHUTT) or head-up tilt tests potentiated with nitroglycerine (SNHUTT) under a quiet circumstance were selected as the syncope group. Ten healthy children (5 males, 5 females) aged 9-15 years with a mean age of (11.4 +/- 2.1) years, were recruited as the control group. SPSS 10.0 software was used for data analysis. RESULTS: In 379 children with unexplained syncope, 67 (17.7%) were of postural orthostatic tachycardia syndrome (POTS), 157 (41.4%) of vasovagal syncope vasoinhibitory pattern, 14 (3.7%) of vasovagal syncope cardioinhibitory pattern, 47 (12.4%) of vasovagal syncope mixed pattern, 1 (0.3%) of orthostatic hypotension (OH) and 93 children (24.5%) of UPS. In syncope group and control group, the positive rate of BHUTT was 55.9% and 0 respectively and it was 75.5% and 20.0% respectively for SNHUTT. During BHUTT, the mean time of positive response occurrence was (16 +/- 12) minutes, and the posture when positive response appeared was at a tilt angle of 60 degrees. For SNHUTT, the mean time of positive response occurrence was (6 +/- 4) minutes and the posture was at a tilt angle of 60 degrees when potentiated with nitroglycerine. CONCLUSION: HUTT is an objective diagnostic tool of UPS. With a high diagnostic positive rate, SNHUTT can improve the diagnostic positive rate of BHUTT. Meanwhile the time of positive response occurrence during SNHUTT is markedly shorter than BHUTT.

Randomized comparison of metoprolol versus conventional treatment in preventing recurrence of vasovagal syncope in children and adolescents.

BACKGROUND: Previous studies that have assessed the effects of beta blockers on preventing vasovagal syncope provide conflicting results. We sought to evaluate the effectiveness of metoprolol versus conventional treatment in preventing the recurrence of syncope in children and adolescents. MATERIAL/METHODS: Twenty-eight children and adolescents (8 boys, 20 girls; mean age, 12+/-3 years; age range, 8-17 years) with vasovagal syncope were randomized to receive either metoprolol (metoprolol group; dosage range, 0.5-1.5 mg/kg/d) or conventional treatment (control group) for 1 year. The main outcome measure was the first recurrence of syncope beginning 2 weeks after the start of treatment. The mean follow-up was 22+/-10 months. Time to first recurrence of syncope was analyzed using Kaplan-Meier curves and compared with a log-rank test. RESULTS: The 2 groups did not differ in terms of clinical characteristics. The number of syncopal episodes before tilt testing was 8+/-6 in patients in the metoprolol group and 9+/-6 in patients in the control group (P=0.150). Syncope recurred in 6 of 14 children in the metoprolol group and in 4 of 14 children in the control group. No significant between-group differences were found regarding the probability of freedom from a recurrent episode of syncope during follow-up (metoprolol vs controls, 43% vs 29%; P=0.389), as demonstrated by Kaplan-Meier curve analyses. CONCLUSIONS: Recurrence of vasovagal syncope in children and adolescents treated with metoprolol is similar to that of patients treated with conventional therapy.

Aetiologic and clinical characteristics of syncope in Chinese children.

AIM: This study aimed to improve diagnostic efficacy of syncope in children by analyzing the aetiology and clinical characteristics of syncope in Chinese children. METHODS: We retrospectively analyzed the causes of syncope and diagnostic workup in 154 consecutive children seen in the Department of Pediatrics, Peking University First Hospital, China, because of a syncope-related event. RESULTS: In all patients with transient loss of consciousness (TLOC), there were 136 (88.31%) patients attributing to syncope, and 18 (11.69%) belonging to nonsyncopal cases. Neurally mediated syncope (NMS) was the most common cause of syncope (99 cases; 64.3%), with cardiac causes ranking second (10 cases; 6.5%). Other nonsyncopal causes included psychiatric problems and neurological and metabolic disorders. In 25 cases (16.2%), the cause was uncertain. Cases of NMS often had clear inducement of syncope and prodromes. Children with cardiac syncope often had a history of cardiac disease, were often younger than those with NMS, and showed exercise-related syncope, syncope spells in any body position or at an early age, or sudden death in family members but no prodromes. Neurological disorder was suspected in cases of TLOC with seizures, TLOC spells in any position, postictal phase of disorientation or abnormal neurological signs. A metabolic cause is suspected with a history of metabolic disease, prolonged anger, or violent vomiting and diarrhoea. Children with psychiatric disorders were adolescent girls, with prolonged TLOC spells, who had more frequent TLOC. Although many tests were used in diagnosis, most were not goal directed. Now, electrocardiography is recommended in almost all children with syncope. Neurological testing, including electroencephalography and computed tomography were rarely helpful unless with evidence of neurological signs and symptoms. Head-up tilt test (HUTT) was most useful in children with recurrent syncope in whom heart disease was not suspected. CONCLUSION: NMS was the most common cause of syncope. We recommended HUTT as the important basis of the TLOC workup.

[Hemodynamic changes during head-up tilt test and predictive value thereof in predicting the efficacy of metoprolol therapy in children with vasovagal syncope].

OBJECTIVE: To investigate the value of hemodynamic changes during head-up tilt (HUT) test and predictive value thereof in evaluating the efficacy of metoprolol therapy in children with vasovagal syncope (VSS). METHODS: Twenty-six consecutive children with history of VSS diagnosed by head-up tilt (HUT) or sublingual nitroglycerin potentiated head-up tilt (SNHUT), who were treated with metoprolol for 6 approximately 12 months and followed up for (18 +/- 9) months (12 approximately 36 months), were divided into two groups according to effect of metoprolol: effective treatment group (n = 16, aged 12 +/- 2) without VSS recurrence during treatment and fellow-up, and futile treatment group (n = 10, aged 12 +/- 3). The heart rate changes during HUT or SNHUT were evaluated between the two groups. RESULTS: There were no significant differences between these 2 groups with regard to the demographic and clinical characteristics including age, gender, history, syncope spells, follow-up time and heart rate, mean blood pressure in supine position and during positive response. For example, the baseline heart rate of the effective treatment group was 81 +/- 12 beats/min, not significantly different from that of the futile treatment group (78 +/- 8 beats/min, P = 0.804). However, during tilt test 16 of the 26 patients in the effective treatment group showed tachycardia before positive response, with the mean heart rate of (123 +/- 15) beats/min, whereas all 10 patients in the futile group did not have tachycardia before positive response, with the mean heart rate of (96 +/- 17) beats/min. If an increase of 30 beats/min was taken as a borderline in heart rate during positive response in HUT compared with that of baseline value, in respect of predicting the metoprolol efficacy in the treatment of VVS, the sensitivity was 81% (13/16), the specificity was 80% (8/10), and the diagnostic value was 81% (21/26). CONCLUSION: A marked increase in heart rate in HUT or SNHUT is a better predictor of metoprolol efficacy in the treatment of children with VVS.

Random forest prediction of mutagenicity from empirical physicochemical descriptors.

Fast-to-calculate empirical physicochemical descriptors were investigated for their ability to predict mutagenicity (positive or negative Ames test) from the molecular structure. Fast methods are highly desired for the screening of large libraries of compounds. Global molecular descriptors and MOLMAP descriptors of bond properties were used to train random forests. Error percentages as low as 15% and 16% were achieved for an external test set with 472 compounds and for the training set with 4083 structures, respectively. High sensitivity and specificity were observed. Random forests were able to associate meaningful probabilities to the predictions and to explain the predictions in terms of similarities between query structures and compounds in the training set.